Identifying Qingkailing ingredients-dependent mesenchymal-epithelial transition factor-axiation "π" structuring module with angiogenesis and neurogenesis effects.

OBJECTIVE: To explore the functional role of the drug-dependent mesenchymal-epithelial transition (Met)-axiation "π" structural module of neurogenesis after processing by three components of Qingkailing injection in neurogenesis and angiogenesis in cerebral ischemia. METHODS: We used a Glutathione S-transferase (GST)-pull down assay, isothermal titration calorimetry assay, and other related methods to identify the relationships among Met, inositol polyphosphate phosphatase like 1 (Inppl1), and death associated protein kinase 3 (Dapk3) in this allosteric module. The biological effects of the modules of neurons generation composed of Met, Inppl1, and Dapk3 were measured through Western blot, apoptosis analysis, and double immunofluorescence labeling. RESULTS: The GST-pull down assay revealed that proline-serine-threonine rich domain of Met binds to the Src homology domain of Inppl1 to form a protein-protein complex; Dapk3 with a C-terminal domain interacts weakly with the protein kinase C domain of Met in the intracellular region. Thus, we obtained a "π" structuring module considered a neural regeneration module. The biological effects of angiogenesis and neurogenesis modules composed of Met, Inppl1, and Dapk3 were also verified. CONCLUSION: The study suggested that understanding the functional modules that contribute to pharmaceutics might provide novel signatures that can be used as endpoints to define disease processes under stroke or cerebral ischemia conditions.

Clinical study of sacubitril valsartan in the treatment of patients with heart failure of midrange ejection fraction after acute myocardial infarction / 天津医药

Objective To investigate the efficacy and safety of sacubitril valsartan in the treatment of heart failure(HF)of midrange ejection fraction(HFmrEF)in patients after acute myocardial infarction(AMI).Methods A total of 102 patients with HFmrEF after AMI were divided into the control group and the experimental group,with 51 cases in each group.The control group was given conventional treatment for AMI and anti-HF treatment,and the angiotensin-converting enzyme inhibitor(ACEI)/angiotensin Ⅱ receptor blocker(ARB)was used without contraindications.The experimental group was replaced by ACEI/ARB with sacubitril valsartan on the basis of the control group.After 6 months of treatment,the total effective rates of the two groups after treatment were analyzed,and the cardiac function,N-terminal pro-brain natriuretic peptide(NT-proBNP)and serum inflammatory factor C-reactive protein(CRP)were compared before and after treatment.The occurrence of adverse reactions after treatment was recorded.Kaplan-Meier method was used to analyze the cumulative cardiovascular mortality,HF rehospitalization rate and end-event-free survival after 6 months of treatment in two groups.Results After treatment,there was no significant difference in the occurrence of adverse reactions between the two groups(P>0.05).The total effective rate was higher in the experimental group than that of the control group(P<0.05).Compared with before treatment,left ventricular ejection fraction(LVEF),stroke volume(SV),mitral diastolic blood flow velocity E peak and A peak ratio(E/A)and 6 min walking distance(6MWD)were increased in the two groups,and left ventricular end-diastolic diameter(LVEDD)and left atrial diameter(LAD)were decreased in the two groups after treatment(all P<0.05).After treatment,LVEF,SV,E/A and 6MWD were higher in the experimental group than those in the control group(P<0.05).LVEDD and LAD were lower than those in the control group(all P<0.05).Compared with results before treatment,NT-proBNP and CRP were decreased after treatment in the experiment group than those in the control group(P<0.05).There was no significant difference in the cumulative cardiovascular mortality between the experiment group and the control group(3.9％vs.5.9％,P=0.524).The cumulative HF rehospitalization rate was lower in the experimental group than that of the control group(9.8％vs.23.5％,P=0.042).The cumulative end-point-free survival rate was higher in the experiment group than that of the control group(86.3％vs.70.6％,P=0.037).Conclusion Sacubitril valsartan is safer and more effective than ACEI/ARB in the treatment of AMI patients with HFmrEF,and it is worthy of clinical promotion.

Correlations between brain function and olfactory function in patients with cerebral small vessel disease and Parkinson's disease based on resting-state functional magnetic resonance imaging / 中国组织工程研究

