Inhaled heparin polysaccharide nanodecoy against SARS-CoV-2 and variants

The heparin polysaccharide nanoparticles block the interaction between heparan sulfate/S protein and inhibit the infection of both wild-type SARS-CoV-2 pseudovirus and the mutated strains through pulmonary delivery.Image 1.

Variation of SARS-CoV-2 spike protein and its effects on neutralization sensitivity / 中华微生物学和免疫学杂志

The COVID-19 epidemic that occurred at the end of 2019 spreads rapidly to all parts of the world, putting the global public health system to a severe test. With the continuation of the epidemic, SARS-CoV-2 variants are constantly emerging. In particular, the mutation of the spike protein can cause changes in the infectivity and antigenicity of the virus, resulting in an increase in the infectivity and a decline in the protective efficacy of existing vaccines, and even the replacement of epidemic strains. This is also one of the reasons why the epidemic has not been effectively controlled so far. Nowadays, the main circulating variants have changed their characteristics to a certain extent, and the neutralization sensitivity of some variants to neutralizing monoclonal antibodies, immune sera and convalescent sera has decreased to a certain extent compared with the original strains. The emergence of variants is not only related to the characteristics of the virus itself, but also to the changes of transmission host and the chronic infection in people with deficient immunity. The emerging variants should be closely monitored, and their functional characteristics should be systematically studied so as to provide data for vaccine research and development and the designation of immunization strategies.

DYNC2H1 gene mutation analysis and prenatal diagnosis in two pedigrees affected with short rib-polydactyly syndrome type Ⅲ / 中华围产医学杂志

Objective:To investigate the molecular genetic etiology of two fetuses with short rib-polydactyly syndrome type Ⅲ (SRPS Ⅲ).Methods:Next-generation sequencing (NGS) was used to detect 226 known genes related to inherited skeletal dysplasia in two fetuses with SRPS Ⅲ diagnosed in the First Affiliated Hospital of Zhengzhou University in August 2015 and June 2020. Suspect pathological variants were verified in the pedigree members using Sanger sequencing. The prenatal genetic diagnosis of the high-risk fetus in pedigree one was conducted to identify the confirmed pathogenic variation.Results:The homozygous mutation of DYNC2H1 gene c.5881A>G(p.Lys1961Glu) was identified in the proband in pedigree one, and the parents were the carriers. The proband in pedigree two carried compound heterozygous mutations in the DYNC2H1 gene with c.10606C>T(p.Arg3536*) inherited from the father and c.8954T>G(p.Val2985Gly) from the mother. Autosomal recessive inheritance was confirmed in both pedigrees. Mutations of c.5881A>G(p.Lys1961Glu) and c.8954T>G(p.Val2985Gly) in the DYNC2H1 gene were likely pathogenic variants and had not been reported before. The prenatal diagnosis did not identify the DYNC2H1 gene c.5881A>G(p.Lys1961Glu) mutation in the fetus (Ⅱ-7) in pedigree one, which was confirmed by the umbilical cord blood sample after birth. Conclusion:DYNC2H1 gene mutation underlies the fetal skeletal dysplasia in the two pedigrees.

Symphony of nanomaterials and immunotherapy based on the cancer-immunity cycle

The immune system is involved in the initiation and progression of cancer. Research on cancer and immunity has contributed to the development of several clinically successful immunotherapies. These immunotherapies often act on a single step of the cancer-immunity cycle. In recent years, the discovery of new nanomaterials has dramatically expanded the functions and potential applications of nanomaterials. In addition to acting as drug-delivery platforms, some nanomaterials can induce the immunogenic cell death (ICD) of cancer cells or regulate the profile and strength of the immune response as immunomodulators. Based on their versatility, nanomaterials may serve as an integrated platform for multiple drugs or therapeutic strategies, simultaneously targeting several steps of the cancer-immunity cycle to enhance the outcome of anticancer immune response. To illustrate the critical roles of nanomaterials in cancer immunotherapies based on cancer-immunity cycle, this review will comprehensively describe the crosstalk between the immune system and cancer, and the current applications of nanomaterials, including drug carriers, ICD inducers, and immunomodulators. Moreover, this review will provide a detailed discussion of the knowledge regarding developing combinational cancer immunotherapies based on the cancer-immunity cycle, hoping to maximize the efficacy of these treatments assisted by nanomaterials.

