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In 2015, the United States put forward the concept of precision medicine, which changed medical treatment from "one size fits all" to personalization, and paid more attention to personalization and drug customization. In the same year, Spritam®, the world's first 3D printed tablet, was in the market, marking the emerging pharmaceutical 3D printing technology was recognized by regulatory authorities, and it also provided a new way for drug customization. 3D printing technology has strong interdisciplinary and high flexibility, which puts forward higher requirements for pharmaceutical staffs. With the development of artificial intelligence (AI), modern society can perform various tasks, such as disease diagnosis and robotic surgery, with superhuman speed and intelligence. As a major AI technology, machine learning (ML) has been widely used in many aspects of 3D printing drug, accelerating the research and development, production, and clinical application, and promoting the new process of global personalized medicine and industry 4.0. This paper introduces the basic concepts and main classifications of 3D printing drug, non-AI drug optimization technology and ML. It focuses on the analysis of the research progress of ML in 3D printing drug, and elucidates how AI can empower the intelligent level of 3D printing drug in pre-processing, printing, and post-processing process. It provides a new idea for accelerating the development of 3D printed drug.
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Based on the dual needs of analgesia and anti-inflammation in trauma treatment, this study uses acetaminophen and moxifloxacin hydrochloride as active pharmaceutical ingredients and develops a composite bilayer tablet with a dual-phase drug release system by using binder jet 3D printing technology. Due to the complexity of the 3D printing process, there is an interaction between the various parameters. Through the optimization of the process, the relationship between the key process parameters can be determined more intuitively. In this study, the process of extended-release tablets was optimized to maintain the mechanical properties of the tablets while realizing the regulation of release. The full-factor experimental design of three central points 23 was used to analyze the factors that significantly affect the quality attributes of extended-release tablets and the interaction between factors. The optimal extended-release process parameters were obtained by the response optimizer: the inkjet quantity of the printing ink was 10 (about 13.8 pL), the powder thickness was 180 μm, and the running speed was 360 mm·s-1. The in vitro of release of 3D printed composite bilayer tablets showed that the in vitro of release of 3D printed tablets and commercially available tablets conformed to the Ritger-Peppas release model. The results of porosity showed that the immediate-release layer of the preparation has many pores and large pore size, and the dissolution of the immediate release layer within 15 min was greater than 85%. The internal pore size of the extended release layer is large, but it can still release slowly for up to 8 h, the mechanism may be related to the extended release of HPMC gelation. On the basis of verifying the rationality of the design goal of 3D printed composite bilayer tablets, this study also provides a theoretical basis for the preparation of 3D printing complex preparations.
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OBJECTIVE@#To build a helical CT projection data restoration model at random low-dose levels.@*METHODS@#We used a noise estimation module to achieve noise estimation and obtained a low-dose projection noise variance map, which was used to guide projection data recovery by the projection data restoration module. A filtering back-projection algorithm (FBP) was finally used to reconstruct the images. The 3D wavelet group residual dense network (3DWGRDN) was adopted to build the network architecture of the noise estimation and projection data restoration module using asymmetric loss and total variational regularization. For validation of the model, 1/10 and 1/15 of normal dose helical CT images were restored using the proposed model and 3 other restoration models (IRLNet, REDCNN and MWResNet), and the results were visually and quantitatively compared.@*RESULTS@#Quantitative comparisons of the restored images showed that the proposed helical CT projection data restoration model increased the structural similarity index by 5.79% to 17.46% compared with the other restoration algorithms (P < 0.05). The image quality scores of the proposed method rated by clinical radiologists ranged from 7.19% to 17.38%, significantly higher than the other restoration algorithms (P < 0.05).@*CONCLUSION@#The proposed method can effectively suppress noises and reduce artifacts in the projection data at different low-dose levels while preserving the integrity of the edges and fine details of the reconstructed CT images.
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Algorithms , Artifacts , Tomography, Spiral Computed , Tomography, X-Ray Computed/methodsABSTRACT
@#Nowadays, the popularization of endoscopic technology makes a substantial increase in the diagnosis rate of esophageal multiple primary carcinoma. However, the multiple primary carcinoma combined with esophageal cancer, lung cancer and cardiac cancer is relatively rare. This paper reported a 64-year-old male with multiple primary cancer who received one-stage complex radical surgery, including radical resection of esophageal cancer, lung cancer and cardiac cancer. After the operation, the patient presented chylothorax and conservative treatment was ineffective. Then we preformed ligation of thoracic duct through single-portal thoracoscope. The patient recovered successfully after surgery and the follow-up results showed well.
