Objective:To design a heating and pressurizing flushing device and to assess its application effect in hysteroscopic surgery.Methods:The heating and pressurizing flushing device was composed of a heating and pressing device,a liquid crystal control panel module,flushing pipeline,heating pipeline and a support frame.A total of 100 female patients who underwent gynecological hysteroscopic surgery at Shengjing Hospital of China Medical University from May 2021 to April 2022 were selected and divided into observation group and control group by random number table method,with 50 cases in each group.The observation group adopted a heating and pressurizing device to perform heating and pressurizing operations during hysteroscopic surgery,the control group adopted manual inflatable pressurized infusion bags to perform heating and pressurizing operations during hysteroscopic surgery by inflating and squeezing the air bag.The clarity of dilated uterus,operation time,preoperative,intraoperative and postoperative body temperature of the patients,and satisfaction of doctors and nurses were compared between the two groups.Results:The clarity rate of dilated uterus and satisfaction of doctors and nurses in the observation group were significantly higher than those in the control group,the difference was statistically significant(x2=7.862,8.392,P<0.05).The operation time of the observation group was significantly lower than that of the control group,the difference was statistically significant(t=51.099,P<0.05).The body temperature of the patients at 15 minutes during operation and 20 minutes after operation in the observation group were higher than those in the control group,the difference was statistically significant(t=-13.153,-17.911,P<0.05).Conclusion:The use of heating and pressurizing device in gynecological hysteroscopic surgery can increase the clarity of dilated uterus,effectively shorten operation time,save human resources,reduce complications and improve the satisfaction of medical staff.The clinical application effect is good.

OBJECTIVE To investigate the efficacy and safety of clobazam in the additional treatment of refractory epilepsy in children， and provide reference for clinically safe and rational drug use. METHODS The literatures about additional clobazam treatment for refractory epilepsy in children were searched from PubMed， The Cochrane Library， Embase， CNKI， VIP and Wanfang database during the inception to November 2023. After literature screening and data extraction， the quality of included literature was evaluated according to quality evaluation tool for methodological evaluation indicators of non-randomized controlled trial， and then meta-analysis of single-group rate and sensitivity analysis were performed by using RevMan 5.3 software. RESULTS Finally， 18 one-arm studies were included， with a total of 1 424 children. The results showed that compared with before additional treatment， the proportion of patients with seizures-free （proportion of patients with seizure reduction of 100%） was 24%[95%CI （0.18，0.32）， P＜0.000 01] after conversion； the proportion of patients with seizure reduction ≥75% was 32%[95%CI（0.25，0.40）， P＜0.000 1] after conversion； the proportion of patients with seizure reduction ≥50% was 53%[95%CI（0.44，0.61），P＜0.000 01]； the proportion of patients with seizure reduction ＜50% or no change was 35%[95%CI（0.24，0.49），P＝0.04] after conversion； the proportion of patients with seizure increase was 9%[95%CI（0.05，0.18），P＜0.000 01] after conversion. The proportion of patients with adverse reactions was 31%[95%CI（0.23，0.40），P＜0.000 1] after conversion； the proportion of patients with discontinuation due to adverse reactions was 10%[95%CI（0.07， 0.15）， P＜0.000 01] after conversion. The common adverse drug reactions were drowsiness， fatigue and behavior change， etc. The results of the sensitivity analysis showed that the study was robust. CONCLUSIONS Clobazam is an effective additional therapy for refractory epilepsy in children， but its adverse effects should be vigilant.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