Novel compound heterozygous SCN9A variations causing congenital insensitivity to pain in a patient / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a child featuring congenital insensitivity to pain (CIP).@*METHODS@#Targeted capture and next generation sequencing (NGS) was carried out for the proband. Suspected pathogenic variants were confirmed by Sanger sequencing of the proband and his parents.@*RESULTS@#The proband was found to harbor compound heterozygous variants of SCN9A gene, namely c.1598delA (p.N533Ifs*31) and c.295_296delCGinsAT (p.R99I), which were respectively inherited from his father and mother. Both variants were predicted to be pathogenic, and neither was reported previously.@*CONCLUSION@#The compound heterozygous variants of the SCN9A gene probably underlay the CIP in this child. Above finding has enabled genetic counseling for this family.

Sedentary behavior and the risk of gestational diabetes mellitus: a systematic review / 中华健康管理学杂志

Objective:To systematically evaluate the relationship between sedentary behavior (SB) and the risk of developing gestational diabetes mellitus (GDM).Methods:PubMed, Medline, EMBASE, CINAHL, the Cochrane Library, the Rehabilitation & Sports Medicine Source, the Sedentary Behavior Research Database (SBRD), Wanfang Database, the China Journal full-text database, and the China Biomedical Literature Database were searched for cohort studies, case-control studies, and cross-sectional studies concerning the risk of SB and GDM from the establishment of the database to January 2021. Two researchers screened the literature, extracted data, evaluated the quality of the data according to the inclusion and exclusion criteria, and, finally, produced a descriptive analysis of the results.Results:A total of 11 studies were included, including eight cohort studies, two cross-sectional studies, and one case-control study. The overall quality of the studies was moderate. The prevalence of GDM was 5.04%-26.81%, and the prevalence of SB before and during pregnancy was 39.47%-40.21% and 28.86%-93.50%, respectively. In terms of the prevalence of SB before pregnancy, four moderate-quality studies reported no association with GDM risk. In terms of SB during pregnancy, four moderate-quality studies reported no association with GDM risks, and four studies (one of high quality and three of moderate quality) reported an association with GDM risks, two of which focused on the second trimester. There was considerable heterogeneity between studies on the diagnosis of GDM and SB.Conclusion:SB before pregnancy is not associated with the risk of GDM, while the relationship between SB and the risk of GDM is unclear, but the level of SB in the second trimester of pregnancy may be positively associated with the risk of GDM.

Research on the application of multidisciplinary linkage teaching based on "Internet+" and SP in the training of intravenous therapy specialized nurses / 中华医学教育探索杂志

Objective:To enhance the comprehensive learning and clinical practice capabilities of intravenous therapy specialized nurses based on the "Internet+" and standardized patient (SP) multidisciplinary linkage teaching.Methods:In this study, 54 nurses who took training of the intravenous therapy specialists in Chaoyang Hospital affiliated to Capital Medical University from July 2019 to December 2019 were selected as research subjects and randomly divided into a control group and a study group, with 27 ones in each group. The control group used traditional training of intravenous therapy specialized nurse, and the research group used the multidisciplinary linkage model of "Internet+" and SP. After the training, the nurses were assessed for theoretical and practical operation and satisfaction surveys, and the incidence of venous catheterization complications during the training of the two groups of nurses was counted. SPSS 22.0 was used for t test and chi-square test. Results:There was no statistically significant difference between the two groups of nurses in the theoretical assessment of basic knowledge and professional knowledge ( P>0.05). The total score of case analysis and theoretical assessment of the study group was higher than that of the control group, and the difference was statistically significant ( P<0.001). The nurses of the study group scored higher than the control group did in such 8 aspects, namely, central venous catheter (CVC) maintenance, peripherally inserted central catheter (PICC) placement, PICC maintenance, infusion port maintenance, peripheral venous catheters, aseptic technique, prevention and treatment of catheterization complications, and health education, with statistically significant differences ( P<0.05). There were statistically significant differences in the average score of nurse satisfaction between the two groups [(85.4±3.7) vs. (95.7±2.6)], and in the incidence of complications between the two groups ( χ2=4.618, P=0.032). Conclusion:"Internet+" and SP multidisciplinary linkage teaching helps to enhance the comprehensive learning and clinical practice ability of intravenous therapy specialized nurses, reduce the incidence of complications, enable patients to receive high-quality intravenous infusion therapy and care, and ensure the safety of patients.