BACKGROUND:Olfactory dysfunction is an early biological marker of various diseases.However,the neuroimaging mechanism by which olfactory dysfunction occurs following cerebral small vessel disease is unclear. OBJECTIVE:To explore the different neuroimaging mechanisms of olfactory function regulation in patients with cerebral small vessel disease and Parkinson's disease,and explore the potential application value of olfactory function assessment in patients with cerebral small vessel disease. METHODS:Neuropsychological and olfactory tests,high-resolution structural magnetic resonance and resting-state functional magnetic resonance data were collected in 80 patients with cerebral small vessel disease,44 healthy controls and 29 patients with Parkinson's disease.DPABI,SPM12 and SPSS were used to analyze and compare the amplitude of low frequency fluctuation,regional homogeneity and functional connectivity values between the cerebral small vessel disease,control and Parkinson's disease groups.Correlations between the significantly altered resting-state functional magnetic resonance imaging measures and olfactory and cognitive scores were evaluated. RESULTS AND CONCLUSION:Compared with the control group,low-frequency fluctuation amplitude of the right dorsolateral superior frontal gyrus and the regional homogeneity of the left wedge leaf were significantly reduced in the cerebral small vessel disease and Parkinson's disease groups.The right dorsolateral superior frontal gyrus and the left cuneiform lobe are the seed points.Compared with the Parkinson's disease group,the functional connectivity values of the right anterior cunei,inferior temporal gyrus,anterior central gyrus and dorsolateral superior frontal gyrus,left posterior central gyrus and inferior temporal gyrus were significantly enhanced in the control and cerebral small vessel disease groups.The left cuneiform lobe was the seed point.Compared with the control group,the functional connectivity of the left lingual gyrus was significantly weakened in the cerebral small vessel disease and Parkinson's disease groups.The functional connectivity values of the left middle temporal gyrus and the right posterior central gyrus were enhanced in the control group compared with the cerebral small vessel disease and Parkinson's disease group,and that was enhanced in the cerebral small vessel disease group compared with the Parkinson's disease group.Correlation analysis showed that the olfactory score and cognitive score were positively correlated in the cerebral small vessel disease group,and the regional homogeneity of the left wedge lobe was negatively correlated with the Montreal Cognitive Assessment Scale score,while the functional connectivity of left wedge lobe-left middle temporal gyrus in the Parkinson's disease group was positively correlated with the olfactory recognition score,and the functional connectivity values of the left wedge lobe-left posterior central gyrus and left wedge lobe-left lingual gyrus were positively correlated with the olfactory identification score and the total olfactory score,respectively.The regulation of olfactory function in patients with cerebral small vessel disease has a different neuroimaging mechanism from that of olfactory dysfunction in patients with Parkinson's disease.The olfactory function of patients with cerebral small vessel disease is related to cognitive function.It is speculated that the olfactory function following cerebral small vessel disease is a secondary change of brain dysfunction,while olfactory dysfunction following Parkinson's disease is directly caused by abnormal function of olfactory-related brain areas.Olfactory function assessment in patients with cerebral small vessel disease has potential application in predicting cognitive function.

Significance of PLCE1 gene polymorphism detection in children with primary nephrotic syndrome in Guangxi Zhuang Autonomous Region / 中华实用儿科临床杂志

Objective:To investigate the correlation between the single nucleotide polymorphism (SNP) of the PLCE1 gene and children with primary nephrotic syndrome (PNS) in Guangxi Zhuang Autonomous Region. Methods:This study was a retrospective study, a case-control study was used to select 155 cases of PNS in Guangxi Zhuang children attending the Affiliated Hospital of Youjiang Medical University for Nationalities from January 2017 to January 2021 (PNS group), and 100 healthy Guangxi Zhuang children who were physically examined during the same period (healthy control group). Genotyping of PLCE1 SNP rs3765524, and rs2274223 were performed using the second-generation gene sequencing technology, and their correlation with the development of PNS was analyzed. Logistic regression analysis was used for correlation analysis, and Chi- square test or Fisher′ s exact probability method was used for comparison between groups. Results:(1)Compared with the healthy control group, PLCE1 rs3765524 was correlated with the risk of PNS in children of PNS group, and the TT genotype may reduce the risk of PNS in the co-dominant model ( OR=0.435, 95% CI: 0.238-0.794, P=0.007). There were no significant differences in the genotype of PLCE1 rs2274223 and the frequency of allele distribution between PNS group and healthy control group (all P>0.05). (2) A strong linkage disequilibrium existed at PLCE1 SNP rs3765524 and rs2274223.(3) There were no significant differences in the frequency of the distribution of haplotypes AC, AT and GT between PNS group and healthy control group (all P>0.05). Conclusions:PLCE1 SNP rs3765524 is correlated with the risk of PNS in children in Guangxi Zhuang Autonomous Region, and the TT genotype may be a protective factor for PNS in children in Guangxi Zhuang Autonomous Region.

