Effects of a Free Electronic Book on Systemic Anatomy with Schematics on Student Learning / Efectos de un Libro Electrónico Gratuito sobre Anatomía Sistémica con Esquemas sobre el Aprendizaje de los Estudiantes

SUMMARY: For students in schools of nursing, health sciences, and premed, a systemic anatomy textbook with minimized contents, schematics, and mnemonics may be helpful for learning an otherwise often unappealing subject. In this study, we assess the educational effect of such a textbook. Schematic drawings, anatomy comics, and easily readable text were generated for the chapters of the book (e.g., skeletal system, articular system). The book was presented without charge via a webpage (anatomy.co.kr). Nursing students who were exposed to the book and those who were not exposed were compared; a survey was administered to those who were exposed. The students who read the presented textbook were more knowledgeable than those who used other textbooks. Hours spent reading the presented textbook and scores of fill-in-the-blank questions were positively correlated. In general, the students replied that the presented textbook was helpful for learning systemic anatomy. The systemic anatomy textbook accompanies preexisting textbooks in regional anatomy, neuroanatomy, and the histology, all of which are written by the same authors. We suggest anatomy instructors generate their own books with unique style to enrich the student learning process.

Para los estudiantes de las escuelas de enfermería, ciencias de la salud y premedicina, un libro de texto de anatomía sistémica con contenidos, esquemas y mnemónicos minimizados puede ser útil para aprender un tema que de otro modo sería poco atractivo. En este estudio, evaluamos el efecto educativo de dicho libro de texto. Se generaron dibujos esquemáticos, cómics de anatomía y texto de fácil lectura para los capítulos del libro (por ejemplo, sistema esquelético, sistema articular). El libro se presentó sin costo a través de una página web (anatomy.co.kr). Se compararon los estudiantes de enfermería que estuvieron expuestos al libro y los que no estuvieron expuestos. Se administró una encuesta a quienes estuvieron expuestos. Los estudiantes que leyeron el libro de texto presentado tenían más conocimientos que aquellos que usaron otros libros de texto. Las horas dedicadas a leer el libro de texto presentado y las decenas de preguntas para completar espacios en blanco se correlacionaron positivamente. En general, los estudiantes respondieron que el libro de texto presentado fue útil para aprender anatomía sistémica. El libro de texto de anatomía sistémica acompaña a los libros de texto preexistentes de anatomía regional, neuroanatomía e histología, todos escritos por los mismos autores. Sugerimos que los instructores de anatomía generen sus propios libros con un estilo único para enriquecer el proceso de aprendizaje de los estudiantes.

Identification,structure elucidation and origin of a common pyridinium-thiocyanate intermediate in electrospray mass spectrometry among the benziamidazole-class proton pump inhibitors / 药物分析学报

During the analysis of benziamidazole-class irreversible proton pump inhibitors,an unusual mass spectral response with the mass-to-charge ratio at[M+10]+intrigued us,as it couldn't be assigned to any literature known relevant structure,intermediate or adduct ion.Moreover,this mysterious mass pattern of[M+10]+has been gradually observed by series of marketed proton pump inhibitors,viz.omeprazole,pantoprazole,lansoprazole and rabeprazole.All the previous attempts to isolate the corresponding component were unsuccessful.The investigation of present work addresses this kind of signal to a pyridinium thiocyanate mass spectral intermediate(10),which is the common fragment ion of series of labile aggregates.The origin of such aggregates can be traced to the reactive intermediates formed by acid-promoted degradation.These reactive intermediates tend to react with each other and give raise series of complicated aggregates systematically in a water/acetonitrile solution by electrospray ioniza-tion.The structure of the corresponding pyridinium thiocyanate species of omeprazole(10a)has been eventually characterized with the help of synthetic specimen(10a').Our structural proposal as well as its origin was supported by in situ nuclear magnetic resonance,chemical derivatization and colorimetric experiments.

