Reprogrammed siTNFα/neutrophil cytopharmaceuticals targeting inflamed joints for rheumatoid arthritis therapy

Rheumatoid arthritis (RA) is an autoimmune disease characterized by severe synovial inflammation and cartilage damage. Despite great progress in RA therapy, there still lacks the drugs to completely cure RA patients. Herein, we propose a reprogrammed neutrophil cytopharmaceuticals loading with TNFα-targeting-siRNA (siTNFα) as an alternative anti-inflammatory approach for RA treatment. The loaded siTNFα act as not only the gene therapeutics to inhibit TNFα production by macrophages in inflamed synovium, but also the editors to reprogram neutrophils to anti-inflammatory phenotypes. Leveraging the active tendency of neutrophils to inflammation, the reprogrammed siTNFα/neutrophil cytopharmaceuticals (siTNFα/TP/NEs) can rapidly migrate to the inflamed synovium, transfer the loaded siTNFα to macrophages followed by the significant reduction of TNFα expression, and circumvent the pro-inflammatory activity of neutrophils, thus leading to the alleviated synovial inflammation and improved cartilage protection. Our work provides a promising cytopharmaceutical for RA treatment, and puts forward a living neutrophil-based gene delivery platform.

Analysis of related factors for postoperative recurrence of antrochoanal polyps in children / 临床耳鼻咽喉头颈外科杂志

Objective:To analyze the correlation between nasal resistance and lung function in children with allergic rhinitis（AR）, and explore whether AR children with increased nasal resistance are accompanied by potential lower respiratory tract involvement. Methods:A total of 88 children diagnosed with AR from December 2021 to December 2022 were selected as the study group, while 20 normal children were selected as the control group during the same period. Both the study group and the control group children underwent lung function tests, bronchodilator tests, and nasal resistance measurements. Spearman correlation analysis and multiple linear regression analysis were performed on the results of nasal resistance and lung function tests to explore the relationship and influencing factors between the two groups.According to the results of nasal resistance measurement, children with increased nasal resistance and abnormal lung function were divided into a mild increase in nasal resistance with abnormal lung function group and a moderate to severe increase in nasal resistance with abnormal lung function group. The degree of increased nasal resistance was analyzed to determine whether it would affect lung function. Results:The FEF25, FEF50, and FEF75 levels in the study group were significantly lower than those in the control group（P<0.05）. The FEV1of children with moderate to severe increase in AR nasal resistance was significantly lower than that of children with mild increase in AR nasal resistance（P<0.05）. There was a correlation between nasal resistance and FEV1/FVC, R20 in AR children, and FEV1/FVC, R20 were the influencing factors of nasal resistance in AR children（P<0.05）. There was no correlation between total serum IgE, lung function, and bronchodilation test in AR patients（P>0.05）. Conclusion:The nasal ventilation function of AR patients has changed, and there is a downward trend in small airway function. Children with moderate to severe increase in AR nasal resistance have a more significant decrease in lung ventilation function than those with mild increase. The nasal resistance of AR children is influenced by FEV1/FVC and R20, and FEV1/FVC and R20 decrease as the nasal resistance value increases. The improvement rate of lung function and FEV1 are not influencing factors for the elevation of total serum IgE.

Role of mitophagy in cognitive dysfunction in rats with sepsis-associated encephalopathy / 中华麻醉学杂志