EB virus-positive discordant lymphoma: report of 1 case and review of literature / 白血病·淋巴瘤

Objective:To investigate the clinical manifestations, laboratory tests, diagnosis and treatment of discordant lymphoma (DL).Methods:The clinical data of a patient with EB virus-positive DL admitted to Taizhou People's Hospital in November 2019 were retrospectively analyzed and the related literature was reviewed.Results:The patient underwent a cervical lymph node biopsy pathology examination at onset, and then results suggested angioimmunoblastic T-cell lymphoma (AITL). The patient subsequently developed gastrointestinal bleeding and underwent resection of small bowel lesions, and postoperative pathology suggested diffuse large B-cell lymphoma (DLBCL). The patient was finally diagnosed as DL. The R2-CHOP chemotherapy regimen was given to the patient, but the patient still had recurrent gastrointestinal bleeding and poor general condition. The patient refused chemotherapy and was changed to lenalidomide monotherapy. Finally, the patient died due to multiorgan failure, with an overall survival of 13 months.Conclusions:DL is rarely seen in lymphoma, whereas the combination of AITL and DLBCL is extremely rare. The clinicians need to improve the understanding of this disease to avoid misdiagnosis and missed diagnosis.

Visual analysis of critical care research based on Web of Science core set / 中国实用护理杂志

Objective:To analyze the data of critical care related literatures published in Web of Science core set by knowledge map visualizing technology, and summarize the research status and hotspots of critical care.Methods:The core set database of Web of Science from January 2011 to December 2020 was searched, the extracted information was standardized and analyzed by knowledge map visualizing technology.Results:A total of 783 articles in the field of critical care were included, and the number of literatures increased year by year, among which the number of articles published in the American Journal of Critical Care(305) was the most. The United States (437) was the country with the most published literatures, and Australia was the country with the highest centrality (centrality=0.67). The number and centrality of articles published from China were at the lower middle level. There was cooperation among countries, but not close cooperation. The cooperation among authors was in the state of small aggregation and large dispersion. Cluster analysis and keyword emergence analysis showed that many aspects in the field of intensive care had been the research hotspots, among which "post intensive care syndrome" and "children′s intensive care" were the research hotspots in recent years.Conclusions:The research field of intensive care is still in the rising stage of development, and post intensive care syndrome and children's intensive care are the latest hotspots in intensive care research.

Effects of mindfulness therapy on self-burden, hope and sleep in patients undergoing perfusion chemotherapy for bladder cancer / 中国实用护理杂志

Objective:To explore the effect of mindfulness therapy on self burden, hope and sleep of middle-aged bladder cancer patients undergoing bladder sparing chemotherapy.Methods:Sixty patients with bladder cancer treated by intravesical instillation chemotherapy with bladder preservation from January 2018 to December 2019 were selected as the study subjects. They were divided into control group and intervention group according to the sequence of chemotherapy time, with 30 cases in each group. Both groups received routine nursing and rehabilitation training in urology, and mindfulness therapy was added to the intervention group for 6 weeks. Before and 6 weeks after the intervention, the sleeping and mental status of the two groups were compared by the Self-Burden Feeling Scale (SPBS), Herth Hope Scale (HHI) and Insomnia Severity Index Scale (lSI).Results:There was no significant difference in SPBS, HHI and ISI scores between the two groups before intervention ( P > 0.05). After 6 weeks of intervention, SPBS score of patients in the intervention group was 47.00±1.41, and that of the control group was 49.50±0.62.After 6 weeks of intervention, the total score of HHI was 32.61±1.94 in the intervention group and 27.22±2.67 in the control group.After 6 weeks of intervention, ISI score of patients in the intervention group was 19.17± 1.72, and that of the control group was 20.67±2.24. The difference between the two groups was statistically significant ( t values were 6.454, -7.042, 2.097, P < 0.01 or 0.05). Conclusions:Mindfulness therapy can effectively improve insomnia and cancer emotional problems in patients with bladder cancer who underwent bladder preservation and perfusion.

Clinical effect of addition and subtraction of Xiaojiyinzi prescription in the treatment of bleeding after bipolar vaporization of prostate for benign prostatic hyperplasia / 中国基层医药

Objective To explore the effect of addition and subtraction of Xiaojiyinzi prescription in the treatment of bleeding after bipolar vaporization of prostate for benign prostatic hyperplasia.Methods From June 2013 to June 2017,90 patients with benign prostatic hyperplasia who underwent bipolar electrovaporization in the Traditional Chinese Medicine Hospital of Wenling were selected in this study.The patients were divided into observation group and control group according to a random number table,with 45 cases in each group.The observation group was givenaddition and subtraction of Xiaojiyinzi prescription,while the control group was treated with finasteride orally.The clinical effects of the two groups were compared and analyzed.Results The amount of bleeding in the control group at 3 days,5 days and 7 days after operation were (13.69 ± 1.27) mL,(8.37 ± 1.23) mL,(6.13 ± 0.58) mL,respectively,which in the observation group were (9.22 ± 1.18) mL,(6.12 ± 0.98) mL,(3.98 ± 0.33) mL,respectively,there were statistically significant differences between the two groups (t =17.297,P =0.000,t =9.597,P =0.000,t =21.613,P =0.000).The amount of bleeding in both two groups decreased with the prolongation of time,and the differences were statistically significant between each two moments (all P ＜ 0.05).After treatment,the I-PSS and NIH-CPSI scores in the control group were (13.22 ± 2.95) points and (13.64 ± 4.22) points,respectively,which in the observation group were (8.11 ± 1.35) points and (7.88 ± 3.06) points,respectively,which were lower than those before treatment,and the differences were statistically significant(t =12.286,P =0.000,t =14.359,P =0.000,t =21.041,P =0.000,t =25.989,P =0.000).The scores in the observation group after treatment were lower than those in the control group,and the differences were statistically significant between the two groups (t =8.217,P =0.000,t =7.413,P =0.000).Conclusion Hemorrhage is the most common complication of transurethral resection of prostate in elderly men,which seriously interferes with postoperative recovery.The addition and subtraction of Xiaojiyinzi prescription can reduce bleeding and improve postoperative recovery.

