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Background/Objectives: Numerical simulation plays an important role in pharmaceutical preparation recently. Mechanistic models, as a type of numerical model, are widely used in the study of pharmaceutical preparations. Mechanistic models are based on a priori knowledge, i.e., laws of physics, chemistry, and biology. However, due to interdisciplinary reasons, pharmacy researchers have greater difficulties in using computer models. Methods: In this paper, we highlight the application scenarios and examples of mechanistic modelling in pharmacy research and provide a reference for drug researchers to get started. Results: By establishing a suitable model and inputting preparation parameters, researchers can analyze the drug preparation process. Therefore, mechanistic models are effective tools to optimize the preparation parameters and predict potential quality problems of the product. With product quality parameters as the ultimate goal, the experiment design is optimized by mechanistic models. This process emphasizes the concept of quality by design. Conclusions: The use of numerical simulation saves experimental cost and time, and speeds up the experimental process. In pharmacy experiments, part of the physical information and the change processes are difficult to obtain, such as the mechanical phenomena during tablet compression and the airflow details in the nasal cavity. Therefore, it is necessary to predict the information and guide the formulation with the help of mechanistic models. [ABSTRACT FROM AUTHOR]

Based on dividing institutional difference into formal institutional difference and informal institutional difference, this study explores the impact of institutional difference on scientific collaboration of six provinces in central China and analyses the moderating effect of provincial innovation environment and provincial research and development capacity using panel data from 2010 to 2019. The study finds that both formal institutional difference and informal institutional difference negatively affect scientific collaboration of six provinces in central China. Moreover, provincial innovation environment and provincial research and development capacity moderate the relationship between institutional difference and scientific collaboration of six provinces in central China. That is, in the context of good provincial innovation environment or high research and development capacity, the negative impact of institutional difference on scientific collaboration of six provinces in central China is stronger. [ABSTRACT FROM AUTHOR]

Introduction: Pancreatic follicular dendritic cell sarcoma (FDCS) is an exceptionally rare and low-to-moderate malignancy, with only seven reported cases to date. Clinical diagnosis of FDCS is challenging due to the lack of distinct biological and radiographic features. Case presentation: A 67-year-old woman presented to the hospital with a 4-day history of severe abdominal pain. Imaging studies (CT and MRI) revealed a large cystic mass located at the tail of the pancreas, which was suspected to be myeloid sarcoma (MS) based on EUS and CT-guided pancreatic puncture. Postoperative pathology and immunohistochemistry confirmed the diagnosis of pancreatic FDCS. After the diagnosis was confirmed, the patient received postoperative chemotherapy with the CHOP regimen. At 11 months of follow-up, there was no evidence of recurrence. Seven published cases have been reviewed to comprehensively summarize the clinical characteristics, diagnosis, and treatment options of FDCS. Conclusion: While imaging can be useful in detecting pancreatic FDCS, it should be interpreted with caution as it can be challenging to differentiate from other pancreatic tumors. Pathology and immunohistochemistry are considered the gold standard for diagnosis, with CD21, CD23, and CD35 being specific tumor cell markers. However, preoperative diagnosis of pancreatic FDCS remains difficult, and the pancreatic puncture may further increase the risk of misdiagnosis. The disease is highly prone to recurrence and metastasis, and surgery is the preferred method for both diagnosis and treatment of localized disease. [ABSTRACT FROM AUTHOR]

However, a number of serious adverse events has been reported including ectopic embolism, especially in bleeding patients with gastric varices and gastrorenal shunts (GOV2 or IGV1 varices) [3][4]. B Video 1 b Nylon ring with titanium clip assists endoscopic cyanoacrylate injection for the treatment of GOV1-type gastric varices. [Extracted from the article]

