With the widespread use of antibiotics, drug-resistant bacterial infections have become a significant threat to human health. Finding new antibacterial strategies that can effectively control drug-resistant bacterial infections has become an urgent task. Unlike small molecule drugs that target bacterial proteins, antisense oligonucleotide (ASO) can target genes related to bacterial resistance, pathogenesis, growth, reproduction and biofilm formation. By regulating the expression of these genes, ASO can inhibit or kill bacteria, providing a novel approach for the development of antibacterial drugs. To overcome the challenge of delivering antisense oligonucleotide into bacterial cells, various drug delivery systems have been applied in this field, including cell-penetrating peptides, lipid nanoparticles and inorganic nanoparticles, which have injected new momentum into the development of antisense oligonucleotide in the antibacterial realm. This review summarizes the current development of small nucleic acid drugs, the antibacterial mechanisms, targets, sequences and delivery vectors of antisense oligonucleotide, providing a reference for the research and development of antisense oligonucleotide in the treatment of bacterial infections.

To guide transfusion practice in critically ill children who often need plasma and platelet transfusions, the Transfusion and Anemia Expertise Initiative-Control/Avoidance of Bleeding (TAXI-CAB) developed Recommendations and Expert Consensus for Plasma and Platelet Transfusion Practice in Critically Ill Children. This guideline addresses 53 recommendations related to plasma and platelet transfusion in critically ill children with 8 kinds of diseases, laboratory testing, selection/treatment of plasma and platelet components, and research priorities. This paper introduces the specific methods and results of the recommendation formation of the guideline.

AIM: To investigate the effects of agkis-trodon halys venom anti-tumor component (AHVAC-) on the biological behavior of gastric cancer MKN-28 cells. METHODS: Gastric cancer MKN-28 cells were treated with the experimental concentrations (5, 10, 15 μg/mL) of AHAVC- for 24 h. Cell proliferation and toxicity assay (cell counting kit-8, CCK-8) was used to detect the inhibition rates of the cells in different concentrations of AHVAC-. The migration ability of the cells was evaluated by wound-healing and Transwell assay. The apoptosis were observed by laser confocal microscopy with annexin V-mCherry/DAPI double staining, and the apoptosis rates were analyzed by flow cytometry with annexin V-FITC/PI double fluorescence staining. The protein level of Caspease-3 was determined by Western blot. RESULTS: Compared with normal control group, the results of AHVAC- concentration groups showed that with the increase of AHVAC- concentration, the proliferative activity of MN-28 cells decreased gradually (P<0.01), the cell migration ability decreased gradually (P<0.01), and the cell apoptosis rate increased (P<0.05). The expression of apoptosis-related protein Caspease-3 was up-regulated (P<0.01). CONCLUSION: AHVAC- inhibits proliferation and migration of gastric cancer MSN-28 cells and induces apoptosis.

Based on the interaction between supramolecule of traditional Chinese medicine and enterobacteria, the material basis of Rhei Radix et Rhizoma and Coptidis Rhizoma was explored. Scanning electron microscopy (SEM) and dynamic light scattering (DLS) were used to characterize the morphological differences of Rhubarb single decoction, Coptis single decoction and Rhubarb and Coptis co-decoction. An in vitro antibacterial model (E. coli, E. faecium and B. subtilis) was established to evaluate the damage effect of the combination of Rhei Radix et Rhizoma and Coptidis Rhizoma on enterobacteria. Ultra high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to analyze the changes of chemical components of single decoctions and co-decoctions. The co-decoction of Rhei Radix et Rhizoma and Coptidis Rhizoma was turbid after decocting. The spherical particles of 300-400 nm were observed under SEM, and the co-decoction was more uniform and stable than that of single decoction. The interaction between supramolecules formed after the combination of Rhei Radix et Rhizoma and Coptidis Rhizoma and enterobacteria was significantly different from that of single decoction. In the process of interaction between supramolecules and enterobacteria, the spherical state was maintained, and the medicinal ingredients in Coptidis Rhizoma or Rhei Radix et Rhizoma were blocked, which could effectively alleviate the damage to enterobacteria. This study provided a reference for subsequent studies on the regulation of intestinal flora homeostasis by the combination of Rhei Radix et Rhizoma and Coptidis Rhizoma.