Role of P2X7 receptor in colon cancer progression / 国际肿瘤学杂志

P2X7 receptor is an ion channel receptor with adenosine triphosphate (ATP) as its ligand, which is widely expressed in various immune cells and tissues. Activated P2X7 receptor is involved in a variety of physiological and pathological processes. P2X7 receptor is abnormally expressed in colon cancer, and plays a duel role of cancer-promoting and cancer-suppressing in colon cancer progression. When P2X7 receptor is activated by extracellular ATP, it can effectively inhibit proliferation and induce apoptosis of colon cancer cells through various mechanisms. In addition, P2X7 receptor can also promote the growth, invasion and metastasis of colon cancer. Understanding the activation of P2X7 receptor and its effect mechanism is of great significance for the treatment of colon cancer.

Effectiveness and safety of mesenchymal stem cells versus hyaluronic acid for treating knee osteoarthritis: a Meta-analysis / 中华风湿病学杂志

Objective:To systematically evaluate the effectiveness and safety of intra-articular in-jection of mesenchymal stem cells (MSCs) and hyaluronic acid (HA) in the treatment of knee osteoarthritis.Methods:The relevant literatures published in both English and Chinese were systematically searched in PubMed, Embase, Wanfang database, China Knowledge Network (CNKI), SinoMed database and other data-bases from inception to May 2020. Two researchers independently extracted data and evaluated the included literature. Risk assessment of literature bias was carried out. RevMan 5.3 software was used for Meta analysis, and the combined sensitivity were calculated.Results:Finally, 13 references were included, including a total of 726 patients with knee osteoarthritis. Meta-analysis results showed that compared with the HA group, the Western Ontario and McMaster University Osteopathic Index Total Score (WOMAC) [ MD=-10.92, 95% CI (-16.87, -4.96), P<0.01], the visual analogue scale (VAS) score [ MD=-1.70, 95% CI(-2.44, -0.95), P<0.01], and the knee joint Lequesne index score of MSCs group all decreased significantly [ MD=-13.78, 95% CI (-15.03,-12.52), P<0.01]. Furthermore, there was no significant difference in the incidence of adverse events (AEs) between the two groups [ RR=1.11, 95% CI(0.90, 1.37), P=0.33]. However, American Knee Association Score (AKS score) [ MD=-10.15, 95% CI(-22.33, 2.03), P=0.10] and whole-organ magnetic resonance imaging score (WORMS) [ MD=-3.93, 95% CI(-11.60, 3.75), P=0.32] were not statistically significant ( P>0.05). Conclusion:Compared with intra-articular injection of HA, intra-articular injection of MSCs can significantly improve the symptoms and dysfunction, and has favorable clinical tolerability and safety, suggesting that MSCs is expected to bea new treatment for knee osteoarthritis.

Astrocytes in depression and Alzheimer's disease / 医学前沿

Astrocytes are an abundant subgroup of cells in the central nervous system (CNS) that play a critical role in controlling neuronal circuits involved in emotion, learning, and memory. In clinical cases, multiple chronic brain diseases may cause psychosocial and cognitive impairment, such as depression and Alzheimer's disease (AD). For years, complex pathological conditions driven by depression and AD have been widely perceived to contribute to a high risk of disability, resulting in gradual loss of self-care ability, lower life qualities, and vast burden on human society. Interestingly, correlational research on depression and AD has shown that depression might be a prodrome of progressive degenerative neurological disease. As a kind of multifunctional glial cell in the CNS, astrocytes maintain physiological function via supporting neuronal cells, modulating pathologic niche, and regulating energy metabolism. Mounting evidence has shown that astrocytic dysfunction is involved in the progression of depression and AD. We herein review the current findings on the roles and mechanisms of astrocytes in the development of depression and AD, with an implication of potential therapeutic avenue for these diseases by targeting astrocytes.