Purpose: The external preparation of the Tibetan medicine formula, Baimai ointment (BMO), has great therapeutic effects on osteoarthritis (OA). However, its molecular mechanism remains almost elusive. Here, a comprehensive strategy combining network pharmacology and molecular docking with pharmacological experiments was adopted to reveal the molecular mechanism of BMO against OA. Methods: The traditional Chinese medicine for systems pharmacology (TCMSP) database and analysis platform, traditional Chinese medicine integrated database (TCMID), GeneCards database, and DisGeNET database were used to screen the active components and targets of BMO in treating OA. A component–target (C-T) network was built with the help of Cytoscape, and the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment through STRING. Autodock Tools which was used to dock the key components and key target proteins was analyzed. Animal experiments were performed to verify the key targets of BMO. Hematoxylin–eosin and toluidine blue staining were used to observe the pathology of joints. Protein expression was determined using enzyme-linked immunosorbent assay. Results: Bioactive compounds and targets of BMO and OA were screened. The network analysis revealed that 17-β-estradiol, curcumin, licochalone A, quercetin, and glycyrrhizic acid were the candidate key components, and IL6, tumor necrosis factor (TNF), MAPK1, VEGFA, CXCL8, and IL1B were the candidate key targets in treating OA. The KEGG indicated that the TNF signaling pathway, NF-κB signaling pathway, and HIF-1 signaling pathway were the potential pathways. Molecular docking implied a strong combination between key components and key targets. The pathology and animal experiments showed BMO had great effects on OA via regulating IL6, TNF, MAPK1, VEGFA, CXCL8, and IL1B targets. These findings were consistent with the results obtained from the network pharmacology approach. Conclusion: This study preliminarily illustrated the candidate key components, key targets, and potential pathways of BMO against OA. It also provided a promising method to study the Tibetan medicine formula or external preparations. [ABSTRACT FROM AUTHOR]

Background: Ectopic pancreas (EP) is defined as pancreatic tissue that lacks anatomical or vascular communication with the normal body of the pancreas. Despite improvements in diagnostic endoscopy and imaging studies, differentiating ectopic pancreatic tissue from gastric submucosal diseases remains a challenge.Case Presentation: Here, we present a case of a 44-year-old woman with severe epigastric pain. Initially, gastric lymphangioma was highly suspected due to a well-demarcated protruding mass with a large size that occurred in the submucosal layer of the gastric antrum and appeared as a cystic lesion. The final correct diagnosis of gastric EP was made during surgery.Conclusion: Gastric EP with serous oligocystic adenoma appearing as a giant gastric cyst is extremely rare. The difficulty of making an accurate diagnosis and differential diagnosis is highlighted, which may provide additional clinical experience for the diagnosis of EP with serous oligocystic adenoma in the stomach. [ABSTRACT FROM AUTHOR]

Maytansine (DM1) is a potent anticancer drug and limited in clinical application due to its poor water solubility and toxic side effects. Zein is widely used in nano drug delivery systems due to its good biocompatibility. In this study, we prepared DM1-loaded zein nanoparticles (ZNPs) to achieve tumor targeting and reduce toxic side effects of DM1. Methods: ZNPs were prepared by phase separation and Box-Behnken design was used to optimize the formulation. Then, confocal fluorescence microscope and flow cytometry were used to determine cellular uptake of ZNPs. A549 cells were cultured in vitro to study cytotoxicity and used to establish tumor xenografts in nude mice. Biodistribution and antitumor activity of ZNPs were performed in vivo experiments. In addition, we also performed histological and immunohistochemical examinations on tumors and viscera. Results: The optimal prescription was obtained by using 120 μL zein added to 2 mL water under stirring in 300 rpm. The encapsulation efficiency and drug loading were 82.97 ± 0.80% and 3.32 ± 0.03%, respectively. We found that DM1-loaded ZNPs have a strong inhibitory effect on A549 cells, which stemmed from the ability of ZNPs to enhance cellular uptake. Furthermore, we demonstrated that DM1-loaded ZNPs exhibits a better antitumor efficacy than DM1, which tumor inhibition rate were 97.3% and 92.7%, respectively. The biodistribution revealed that ZNPs could targeted to tumor. Finally, we confirmed by histological that DM1-loaded ZNPs are nontoxic. Conclusion: DM1-loaded ZNPs have considerable antitumor activity. Thus, DM1-loaded ZNPs are a promising treatment of non-small cell lung cancer. [ABSTRACT FROM AUTHOR]

