Ozone therapy improves early stages of osseointegration in ovariectomized rats

Abstract Objective the aim of this study was to analyze the influence of ozone therapy (OZN) on peri-implant bone repair in critical bones by installing osseointegrated implants in the tibia of ovariectomized rats. Methodology ovariectomy was performed on 30 Wistar rats, aged six months (Rattus novergicus), and, after 90 days, osseointegrated implants were installed in each tibial metaphysis. The study groups were divided into the animals that received intraperitoneal ozone at a concentration of 700 mcg/kg — OZ Group (n=15) — and a control group that received an intraperitoneal saline solution and, for this reason, was named the SAL group (n=15). The applications for both groups occurred during the immediate post-operative period on the 2nd, 4th, 6th, 8th, 10th, and 12th day post-surgery. At various stages (14, 42, and 60 days), the animals were euthanized, and tests were performed on their tibiae. These tests include histomorphometric and immunohistochemical analyses, computerized microtomography, sampling in light-cured resin for calcified sections, and confocal microscopy. The obtained data were then analyzed using One-way ANOVA and the Shapiro-Wilk, Kruskal-Wallis, and student t-tests (P<0.05). Results our findings indicate that the OZ group (3.26±0.20 mm) showed better cellular organization and bone neoformation at 14 days (SAL group, 0.90±1.42 mm) (P=0.001). Immunohistochemistry revealed that osteocalcin labeling was moderate in the OZ group and mild in the SAL group at 14 and 42 days post-surgery. The data from the analysis of calcified tissues (microtomography, histometric, and bone dynamism analysis) at 60 days showed no statistically significant differences between the groups (P=0.32). Conclusion it was concluded that ozone therapy anticipated the initial phases of the peri-implant bone repair process.

Evaluation of anxiolytic effect of combination of tramadol with gabapentin and pregabalin in Wistar rats

Background: Anxiety is a widespread disorder that approximately 18% of the population experience at some stage in their lives. Pain is a common stimulus that induces anxiety in both animals and human beings. Combination of drugs with good anti-anxiety and analgesic effect can be used for the treatment of chronic pain induced anxiety, post-operative, and procedure-related pain-induced anxiety. Aims and Objectives: The study was conducted to evaluate the anxiolytic activity of combination of gabapentin with tramadol, pregabalin with tramadol compared to standard fluoxetine, in elevated plus maze (EPM) and light-dark arena (LDA) models of anxiety in Wistar albino rats. Materials and Methods: Twenty-four male or female albino Wistar rats from Central Animal House, MRMC, Kalaburagi, were utilized. Fluoxetine 10 mg/kg, gabapentin 30 mg/kg, tramadol 30 mg/kg, and pregabalin 30 mg/kg were used. Eddy’s hot plate method used for inducing anxiety. EPM and LDA models were used to study the effect of drugs in reducing the pain and anxiety. Results: The present study showed that the exposure to hot plate induces pain, creates anxiety, and reduces locomotor and explorative activity among the rats when exposed to hot plate. There was reduction in anxiety after drug administration, in fluoxetine and gabapentin with tramadol groups with >75% increase in entry into the light chamber or open arm at least once or more during the time period of 5 min when compared to hot plate post-exposure readings. Whereas in pregabalin and tramadol group, it was observed that 25% increase in entry of rats into open arm at least once during the time period of 5 min and 25% decrease in entry of rats into light chamber as compared to those rats after exposure to hot plate. Conclusion: Our study has demonstrated that tramadol, pregabalin, and gabapentin have got analgesic as well as anti-anxiety effects in rats when given in combination. All these experimental data, together with the previous experimental studies and the results reported in this work, suggest that combination of these drugs could be more effective in treating anxiety-related disorders such as chronic pain, pain-induced anxiety, post-operative, and procedure-related pain-induced anxiety with minimal side effects. Further dose ranging studies and models might be necessary to better understand the effects of these drugs in combination.