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The development of printing ink is a challenge for binder jetting 3D printed preparations, which directly determines the quality of the printed product. This study adopted a 23 full-factor Design of Experiment (DoE) with three central points to optimize the printing ink composition of levetiracetam 3D printed dispersible tablet based on the concept of Quality by Design. Firstly, using polyvinyl pyrrolidone K30, glycerin and polysorbate 20 as independent variables based on 40% (v/v) isopropanol aqueous solution, and weight variation, hardness, friability and dispersion uniformity of the printed tablets were used as dependent variables. Then obtained the design space of the printing ink prescription by DoE model analysis, and the response optimizer was used to obtain the optimal printing ink prescription: isopropanol aqueous solution containing 0.1% (w/w) polyvinyl pyrrolidone K30 and 4.0% (w/w) glycerin. The jetting mechanism and wettability of the printing ink were analyzed, and different strengths of personalized 3D printed tablets were prepared and characterized, which verified the rationality of the printing ink formulation. This study provided a reference for the development of printing ink for binder jetting 3D printed preparations.
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The efficient and safe delivery of drugs to the therapeutic site through the biofilm has traditionally been a difficult and hot topic in the field of drug delivery. In recent years, alkyl polyglycoside (APG) have become ideal penetration enhancers for drug delivery systems because of their high permeability, good safety and biodegradability, which has attracted wide attention of domestic and foreign researchers. In this paper, the physical and chemical properties, characteristics, action mechanism and application of APG in drug delivery system are reviewed, and its application prospect in drug delivery system is prospected.
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Objective: The reverse engineering technology was used to analyze the prescription and process of Good Sense Stay Awake®, the reference listed drug of caffeine tablets, in order to provide guidance for the development of generic caffeine tablets. Methods: Firstly, the prescription information of the reference listed drug was obtained by literature research. Then, quantitative analysis of the composition of the prescription was achieved by the high-performance liquid chromatography with a crystal refractive index detection and the gravimetric analysis method;the particle size of raw and auxiliary materials was analyzed by Raman imaging technology;the crystal habit and crystal form of active pharmaceutical ingredient(API)were characterized by the optical microscope and X-ray powder diffraction technology, respectively;the preparation process of reference listed drug was determined by disintegration method;and finally, the package material was identified by the morpholine reagent. Moreover, three batches of samples were pre-pared according to the determined prescription and process, and the quality was compared with the reference listed drug. Results: By the reverse engineering analysis of the reference listed drug, the prescription composition of the reference listed drug was determined to be composed of glucose, microcrystalline cellulose, pregelatinized starch, maltodextrin, magnesium stearate, colloidal silica and yellow lake, in which the glucose content was 32% and the microcrystalline cellulose content was <23%. The API crystal form of the reference listed drug was consistent with that of the self-made preparation. The average particle size of caffeine, microcrystalline cellulose, glucose, maltodextrin and pregelatinized starch was approximately 206, 112, 172 and 61 μm, respectively. The tablet preparation process was the direct compression method, and the packaging material was polyvinyl chloride aluminum foil. The quality of the three batches of home-made preparations was the same as that of the reference listed drug. Conclusion: Caffeine tablets with the same quality as Good Sense Stay Awake® were successfully prepared by reverse engineering of the reference listed drug, which provides a reference for the application of reverse engineering in the generic drug development and consistency evaluation.
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There are two ways for marketing Over The Counter(OTC)drugs in the US: the OTC monographs and new drug application/simple application(NDA/ANDA) review procedures. New products that meet the final monograph can be marketed without FDA approval, but the reference preparations and standard preparations are not searchable in the FDA database, so the reference preparation cannot be determined for such products generally. For the convenience of finding out and confirming the US non-prescription generic reference preparation, this paper introduces the US OTC drug review procedure and inquiry method, taking the US OTC product caffeine tablet as an example to show how to determine the US OTC generic drug reference preparations, so as to provide a reference for the selection of reference preparations in the consistency evaluation of generic drugs in China.