Background: Chronic lead poisoning (CLP) is a rare cause of abdominal pain and is common in young children, in whom the incidence is higher than it is in adults. As the symptoms of CLP are nonspecific, misdiagnoses or missed diagnoses often occur, especially in sporadic cases.Case Presentation: We report a 28-year-old young man who was misdiagnosed with renal colic due to sudden acute abdominal pain. After a detailed medical history and physical examination, other possible causes were excluded, CLP was finally diagnosed, and he recovered after chelation treatment.Conclusion: Abdominal pain is a very common clinical symptom in adults, which has many causes. We should be vigilant against chronic poisoning, especially CLP. Detailed diagnosis and physical examination are crucial in early diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Breast cancer is a common malignancy in women. Among breast cancer types, triple-negative breast cancer (TNBC) tends to affect younger women, is prone to axillary lymph node, lung, and bone metastases; and has a high recurrence rate. Due to a lack of classic biomarkers, the currently available treatments are surgery and chemotherapy; no targeted standard treatment options are available. Therefore, it is urgent to find a novel and effective therapeutic target. As alteration of ion channels and transporters in normal mammary cells may affect cell growth, resulting in the development and progression of TNBC, ion channels and transporters may be promising new therapeutic targets for TNBC. This review summarizes ion channels and transporters related to TNBC and may provide new tumor biomarkers and help in the development of novel targeted therapies. [ABSTRACT FROM AUTHOR]

Background: Gastric tuberculosis mimicking submucosal tumors is extremely rare and often misdiagnosed.Case Presentation: Three cases of gastric tuberculosis mimicking submucosal tumors were identified among patients admitted to local county hospitals because of upper abdominal discomfort and pain, with gastroscopy showing gastric submucosal tumors. The patients were admitted to our hospital for endoscopic ultrasonography (EUS). As EUS revealed evidence of tuberculosis for the first two patients, we first considered gastric tuberculosis. However, because of atypical characteristics of the miniature ultrasonic probe and EUS, the lesion in the third patient was misdiagnosed as a stromal tumor, and the patient underwent endoscopic submucosal dissection (ESD), and intraoperative characteristics and postoperative pathology confirmed the lesion to be tuberculosis.Conclusions: EUS is of great value in the diagnosis of gastric tuberculosis, especially gastric tuberculosis mimicking submucosal tumors. Here, we summarize some significant characteristics of gastric tuberculosis by EUS, which will be of substantial value to clinical work. [ABSTRACT FROM AUTHOR]

High magnitude impact loads caused by polygonal wear of the wheels have been associated with in-service failures of structural components of high-speed railways, although the mechanisms leading to wheels' polygonalisation is not yet fully understood. In this study, a long-term field test programme is undertaken and the data are analysed to gain better understanding of the growth in polygonal wear, and its characteristics and correlation with the axle box acceleration. The field measurements on a high-speed railway involved monitoring of wheels profiles between successive re-profiling of the wheels so as to identify the rate of growth of wear in addition to the axle box acceleration. The data suggested rapid growth in wheel wear, which could be characterised by polygonal wear of nearly 18th and 19th harmonic order. It is further shown that the magnitude of axle box acceleration increased considerably with increasing wear magnitude of the wheel. [ABSTRACT FROM AUTHOR]

Objective: We investigated syphilis prevalence among men who have sex with men (MSM) in China, as well as potential risk factors. Our principal hypothesis was that syphilis would be associated with the use of recreational drugs such as methamphetamines.Methods: From April to October 2013, we used several methods to recruit MSM in Qingdao, collecting demographic/behavioural information via self-administrated questionnaires. Trained health workers collected blood for the Treponema pallidum particle assay (TPPA) with positives confirmed by a toluidine red unheated serum test. We used an unmatched case-control study to identify factors that might predict syphilis infection using multivariable logistic regression.Results: We recruited 447 MSM who agreed to participate and who completed syphilis testing. Of 71 (15.9%) syphilis-positive MSM, 44 (62.0%) used drugs. Of 376 (84.1%) syphilis-negative MSM, 186 (49.5%) used drugs. We found a positive association with syphilis for any recreational drug use (crude OR (cOR) 1.7, 95 % CI 1.0 to 2.8), frequent methamphetamine use (cOR 2.4, 95% CI 1.1 to 5.3) and multiple drug use (adjusted OR (aOR) 3.4, 95% CI 1.3 to 9.2). Syphilis-positive men were more likely to have a higher physical depression score (aOR 5.2, 95% CI 1.1 to 24.4), be > 30 years old (aOR 2.7, 95% CI 1.5 to 4.8), report a prior STI (aOR 4.1, 95% CI 2.3 to 7.3) and report a sex party experience (aOR 2.2, 95% CI 1.1 to 4.4).Conclusions: Recreational drug use, depression and high-risk sexual behaviours were associated with syphilis infection among MSM in China. Only a multifaceted approach is likely be effective in control of both syphilis and HIV . [ABSTRACT FROM AUTHOR]