Objective:To evaluate the role of mitophagy in cognitive dysfunction in rats with sepsis-associated encephalopathy (SAE).Methods:Twenty-four clean-grade healthy male Sprague-Dawley rats, aged 13-14 weeks, weighing 230-250 g, were divided into 3 groups ( n=8 each) using a random number table method: sham operation group (Sham group), SAE group and SAE+ autophagy inhibitor 3-methyladenine (3-MA) group (3-MA group).The SAE models were developed by cecal ligation and puncture in anesthetized animals.3-MA 10 mg/kg was intraperitoneally injected at 30 min after developing the model in 3-MA group.Cognitive function was assessed by Morris water maze test, and the escape latency and ratio of the time of staying at the target quadrant were recorded.After the end of Morris water maze test, the rats were sacrificed and hippocampal tissues were collected for microscopic examination of the pathological changes which were scored after hematoxylin-eosin staining and for determination of the expression of autophagy-related proteins LC3, Beclin1 and p62 (by Western blot).The ratio of LC3Ⅱ/LC3Ⅰwas calculated.The hippocampal mitochondria were isolated to measure mitochondrial membrane potential (MMP), ATP content and ATPase activity by spectrophotometry. Results:Compared with Sham group, the escape latency was significantly prolonged, the ratio of the time of staying at the target quadrant was decreased, the pathological score of hippocampus was decreased, and the contents of MMP and ATP and ATPase activity were decreased in SAE and 3-MA groups, the ratio of LC3Ⅱ/LC3Ⅰwas significantly increased, the expression of Beclin1 was up-regulated, and the expression of p62 was down-regulated in SAE group, and the ratio of LC3Ⅱ/LC3Ⅰwas significantly decreased, and the expression of Beclin1 and p62 was up-regulated in 3-MA group ( P<0.05).Compared with SAE group, the escape latency was significantly prolonged, the ratio of the time of staying at the target quadrant was decreased, the pathological score of hippocampus was decreased, the ratio of LC3/LC3Ⅰwas decreased, the expression of Beclin1 was down-regulated, the expression of p62 was up-regulated, and the contents of MMP and ATP and ATPase activity were decreased in 3-MA group ( P<0.05). Conclusions:Hippocampal mitophagy is involved in cognitive dysfunction in the rats with SAE.

Application of chest imaging changes in result validation for occupational health risk assessment of alumina dust-exposed operations / 环境与职业医学

Background Occupational health risk assessment of dust-exposed operations is an important part of occupational health work. However, there is a lack of objective and effective methods for validating the risk assessment results. Objective To explore the application value of chest imaging changes in validating occupational health risk assessment results of dust-exposed operations. Methods Alumina dust-exposed workers in an abrasive manufacturing company were selected as study subjects. The Australian Occupational Health and Safety Risk Assessment model (Australian model), and the Singapore semi-quantitative risk assessment model of occupational exposure to chemical substances (Singaporean model) were used to conduct occupational health risk assessment for the target group. Consistency of the assessment results was compared. The cumulative risk value and cumulative risk level of the subjects were calculated. The subjects were examined and diagnosed by chest radiographs, and the differences in the positive rates of aluminum dust shadows of workers at different job risk levels and different cumulative risk levels were compared. Results The average risk ratios (RR) of selected alumina dust-exposed workers estimated by the Australian model and the Singapore model were both 0.49±0.10, indicating generally medium occupational health risk level. The evaluation results of the two models were obviously consistent (kappa test, k = 0.823, P < 0.001). Among the 192 subjects, 62 (32.3%) were found to have aluminum dust shadows on their chest radiographs, and there were no case of pneumoconiosis. The aluminum dust shadows were mainly classified by shape and size as “s” (30.7%); the profusion of small opacities was mainly "less than 0/1" (31.3%); they were mostly distributed in 2 pulmonary zones (18.8%), and mostly in the right lower lung (18.8%), and none was seen in the two upper lung zones. The positive rate of aluminum dust shadows in the high-risk workplaces (41.7%) assessed by the Australian model was significantly higher than that in the medium-risk workplaces (22.9%) (P < 0.01). The positive rate of aluminum dust shadows in the medium-risk workplaces (42.7%) assessed by the Singapore model was significantly higher than that in the low-risk workplaces (23.3%) (P < 0.01). The cumulative risk levels evaluated by the two models were all atⅠ- Ⅲ levels. With the increase of cumulative risk level by the two models, the positive rates of aluminum dust shadows in the subjects both showed an obvious increase trend (P < 0.05). Conclusion The risk assessment results of the Australian model and the Singapore model are obviously consistent for the target group. They can be jointly applied to the risk assessment of dust-exposed operations. The application of chest imaging changes is of certain value to validate the results of occupational health risk assessment for dust-exposed operations.

