Objective To optimize the spray drying process of Banlangen(Isatidis Radix)formula granules based on quality by design(QbD)concept.Methods Using powder yield and the contents of uridine,adenosine,guanosine,and(R,S)-goitron as the critical quality attributes(CQAs),Plackett-Burman design was used to screen out critical process parameters(CPPs)for inlet temperature,spray pressure,liquid temperature,pump speed,and liquid relative density.The central-composite design(CCD)test was used to optimize the CPPs,which were screened.Based on the quadratic polynomial regression model,the design space of spray drying process of Banlangen(Isatidis Radix)formula granules was established,and further validated by experiments.Results Plackett-burman test results show that liquid relative density and inlet velocity are the key parameters for the study.The variance analysis results of CCD test showed that the constructed model in a good prediction ability,since the P-values of model was less than 0.01 and P-values of items lack of fit was more than 0.05.The optimized design space of CPPs was the liquid relative density 1.05-1.08,and pump speed 30%-40%.Conclusion Based on the QbD concept,the design space for the spray drying process of Banlangen(Isatidis Radix)formula granules can improve the stability of its process and help ensure the consistency of product quality.

Objective To explore the value of transesophageal echocardiography(TEE)for surgical therapy of pediatric atrioventricular valve diseases.Methods Data of 273 children with atrioventricular valve diseases who underwent surgical operation under extracorporeal circulation were retrospectively analyzed.Transthoracic echocardiography(TTE)was performed within 1 week before,while TEE was performed before and after surgical operation.Whether TTE diagnosis should be adjusted were evaluated according to findings of TEE,so were the effects of surgical treatments,and the ultrasonic diagnostic coincidence rate before operation were compared taken surgical findings as standards.Results TEE was successfully completed in all 273 children.The diagnostic coincidence rate of preoperative TTE was 83.88％(229/273).After adjustment or supplement according to TEE in 44 cases(44/273,16.12％),the ultrasonic diagnostic coincidence rate reached 100％(273/273),higher than that of preoperative TTE alone(P＜0.001).Residual shunt was found in 5 cases,while no obvious improvement of valvular regurgitation was noticed in 3 cases with post operative TEE,and after corresponding treatments,re-examination of TEE showed satisfactory efficacy in all the above cases.Conclusion TEE could be used to accurately diagnose pediatric atrioventricular valve diseases before and evaluate the efficacy after surgical treatments,having important clinical application value.

Objective To observe the value of MR lymphangiography(MRL)radiomics for evaluating central conducting lymphatic anomaly(CCLA).Methods Sixty-one patients with complex lymphatic anomaly,including 41 CCLA(group A),20 non-CCLA(generalized lymphatic anomaly and Gorham-Stout disease)and 20 subjects with normal thoracic duct(group B,n=38)were retrospectively enrolled.Cervical and thoracic(combined with abdominal if necessary)MRL was acquired using three-dimensional heavily T2W fast spin echo sequence.ROI was delineated along overall thoracic duct,and radiomics features were extracted.Data sets of group A and B were divided into K subsets using 5-fold cross-validation.The union of(K-1)subset was always used as training set,while the other subsets were used as validation set.Radiomics model was constructed based on support vector machine(SVM)algorithm.Receiver operating characteristic curve was drawn,the area under the curve(AUC)was calculated to evaluate the efficacy of SVM model for assessing CCLA.Results The proportions of bifurcation,cystoid change and extension of main thoracic duct,and extension of terminal thoracic duct in group A were all higher,while of normal main and terminal thoracic duct in group A were both lower than those in group B(all P＜0.05).No significant difference of proportions of multiple thoracic ducts,dextral thoracic duct,part of thoracic duct invisible,multiple terminal thoracic ducts,cystoid change of terminal thoracic duct nor terminal thoracic duct pampiniform was found between groups(all P＞0.05).The sensitivity,specificity,accuracy,positive predictive,negative predictive and AUC of SVM model for evaluating CCLA in training set was 78.95％,97.56％,88.61％,96.77％,83.33％and 0.920,respectively,which in validation set was 78.95％,83.57％,82.28％,83.33％,81.40％and 0.833,respectively.Conclusion MRL radiomics could be used to effectively evaluate CCLA.