Abstract: Objective: Our objective of this research was (1) to investigate the transport characteristics of puerarin through MDCK‐MDR1 and MDCK cells and (2) to evaluate the effects of paeoniflorin and menthol on puerarin transport so as to (3) explore the enhancement mechanism. Methods: The cytotoxicity of drugs on MDCK and MDCK‐MDR1 was evaluated by the MTT assay, and the transport studies were performed in both directions. The membrane fluidity was evaluated by fluorescence recovery after photobleaching, and the membrane potential was estimated by the accumulation of DiBAC4(3) in the cells. Key findings: Puerarin showed relatively poor absorption and purely passive diffusion. However, the efflux ratio of puerarin was <2 in MDCK‐MDR1 models, which suggested puerarin was not P‐gp substrates so as to the P‐glycoprotein activity determination of puerarin. With the existence of menthol, the transcellular transport of puerarin increased and puerarin transport significantly increased when co‐administrated with paeoniflorin and menthol. Conclusions: The enhancing effect of paeoniflorin and menthol may be attributed to the significant enhancement on cell membrane fluidity, the decrease in membrane potential. Immunostaining results indicated that menthol behaved as transport enhancer by disassembly effect on tight junction integrity. [ABSTRACT FROM AUTHOR]

Background: Adequate working space and a clear view for the dissected lesion are crucial for endoscopic submucosal dissection (ESD). Pharyngeal ESD requires that an otorhinolaryngologist creates working space by lifting the larynx with a curved laryngoscope. However, many countries do not have this kind of curved laryngoscope, and the devices could interfere with endoscope because of the narrow space of the pharynx. To overcome these issues, we used a transparent hood (Elastic Touch, slit and hole type, M (long), Top company, Tokyo Japan) instead of the curved laryngoscope to create adequate working space by pushing the larynx, and pharyngeal ESD could be done by gastroenterologists.Case Presentation: A 64-year-old male patient was admitted to our hospital because of chronic persistent swallowing dysfunction for 2 years. Oesophagogastroduodenoscopy showed a superficial hypopharyngeal cancer in the right pyriform sinus. We used a transparent hood (Elastic Touch, slit and hole type, M (long), Top company, Tokyo Japan) instead of the curved laryngoscope to create adequate working space by pushing the larynx, and dental floss tied to a haemoclip was applied to create counter traction during ESD. The lesion was pathologically confirmed as superficial squamous cell carcinoma and resected completely.Conclusions: This is the first report of modified ESD for a superficial hypopharyngeal cancer. The modified ESD enables early pharyngeal superficial cancer to be removed completely under endoscope by gastroenterologist. [ABSTRACT FROM AUTHOR]

Skidding may cause wear and incipient failure of rollers and races of cylindrical roller bearings when the roller is loaded. The previous skidding studies on bearings are mainly focused on steady state condition. However, bearings often operate under different accelerations. This paper proposes an analytical model to investigate skidding between the maximum loaded roller and the races taking account of contact force and friction force between the roller, the cage and the races, fluid pressure and centrifugal force of roller. This model consists of nonlinear first-order ordinary differential equations which can be solved using Euler method. The results of this model are compared to the results of Harris model (steady-state condition) to analyze the effect of acceleration on skidding. A mixed elastohydrodynamic lubrication model which is capable of handling practical case with 3D machined roughness is used to study the lubricating performance between the maximum loaded roller and the inner race during acceleration. The results indicate that acceleration has a great impact on hydrodynamic pressure, friction coefficient, and contact stress, however, the acceleration can hardly affect oil film thickness and contact area ratio. [ABSTRACT FROM AUTHOR]

The article presents details of an e-video of a video endoscopic procedure on a 46-year-old man suffering dysphagia as the patient is diagnosed to have Lymphangioma of the esophagus safely resected by endoscopic submucosal dissection (ESD)