Recent advances in research on chelators as metallo-β-lactamase inhibitors / 中国药科大学学报

@#The major reason for the resistance of Gram-negative bacteria to β-lactam antibiotics is the expression of β-lactamases.Metallo-β-lactamases (MBL) hydrolyze almost all types of β-lactam antibiotics including carbapenems, posing a challenge to global public health. Developing MBL inhibitors is an important method to treat the infections caused by resistant bacteria. As an important type of MBL inhibitors, chelating agents can inhibit MBL by chelating, stripping, and binding Zn2+ in the active center of MBL.This review summarizes recent publications on chelators as MBL inhibitors, discussing their chemical structures, inhibitory potency, synergistic effects with antibiotics, selectivity and mechanism of action, including EDTA and related compounds, aspergillomarasmine A (AMA) and its derivatives, NOTA and related compounds, pyridine carboxylic acid and pyridine methylamine compounds, aiming to provide reference for future development of potent, selective and safe clinical MBL inhibitors.

Clinical characteristics and risk factors in 118 patients with systemic lupus erythematosus and osteonecrosis / 中华内科杂志

Objective:To investigate the clinical characteristics and risk factors for osteonecrosis (ON) in patients with systemic lupus erythematosus (SLE).Methods:This is a case-control study. A total of 118 patients diagnosed with SLE complicated with ON (study group) were retrospectively analyzed between 2014 and 2019. Gender, age, and course matched 118 SLE patients without ON were selected as controls. Clinical manifestations, laboratory findings, medical history, and treatments were recorded and analyzed.Results:Among 118 patients, the male to female ratio was 20 to 98 with a median age of 27 years and course of disease 1-168 months. Compared with the control group, the study group presented a longer cumulative duration of glucocorticoid therapy [36.5 (0-168) months vs. 19.0(0-168) months on average, P<0.05], a higher incidence of osteoporosis (29.7% vs. 4.2%, P<0.001), a higher frequency of immune-suppressive therapy (83.9% vs. 64.4%, P=0.035), more organs involveed [median 2 (0-5) vs. 1 (0-4)], and a higher SLE disease activity index (SLEDAI) (14.22±7.40 vs. 11.63±6.11, P<0.05) in univariate logistic regression. The control group had a higher rate of positive Coombs test (39.8% vs. 7.6%, P<0.05). No statistical difference on methylprednisolone (MP) pulse therapy ( P>0.05) was observed. Multivariate logistic regression suggested that SLEDAI ( OR= 1.070, 95% CI 1.026-1.116, P<0.005), osteoporosis ( OR=10.668, 95% CI 3.911-29.103, P<0.001) and a positive Coombs test( OR=0.492, 95% CI 0.266-0.910, P<0.05) were related to the development of ON in SLE patients. Conclusion:A higher disease activity and the presence of osteoporosis are associated with an increased risk of ON in patients with SLE, and positive Coombs test seems a protective factor of ON.

Role of p38 MAPK/CREB signaling pathway in tetramethylpyrazine-induced reduction of hippocampal inflammatory responses in mice with sepsis-associated encephalopathy / 中华麻醉学杂志