Methodology, safety and applications of colonic transendoscopic enteral tubing (with video) / 中华消化内镜杂志

Objective@#To evaluate the methodology, safety and clinical applications of colonic transendoscopic enteral tubing (TET) as a new method of fecal microbiota transplantation (FMT) and colonic administration.@*Methods@#This prospective study included patients who underwent colonic TET for FMT and(or) colonic administration in the Second Affiliated Hospital of Nanjing Medical University from October 2014 to December 2018. The TET procedure time, success rate, retention time of TET tube, factors influencing TET tube retention, adverse events and satisfaction degree were evaluated.@*Results@#A total of 257 patients underwent TET, among whom 130 patients (50.6%) for microbiota tronsplantation, 8 patients (3.1%) for colon-drip medication, 118 patients (45.9%) for FMT and colon-drip medication, and 1 patient (0.4%) without treatment after TET. The TET procedure time was 10.0±2.8 min. The number of endoscopic clips used was 3.5±1.0. The success rate of the TET procedure was 100.0% (257/257). The retention time of TET tube for 160 patients maintaining the tube for treatment was 9.3±3.8 days. Multivariate analysis indicated that endoscopic clip type (P=0.001) was an independent influencing factor for the retention time of the tube. A total of 9 patients (3.5%) reported adverse events of mild anus discomfort, 4 patients (1.6%) of mobile inconvenience, 3 (1.2%) of anal pain, 2 (0.8%) of mild abdominal pain, 2 (0.8%) of mild bloating, and 1 (0.4%) of mild anal bleeding. No severe adverse events were observed in this study. The total satisfaction degree on colonic TET was 97.3% (250/257) in all patients.@*Conclusion@#The colonic TET, a safe and easy-operating endoscopic interventional technology with a high degree of patients satisfaction, can be used for colonic delivering of FMT and medications for various diseases.

Methodology, safety and applications of colonic transendoscopic enteral tubing (with video) / 中华消化内镜杂志

Objective:To evaluate the methodology, safety and clinical applications of colonic transendoscopic enteral tubing (TET) as a new method of fecal microbiota transplantation (FMT) and colonic administration.Methods:This prospective study included patients who underwent colonic TET for FMT and(or) colonic administration in the Second Affiliated Hospital of Nanjing Medical University from October 2014 to December 2018. The TET procedure time, success rate, retention time of TET tube, factors influencing TET tube retention, adverse events and satisfaction degree were evaluated.Results:A total of 257 patients underwent TET, among whom 130 patients (50.6%) for microbiota tronsplantation, 8 patients (3.1%) for colon-drip medication, 118 patients (45.9%) for FMT and colon-drip medication, and 1 patient (0.4%) without treatment after TET. The TET procedure time was 10.0±2.8 min. The number of endoscopic clips used was 3.5±1.0. The success rate of the TET procedure was 100.0% (257/257). The retention time of TET tube for 160 patients maintaining the tube for treatment was 9.3±3.8 days. Multivariate analysis indicated that endoscopic clip type ( P=0.001) was an independent influencing factor for the retention time of the tube. A total of 9 patients (3.5%) reported adverse events of mild anus discomfort, 4 patients (1.6%) of mobile inconvenience, 3 (1.2%) of anal pain, 2 (0.8%) of mild abdominal pain, 2 (0.8%) of mild bloating, and 1 (0.4%) of mild anal bleeding. No severe adverse events were observed in this study. The total satisfaction degree on colonic TET was 97.3% (250/257) in all patients. Conclusion:The colonic TET, a safe and easy-operating endoscopic interventional technology with a high degree of patients satisfaction, can be used for colonic delivering of FMT and medications for various diseases.