Analysis of the direct economic burden of measles cases and its influencing factors in Shanghai from 2017 to 2019 / 中华预防医学杂志

Objective: To analyze the direct economic burden caused by measles cases in Shanghai from 2017 to 2019 and its influencing factors. Methods: A total of 161 laboratory-confirmed measles cases reported from January 1, 2017, to December 31, 2019, in Shanghai were included in the study through the "Measles Surveillance Information Reporting and Management System" of the "China Disease Surveillance Information Reporting and Management System". Through telephone follow-up and consulting hospital data, the basic information of population, medical treatment situation, medical treatment costs and other information were collected, and the direct economic burden of cases was calculated, including registration fees, examination fees, hospitalization fees, medical fees and other disease treatment expenses, as well as transportation and other expenses of cases. The multiple linear regression model was used to analyze the main influencing factors of the direct economic burden. Results: The age of 161 measles cases M (Q1, Q3) was 28.21 (13.33, 37.00) years. Male cases (56.52%) were more than female cases (43.48%). The largest number of cases was≥18 years old (70.81%). The total direct economic burden of 161 measles cases was 540 851.14 yuan, and the per capita direct economic burden was 3 359.32 yuan. The direct economic burden M (Q1, Q3) was 873.00 (245.01, 4 014.79) yuan per person. The results of multiple linear regression model analysis showed that compared with other and unknown occupations, central areas and non-hospitalized cases, the direct economic burden of measles cases was higher in scattered children, childcare children, students, and cadre staff in the occupational distribution, suburban areas and hospitalized, with the coefficient of β (95%CI) values of 0.388 (0.150-0.627), 0.297 (0.025-0.569), 0.327 (0.148-0.506) and 1.031 (0.853-1.209), respectively (all P values<0.05). Conclusion: The direct economic burden of some measles cases in Shanghai is relatively high. Occupation, area of residence and hospitalization are the main factors influencing the direct economic burden of measles cases.

Research and application of the SARS-CoV-2 vaccine based on adenovirus vector technology platform / 中华预防医学杂志

During the global efforts to prevent and control the COVID-19 pandemic, extensive research and development of SARS-CoV-2 vaccines using various technical approaches have taken place. Among these, vaccines based on adenovirus vector have gained substantial knowledge and experience in effectively combating potential emerging infectious diseases, while also providing novel ideas and methodologies for vaccine research and development (R&D). This comprehensive review focuses on the adenovirus vector technology platform in vaccine R&D, emphasizing the importance of mucosal immunity induced by adenoviral vector-based vaccine for COVID-19 prevention. Furthermore, it analyzes the key technical challenges and obstacles encountered in the development of vaccines based on the adenovirus vector technology platform, with the aim of providing valuable insights and references for researchers and professionals in related fields.

Pharmacological importance of Kunxian Capsule in clinical applications and its adverse effects: A review / 中草药·英文版

Kunxian Capsule (KX) is a popular Chinese patent medicine for the treatment of rheumatoid arthritis, nephrotic syndrome, systemic lupus erythematosus, Henoch-Schönlein purpura, ankylosing spondylitis, psoriatic arthritis and eczema. However, there is scarcity of comprehensive information on the significance of KX in the clinical application and its side effects. Hence, it is aimed to provide a review of the significance of KX, with a focus on the pharmacological effects, clinical applications, and its adverse reactions. This review was based on the published literatures in PubMed, China National Knowledge Infrastructure and WanFang database. The articles were collected by two independent authors with no time limits applied until November 30, 2022. The search term includes Kunxian Capsule and/or clinical effect, pharmacology, disease, therapy, adverse effects and quality control. KX has been shown to be effective in the treatment of autoimmune arthritis by inhibiting inflammatory responses and inducing apoptosis. Many studies suggest that KX has anti-inflammatory and analgesic properties that aid in the improvement of joint functions. KX dispels wind, removes dampness, invigorates the kidneys, and promotes blood circulation, thereby curing various diseases. However, studies also suggest KX-related adverse reactions in multiple systems. Overall, this review highlights the scientific basis of KX in curing or preventing various diseases and provides novel insights for further research and clinical applications.