Objective:To evaluate the role of p38 mitogen-activated protein kinase (MAPK)/cyclic adenosine monophosphate response element-binding protein (CREB) signaling pathway in tetramethylpyrazine-induced reduction of hippocampal inflammatory responses in mice with sepsis-associated encephalopathy (SAE).Methods:Sixty healthy male C57BL6 mice, weighing 24-27 g, were divided into 4 groups ( n=15 each) using a random number table method: sham operation group (group Sham), sepsis group (group Sep), tetramethylpyrazine group (group TMP) and p38 MAPK inhibitor SB203580 group (group SB). The model of SAE was established by cecal ligation and puncture in anesthetized mice.Tetramethylpyrazine 10 mg/kg was injected intraperitoneally once a day at 3 days before the establishment of the model in TMP group, and SB203580 2.0 mg/kg was intraperitoneally injected at 30 min after the establishment of the model in SB group.The equal volume of normal saline was given intraperitoneally in Sham and Sep groups.At 1 day after operation, cognitive function was assessed by Morris water maze, and the escape latency and ratio of time spent in the target quadrant were recorded.The animals were sacrificed after the test, and hippocampal tissues were taken for determination of the contents of interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and IL-6 (by enzyme-linked immunosorbent assay) and for detection of the expression of phosphorylation of p38 MAPK, GSK3 and CREB and expression of brain-derived neurotrophic factor (BDNF) (by Western blot). Results:Compared with group Sham, the escape latency was significantly prolonged, the ratios of time spent in the target quadrant were decreased, the contents of IL-1β, TNF-α and IL-6 were increased, the phosphorylation of hippocampus p38 MAPK was increased, the phosphorylation of GSK3 and CREB were decreased, and the expression of BDNF was down-regulated in Sep, TMP and SB groups ( P<0.05). Compared with group Sep, the escape latency was significantly shortened, the ratios of time spent in the target quadrant were increased, the contents of IL-1β, TNF-α and IL-6 were decreased, the phosphorylation of hippocampus p38 MAPK was decreased, the phosphorylation of GSK3 and CREB were increased, and the expression of BDNF was up-regulated in TMP and SB groups ( P<0.05). Compared with group TMP, no significant change was found in the parameters mentioned above in group SB ( P>0.05). Conclusion:p38 MAPK/CREB signaling pathway is involved in the process of tetramethylpyrazine-induced reduction of hippocampal inflammatory responses in mice with SAE.

Effect of tetramethylpyrazine on hippocampal inflammatory responses in rats with sepsis-associated encephalopathy / 中华麻醉学杂志

Objective:To evaluate the effect of tetramethylpyrazine on hippocampal inflammatory responses in rats with sepsis-associated encephalopathy.Methods:Sixty healthy male Sprague-Dawley rats, aged 12-14 weeks, weighing 240-270 g, were divided into 4 groups ( n=15 each) using a random number table method: sham operation group (group Sham), sepsis-associated encephalopathy group (group SAE), low-dose tetramethylpyrazine group (group L-TMP), and high-dose tetramethylpyrazine group (group H-TMP). Sepsis-associated encephalopathy was induced by cecal ligation and puncture (CLP) in anesthetized rats.Tetramethylpyrazine 5 and 20 mg/kg were intraperitoneally injected once a day in L-TMP and H-TMP groups, respectively, at 5 days prior to CLP.Morris water maze test was performed at 1-5 days after CLP to assess the cognitive function, and the escape latency and ratio of time spent in the target quadrant were recorded.Five rats were sacrificed at 1 day after CLP, the brains were removed, and the hippocampi were isolated for determination of the contents of interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and IL-6 by enzyme-linked immunosorbent assay.Rats were sacrificed after the end of Morris water maze test, and hippocampi were removed for detection of the expression of Toll-like receptor 1 (TLR1), activated caspase-3, Bax and Bcl-2 by using Western blot. Results:Compared with group Sham, the escape latency was significantly prolonged, the ratios of time spent in the target quadrant were decreased, the expression of TLR1, activated caspase-3 and Bax was up-regulated, and the expression of Bcl-2 was down-regulated in group SAE, group L-TMP and group H-TMP, and the contents of IL-1β, TNF-α and IL-6 were significantly increased in group SAE and group L-TMP ( P<0.05). Compared with group SAE, the escape latency was significantly shortened, the ratio of time spent in the target quadrant was increased, the contents of IL-1β, TNF-α and IL-6 were decreased, the expression of TLR1, activated caspase-3 and Bax was down-regulated, and the expression of Bcl-2 was up-regulated in group L-TMP and group H-TMP ( P<0.05). Conclusion:The mechanism by which tetramethylpyrazine reduces sepsis-associated encephalopathy may be related to inhibiting hippocampal inflammatory responses in rats.