Geniposide is widely used in the treatment of cerebral ischemic stroke and cerebrovascular diseases for its anti-thrombotic and anti-inflammatory effects. Recent studies demonstrated that geniposide could be absorbed promptly and thoroughly by intranasal administration in mice and basically transported into the brain. Here, we explored its transport mechanism and the effect of borneol and muscone on its transport by human nasal epithelial cell (HNEC) monolayer. The cytotoxicity of geniposide, borneol, muscone and their combinations on HNECs was evaluated by the MTT assay. Transcellular transport of geniposide and the influence of borneol and muscone were studied using the HNEC monolayer. Immunostaining and transepithelial electrical resistance were measured to assess the integrity of the monolayer. The membrane fluidity of HNEC was evaluated by fluorescence recovery after photobleaching. Geniposide showed relatively poor absorption in the HNEC monolayer and it was not a P-gp substrate. Geniposide transport in both directions significantly increased when co-administrated with increasing concentrations of borneol and muscone. The enhancing effect of borneol and muscone on geniposide transport across the HNEC may be attributed to the significant enhancement on cell membrane fluidity, disassembly effect on tight junction integrity and the process was reversible. These results indicated that intranasal administration has good potential to treat cerebrovascular diseases. [ABSTRACT FROM AUTHOR]

The combined use of Panax notoginseng saponins (PNS)–based drugs and aspirin (ASA) to combat vascular diseases has achieved good clinical results. In this study, the superior efficacy was observed via the combined use of PNS and ASA on acute blood stasis rats, and untargeted metabolomics was performed to holistically investigate the therapeutic effects of coupling application and its regulatory mechanisms. The combined use of PNS and ASA exhibited better improvement effects when reducing the evaluated hemorheological indicators (whole blood viscosity, plasma viscosity, platelet aggregation, and fibrinogen content) in the blood stasis rats vs. single use of PNS or ASA at the same dose. The combined use of both drugs was the most effective application method, as shown by the relative distance in partial least-squares discriminant analysis score plots. Twelve metabolites associated with blood stasis were screened as potential biomarkers and were mainly involved in amino acid metabolism, lipid metabolism, and energy metabolism. After coherently treated with PNS and ASA, the altered metabolites could be partially adjusted to be closer to normal levels than single use. The collective results revealed that PNS could cooperate with ASA to treat blood stasis and provided a scientific explanation for the superior efficacy of their combined use. [ABSTRACT FROM AUTHOR]

Background: Esophageal tuberculosis (ET) is relatively rare, and the diagnosis is challenging. The aim of this study was to evaluate the clinical features of ET and highlight the role of endoscopic ultrasonography (EUS) in the diagnosis of pathologically undiagnosed ET.Methods: We retrospectively analysed the clinical features, radiological performances, conventional endoscopic appearances, EUS features, treatment and outcomes of pathologically undiagnosed ET between January 2011 and December 2018. All 9 patients failed to be diagnosed by at least two repeated biopsies (such as routine biopsy, multipoint or deep biopsy, and even or EUS-guided fine-needle aspiration (EUS-FNA)).Results: Nine patients (66.7% female) with a mean age of 45 years (range 29-59) complained of retrosternal pain or discomfort, or (and) dysphagia. Esophagoscopy demonstrated protruding lesions in the mucosa with central ulcers or erosion in five patients, submucosal bulges with smooth surfaces in one patient, submucosal bulges with diverticula in one patient, ulcers with suspicious fistula formation in one patient, and multiple ulcers in one patient. None of the patients received confirmed histopathological or bacteriological diagnoses by repeated biopsies. However, they were first suspected to have ET based on EUS examination. Because EUS found some characteristic ultrasonographic changes, which were very helpful for the diagnosis of ET when combined with clinical manifestations, the patients subsequently received diagnostic antituberculosis therapy. Finally, the patients recovered or improved with follow-up times ranging from 3 to 10 months.Conclusions: EUS could help in the diagnosis of ET on basis of EUS features like poorly defined esophageal wall structure, enlarged paraesophageal or mediastinal lymph nodes, hypoechoic lesions of esophageal wall that are linked to the enlarged paraesophageal lymph nodes. However all attempts should be made to obtain histological or microbiological diagnosis. [ABSTRACT FROM AUTHOR]