Chinese Guideline on the Management of Polypoidal Choroidal Vasculopathy (2022) / 中国医学科学杂志(英文版)

Background In mainland China, patients with neovascular age-related macular degeneration (nAMD) have approximately an 40% prevalence of polypoidal choroidal vasculopathy (PCV). This disease leads to recurrent retinal pigment epithelium detachment (PED), extensive subretinal or vitreous hemorrhages, and severe vision loss. China has introduced various treatment modalities in the past years and gained comprehensive experience in treating PCV.Methods A total of 14 retinal specialists nationwide with expertise in PCV were empaneled to prioritize six questions and address their corresponding outcomes, regarding opinions on inactive PCV, choices of anti-vascular endothelial growth factor (anti-VEGF) monotherapy, photodynamic therapy (PDT) monotherapy or combined therapy, patients with persistent subretinal fluid (SRF) or intraretinal fluid (IRF) after loading dose anti-VEGF, and patients with massive subretinal hemorrhage. An evidence synthesis team conducted systematic reviews, which informed the recommendations that address these questions. This guideline used the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach to assess the certainty of evidence and grade the strengths of recommendations. Results The panel proposed the following six conditional recommendations regarding treatment choices. (1) For patients with inactive PCV, we suggest observation over treatment. (2) For treatment-na?ve PCV patients, we suggest either anti-VEGF monotherapy or combined anti-VEGF and PDT rather than PDT monotherapy. (3) For patients with PCV who plan to initiate combined anti-VEGF and PDT treatment, we suggest later/rescue PDT over initiate PDT. (4) For PCV patients who plan to initiate anti-VEGF monotherapy, we suggest the treat and extend (T&E) regimen rather than the pro re nata (PRN) regimen following three monthly loading doses. (5) For patients with persistent SRF or IRF on optical coherence tomography (OCT) after three monthly anti-VEGF treatments, we suggest proceeding with anti-VEGF treatment rather than observation. (6) For PCV patients with massive subretinal hemorrhage (equal to or more than four optic disc areas) involving the central macula, we suggest surgery (vitrectomy in combination with tissue-plasminogen activator (tPA) intraocular injection and gas tamponade) rather than anti-VEGF monotherapy. Conclusions Six evidence-based recommendations support optimal care for PCV patients' management.

Research status and prospect of remyelination in multiple sclerosis based on "inflammation-tissue" homeostatic coupling / 中国中药杂志

Multiple sclerosis(MS) shows the pathological characteristics of "inflammatory injury of white matter" and "myelin repair disability" in the central nervous system(CNS). It is very essential for MS treatment and reduction of disease burden to strengthen repair, improve function, and reduce disability. Accordingly, different from the simple immunosuppression, we believe that key to strengthening remyelination and maintaining the "damage-repair" homeostasis of tissue is to change the current one-way immunosuppression strategy and achieve the "moderate pro-inflammation-effective inflammation removal" homeostasis. Traditional Chinese medicine shows huge potential in this strategy. Through literature research, this study summarized the research on remyelination, discussed the "mode-rate pro-inflammation-effective inflammation removal" homeostasis and the "damage-repair" homeostasis based on microglia, and summed up the key links in remyelination in MS. This review is expected to lay a theoretical basis for improving the function of MS patients and guide the application of traditional Chinese medicine.

A nomogram for preoperative prediction of lymph node metastasis in patients with intrahepatic cholangiocarcinoma based on inflammation-related markers / 中华外科杂志