Advances in strategies for activating silent biosynthetic gene clusters in Streptomyces / 中国药科大学学报

@#Microbial secondary metabolites have always been one of the important sources of discovery and development of new drugs due to their remarkable biological activities. The explosion of genome sequences has revealed that Streptomyces harbor an immensely untapped biosynthetic potential. However, the number of active secondary metabolites with new skeletons or structural units found from Streptomyces is much lower than that of biosynthetic gene clusters(BGCs), mainly due to the fact that many BGCs are either expressed weakly or transcriptionally silent under conventional laboratory conditions. Beginning with the bioinformatics tools for BGCs prediction, this review focuses on the classical approaches to activate silent BGCs of Streptomyces in native and heterologous hosts. Moreover, several new strategies including transcriptional factors decoy, reporter-guided high-throughput selection and muliplexed CRISPR-TAR were detailed, which provide methodological references for mining new secondary metabolites from Streptomyces.

Effect of transversus abdominis plane block on postoperative cognitive function in elderly patients undergoing laparoscopic surgery under general anesthesia / 中华麻醉学杂志

Objective To evaluate the effect of transversus abdominis plane (TAP) block on postoperative cognitive function in elderly patients undergoing laparoscopic surgery under general anesthesia.Methods Forty-eight male patients undergoing laparoscopic tension-free repair of inguinal hernia under general anesthesia,aged 65-75 yr,of American Society of Anesthesiologists physical status Ⅱ or Ⅲ,with body mass index of 20-28 kg/m2,were divided into 2 groups (n =24 each) using a random number table method:TAP block combined with general anesthesia group (group TG) and general anesthesia group (group G).Anesthesia was induced with midazolam,cisatracurium besylate,sufentanil and etomidate,and the patients were mechanically ventilated after laryngeal mask airway insertion.TAP block was performed through the anterior superior iliac spine approach,and 0.25％ ropivacaine 30 ml was injected in group TG.Anesthesia was maintained by target-controlled infusion of propofol and remifentanil and muscle relaxation by intravenously injecting cisatracurium.The occurrence of cerebral regional oxygen saturation (rSO2) and low rSO2 events (rSO2 ＜60％) was recorded at 1 min before anesthesia induction (T0),5 min after inserting the laryngeal mask airway (T1),at skin incision (T2),30 min after skin incision (T3),and at the end of surgery (T4).The consumption of propofol and remifentanil was recorded during surgery.Montreal Cognitive Assessment (MoCA) was used to evaluate the cognitive function of patients at 1 day before surgery and 7 days after surgery,and the development of postoperative cognitive dysfunction (POCD,MoCA scores＜ 26) was recorded.Results Compared with group G,the intraoperative consumption of propofol and remifentanil was significantly reduced,rSO2 was increased at T2~,and the incidence of low rSO2 events was decreased,MoCA scores were increased at 7 days after surgery,and the incidence of POCD was decreased in group TG (P＜0.05).Conclusion TAP block can reduce the incidence of POCD in elderly patients undergoing laparoscopic surgery under general anesthesia.

Analysis of results of genotyping and screening for infertile subjects with alpha-thalassemia in Guangxi / 实用医学杂志