OBJECTIVE To investigate the efficacy and safety of different doses of zinc in the treatment of diarrhea in children， and to provide a reference for clinical safe and rational drug use. METHODS Retrieved from PubMed， Cochrane Library， Embase database， randomized controlled trials about zinc （zinc group） versus placebo or conventional treatment （control group） in the treatment of diarrhea in children were collected from the inception to October 2022. Then， the quality of the included literature was evaluated by the Cochrane Handbook 6.0， and meta-analysis and sensitivity analysis were performed by RevMan 5.3 software. RESULTS Finally， 25 RCTs were included， with a total of 8 618 children. The results of meta-analysis showed that in terms of duration of diarrhea， in zinc ＜20 mg group， the zinc group was significantly shorter than the control group [SMD＝ －0.39， 95%CI（－0.71， －0.08）， P＝0.01]， but in subgroups of ＜6 months old， there was no significant difference between the two groups [SMD＝0.01， 95%CI（－0.10， 0.11）， P＝0.88]. In zinc 20 mg group， the zinc group was significantly shorter than the control group [SMD＝－0.52， 95%CI（－0.80， －0.23）， P＝0.000 3]. In zinc ＞20 mg group， the zinc group was significantly shorter than the control group [SMD＝－0.83， 95%CI（－1.39， －0.27）， P＝0.004]. In zinc ＞10 mg （age ≤12 months） or zinc ＞ 20 mg （age ＞12 months） group （short for “constant dose group”）， the zinc group was significantly shorter than the control group [SMD＝－0.16， 95%CI（－0.27， －0.06）， P＝ 0.003]. In the aspect of diarrhea rate after 7 days of treatment，there was no significant difference in the diarrhea rate after 7 E-mail：lihuiying@etyy.cn days of treatment between the zinc group and the control group： in zinc ＜20 mg group[OR＝1.28，95%CI （0.96，1.70），P＝0.09]， in zinc 20 mg group [OR＝0.40， 95%CI （0.15，1.01），P＝ 0.05]， in constant dose group [OR＝0.64， 95%CI （0.28， 1.44）， P＝0.28]. In terms of vomiting rate， in zinc ＜20 mg group， the vomiting rate of zinc group was significantly higher than that of the control group [OR＝2.13， 95%CI （1.68， 2.70）， P＜0.001]； in constant dose group， vomiting rate of zinc group was significantly higher than that of the control group [OR＝1.84， 95%CI （1.44， 2.34）， P＜0.001]. CONCLUSIONS Zinc can significantly shorten the duration of diarrhea in children（6 months and above）， but low doses can increase the risk of vomiting， which should be taken attention in clinical.

Acute mountain sickness (AMS) is a clinical syndrome of multi-system physiological disorder after acute exposure to low pressure and low oxygen at high altitude. Quantitative proteomics can systematically quantify and describe protein composition and dynamic changes. In recent years, quantitative proteomics has been widely used in the prevention, diagnosis, treatment and pathogenesis of many diseases. This review summarizes the progress of quantitative proteomics techniques and its application in the prevention, diagnosis, treatment of AMS and mechanisms of rapidly acclimatizing to plateau, in order to provide a reference for the pathogenesis, early intervention, clinical treatment and proteomic research of AMS.
Humans ; Altitude Sickness/prevention & control* ; Proteomics ; Acute Disease ; Oxygen/metabolism*

Pectin methylesterase (PME) is an important pectinase that hydrolyzes methyl esters in pectin to release methanol and reduce the degree of methylation of pectin. At present, it has broad application prospects in food processing, tea beverage, paper making and other production processes. With the in-depth study of PME, the crystal structures with different sources have been reported. Analysis of these resolved crystal structures reveals that PME belongs to the right-hand parallel β-helix structure, and its catalytic residues are two aspartic acids and a glutamine, which play the role of general acid-base, nucleophile and stable intermediate, in the catalytic process. At the same time, the substrate specificity is analyzed to understand the recognition mechanism of the substrate and active sites. This paper systematically reviews these related aspects.
Carboxylic Ester Hydrolases ; chemistry ; metabolism ; Catalytic Domain ; Crystallography ; Pectins ; metabolism ; Protein Structure, Tertiary ; Substrate Specificity

OBJECTIVE： To study the effects of ADRB2 （rs1042713） gene polymorphism on therapeutic efficacy of anticholinergic drug in the treatment for refractory asthma pediatric patients. METHODS： 171 children with refractory asthma were selected from outpatient department of Kunming Children’s Hospital during Nov. 2016 to Jul. 2019. The distribution of ADRB2 （rs1042713） genotype， the clinical efficacy [asthma control test （C-ACT） score， FEV1， FVC， PEF， maximal mid-expiratory flow （MMEF）] of anticholinergic drug were analyzed statistically； the response of different genotypes to the use of anticholinergic drug were also analyzed statistically. RESULTS： 148 of 171 refractory asthmatics pediatric patients were administered anticholinergic drug， among them 50 of the 71 AA genotype and 36 of the 77 GA genotype responded to anticholinergic drug treatment. Statistical analysis showed that 71 children with AA refractory asthma had improved C-ACT score， FEV1， FVC， PEF and MMEF， there was statistical significance， compared with GA genotype （P＜0.05）； the response rate of the AA genotype to anticholinergic drugs was 2.71 times that of the GA genotype [OR＝2.71， 95％CI （1.38， 5.34）， P＝0.005]. CONCLUSIONS： The detection of ADRB2 （rs1042713） gene polymorphism has some guiding significance in the treatment of refractory asthma with anticholinergic drugs， and the response of AA genotype is better.