Objectives: To construct a nomogram for prediction of intrahepatic cholangiocarcinoma (ICC) lymph node metastasis based on inflammation-related markers,and to conduct its clinical verification. Methods: Clinical and pathological data of 858 ICC patients who underwent radical resection were retrospectively collected at 10 domestic tertiary hospitals in China from January 2010 to December 2018. Among the 508 patients who underwent lymph node dissection,207 cases had complete variable clinical data for constructing the nomogram,including 84 males,123 females,109 patients≥60 years old,98 patients<60 years old and 69 patients were pathologically diagnosed with positive lymph nodes after surgery. Receiver operating characteristic curve was drawn to calculate the accuracy of preoperative imaging examinations to determine lymph node status,and the difference in overall survival time was compared by Log-rank test. Partial regression squares and statistically significant preoperative variables were screened by backward stepwise regression analysis. R software was applied to construct a nomogram,clinical decision curve and clinical influence curve,and Bootstrap method was used for internal verification. Moreover,retrospectively collecting clinical information of 107 ICC patients with intraoperative lymph node dissection admitted to 9 tertiary hospitals in China from January 2019 to June 2021 was for external verification to verify the accuracy of the nomogram. 80 patients with complete clinical data but without lymph node dissection were divided into lymph node metastasis high-risk group and low-risk group according to the score of the nomogram among the 858 patients. Log-rank test was used to compare the overall survival of patients with or without lymph node metastasis diagnosed by pathology. Results: The area under the curve of preoperative imaging examinations for lymph node status assessment of 440 patients was 0.615,with a false negative rate of 62.8% (113/180) and a false positive rate of 14.2% (37/260). The median survival time of 207 patients used to construct a nomogram with positive or negative postoperative pathological lymph node metastases was 18.5 months and 27.1 months,respectively (P<0.05). Five variables related to lymph node metastasis were screened out by backward stepwise regression analysis,which were combined calculi,neutrophil/lymphocyte ratio,albumin,liver capsule invasion and systemic immune inflammation index,according to which a nomogram was constructed with concordance index(C-index) of 0.737 (95%CI: 0.667 to 0.806). The C-index of external verification was 0.674 (95%CI:0.569 to 0.779). The calibration prediction curve was in good agreement with the reference curve. The results of the clinical decision curve showed that when the risk threshold of high lymph node metastasis in the nomogram was set to about 0.32,the maximum net benefit could be obtained by 0.11,and the cost/benefit ratio was 1∶2. The results of clinical influence curve showed that when the risk threshold of high lymph node metastasis in the nomogram was set to about 0.6,the probability of correctly predicting lymph node metastasis could reach more than 90%. There was no significant difference in overall survival time between patients with high/low risk of lymph node metastasis assessed by the nomogram and those with pathologically confirmed lymph node metastasis or without lymph node metastasis (Log-rank test:P=0.082 and 0.510,respectively). Conclusion: The prediction accuracy of preoperative nomogram for ICC lymph node metastasis based on inflammation-related markers is satisfactory,which can be used as a supplementary method for preoperative diagnosis of lymph node metastasis and is helpful for clinicians to make personalized decision of lymph node dissection for patients with ICC.

Advances in the classification and treatment of isolated superior mesenteric artery dissection / 中华外科杂志

Isolated superior mesenteric artery dissection (ISMAD) has attracted more and more clinicians' attention in recent years. Patients onset of ISMAD often present with abdominal pain. The misdiagnosis or miss diagnosis is common because of the non-specific symptoms and signs, which even can endanger lives in serious cases. Imaging classification is of great significance for diagnosis and treatment of ISMAD. The Sakamoto classification and the Yun classification are two classical classified methods. However, with the further study of ISMAD, various new classifications emerge. Conservative treatment was once considered as the preferred. As the rapid development of endovascular therapy and the great progress of new devices, stenting therapy can significantly improve symptoms and achieve satisfactory long-term effects, and be even expected to become the preferred method for clinical therapy of ISMAD. However, the long-term effects of endovascular therapy still need a large number of follow-up data, and complications after stent implantation can't be ignored.

The characteristics of the patients who visited the emergency department with fever, after the chronification of COVID-19 pandemic

Objective@#This study examined the characteristics of patients visiting the emergency department (ED) with fever after the chronification of the coronavirus disease 2019 (COVID-19) pandemic. @*Methods@#This retrospective observational study analyzed the medical records of patients who visited the ED with fever from May 1 to October 31, 2021, and the corresponding period in 2019. This study was conducted at a single center in Seoul, Korea. @*Results@#There was no statistical difference in the comorbidities of the patients of the two groups: the AC (after the COVID-19 pandemic) group and the BC (before the COVID-19 pandemic) group. As for the level of consciousness at the time of ED arrival, there was a significantly larger decrease in consciousness (verbal response or less) in the AC group than in the BC group (P=0.002). In the case of the National Early Warning Score (NEWS), the proportion was higher in the AC group in the moderate-risk and high-risk groups (P=0.003). The median time from symptom onset to ED arrival was 15.7 hours in the BC group and 13.8 hours in the AC group, and there was no significant difference (P=0.137). When leaving the ED, the AC group had a higher admission rate to the ward and intensive care unit than the BC group. There was no statistical difference in the in-hospital mortality between the two groups (2.9% and 2.4%, respectively; P=0.62). @*Conclusion@#Patients who visited the emergency room with fever after one year of the COVID-19 pandemic showed a similar time from symptom onset to ED arrival compared to patients who visited before the COVID-19 pandemic. In addition, there was no difference in in-hospital mortality among these patients compared to those with fever before the COVID-19 pandemic.