OBJECTIVE To optimize the water extraction process of Flos Lonicerae-Fructus Forsythuae and determine the range of water extraction process parameters.METHODS The active components were screened by network pharmacology,and the indica-tor ingredients were determined in combination with the quality markers under the relevant terms of Chinese Pharmacopoeia 2020 edition and the literature.Take extraction yield and the extraction rate of the indicative component as the critical quality attributes of the water extraction process to screen critical process parameters.The mathematical model was established by Box-Behnken experimental design to investigate the interaction between CQAs and CPPs and build the design space of the water extraction process of Flos Lonicerae-Fruc-tus Forsythuae.RESULTS The extraction percentages of phenolic acids,forsythoside A and forsythin were screened as the index components;specifications of medicinal slices,extraction time and water addition were the key process parameters.Based on the estab-lishment and optimization of the design space,the optimum water extraction process was obtained as follows:the medicinal slice of Lian-Qiao was broken into 0.8-1.2 cm,adding 12 times the amount of water in the first and extract for 30-50 min,10 times the a-mount of water in the second and extract for 25-30 min.CONCLUSION The verification results show that the measured value ob-tained by using the design space method to optimize the water extraction process is close to the predicted value,indicating that the method is stable and reliable,which can provide ideas for its further process development and quality control for the couple medicines of Flos Lonicerae-Fructus Forsythuae.

AIM: To explore the role of ZKSCAN3 in acute lung injury (ALI) induced by lipopolysaccharide (LPS). METHODS: After verifying the efficacy of ZKSCAN3 siRNA, male C57BL/6 mice were randomly divided into 4 groups (n = 8): control group(group A), LPS group (group B), scrambled siRNA group (group C) and ZKSCAN3 siRNA group (group D). Mice in groups A and B were given 1 mL of PBS via tail vein; mice in groups C were given corresponding doses of PBS containing scrambled siRNA; and mice in group D were given corresponding doses of RNase-free PBS containing ZKSCAN3 siRNA (50 μg). After 24 hours, mice in groups B, C, and D were instilled with LPS solution (5 mg/kg) through tracheal intubation to create an ALI model; group A was given the corresponding dose of PBS (20 ΜL). The samples were collected and tested 24 hours after the modeling administration. RESULTS: Compared with group B, silencing ZKSCAN3 gene expression reduced SOD activity and Bcl-2 level; while MDA, Bax and caspase-3 increased; correspondingly, the content of protein and cells in BAL, the apoptosis rate of lung tissue and the pathological score significantly increased (P < 0.05).CONCLUSION: Silencing ZKSCAN3 gene expression aggravates the lung injury caused by LPS, which may aggravate the pathological damage of lung tissue in mice by weakening the antioxidant function and aggravating tissue necrosis.

Objective:To constructe an evaluation index system for clinical research innovation in medical institutions, for references for enhancing the research and innovation capabilities of medical institutions and formulating policies related to clinical research innovation.Methods:From March 2022 to May 2023, relevant literature and policies on the evaluation system of scientific and technological innovation at home and abroad were analyzed to establish the preliminary screening clinical research innovation indicators. Two rounds of Delphi method were used to construct a clinical research innovation index evaluation system, analytic hierarchy process was used to calculate the weights of each indicator.Results:The effective response rates of the two rounds of consultation questionnaires were both 100.00%, with expert authority coefficients of 0.95 and Kendall coordination coefficients of 0.85 and 0.87, respectively. The clinical research innovation index evaluation system ultimately established 4 primary indicators, 13 secondary indicators, and 42 tertiary indicators. The first level indicators included infrastructure construction, innovation support environment, clinical research activity, and innovation effectiveness, with weight coefficients of 18.00%, 21.00%, 30.00%, and 31.00%, respectively.Conclusions:The clinical research innovation evaluation index system constructed in this study covered the investment, environment, and output aspects of research innovation, and could comprehensively and objectively reflect the clinical research innovation ability of medical institutions.

【Objective】 To study the application effect of gel adsorbent tank in the production of human prothrombin complex concentrate(PCC). 【Methods】 Six batches of PCC were produced from 1000 L cryoprecipitated plasma, using the same gel twice for adsorption within the tank.The number of gel repeated application was examined by retrospective confirmation, and the adsorption rate, specific activity and residue of finished virus inactivation reagent were determined before and after adsorption. 【Results】 All 6 batches of PPC, produced by the same gel, satisfied quality criteria. Both PPC solution and the gel presented good color. The average activities of coagulation Factors Ⅱ, Ⅶ, Ⅸ and Ⅹ of six batches of PCC were 118.2%, 157.0%, 140.5% and 176.8%, respectively. The The adsorption capacity of coagulation factor Ⅱ, Ⅸ and Ⅹ were both 100% in the first and second adsorption, while coagulation factor Ⅶ were 75% and 81%, respectively. The average specific activity of coagulation factor Ⅸ was 0.7 IU/mg. The average residues of polysorbate 80 and tributyl phosphate products were 0 μg/mL and 33 μg/mL, respectively. The same batch of gel can be repeatedly used up to 6 times during the PCC process. 【Conclusion】 The gel adsorption tank presents good application value in the production of PCC, which can realize process amplification and automatic control.