Objective Investigation of the carrier rate, genotyping and genotype frequency of alpha-thalassemia among infertile subjects in Guangxi, and analysis of the relationship between the results of hemoglobin electrophoresis and hematologic parameters among patients with three phenotypes of alpha-thalassemia and subjects with non-thalassemia. Methods The preliminarily patients who were diagnosed as beta-thalassemia via HbA2>3.5％ and/or HbF> 2％ were excluded. Alpha-thalassemia genes of 10 020 infertile subjects were detected in our center from 2017 to 2018, and the results of hemoglobin electrophoresis and hematologic parameters in patients with three phenotypes of alpha-thalassemia were compared. Results 624 patients with alpha-thalassemia were confirmed via gene diagnostic technique, including 19 genotypes, total carrier rate for 6.23％, 275 (2.74％) patients with silent alpha-thalassemia, 326 (3.25％) patients with alpha-thalassemia trait and 23 (0.23％) patients with HbH disease. The most common genotype was--SEA/αα, followed by-α3.7/αα and α, CSα/αα. The parameters of MCV, MCH, MCHC, Hb, HCT, HbA2 were lower, but the value of RBC were higher (both P < 0.05) , in patients with three phenotypes of alpha-thalassemia than subjects with non-thalassemia. The parameters mentioned above excluding HbA2 in patients with alpha-thalassemia showed the following regularity : silent alpha-thalassemia> potential alpha-thalassemia> HbH disease. RBC value tended to increase gradually in patients with silent alpha-thalassemia, potential alpha-thalassemia and HbH disease. Conclusion Infertility with alpha-thalassemia is very popular in Guangxi, especially--SEA/αα which is the most common genotype. The value of MCV, MCH, MCHC, Hb, RBC and HCT are conducive to screening for infertile subjects with alpha-thalassemia, and have certain clinical value for differentiating three phenotypes of alpha-thalassemia.

Rapid and sensitive high-throughput determination method for alanine-dependent transaminase / 中国药科大学学报

@#A new method for determining transaminase activity based on the color change of the reaction solution was established, by using alanine-dependent transaminase VfTA from Vibrio fluvialis JS17 as the research object coupled with pyruvate oxidase and horseradish peroxidase. After the optimization of the conditions, the linear relationship between VfTA activity units and the absorbance at 400 nm was investigated. This method was also applied to determine the activity of commercial transaminase ATA117. The results showed that the detection limit of transaminase VfTA activity was up to 0. 45 U/mL and the detection limit of ATA117 activity was up to 0. 5 U/mL. The transaminase activity could be quickly judged according to the color depth of the reaction solution.

Application of TAR cloning in microbial secondary metabolites / 中国药科大学学报

@#Microbial secondary metabolites have been a major source for drug discovery and development due to their structural novelty and diversity. Microbial secondary metabolites, typically encoded by specific biosynthetic gene cluster(BGC), are non-essential for the growth and propagation of the microbes. Despite the abundant existence of microbes, the majority of them are unculturable under laboratory conditions. Moreover, given that most of the BGCs from culturable microbes are silent, the discovery of novel microbial secondary metabolites has been hampered. Recently, the heterologous expression of BGCs has become an attractive approach to discover various microbial secondary metabolites, among which TAR-based heterologous expression is one of the important tools. This review summarized the principle of TAR, the applications and the advanced strategies of TAR-based methods for heterologous expression of secondary metabolites, which may help the advancements of drug discovery and development from microbial sources.

Enzymatic synthesis of mogroside ⅢE / 中国药科大学学报

The aim was to develop the simple preparation method of mogroside ⅢE,and to lay the foundation for the development of the mogroside sweeteners. In the present study,the glycosidase CPU-GH17,which can regio-selectively biosynthesize mogroside ⅢE from mogroside V,was screened from the established library of glycosi-dases. Then,the soluble expression condition of CPU-GH17 in E. coli was exploited by investigating isopropyl β-D-thiogalactoside (IPTG)concentration,culture temperature and induction time,and 0. 4 mmol/L IPTG,15 °C and 12 h was used as optimal condition. The result showed that mogroside V could be completely converted into mogroside ⅢE under the conditions of pH 6. 0,45 °C,3 U/mL enzyme loading,5 mg/mL substrate concentration for 20 h. In conclusion,a biosynthetic system for the regio-selective preparation of mogroside ⅢE by recombinant CPU-GH17 was successfully established and verified at a preparative scale.