OBJECTIVE To explore the construction of a pediatric pharmaceutical care cloud platform based on Western Pediatric Development Union， to provide a reference for narrowing the difference of pediatric pharmaceutical care in western regions and medical institutions. METHODS Based on the Western Pediatric Development Union， the “1+3+3” pediatric pharmaceutical care cloud platform had been built by relying on the alliance telemedicine service network. That was， with Children’s Hospital of Chongqing Medical University as one center， three core pharmaceutical services， including prescription dispensing， pharmaceutical guidance and health education， were carried out in the union through standardized 3 aspects of management of resource information， service process and component interface. RESULTS & CONCLUSIONS Established “1+3+ 3” pediatric pharmaceutical care cloud platform based on the remote service network of the Western Pediatric Development Union registered 1 208 thousands registrations since its operation， with 112 thousands online prescriptions and 44 thousands circulation prescriptions completed； the total number of medication consultation cases was 10 694， and the number of online training people exceeded 15 thousands. However， during the operation， there are also problems such as limited clinical medication data and insufficient coverage of the region. With the accumulation of clinical medication data on the platform， the artificial intelligence technology will be used to extract the data of prescriptions， medication behavior， and physical indicators after medication， the correlation analysis of data will be conducted under the conditions of different geographical environments， different age groups， different heights and weights in the region to obtain clinical medication characteristics for children in the region， providing decision support for further guiding rational and safe medication in pediatric clinical practice.

BACKGROUND:In recent years,some scholars in the field of tendon bone injury have attached stromal cell-derived factor 1 to tissue engineering scaffolds to promote tendon bone healing,and achieved good results.However,whether stromal cell-derived factor 1 promotes tendon bone healing mechanisms and participates in the repair of natural healing has not yet been defined. OBJECTIVE:To study the expression of stroma-cell derived factor 1 during tendon bone healing after rupture of the whole supraspinatus muscle of the rabbit rotator cuff and its migration effect and optimal in vitro migration promoting concentration on stem cells during tendon bone injury. METHODS:Totally 18 adult New Zealand rabbits were randomly selected to establish rotator cuff injury models,and an additional 3 rabbits were selected as blank controls.At 3,5,7,14,21,and 28 days after modeling,three rabbits were executed separately and the rabbits in the blank group were sacrificed.The tissues of tendon bone junction were taken and stored in a-80℃refrigerator.The expression of stromal cell-derived factor 1 was detected by ELISA at each time point after injury.Mesenchymal stem cells were isolated from the bone marrow of young rabbit femur,cultured,and identified.Transwell assay was performed to verify the migration-promoting effect of stromal cell-derived factor 1 on stem cells and the optimal migration-promoting concentration in vitro.The stem cells cultured to P3 were co-cultured with BrdU and injected into the rabbit ear marginal vein,and immunohistochemical staining was used to verify whether the stem cells migrated to the injury site. RESULTS AND CONCLUSION:(1)Stromal cell-derived factor 1 gene expression was bimodal during rotator cuff tendon bone healing.Stromal cell-derived factor 1 gene expression increased significantly at 3 days post-injury(P<0.01)and then decreased,reaching a minimum at 5 days post-injury.It increased again and reached a peak 14 days after injury(P<0.01)and then decreased.(2)Cell immunohistochemical staining displayed that stem cells labeled with BrdU did migrate to the injury site.(3)The results of the transwell experiment exhibited that 60-80 ng/mL stromal cell-derived factor 1 had the best effect on promoting migration of stem cells,while a concentration of 200 ng/mL inhibited migration.(4)Stromal cell-derived factor 1 is involved in the healing of rotator cuff tendon bone during the inflammatory response phase and the proliferation phase.The mechanism of action may be to promote the migration of stem cells to the injury and their differentiation into various types of cells to promote repair.In addition,the pro-migration effect of stromal cell-derived factor 1 exists at a range of concentrations,beyond which it may act as an inhibitor.