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Objective To investigate the epidemiological characteristics and the influencing factors of the unintentional injuries among Wenzhou elementary school children. Methods A total of 3 050 students were selected from the 1st to 6th grades in 6 primary schools in Wenzhou urban area by multi - stage sampling and were investigated during 2013 to 2015. Results 2 859 students completed the investigation. The morbidity of annual average unintentional injuries was 30. 81%(95% CI:29. 12% - 32. 50% )and the occurrence density was 2. 79. Unintentional injuries occurred mainly at home (37. 69% )and school(32. 39% ),and the most common site of injuries were leg(35. 02% )and hand(33. 79% ). For overall incidence,the slip falling injury(35. 64% )was highest,followed by cut or pierced(33. 40% )and crush injury (25. 08% ). Schoolgirl was a protective factor of the injury of crushed,electrical,traffic accident,bashed,burn , exploded,drown,poisoning and bit(OR ﹤ 1),but was a risk factor of multiple injuries(OR = 1. 323). Age was a risk factor of injury of fallen,crushed,bashed,burn,cut or pierced,exploded and bit(OR ﹥ 1. 1),but was a protective factor of poisoning(OR = 0. 671). compared with the students who walked to school alone,the children who were accompanied by their family member and rode alone to school were protective factors of the traffic accident. Conclusion The incidences of the unintentional injuries of elementary school children were increased with the age,and the boy was easier to be hurt. It was suggested for parents,schools and the government to strengthen healthy education for children at the early age.
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Objective To assess the quality of life among residents along rivers in Wenzhou and to analyze its influencing factors.Methods Through stratified random sampling,228 residents from 6 residential districts along rivers in Wenzhou were evaluated by the Short -Form Health Survey (SF -36).Association between independent and dependent variables were assessed by the univariate analysis and forward multiple regression.Results In 21 0 residents along rivers,the score of Physiological Function was 96.67 (1 0.00),followed by Vitality(86.1 2 ±1 .06),Bodily Pain 80.00 (20.00),Role Physical 87.50 (25.00),Social Function 83.33 (1 6.67 ),Role Emotional 66.67 (33.33 ),Physical Health Summary (73.1 1 ±0.94),and Mental Health Summary (72.27 ±0.93 ).The water environmental pollution,as the foremost influencing factors,may has impact on the Physical Function,Role Physical,Bodily Pain,Social Function,Role Emotional,Physical Health Summary and Mental Health Summary of residents.Being the longer living time,the residents may have higher scores in Physical Health Summary,Physical Function,Role Physical,General Health and Vitality.The residents,who had higher social strata,may have higher scores in the Role Physical,Bodily Pain and General Health.The male residents had the higher scores in General Health.Conclusion There were significant effects of water environmental pollution on the quality of life among residents along rivers in Wenzhou.It is high time that the government managed the water pollution and propagated the knowledge of environmental protection to enhance the quality of life of residents along rivers.
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Objective To evaluate the influence of fast-track surgery in perioperative period on the clinical outcomes of patients at nutritional risk in respectable esophageal cancer surgery perioperatively.Methods A total of 170 esophageal carcinoma patients receiving radical operation in our hospital from January 2008 to December 2013 were randomly divided into two groups by simple random method (n =85 each):one group was treated with the new concept of FTS-based on nutritional risk screening (FTS group),and the other control group received conventional perioperative management (CPM group).The postoperative first passage of flatus and defecation,time to drainage tube removal,postoperative hospital stay,and morbidity of the postoperative complication were recorded and compared.Results The time to drainage tube removal and length of postoperative hospital stay were significantly lower in the FTS group than those in the CPM group,and the overall postoperative complication rate was 7.06％ (6/85) in the FTS group and 20.00％ (17/85) in the CPM group (all P ＜0.05).In FTS group,the first flatus time was (59.01 ±2.73) h,the first defecation time was (3.35 ± 1.37) d,removing time of chest tube was (2.76 ±0.34) d,and postoperative hospital days was (8.16 ± 0.80) d; in the control group,they were (90.16 ±2.82) h,(4.78 ± 1.74) d,(4.39 ±0.25) d,and (10.93 ± 1.39) d respectively,showing significant differences (all P ＜0.05).The operative time was similar between these two groups.Conclusion The new concept of FTS by nutrition risk screening and intervention apparently can accelerate recovery after esophagngastrectomy,reduce the rate of overall complications,promote bowel function recovery,and decrease morbidity in the perioperative period for patients with esophageal carcinoma.
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BACKGROUND:There is no effective therapy for obliterative bronchiolitis after tracheal transplantation. A therapeutic strategy at microRNA (miRNA) molecular level plays a crucial role in the prevention and treatment of complications after organ transplantation. OBJECTIVE:To analyze the miRNA differential expression profile in response to obliterative bronchiolitis after orthotopic tracheal transplantation in rats. METHODS:The obliterative bronchiolitis model after lung transplantation was established through orthotopic tracheal transplantation in inbred strains of rats, and then was identified using histoIogical examination. Total miRNAs were detected by miRNA array and significantly differential expressed miRNAs were filtrated in the transplanted trachea tissues. The miRNA-146a, miRNA-155 and miRNA-451 with significantly differential expressions were used for relative quantitative study. Quantitative real-time reverse transcription-polymerase chain reaction was applied to verify the reliability of miRNA array results. RESULTS AND CONCLUSION:The pathological examination showed that, obliterative bronchiolitis model in rats was successful y established at 4 weeks after orthotopic tracheal transplantation. A total of obliterative bronchiolitis-related 29 miRNAs were found in miRNA expression profiles, including 14 miRNAs with significantly down-regulated expression and 15 miRNAs with significantly up-regulated expression. Among them, the significantly up-regulated miRNAs (miRNA-146a and miRNA-155) and the significantly down-regulated miRNA-451 were involved in immuno-inflammatory reaction. The miRNAs play an important role in regulating pathophysiological changes of obliterative bronchiolitis after lung transplantation.