Root cause analysis method applied in the reduction of return-cleaning rate with pediatric aspirator luminal instruments / 中国实用护理杂志

Objective To explore the continuous improvement to reduce the suctioning pediatrics lumen instruments return-cleaning rate of the first time washing, improve work efficiency and reduce the cost by applying root cause analysis. Methods Using causal analysis of fishbone diagram to analysis and verify the main reason of leading to high lumen instruments return-cleaning rate. According to the three terminal factors of continuous quality improvement, quality control group was set up, lumen instruments cleaning quality control standards was made, water flow mode of lumen instruments cleaning was changed, selected the appropriate cleaning tools and real picture show, synchronize quality control measures of publishing the quality and safety board. Compared before and after return-cleaning rate of three different detection methods and the different parts of the same suction lumen instruments. Results Before carrying out eye-measurement, cotton swab to wipe, ATP bioluminescence back washing rate was 0.89% (2/225), 7.11%(16/225), 27.11%(61/225), respectively after implementation of 0, 0.44%(1/226), 3.98%(9/226), visual observation before and after the return rate of washing was no statistically significant difference (χ2=2.018, P>0.05);Cotton swab to wipe, ATP bioluminescence back washing rate difference was statistically significant (χ2=13.820, 45.999, P0.05). Conclusions ATP bioluminescence assay has fine effects to detect the return-washing rate of the inner wall of the lumen instruments. The Root Cause Analysis method significantly reduced the return-washing rate of the inside surface of the suction lumen instruments, improve the efficiency, save the medical cost and reduce the hospital infection.

Construction and application of cloud-based hospital information system / 医疗卫生装备

Objective To explore the construction and application of cloud-based healthcare information system (CHIS).Methods The process of CHIS employment and implementation for primary-level medical and healthcare institutions was elaborated by the example of a city after the analysis and comparison of mode difference between traditional and cloud construction.Results CHIS integrated regional medical resources and realized integrated application of medical and public healthcare resources,mobile integration of regional operation and continuous innovation in construction mode,and facilitated uniformed management,high-efficiency running and maintenance as well as business development.Conclusion CHIS contributes to enhancing medical inforrnatization in primary institutions,promoting continuous medical innovation and innovating medical informatization mode.

Applications of glycosyltransferases in the improvement of druggability of natural products / 中国药科大学学报

Natural products are one of the most important sources for druggable lead compounds given their diverse structures and activities.Nevertheless,very few of them can be directly developed to drugs.The undesirable druggability of natural products result from their weaker activity,lower aqueous solubility and poorer stability.Since improving druggability by chemical modifications is restricted by the limited access to the complex structures of natural products,enzymatic modification has gradually become one of important tools for the structural modification of natural products.Meanwhile,since enzymatic glycosylation by glycosyltransferases has shown certain advantages such as excellent regio-and stereo-selectivity,high catalytic efficiency and mild conditions.It has been a promising route for the improvement of druggability for natural products.In the present review,we summarize different glycosyltransferases and their application for structural modification of natural products as well as the challenges issues involved in the glycosylation,which provides a general perspective on the enzymatic modification of natural products for the improvement of their draggability.

Risk factors for blood coagulation abnormality in patients undergoing off-pump coronary artery bypass grafting / 中华麻醉学杂志

Objective To screen the risk factors for blood coagulation abnormality in patients undergoing off-pump coronary artery bypass grafting (OPCABG).Methods A total of 140 patients undergoing elective OPCABG were included in this study,and combined intravenous-inhalational anesthesia was performed during operation.The patients were divided into normal group and abnormal group according to whether or not blood coagulation abnormality developed during operation and within 48 h after operation.The data such as gender,age,body mass index,American Society of Anesthesiologists physical status,the number of operation per year for surgeons,comorbidities (hypertension and diabetes mellitus),preoperative hematocrit (Hct),left ventricular ejection fraction,arterial oxygen pressure,liver function,operation time and requirement for intraoperative continuous cardiac output monitoring,positive end expiratory pressure,tranexamic acid,ulinastatin and hydroxyethyl starch,postoperative acidosis and hypothermia were recorded.Results Blood coagulation abnormality was found in 43 patients,and the incidence was 31％.The results of logistic regression analysis showed that the number of operation per year for surgeons＜ 50,preoperative abnormal liver function,preoperative Hct＜35％,surgery time≥240 min,no use of continuous cardiac output monitoring during operation and postoperative hypothermia were risk factors for blood coagulation abnormality in patients undergoing OPCABG.Conclusion The number of operation per year for surgeons＜50,preoperative abnormal liver function,preoperative Hct ＜ 35％,operation time ≥ 240 min,no use of continuous cardiac output monitoring during operation and postoperative hypothermia are risk factors for blood coagulation abnormality in patients undergoing OPCABG.