The lung is the second most common site of neuroendocrine tumors (NETs). Typical and atypical carcinoids are low-grade NETs of the lung. These rare tumors have received little attention and education is needed for treating physicians. The article describes the classifcation of lung NETs, the epidemiology and pathological characteristics. When lung NETs are diagnosed at an early stage, surgical intervention is often curative. For advanced lung NETs patients, different treatment methods including chemotherapy, somatostatin analogs, m-TOR inhibition, peptide receptor radioligand therapy, and biologic systemic therapy are discussed. The conclusions are generally extrapolated from the outcome of extra-pulmonary carcinoids. Prospective randomized well-designed trials are urgently needed to inform current recommendations on systemic treatment.
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Disease-Free Survival ; Drug Therapy ; methods ; Humans ; Lung ; drug effects ; radiation effects ; surgery ; Lung Neoplasms ; pathology ; surgery ; therapy ; Neoplasm Grading ; Neuroendocrine Tumors ; pathology ; surgery ; therapy ; Outcome Assessment (Health Care) ; Radiotherapy ; methods

Objective To explore the mechanisms of ligament of Marshall (LOM) initiat and sustain atrial fibrillation (AF).Methods The electrophysiologic properties of canine LOM were investigated using multipolar catheter mapping(normal canines,n =4,group A;AF canines,n =5,group B).The programmed stimulation were performed in the LOM,PV-left atrium(LA)junction and LA,respectively.Activations maps of LOM were analyzed from episodes of spontaneous onset of AF and initiation of induced AF by a single extrastimulus.The effectives refractory period of each part was compared and statistically analyzed among three parts in each group and between the two groups.LOM were cutted with surgical incision technology.The inducing rate of AF and the mapping rate of double potential and fragmented electrocardiogram were compared and statistically analyzed pro and post isolation of LOM.Results The incidence of abnormal potential of LOM in the two groups was significantly different(P ＜0.01),re-entry cycle(group A 25％ vs.B group 80％),tachycardia(group A 25％ vs.B 100％),double potential(group A 25％ vs.group B 80％),fragmentation potential(group A 25％ vs.group 80％).There was a significant difference in the rate of LOM tachycardia induction before and after LOM intervention in group B (P ＜ 0.05,before 100％ vs.after 20％).Conclusion There are two possible mechanisms of LOM involved in the occurrence and maintenance of AF:one is that LOM induces AF through spontaneous excitation,the other is that LOM participates in the reentry of left atrium and pulmonary vein in the form of bypass to induce and maintain AF.

Objective: To evaluate the effect of computer-assisted design based on three-dimensional reconstruction technique on the reduction accuracy of tibial and fibular fractures with Taylor external fixation. Methods: A retrospective review was conducted on the clinical data of 69 patients who had tibia and fibula fractures treated with Taylor external fixation in department of orthopedic trauma of Tianjin Hospital from January 2016 to January 2018 to compare the residual deformity after fracture reduction between computer-assisted design method (experimental group) and the standard measurement method (control group). The frontal and lateral tibia and fibula X-ray of all the affected limbs were taken. In experimental group, all the patients took bilateral tibial CT tomography, and then DICOM format documents were input into the Mimics 17.1 software and got three-dimensional models of targeted bone and external fixation ring. After that the visual image matching was performed between external fixation ring three-dimensional reconstruction model and the standard model and also between the affected limb and the contralateral limb. Then the reduction trajectory plan of bone broken end and the position of external fixation ring were obtained. The STL files were input to Solid Works software and got the length of six rods to adjust the Taylor external fixation. In control group, the films were measured by Coreldraw X7 X-ray measurement software and the parameters were input in Taylor Spatial Frame system software. And then six calibrated threaded rods were adjusted according to the prescription of the software. Finally, all the patients took the X-ray films again to evaluate the degree of residual displacement. Skew distributional data are indicated with M(Q_R), and method of non-parameter was used to analyze variances between groups. Results: All patients had better fracture reduction and achieved functional reset criteria. In the control group, the amount of displacement and angle residual aberration (improvement) in the frontal and lateral radiographs were 0.50(2.30)mm(90%), 0.00(0.85)mm(100%)and 0.00°(1.50°)(100%), 0.00°(0.00°)(100%), respectively. In the control group, the amount of displacement and angle residual aberration (improvement) in the frontal and lateral radiographs were 1.40(3.28)mm(69%), 2.15(4.27)mm(46%)and 1.15°(1.85°)(73%), 0.80°(2.10°)(67%). The positive and lateral angles and lateral displacements in the two groups were significantly different(P<0.05), but there was no statistically significant difference in positive displacement (P=0.099). Conclusion Both computer-assisted design method and the standard measurement method have satisfactory reduction effect, but computer-assisted design can accurately correct fracture deformity, which is good for fracture healing and functional recovery of affected limb.