Higher Non-High-Density Lipoprotein Cholesterol Was Higher Associated With Cardiovascular Disease Comparing Higher LDL-C in Nine Years Follow Up: Cohort Study

Objective@#Non-high-density lipoprotein cholesterol (non-HDL-C) may be equivalent to or superior to low-density lipoprotein cholesterol (LDL-C) for the prediction of cardiovascular disease (CVD). However, studies comparing the predictive values of LDL-C and non-HDL-C levels for CVD have yielded conflicting results. In this study, we evaluated the relationship between non-HDL-C, LDL-C, and CVD using a large-scale population dataset from the National Health Information Database (NHID). @*Methods@#We performed a retrospective observational cohort study of 3,866,366 individuals ≥ 20 years, from 2009 to 2018, using the NHID. The participants were divided into LDL-C and non-HDL-C quartiles. The outcome variables included stroke, myocardial infarction (MI), and both. All outcomes were analyzed using Cox proportional hazards regression analysis while controlling for baseline covariates (age, sex, smoking, drinking, regular exercise, body mass index, diabetes, hypertension, and statin use). @*Results@#During 9.1 years of mean follow-up, stroke was diagnosed in 60,081 (1.55%), MI in 31,234 (0.81%), and both stroke and MI in 88,513 (2.29%) participants. Multivariate-adjusted hazard ratios (HRs) for patients in the highest non-HDL-C quartile demonstrated that these patients had a higher risk of stroke (HR, 1.254; 95% confidence interval [CI], 1.224–1.285), MI (HR, 1.918; 95% CI, 1.853–1.986), and both (HR, 1.456; 95% CI, 1.427–1.486) compared with participants in the lowest quartile. These were higher than the HRs for patients in the highest LDL-C quartile for stroke (HR, 1.134; 95% CI, 1.108–1.160), MI (HR, 1.601; 95% CI, 1.551–1.653), and both (HR, 1.281; 95% CI, 1.257–1.306). @*Conclusion@#In our large population study, higher non-HDL-C levels were associated with CVD than LDL-C levels.

An evidence-based clinical guideline for the treatment of infectious bone defect with induced membrane technique (version 2023) / 中华创伤杂志

Infectious bone defect is bone defect with infection or as a result of treatment of bone infection. It requires surgical intervention, and the treatment processes are complex and long, which include bone infection control,bone defect repair and even complex soft tissue reconstructions in some cases. Failure to achieve the goals in any step may lead to the failure of the overall treatment. Therefore, infectious bone defect has been a worldwide challenge in the field of orthopedics. Conventionally, sequestrectomy, bone grafting, bone transport, and systemic/local antibiotic treatment are standard therapies. Radical debridement remains one of the cornerstones for the management of bone infection. However, the scale of debridement and the timing and method of bone defect reconstruction remain controversial. With the clinical application of induced membrane technique, effective infection control and rapid bone reconstruction have been achieved in the management of infectious bone defect. The induced membrane technique has attracted more interests and attention, but the lack of understanding the basic principles of infection control and technical details may hamper the clinical outcomes of induced membrane technique and complications can possibly occur. Therefore, the Chinese Orthopedic Association organized domestic orthopedic experts to formulate An evidence-based clinical guideline for the treatment of infectious bone defect with induced membrane technique ( version 2023) according to the evidence-based method and put forward recommendations on infectious bone defect from the aspects of precise diagnosis, preoperative evaluation, operation procedure, postoperative management and rehabilitation, so as to provide useful references for the treatment of infectious bone defect with induced membrane technique.