BACKGROUND:Osteonecrosis of the femoral head is one of the refractory diseases in orthopedic diseases.The natural collapse course of osteonecrosis of the femoral head under different stages and types affects the progression and prognosis of the disease. OBJECTIVE:To explore the progression of natural collapse within 5 years in patients under the different classifications of China-Japan Friendship Hospital(CJFH)with stage Ⅱ osteonecrosis of the International Association for Research Circulation Osseous(ARCO),and to analyze the collapse rate and collapse risk of the femoral head under the different classifications of CJFH. METHODS:A retrospective study was performed to select patients diagnosed with ARCO Ⅱ stage osteonecrosis of the femoral head without collapse in the Honghui Hospital Affiliated to Xi'an Jiaotong University from October 2016 to October 2017.According to whether it collapsed,the number of hips was divided into the collapse group(n=82)and the non-collapsed group(n=70).The collapse risk of patients with osteonecrosis of the femoral head under different CJFH classifications,as well as the collapse time,number of collapses,and collapse rate within 5 years were counted,and then the Kaplan-Meier survival curve of the femoral head under different classification of CJFH was plotted. RESULTS AND CONCLUSION:(1)A total of 97 patients with 152 hips were enrolled,and 82 hips collapsed during the follow-up period,with a total collapse rate of 53.9%,of which the collapse rates of M type,C type,L1 type,L2 type,and L3 type were 0.0%,36.7%,51.4%,72.2%,and 77.8%,respectively,and the comparison between the groups was statistically significant(P<0.05).(2)In terms of collapse risk,the collapse risk of L1 type was 1.704 times that of C-type(P>0.05),while the collapse risks of L2 type and L3 type were 3.866 times and 6.423 times that of C type(P<0.05),respectively.(3)In terms of the Kaplan-Meier survival curve,the median survival time of the femoral head of ARCO Ⅱ stage patients was 3 years,with a 95%confidence interval of 2.885-3.471 years,and the survival rates of the femoral head at the first,third and fifth years were 65.1%(99/152),50.7%(77/152),and 46.1%(70/152),respectively.(4)These findings conclude that different CJFH classifications affect the collapse rate of ARCO Ⅱ stage osteonecrosis of the femoral head patients,among which L3 type patients have the highest collapse rate,followed by L2 type and L1 type patients;C type patients have a lower collapse rate,and M type patients do not collapse,which indicates that the preservation of the lateral column of the femoral head is of great significance for the natural collapse course of osteonecrosis of the femoral head.