Effect of tetramethylpyrazine on autophagy in hippocampal neurons of rats with sepsis-associated en-cephalopathy / 中华麻醉学杂志

Objective To evaluate the effect of tetramethylpyrazine on autophagy in the hippocam-pal neurons of rats with sepsis-associated encephalopathy. Methods Sixty SPF healthy male Sprague-Daw-ley rats, aged 11-14 weeks, weighing 200-240 g, were divided into 3 groups(n=20 each)using a ran-dom number table: sham operation group(group Sham), sepsis group(group Sep)and tetrameth-ylpyrazine group(group TMP). Sepsis was induced by cecal ligation and puncture(CLP), and group Sham only underwent simple laparotomy. Tetramethylpyrazine 10 mg∕kg was injected intraperitoneally at 1 h before CLP in group TMP. Morris water maze test was performed in 10 rats randomly selected at 12 and 36 h after CLP. Then the rats were sacrificed, and hippocampi were isolated for determination of the expres-sion of microtubule-associated protein 1 light chain 3Ⅰ(LC3Ⅰ), LC3Ⅱ, Beclin-1 and p62 in hipp-ocampal tissues by Western blot, and the LC3Ⅱ∕LC3Ⅰratio was calculated. Results Compared with group Sham, the escape latency was significantly prolonged, the rate of time spent in the target quadrant was decreased, the LC3Ⅱ∕LC3Ⅰratio was increased, the expression of Beclin-1 was up-regulated, and the expression of p62 was down-regulated at 12 and 36 h after CLP in group Sep and group TMP(P<005). Compared with group Sep, the escape latency was significantly shortened, the rate of time spent in the target quadrant was increased, the LC3Ⅱ∕LC3Ⅰratio was decreased, the expression of Beclin-1 was down-regulated, and the expression of p62 was up-regulated at 12 and 36 h after CLP in group TMP(P<005). Conclusion The mechanism by which tetramethylpyrazine reduces sepsis-associated encephalopa-thy is related to inhibiting autophagy in the hippocampal neurons of rats.

Effects of different degrees of coagulation disorders after surgery on short-term prognosis in patients undergoing cardiac surgery with cardiopulmonary bypass / 中华麻醉学杂志

Objective To evaluate the effects of different degrees of coagulation disorders after surgery on short-term prognosis in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB).Methods A total of 410 patients of both sexes,aged 18-79 yr,with body mass index of 16-28 kg/m2,of American Society of Anesthesiologists physical status Ⅲ or Ⅳ,scheduled for elective cardiac surgery with CPB,were enrolled in the study.After induction of general anesthesia,the patients were tracheally intubated and mechanically ventilated.Combined intravenous-inhalational anesthesia was used.The patients were divided into 3 groups according to the coagulation function at 6 h after surgery:normal function group (n =55),mild disorder group (n =237) and severe disorder group (n =118).Postoperative mechanical ventilation time,duration of intensive care unit stay,length of hospitalization and complications during hospitalization were recorded.Results Compared with normal function group,the length of hospitalization was significantly prolonged,and the rate of delayed discharge from hospital was increased in mild disorder group,and the ventilation time,duration of intensive care unit stay and length of hospitalization were significantly prolonged,the rate of delayed extubation,rate of prolonged intensive care unit stay and rate of delayed discharge from hospital were increased,and the hepatic and nephritic insufficiency and incidence of re-thoracotomy for bleeding were increased in severe disorder group (P＜0.05),and no significant change was found in the incidence of postoperative complications in mild disorder group (P＞0.05).Conclusion For the patients undergoing cardiac surgery with CPB,postoperative mild coagulation disorders exert no effect on short-term prognosis,however,postoperative severe coagulation disorders produce poor prognosis,and correction of severe coagulation disorders should be taken into account.