Usefulness of Early Warning Scores, ROX index, and CURB-65 in the prognostic evaluation of patients with COVID-19

Objective@#Early identification of COVID-19 in patients is important to prevent significant worsening of the disease. This study was undertaken to verify whether MEWS (Modified Early Warning Score), NEWS(National Early Warning Score), ROX index, and CURB-65, which are early diagnostic tools for severe respiratory diseases, could be applied to patients visiting the emergency room for COVID-19. @*Methods@#This retrospective observational study included patients who visited an emergency medical center from September 1 to October 31, 2020, and from January 1 to February 28, 2021. Based on the vital signs and blood tests during the emergency room visit, severity evaluation tools and early diagnostic tools for severe cases were used and compared according to their area under the curve (AUC) values. The primary outcome was in-hospital mortality, while the secondary outcomes were intensive care unit admission rate and the need for mechanical ventilation based on these four tools (MEWS, NEWS, ROX index, and CURB-65). @*Results@#A total of 667 patients were analyzed. No significant difference was determined between the non-survivor group and survivor group in the MEWS values (P=0.13), but statistically significant differences were observed for NEWS (5 vs. 1, P<0.05), CURB-65 (2 vs. 1, P<0.05), and ROX index (16.61 vs. 23.1, P<0.01). The AUC value of NEWS for death prediction indicated a good predictive power at 0.80, while that of MEWS showed a low predictive power at 0.57, which was statistically significant. Moreover, the AUC values of CURB-65 and ROX index did not differ significantly from values obtained for NEWS. @*Conclusion@#As early diagnostic tools for predicting death in COVID-19 patients, NEWS, ROX index, and CURB-65 showed excellent discrimination ability, whereas MEWS showed statistically and significantly lower discrimination ability.

Establishment of a rapid risk assessment system for imported COVID-19 cases / 中华流行病学杂志

Objective: To develop a rapid risk assessment tool for imported COVID-19 cases and provide reference evidences for prevention and control of COVID-19 at ports. Methods: The information about COVID-19 pandemic and control strategies of 12 concerned countries was collected during July to August 2021, and 12 indexes were selected to assess the importation risk of COVID-19 by risk matrix. Results: The risk for imported COVID-19 cases from 12 countries to China was high or extremely high, and the risk from Russia and the USA was highest. Conclusions: The developed rapid risk assessment tool based on the risk matrix method can be used to determine the risk level of countries for imported COVID-19 cases to China at ports, and the risk of imported COVID-19 was high at Beijing port in August 2021.

Proportion and rate: connotation and understanding route / 中华流行病学杂志

Proportion and rate have multiple and overlapping meanings, which blur their concepts. Based on the existence of the states and the occurrence of the events and their measuring process, we first put forward the concept of "cumulative number of states in point time". Considering the general meaning of "rate" in mathematics and the units of the elements in indexes, this paper puts forward the concept of "the change of cumulative number of states in point time", which is equal to the commonly acknowledged concept "number of incident event within observation period" or "absolute rate", and further constructs relative rate and proportion. Proportions can be classified into three types: time-point (or rate-type) constitutional proportion, time-period incidence proportion and their synthesis, time-period constitutional proportion. The essential difference between relative rate and time-period proportions is whether the observation period is regarded as a one-unit-length fixed period which would be further moved to the description of the indexes. Furthermore, the sources populations of relative rate and proportions are exclusively those at the beginning of the observation period. Thus, we established a unified identification route about ratios, proportions, and rates, the basic indicators of categorical data in populations. These are applicable to both fixed and dynamic populations. The paper aims to clarify the connotation of the indexes and the feasible understanding route and provide some reference for the population researchers.

Mechanism of Xianlian Jiedu Prescription in Maintaining Cancer Relative Vascular Endothelial Cell Homeostasis and Inhibiting Tumor Neovascularization / 中国实验方剂学杂志