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Objective To study the effects of improving elderly patients with bowel dysfunction after cardiopulmonary bypass.Methods Choose 54 elderly patients with CPB were randomly divided into tree groups:the control group and the Gln group and the Combination group,every group has 18 patients.Glutamine(Gln) at 0.4 g/kg was administrated to the patients in the Gln group and the combination group during the beginning at CPB and two days after the operation.Based on the Gln group,the patients of The Combination group were given the different oral Chinese medicine before and after operation,according to syndrome differentiation classification.Plasma endotoxin,IL-6 and DAO were measured before operation and at the endof operation and 24 h,48 h after operation.At the same time,we used German Siemens Company's X3000 Color Doppler machine to test every group of patients superior mesenteric artery.We tested before surgery,and one to two days after operation,from the starting point within 2cmof the superior mesenteric artery and the angle between the ultrasound beam flow was less than 60 °,the probe frequency was 3.5 MHz.The detection of hemodynamic indexes were EDV and PI.Results After the test,the plasma endotoxin and IL-6 levels and DAO levels of the Gln group were reduced than the Control group after cardiopulmonary bypass.The plasma endotoxin and IL-6 levels and DAO levels of the Combined gnup were decreased than the Gln group after cardiopulmonary bypass and one day after operation.Analyze superior mesenteric artery diastolic velocity (EDV)and pulsatility index (PI) by the Color Doppler.After operation,the EDV in the Gln group and the Combined grup were significantly higher than the control group,the Pl were lower than the control group.The parameters levels have significant difference after cardiopulmonary bypass and one day after operation(P ＜ 0.05 ).The Combined group was improved than the Gln group after cardiopulmonary bypass and one day after operation.According to the traditional Chinese medicine diagnosis,there were eighteen patients in the Combined group,including fifteen patients in type of deficiency of both qi and yin and three patients in type of fu-viscera syndnome.All of the patients have defecated within tree days after operation.In the type of deficiency of both qi and yin nine patients were cured and six were shown to be effective after operation.All the patients in type of fuviscera syndrome were cured.Conclusion N(2)-L-Alanyle-L-Glutmaine have protective effect on the intestinal mucosal barrier after CPB.Combined traditional Chinese Medicine preparation was more conducive to the intestinal function recovery of elderly patients after cartiopulmonary bypass.
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Objective In a prospective randomized controlled pilot study, effects of postoperative pulmonary complications on a conservative treatment surgery (CTS) and fast track surgery (FTS) treatment regimen in non-small cell lung cancer (NSCLC) patients undergoing pulmonary lobectomy were compared.Methods Eighty patients who underwent radical pulmonary lobectomy surgical treatment for non-small cell lung cancer disease from January 2008 to May 2010 in our hospital were random assigned to either fast track surgery treatment (40 FTS group) or conservative treatment surgery regimen (40 CTS group). Study endpoints were pulmonary complications ( pneumonia, atelectasis, prolonged air leak ＞ 7 days); Further parameters assessed in the postoperative course of patients were the need for postoperative mechanical ventilation, temperature at the end of the operation, length of stay (LOS) on intensive care unit (ICU) and day of discharge. Results The rate of postoperative pulmonary complications was 34. 21% in CTS group and 8. 33% in FTS group ( P ＜0. 05). Median length of stay on ICU was comparable in both groups ( 1 day),but the day of discharge was significantly different in both groups [( 11. 1 ±3.6)d vs ( 16. 6 ±5.7)d, P ＜0. 01]. Conclusion Using this fast track clinical pathway, the rate of pulmonary complications could be significantly decreased as compared to a conservative treatment regimen. Our results supported the implementation of an optimized perioperative treatment in lung surgery for non-small cell lung cancer patients undergoing radical pulmonary in order to reduce pulmonary complications after major lung surgery.