Effect of PDCA mode on shortening blood transfusion waiting time in hematology ward / 中国实用护理杂志

Objective:To analyze the application of PDCA mode in the management of blood transfusion waiting time.Methods:Using random block design, 98 patients received blood transfusion during January to December 2018 were included into the before improvement; 32 patients received blood transfusion during January to June 2019 were included into the after improvement. Standard process of blood taking and transfusion was applied to the before improvement, while based on standard process, found out the deficiencies in the previous clinical practice, continuously improved the details of the process for the after improvement. Then blood transfusion waiting times were compared between the two groups.Results:The blood transfusion waiting time was (26.95±9.20) min before improvement and (25.59±4.16) min after improvement, with a significantly lower disqualification rate 6.25% (2/32) comparing with 26.53% (26/98) before improvement. The differences were statistically significant ( t value was 3.75, P<0.01; χ2 value was 5.87, P<0.05). Conclusions:The application of PDCA circulation management mode can shorten the blood transfusion waiting time and transfusion can be made within 30 minutes after blood taking so that nursing quality of transfusion in the ward can be improved.

Comparison of ID-LC-MS/MS and two CLIAs in measuring plasma aldosterone / 中华检验医学杂志

Objective Accurate measurement of aldosterone is critical in the diagnosis of primary aldosteronism. We compared the harmonization of three assays including isotope dilution liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS) and two chemiluminescence immunoassays (CLIAs:system A and system B) for the aldosterone measurement. Methods A total of 45 plasma samples, 4 quality control materials, 5 lyophilized bovine serums, and 3 fresh frozen human serum pools were measured by three assays respectively. Based on CLSI EP15-A3 rule, the precision was assessed by coefficient of variance. Deming regression and Bland&Altman plots was performed for method comparison, and correlation coefficient was calculated for concordance (CCC). Results All three methods met the performance criteria based on desirable biological variation for precision (<7.35％). System A showed a relevantly good correlation and comparability with ID-LC/MS/MS (R2=0.985, CCC=0.967), while System B showed relevantly bad correlations and comparability with both System A (R2=0.538, CCC=0.605) and ID-LC/MS/MS (R2=0.547, CCC=0.528).. However, the average relevant bias of two CLIAs exceeded the bias requirement derived from biological variation (18.60％). Conclusion Significant differences were found in the measurement of plasma aldosterone using ID-LC-MS/MS and two CLIAs, which urges the establishment of traceability hierarchy and improvement of reagents' specificity for standardization of aldosterone measurement in clinical settings.

Effect of oral probiotics in the treatment of nonalcoholic fatty liver disease / 中国基层医药

Objective To investigate the clinical value of probiotics in the treatment of patients with nonal -coholic fatty liver disease ( NAFLD) .Methods The clinical data of 100 patients with NAFLD were retrospectively analyzed.According to different treatment methods ,the patients were divided into two groups ,with 50 cases in each group.The control group received basic treatment ,the observation group received probiotics treatment on the basis of the control group .The treatment effects of the two groups were analyzed .Results The total effective rate in the obser-vation group (54.00%) was significantly higher than that in the control group (30.00%)(χ2 =5.911,P=0.015) .After treatment,the ALT,TG,HOMA-R,TNF-α,D-lactic acid,endotoxin levels in the observation group were significantly better than those in the control group (all P<0.05).The incidence rate of adverse reactions between the two groups had no statistically significant difference (4.00% vs.2.00%,χ2 =0.343,P =0.558).Conclusion Probiotics in the treatment of NAFLD can reduce the intestinal permeability ,improve the intestinal endotoxemia and the prognosis of the patients .

Relationship between multifunctional protein "clusterin" and Alzheimer's disease / 中华神经科杂志

Alzheimer's disease (AD) is a neurodegenerative disease of the central nervous system that starts slowly and progressively leads to cognitive impairment.Clusterin,as an apolipoprotein,is usually widely expressed in mammalian brain tissue.In previous studies,below theories have been demonstrated:clusterin influences the aggregation,clearance and neurotoxicity of β-amyloid;compared to healthy people,AD patients show higher clusterin level in plasma and cerebrospinal fluid;the polymorphisms of clusterin gene encoding clusterin can enhance the incidence risk of AD.In addition,regulating the expression of clusterin in AD animals model has certain therapeutic effect on AD.Further investigating intrinsic relationship between clusterin and AD will help clarify the pathogenesis and establish a new therapeutic target of AD thus contributing to the prevention of Alzheimer's disease.