ObjectiveTo observe the effect of Xianlian Jiedu prescription （XLJDP） on the proliferation， apoptosis， and migration of cancer-relative endothelial （CRE） cells， and to decipher the mechanism of XLJDP in regulating angiopoietin2 （Ang2） to maintain CRE cell homeostasis and inhibit tumor neovascularization. MethodHuman umbilical vein endothelial cell line （HUVEC-c） was induced into CRE cells in the human colorectal cancer HCT-116 cell-conditioned medium. The CRE cells were assigned into the blank group， conditioned medium group， and XLJDP groups （1， 2， 3 g·L-1） and treated for 48 h. The proliferation of CRE cells was detected by methyl thiazolyl tetrazolium （MTT） colorimetry. The morphological changes of CRE cells were observed via an inverted microscope. The apoptosis rate was detected by flow cytometry. Wound healing test and Transwell migration assay were employed to detect the 2D/3D migration ability of CRE cells. The protein levels of vimentin， N-cadherin， matrix metalloproteinase-9 （MMP-9）， and Ang2 in CRE cells were measured by Western blot. ResultThe MTT results showed that the cell viability was higher in the conditioned medium group than in the blank group （P<0.05）. Compared with the conditioned medium group， XLJDP decreased the cell proliferation rate （P<0.01） and changed the cell morphology. The total apoptosis rates of all the XLJDP groups were higher than that of the conditioned medium group （P<0.01）. The 2D and 3D migration abilities of the conditioned medium group were higher than those of the blank group （P<0.05， P<0.01）. Compared with the conditioned medium group， XLJDP at all the concentrations weakened the 2D migration ability （P<0.01） and medium- and high-concentration XLJDP weakened the 3D migration ability （P<0.01）. The protein levels of N-cadherin， Vimentin， MMP-9， and Ang2 were up-regulated in the conditioned medium group compared with those in the blank group （P<0.05， P<0.01）. Compared with the conditioned medium group， XLJDP at all the concentrations down-regulated the protein level of Ang2 （P<0.05， P<0.01）， and medium- and high-concentration XLJDP down-regulated those of N-cadherin， vimentin， and MMP-9 protein （P<0.01）. ConclusionXLJDP may inhibit the proliferation， migration， differentiation， and apoptosis of CRE cells by down-regulating the expression of Ang2， inhibiting tumor neovascularization， and maintaining the cell homeostasis.

Effect and Mechanism of Xianlian Jiedu Prescription Against Proliferation of Colorectal Cancer Cells in Hypoxic Microenvironment / 中国实验方剂学杂志

ObjectiveTo study the effect of Xianlian Jiedu prescription （XLJDP） on the activation of nuclear transcription factor-κB （NF-κB） signaling pathway induced by bromodomain-containing protein 4 （Brd4） in hypoxic microenvironment and to explore its mechanism in inhibiting the proliferation of colorectal cancer HT-29 cells. MethodThe human colorectal cancer HT-29 cells were cultured in a hypoxic incubator or normoxia incubator and treated with XLJDP at 0.8，1，1.2，1.6，3.2，6.4，and 12.8 g·L-1 for 48 h， respectively. Following the detection of cell vitality using methyl thiazolyl tetrazolium （MTT） colorimetry， the effects of XLJDP （1.25，2.5，and 5 g·L-1） on the cell mitochondrial membrane potential were determined using a fluorescent probe （JC-1）， and the apoptosis of colorectal cancer HT-29 cells was detected by flow cytometry. The cell colony formation assay and 5-ethynyl-2'-deoxyuridine （EDU） staining were conducted to test the proliferation of colorectal cancer HT-29 cells. The Western blot was carried out to measure the expression levels of Brd4 and its downstream relevant proteins such as c-Myc and hexamethylene bisacetamide-inducible protein 1 （HEXIM1）， as well as the effects of XLJDP on related proteins in the NF-κB signaling pathway. ResultCompared with the blank control group， XLJDP at 0.8，1，1.2，1.6，3.2，6.4，and 12.8 g·L-1 inhibited the vitality of colorectal cancer HT-29 cells （P<0.05 ， P<0.01）， with the median inhibitory concentration （IC50） under the hypoxic condition higher than that under the normoxia condition. Compared with the blank control group， XLJDP at 1.25，2.5，and 5 g·L-1 significantly decreased the mitochondria membrane potential， enhanced the apoptosis （P<0.05，P<0.01）， and lowered the number of cell colonies and also the EDU-positive cells （P<0.05， P<0.01）. The results of Western blot showed that compared with the blank control group， XLJDP at 1.25，2.5，and 5 g·L-1 down-regulated Brd4， c-Myc， p-NF-κB p65， and p-IκBα protein expression to varying degrees and up-regulated the expression of HEXIM1 （P<0.05， P<0.01）. ConclusionIn the hypoxic microenvironment， XLJDP inhibits the proliferation of colorectal cancer HT-29 cells regulated by Brd4， which may be related to its inhibition of the activation of NF-κB signaling pathway.