Mesoporous silica nanoparticles for drug and gene delivery

Mesoporous silica nanoparticles (MSNs) are attracting increasing interest for potential biomedical applications. With tailored mesoporous structure, huge surface area and pore volume, selective surface functionality, as well as morphology control, MSNs exhibit high loading capacity for therapeutic agents and controlled release properties if modified with stimuli-responsive groups, polymers or proteins. In this review article, the applications of MSNs in pharmaceutics to improve drug bioavailability, reduce drug toxicity, and deliver with cellular targetability are summarized. Particularly, the exciting progress in the development of MSNs-based effective delivery systems for poorly soluble drugs, anticancer agents, and therapeutic genes are highlighted.

Effect of Yiqihuoxue Paishiyin combined with levofloxacin on renal calculus and inflammatory state / 中国生化药物杂志

Objective To study the effect of Yiqihuoxue Paishiyin combined with levofloxacin on renal calculus and inflammatory state. Methods 76 patients with kidney stones in our hospital from February 2015 to September 2016 were selected as the study object,and they were divided into control group 38 cases and observation group 38 cases by the method of random number table,then the control group were treated with levofloxacin, the observation group were treated with supplementing qi,promoting blood circulation and removing stones combined with levofloxacin,then the clinical effective rates,serum fever and pain related inflammatory factors before and after the treatment of two groups were analyzed .Results The total effective rates of observation group with different stone diameters and stone locations were all higher than those of control group,the serum fever and pain related inflammatory factors at different time after the treatment were all lower than those of control group , the differences were all significant ( P <0.05 ) . Conclusion Yiqihuoxue Paishiyin combined with levofloxacin treatment of kidney stones in patients with significant effect , can effectively control the body's inflammatory state, improve the level of inflammatory factors.

Research progress of inflammation reaction related to endoplasmic reticulum stress in ischemic endoplasmic reticulum stress / 中国药理学通报

Endoplasmic reticulum plays a key role in both basic structure formation and function performance of microenviron-ment. Endoplasmic reticulum homeostasis unbalance caused by endoplasmic reticulum stress has become a hot research topic in recent years. This paper focuses on the role of endoplasmic retic-ulum stress in ischemic stroke. Research progress of related sig-naling pathways were reviewed, especially mechanisms through which endoplasmic reticulum stress trigger the inflammatory reac-tion, so as to provide a new research method for prevention of is-chemic stroke.

Pathogen-Host Adhesion between SARS-CoV-2 S Proteins from Different Variants and Human ACE2 Probed at Single-Molecule and Single-Cell Levels

Pathogen-Host adhesion is considered the first step of infection for many pathogens such as bacteria and virus. The binding of the receptor binding domain (RBD) of SARS-CoV-2 Spike protein (S protein) onto human angiotensin-converting enzyme 2 (ACE2) is considered as the first step for the SARS-CoV-2 to adhere onto the host cells during the infection. Within three years, a number of variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been found all around the world. Here, we investigated the adhesion of S Proteins from different variants and ACE2 using atomic force microscopy (AFM)-based single-molecule force spectroscopy (SMFS) and single-cell force spectroscopy (SCFS). We found that the unbinding force and binding probability of the S protein from Delta variant to the ACE2 was the highest among the variants tested in our study at both single-molecule and single-cell levels. Molecular dynamics simulation showed that ACE2-RBD (Omicron) complex is destabilized by the E484A and Y505H mutations and stabilized by S477N and N501Y mutations, when compared with Delta variant. In addition, a neutralizing antibody, produced by immunization with wild type RBD of S protein, could effectively inhibit the binding of S proteins from wild type, Delta and Omicron variants onto ACE2. Our results provide new insight for the molecular mechanism of the adhesive interactions between S protein and ACE2 and suggest that effective monoclonal antibody can be prepared using wild type S protein against the different variants.