Synthesis and biological evaluation of novel tricyclic matrinic derivatives as potential anti-filovirus agents

Twenty-six novel tricyclic sophoridinic and matrinic derivatives containing a common chlorinated benzene fragment were designed, synthesized and evaluated for their anti-ebolavirus (EBOV) activities. Structure-activity relationship analysis indicated: (i) 12-dichlorobenzyl motif was beneficial for the activity; (ii) the chiral configuration at C5 atom might not affect the activity much. Among the target compounds, compound exhibited the most potent potency against EBOV with an IC value of 5.29 μmol/L and an SI value of over 37.8. Further anti-EBOV assay of identified its high effectiveness, and anti-MARV assay of suggested its inspiring broad-spectrum anti-filovirus activity. The results provided powerful information on further strategic optimization and development of this kind of compounds against filoviruses.

Two-dimensional speckle tracking imaging in predicting myocardial injury of Kawasaki disease patients with intravenous immunoglobulin resistant during acute phase / 中国医学影像技术

Objective To analyze the characteristics of left ventricular systolic function in Kawasaki disease (KD) patients with intravenous immunoglobulin (IVIG) resistant during acute phase by two-dimensional speckle tracking imaging (2D STI).Methods IVIG resistant patients (n=40) as well as age and gender matched IVIG responder patients (n=40) were selected from KD patients in acute phase.Patients in IVIG resistant group were further divided into coronary artery dilation (CAD) subgroup and no coronary artery dilation (NCAD) subgroup.Then conventional echocardiography,2D STI and laboratory indexes were acquired and compared between IVIG resistant group and IVIG responder group,as well as between CAD and NCAD subgroup.ROC curve analysis was used to determine threshold values of 2D STI measurements associated with IVIG resistance.Results Compared with IVIG responder group,coronary artery dilation,left ventricular mass and left ventricular mass index increased,systolic global longitudinal strain (GLS) and systolic global circumferential strain (GCS) decreased,albumin,erythrocyte sedimentation rate,C-reactive protein and platelet increased in IVIG resistant group (all P＜0.05).Taking absolute GLS 16.8％ as a threshold,the area under curve (AUC) was 0.769 (P=0.021),sensitivity,specificity in diagnosis of IVIG resistant was 79.27％,68.36％.Taking absolute GCS 15.9％ as a threshold,AUC was 0.749 (P=0.038),sensitivity,specificity in diagnosis of IVIG resistant was 71.43％,57.28％.Conclusion IVIG resistant KD patients present significantly greater systolic dysfunction compared with responders in patients with KD,which may be the results of myocardium infection other than coronary artery lesions.2D STI may predict myocardial injury in IVIG resistant KD patients.

Clinical Observation of Acupuncture plus Auricular Point Sticking for Polycystic Ovary Syndrome / 上海针灸杂志

Objective To observe the clinical efficacy of acupuncture plus auricular point sticking in treating polycystic ovary syndrome (PCOS). Method A total of 80 PCOS patients were randomly divided into a treatment group of 40 cases and a control group of 40 cases. The treatment group was intervened by acupuncture plus auricular point sticking, while the control group was intervened by acupuncture only. The clinical efficacy was observed in the two groups after 3 treatment courses. Result The menstrual condition and basal body temperature (BBT) were compared in the two groups before and after the treatment. The menstrual condition and BBT in the treatment group were significantly improved (P<0.01); the menstrual condition was improved (P<0.05) and the BBT condition was significantly improved in the control group (P<0.01). The total effective rate was 82.5% in the treatment group, significantly different from that in the control group (P<0.05). Conclusion Acupuncture plus auricular point sticking can produce a satisfactory efficacy in treating PCOS.

Antibodies and vaccines against glycoprotein of Marburg virus / 中华微生物学和免疫学杂志

Marburg virus (MARV) is a lethal virus that causes fatal hemorrhagic fever.It belongs to the Filoviridae family which also includes Ebola virus.MARV is similar to Ebola virus in structure and infection mechanism.Moreover,the diseases caused by them have similar clinical symptoms.However,researches on MARV are less than those on Ebola virus.In this review,we focus on the viral structure,especially the structure of MARV glycoprotein (GP) which determines its infectivity,functions of MARV GP as well as protective antibodies and vaccines against this protein.