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<p><b>OBJECTIVE</b>To study the effect of vinorelbine on apoptosis, telomerase activity and expression of hTERT gene in human lung adenocarcinoma cell line Anip973 cells.</p><p><b>METHODS</b>Anip973 cells were cocultured with Vinorelbine at different concentrations and collected at 24 h, 48 h and 72 h after treatment, respectively. The inhibition rate of cell growth was determined by methyl thiazolyl tetrazolium (MTT) assay to evaluate the effect of vinorelbine. The percentage of apoptosis was detected by flow cytometry. The cellular morphology was observed under inverted microscope and electron microscope. Telomerase activity of Anip973 cells was determined by the method of TRAP-PAGE-silver staining. RT-PCR was used to detect the expression of hTERT mRNA.</p><p><b>RESULTS</b>Vinorelbine down-regulated the telomerase activity and expression of hTERT gene mRNA, inhibited the growth of Anip973 cells, and induced cell apoptosis in a time- and concentration-dependent manner. Annexin V-FITC assay showed 0.08 µg/ml NVB group could inhibited cell proliferation in 24 hour, and apoptosis rate was (7.37 ± 0.35)%, RT-PCR detection of hTERT mRNA expression in this group was (57.01 ± 1.71), and they were very significantly different from that in the control group (P < 0.01), but telomerase activity was (6.36 ± 0.06), compared with the control group showed no significant difference(P > 0.05). The change of hTERT mRNA expression is more sensitive than telomerase activity. The apoptosis rate, telomerase activity and hTERT mRNA expression of 0.4 µg/ml group and 2.0 µg/ml group were very significantly different from that in the control group (P < 0.01). The telomerase activity of 2.0 µg/ml at 72 hour group was (1.36 ± 0.27), basically completely inhibited, while the apoptosis rate was (74.87 ± 1.88)%, showed the cell apoptosis rate was in a negative correlation with the down-regulation of the hTERT mRNA (r = -0.96046, P < 0.01).</p><p><b>CONCLUSIONS</b>Vinorelbine can induce apoptosis in Anip973 cells, and its mechanism of action is related to telomerase activity. The detection of telomerase activity and expression of hTERT gene is useful in predicting prognosis of patients with lung adenocarcinoma.</p>
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Humans , Adenocarcinoma , Metabolism , Pathology , Antineoplastic Agents, Phytogenic , Pharmacology , Apoptosis , Cell Line, Tumor , Cell Proliferation , Dose-Response Relationship, Drug , Down-Regulation , Gene Expression Regulation, Neoplastic , Lung Neoplasms , Metabolism , Pathology , RNA, Messenger , Metabolism , Telomerase , Genetics , Metabolism , Vinblastine , PharmacologyABSTRACT
@#Objective To establish an animal model for implantable ventricular assist device. Methods Seven male calves, body weight 120 to 180 kg, were anesthetized and underwent surgical implantation through a left thoracotomy at the 4th intercostal space. The domestic-made implantable ventricular assist device (DIVAD) was implanted after cardiopulmonary bypass and induction of ventricular fibrillation. The major indexes of mechanical properties of the DIVAD are similar to those of imported devices. The DIVAD was 29.5 mm × 72 mm, with a total weight of 158 g. The maximal pump speed was 9000 rpm and the maximal pump flow was 8 L/min in in vitro experiment. A flow meter was incorporated into the pump. The DIVAD was constructed with an external controller, and the pump can be monitored and adjusted through it. The inflow cannula was positioned into the left ventricle and the outflow cannula was sutured to the descending aorta. The pump was run at 3,500 to 8,000 rpm. The cardiopulmonary bypass was weaned. The pump output and animal condition was continuously monitored. Heparin was administered to maintain the activated clotting time at 1.5 to 2 times its baseline value. Results All the seven calves weaned from cardiopulmonary bypass. The mean survival time is 20.28 hours with a range from 0.5 to more than 93 hours. Conclusion Calf is the right animal model for NIVAD implantation and there are some characteristics in its perioperative treatment. The establishment of this animal model may play important role for further improvement of NIVAD.
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Through the study of 980 Khmer pupils of 2 groups of schools at Kien Giang province, results showed that: in the intervened group mainly by health education, the pupils' knowledge, attitudes and practice are significantly better than before the intervention
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Health Knowledge, Attitudes, Practice , PupilABSTRACT
Through the process of studying pupil's family environment relating to learning results and health state of pupil in Kien Giang province, we concluded that economy and literacy proficiency of the Kien Giang pupil's family are lower than those of Kinh people, the Khmer pupil's abilities lag behind Kinh one's, probably due to a lack of the family concern. More attentions need to be paid to the health education and environmental hygiene for the primary and secondary schools in Kien Giang, especially for the Khmer pupils and their families.