Biological fate and interaction with cytochromes P450 of the nanocarrier material, d-α-tocopheryl polyethylene glycol 1000 succinate

d-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS, also known as vitamin E-TPGS) is a biodegradable amphiphilic polymer prepared by esterification of vitamin E with polyethylene glycol (PEG) 1000. It is approved by the US Food and Drug Administration (FDA) and has found wide application in nanocarrier drug delivery systems (NDDS). Fully characterizing the in vivo fate and pharmacokinetic behavior of TPGS is important to promote the further development of TPGS-based NDDS. However, to date, a bioassay for the simultaneous quantitation of TPGS and its metabolite, PEG1000, has not been reported. In the present study, we developed such an innovative bioassay and used it to investigate the pharmacokinetics, tissue distribution and excretion of TPGS and PEG1000 in rat after oral and intravenous dosing. In addition, we evaluated the interaction of TPGS with cytochromes P450 (CYP450s) in human liver microsomes. The results show that TPGS is poorly absorbed after oral administration with very low bioavailability and that, after intravenous administration, TPGS and PEG1000 are mainly distributed to the spleen, liver, lung and kidney before both being slowly eliminated in urine and feces as PEG1000. In vitro studies show the inhibition of human CYP450 enzymes by TPGS is limited to a weak inhibition of CYP3A4. Overall, our results provide a clear picture of the in vivo fate of TPGS which will be useful in evaluating the safety of TPGS-based NDDS in clinical use and in promoting their further development.

Multi-index components of Scutellariae Barbatae Herba according to UHPLC-QTRAP-MS coupled with chemometrics / 中国中药杂志

The present study developed an ultra-fast liquid chromatography coupled with triple quadrupole-linear ion trap composite mass spectrometry(UHPLC-QTRAP-MS) to simultaneously determine the content of potential active components in Scutellariae Barbatae Herba and also to provide a reference approach for screening out the differential quality control components among different batches of Scutellariae Barbatae Herba. Chromatographic separations were conducted on a Thermo Acclaim~(TM) RSLC 120 C_(18) column(3.0 mm×100 mm, 2.2 μm) in a gradient program. The mobile phase consisted of 0.1% aqueous formic acid and acetonitrile, and the column temperature was maintained at 40 ℃. The flow rate was 0.4 mL·min~(-1) and the injection volume was 2 μL. The targeted compounds were monitored in the multiple reaction monitoring(MRM) mode. The acquired data were processed by hierarchical cluster analysis(HCA) and partial least square discriminant analysis(PLS-DA). Sixteen compounds all showed good linear relationship within the corresponding linear ranges and the R~2 values were all higher than 0.993 2. The RSDs of precision, repeatability, and stability were less than or equal to 3.7%. Mean recovery rates were in the range of 95.67% and 104.8% with RSDs≤3.2%. According to HCA and PLS-DA, all samples were clustered into four categories. Scutellarin, acteoside, scutellarein, and scutebarbatine X(VIP>1) were considered as differential chemical markers in the four categories. In conclusion, the developed method can be used for the simulta-neous determination of the multiple components and quality control of Scutellariae Barbatae Herba.

Research progress and therapeutic perspective of iron transport balance based on "iron-inflammation" homeostatic coupling theory / 药学学报

The iron and inflammation homeostasis are closely coupled, forming an integrated functional unit under physiological conditions. "Iron transport balance" has become the key mechanism to maintain iron homeostasis through bidirectional regulation of iron uptake and release and dynamic management of transmembrane concentration. It is also the physiological basis for the inflammatory balance between promotion and resolution. Under pathological conditions, represented by inflammatory bowel disease (IBD), disturbed iron transportation was highly involved in almost every step of inflammatory diseases. Therefore, the iron transporting rebalancing provides the mechanistic basis and effective approach for the normalization of inflammatory microenvironment. Macrophage is the key regulator of inflammation homeostasis and determinant for iron transport balance. Unfortunately, the current clinical transformation based on iron transport balance theory has still been insufficient. Sometimes, this strategy even showed high complexity and contradiction, severely restricting its clinical application. By summarizing the theoretical research progress of iron transport balance, especially its relevance to macrophage phenotypic polarization, this review aims to explore the therapeutic value in inflammation intervention by targeting iron transporting balance. This review will provide the necessary knowledge and hints for the research and development of candidate drugs in treating inflammatory diseases.