Objective:To investigate the prognosis of patients with initially resectable gastric cancer liver metastasis (GCLM) who were treated by different modalities, and analyze the influencing factors for prognosis of patients.Methods:The retrospective cohort study was conducted. The clinicopathological data of 327 patients with initially resectable GCLM who were included in the database of a nationwide multicenter retrospective cohort study on GCLM based on real-world data from January 2010 to December 2019 were collected. There were 267 males and 60 females, aged 61(54,68)years. According to the specific situations of patients, treatment modalities included radical surgery combined with systemic treatment, palliative surgery combined with systemic treatment, and systemic treatment alone. Observation indicators: (1) clinical characteristics of patients who were treated by different modalities; (2) prognostic outcomes of patients who were treated by different modalities; (3) analysis of influencing factors for prognosis of patients with initially resectable GCLM; (4) screening of potential beneficiaries in patients who were treated by radical surgery plus systemic treatment and patients who were treated by palliative surgery plus systemic treatment. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. The Kaplan-Meier method was used to calculate survival rate and draw survival curve, and Log-Rank test was used for survival analysis. Univariate and multivariate analyses were conducted using the COX proportional hazard regression model. The propensity score matching was employed by the 1:1 nearest neighbor matching method with a caliper value of 0.1. The forest plots were utilized to evaluate potential benefits of diverse surgical combined with systemic treatments within the population. Results:(1) Clinical characteristics of patients who were treated by different modalities. Of 327 patients, there were 118 cases undergoing radical surgery plus systemic treatment, 164 cases undergoing palliative surgery plus systemic treatment, and 45 cases undergoing systemic treatment alone. There were significant differences in smoking, drinking, site of primary gastric tumor, diameter of primary gastric tumor, site of liver metastasis, and metastatic interval among the three groups of patients ( P<0.05). (2) Prognostic outcomes of patients who were treated by different modalities. The median overall survival time of the 327 pati-ents was 19.9 months (95% confidence interval as 14.9-24.9 months), with 1-, 3-year overall survival rate of 61.3%, 32.7%, respectively. The 1-year overall survival rates of patients undergoing radical surgery plus systemic treatment, palliative surgery plus systemic treatment and systemic treatment alone were 68.3%, 63.1%, 30.6%, and the 3-year overall survival rates were 41.1%, 29.9%, 11.9%, showing a significant difference in overall survival rate among the three groups of patients ( χ2=19.46, P<0.05). Results of further analysis showed that there was a significant difference in overall survival rate between patients undergoing radical surgery plus systemic treatment and patients undergoing systemic treatment alone ( hazard ratio=0.40, 95% confidence interval as 0.26-0.61, P<0.05), between patients undergoing palliative surgery plus systemic treatment and patients under-going systemic treatment alone ( hazard ratio=0.47, 95% confidence interval as 0.32-0.71, P<0.05). (3) Analysis of influencing factors for prognosis of patients with initially resectable GCLM. Results of multivariate analysis showed that the larger primary gastric tumor, poorly differentiated tumor, larger liver metastasis, multiple hepatic metastases were independent risk factors for prognosis of patients with initially resectable GCLM ( hazard ratio=1.20, 1.70, 1.20, 2.06, 95% confidence interval as 1.14-1.27, 1.25-2.31, 1.04-1.42, 1.45-2.92, P<0.05) and immunotherapy or targeted therapy, the treatment modality of radical or palliative surgery plus systemic therapy were independent protective factors for prognosis of patients with initially resectable GCLM ( hazard ratio=0.60, 0.39, 0.46, 95% confidence interval as 0.42-0.87, 0.25-0.60, 0.30-0.70, P<0.05). (4) Screening of potentinal beneficiaries in patients who were treated by radical surgery plus systemic treatment and patients who were treated by palliative surgery plus systemic treatment. Results of forest plots analysis showed that for patients with high-moderate differentiated GCLM and patients with liver metastasis located in the left liver, the overall survival rate of patients undergoing radical surgery plus systemic treatment was better than patients undergoing palliative surgery plus systemic treatment ( hazard ratio=0.21, 0.42, 95% confidence interval as 0.09-0.48, 0.23-0.78, P<0.05). Conclusions:Compared to systemic therapy alone, both radical and palliative surgery plus systemic therapy can improve the pro-gnosis of patients with initially resectable GCLM. The larger primary gastric tumor, poorly differen-tiated tumor, larger liver metastasis, multiple hepatic metastases are independent risk factors for prognosis of patients with initial resectable GCLM and immunotherapy or targeted therapy, the treatment modality of radical or palliative surgery plus systemic therapy are independent protective factors for prognosis of patients with initially resectable GCLM.