Glucoamylase is a critical ingredient for saccharification in the starch decomposition, and widely used in food, pharmaceutical and fermentation industries. Glucoamylases are usually thermostable and have peak activities at high temperature, as required for the industrial process of glucose production. In this study, a glucoamylase gene belonging to the glycoside hydrolase (GH) family 15, Tlga15A, was cloned from Talaromyces leycettanus JCM12802, and successfully expressed in Pichia pastoris GS115. Recombinant glucoamylase TlGA showed optimal activities at pH 4.5 and 75 °C. The result of thermostability analysis showed that TlGA retained above 70% activity after incubating for 1 h at 65 °C, and 43% residual activity after 30 min at 70 °C. Moreover, TlGA had high resistance to most metal ions and chemical reagents tested. Various starch substrates could be hydrolyzed by TlGA, including soluble starch (255.6±15.3) U/mg, amylopectin (342.3±24.7) U/mg, glycogen (185.4±12.5) U/mg, dextrin (423.3±29.3) U/mg and pullulan (65.7±8.1) U/mg. The primary, secondary and tertiary structures of glucoamylase were further analyzed. The low ratio of Gly in the primary structure and low exposed nonpolarity solvent accessible surface in the tertiary structure may be the main reasons for TlGA's thermostability. These results show that TlGA is great promising for potential use in the commercial production of glucose syrups. Moreover, this research will provide knowledge and innovating ideas for the improvement of glucoamylase thermostability.
Cloning, Molecular ; Enzyme Stability ; Glucan 1,4-alpha-Glucosidase ; Hydrogen-Ion Concentration ; Pichia ; Talaromyces ; Temperature

Efficient utilization of cellulose and xylan is of importance in the bioethanol industry. In this study, a novel bifunctional xylanase/cellulase gene, Tcxyn10a, was cloned from Thermoascus crustaceus JCM12803, and the gene product was successfully overexpressed in Pichia pastoris GS115. The recombinant protein was then purified and characterized. The pH and temperature optima of TcXyn10A were determined to be 5.0 and 65-70 °C, respectively. The enzyme retained stable under acid to alkaline conditions (pH 3.0-11.0) or after 1-h treatment at 60 °C. The specific activities of TcXyn10A towards beechwood xylan, wheat arabinoxylan, sodium carboxymethyl cellulose and lichenan were (1 480±26) U/mg, (2 055±28) U/mg, (7.4±0.2) U/mg and (10.9±0.4) U/mg, respectively. Homologous modeling and molecular docking analyses indicated that the bifunctional TcXyn10A has a single catalytic domain, in which the substrate xylan and cellulose shared the same binding cleft. This study provides a valuable material for the study of structure and function relationship of bifunctional enzymes.
Cellulase ; Endo-1,4-beta Xylanases ; Enzyme Stability ; Hydrogen-Ion Concentration ; Molecular Docking Simulation ; Pichia ; Substrate Specificity ; Thermoascus

OBJECTIVE: To study the value of ADRB2, GLCCI1, FCER2 gene detection in individualized medication of children with refractory asthma.METHODS: Clinical pharmacists participated in therapy for 2 cases of refractory asthma, and comprehensively analyzed risk factors as its pathogenic factors (allergens and pathogens of respiratory infections), lung function indexes and family history. It was suggested to conduct anti-asthmatic drugs gene [p2-adrenergic receptor (ADRB2), glucocorticoid induced transcriptional 1 gene (GLCCI1), low affinity IgE receptor (FCER2)] testing. According to detection results, the suggestions were put forward such as increasing the dose of Glucocorticoid for inhalation, stopping β2 receptor agonist, additionally using anticholinergic drug. RESULTS: The clinical physicians adopted the suggestions of clinical pharmacists. After optimizing refractory asthma therapy plan according to the results of gene testing and clinical factors, 2 patients were stable and the number of seizures decreased significanthy. CONCLUSIONS: Gene test can provide evidence for the formulation of individualized therapy in asthma children.