Objective:To explore the application of the semi-flipped classroom combined with knowledge point auction learning method in the theoretical teaching among stomatological students and its effectiveness.Methods:Undergraduates from four classes at Guanghua School of Stomatology, Sun Yat-Sen University were taken as research subjects. Students from two classes ( n=198) were taught using the semi-flipped classroom combined with the knowledge point auction learning method, while students from the other two classes ( n=172) were taught with the regular classroom teaching method as controls. Classroom quizzes were used to compare the two classes' mastery of important and difficult points, and a questionnaire was used to investigate students' feedback on the class outcomes. SPSS 22.0 was used for the independent samples t-test. Results:The mean test score of the experimental class was higher than that of the control class (88.51±11.02 vs. 80.40±8.53). The results of the questionnaire showed that students' interest in the course, comprehension and absorption of knowledge points, degree of satisfaction with the class, and mastery of the contents in sections in the experimental class were significantly higher than those in the control class (7.28±1.51 vs. 9.10±0.73, 6.92±1.44 vs. 8.69±1.62, 6.09±1.87 vs. 7.61±1.46, 6.40±1.04 vs. 7.70±0.86 ).Conclusions:The semi-flipped classroom combined with the knowledge point auction learning method is innovative and achieves good teaching outcomes. It holds promise for wider use in the theoretical teaching of various clinical subjects. To explore the application of the semi-flipped classroom combined with knowledge point auction learning method in the theoretical teaching among stomatological students and its effectiveness.

Obiective Alzheimer’s disease (AD) is a degenerative disease of the central nervous system (CNS) caused by a variety of risk factors. There are various pathological changes, but apoptosis of the neurological meridian cells is one of the most important pathological bases. Hyperlipidemia is a high-risk factor for the development of AD, which can lead to increased levels of oxidized low-density lipoprotein (ox-LDL) in brain tissues. PCSK9 is a protease closely related to lipid metabolism, but studies have shown that it may be related to the development of AD. LRP1 is abundantly expressed in neuronal cells, and it is an important transporter for the clearance of Aβ. There is now a large amount of literature confirming that PCSK9 can induce the degradation of LRP1. PI3K/AKT is an important signaling pathway in vivo, which plays an important role in apoptosis, and there is now a large amount of literature confirming that LRP1 activates the PI3K/AKT pathway, which has an anti-apoptotic effect. So can PCSK9 affect the PI3K/AKT pathway through LRP1 and thus regulate neuronal apoptosis? This deserves further investigation.The aim of this study was to explore the role of PCSK9 in mediating ox-LDL pro-apoptotic neuronal cell death and its mechanism, and then further elaborate the mechanism of hyperlipidemia leading to neurodegenerative diseases such as AD. MethodsFirstly, PC12 cells were treated with different concentrations of ox-LDL (0, 25, 50, 75 and 100 mg/L) for 24 h. Oil red O staining was used to detect lipid accumulation in PC12 cells, Hoechst33258 staining and flow cytometry to detect apoptosis in PC12 cells, ELISA to detect the content of Aβ secreted by PC12, Western blot to detect expression of SREBP2, PCSK9 and LRP1. Then PC12 cells were treated with 75 mg/L ox-LDL for different times (0, 6, 12, 24, 48 h), and Western blot were performed to detect the expression of SREBP2, PCSK9 and LRP1. Finally, after transfecting 100 nmol/L PCSK9 siRNA into PC12 cells for 48 h, PC12 cells were treated with 75 mg/L ox-LDL for 24 h, Hoechst33258 staining and flow cytometry to detect apoptosis rate of PC12 cells, and Western blot to detect PCSK9, LRP1, PI3K, AKT, P-PI3K , P-AKT, NF-κB, Bcl-2, Bax, Caspase-9 and Caspase-3 expression, and ELISA detected Aβ content secreted by PC12 cells. Resultsox-LDL increased lipid accumulation and promoted apoptosis and Aβ secretion in PC12 cells, as well as increasing the expression of SREBP2 and PCSK9 and decreasing the expression of LRP1 in PC12 cells. pCsk9 siRNA could be inhibited through the PI3K/AKT pathway and the NF-κB-Bcl-2/Bax-Caspase-9/3 pathway to inhibit ox-LDL-induced apoptosis in PC12 cells while increasing Aβ secretion in PC12 cells. Conclusionox-LDL plays a bidirectional regulatory role in ox-LDL-induced apoptosis of PC12 cells by inducing an increase in PCSK9 expression and a decrease in LRP1 expression in PC12 cells, which in turn affects different signaling pathways downstream.