Effect of "Teddy Bear Simulation Hospital" in cultivating the humanistic care ability for pre-clinical medical students / 中华医学教育探索杂志

The cultivation of medical students' humanistic care ability is one of the most important tasks of medical education. In this study, "Teddy Bear Simulation Hospital" was launched to cultivate humanistic care ability for pre-clinical medical students in the early stage. Firstly, pre-clinical students were organized to visit clinical functional zoning and diagnosis and treatment processes, listen to pediatrician lectures, and understand the diagnosis and treatment process of pediatric patients. Then, students were organized to build a simulated hospital for kids in the kindergarten with reference to the actual situation and carry out simulated diagnosis and treatment. In the process of implementation, students divide the labor, make the plan and take the action independently. After the simulation scenario was created, the kids played the role of parents of the sick children, and their favorite plush toy was pretended to be the sick baby; the medical students played the various roles of the medical staffs in the simulated hospital to carry out various diagnosis and treatment activities in an orderly manner. The results showed that the activity has provided a safe and friendly simulation diagnosis and treatment platform for pre-clinical students. In the interaction with children, the humanistic care ability of the students was significantly improved.

Evaluation of an integrated teaching model of oral preclinical practice based on endodontic-restorative sequential treatment / 口腔疾病防治

Objective@#Evaluate the effect of an integrated teaching model of oral preclinical practice based on endodontic-restorative sequential treatment to provide a reference for the exploration of the teaching mode of the stomatology specialty. @* Methods @#This retrospective study was reviewed and approved by the Ethics Committee. The study was divided into 2 groups. There were 450 2018-grade and 2019-grade students in the discipline integration teaching method (DIT) group, and a preclinical practice course (root canal therapy and fixed prosthetic treatments were integrated into an endodontic-restorative sequential treatment) using the DIT method was applied. There were 443 2016-grade and 2017-grade students in the traditional teaching method (TT) group, and a TT preclinical practice course (root canal therapy and fixed prosthetic treatments training courses were taught separately) was applied. Both groups were taught by the same two teachers. The scores of clinical skills examination and treatment planning were compared between the two groups. In addition, students in the two groups were asked to complete the questionnaires about the teaching methods, and students in Group DIT and their teachers were asked to complete the questionnaires on their degree of satisfaction with the DIT method in the preclinical course. @*Results @# Students in the DIT group had an average score of 90.2 ± 4.16 in the practical skill evaluation, which was higher than that of the TT group (86.3±3.57) (P = 0.001). In the case analysis, 91.8% (413/450) of the students in the DIT group successfully planned the treatment, compared to a significantly lower rate in the TT group of 74.7% (331/443) (P = 0.001). The questionnaire results showed that recognition degrees of cultivated clinical thinking, improved indication analysis ability, improved operational skills, stimulated enthusiasm for learning, and improved autonomous learning were higher in the DIT group than in the TT group, and both teachers (2/2) and 98.4% (443/450) of students recognized the DIT method. @*Conclusions@#The DIT method significantly improved students’ learning quality and ability, proved effective in the endodontic-restorative sequential treatment practice course and was more acceptable to teachers and students. The DIT method is more effective than the TT method in improving students’ clinical thinking and operation ability.

Preclinical anti-apoptotic properties of salidroside for hypoxic-ischemic cerebral damage: a systematic review and meta-analysis / 数字中医药（英文）

@#【Objective】   As the main active ingredient of Tibetan medicine Hongjingtian (Rhodiolae Crenulatae Radix et Rhizoma), salidroside (Sal) has a good anti-apoptotic potential. Currently, there are some conflicting results on the anti-apoptotic mechanisms of Sal. Here we conducted a systematic review and meta-analysis to provide the preclinical evidence of its anti-apoptotic properties in preventing and treating hypoxic-ischemic cerebral damage(HICD). 【Methods】   The literature on the anti-apoptotic potential of Sal in the treatment of HICD from January 1, 1980 to November 9, 2021 was searched online using Chinese databases including Chinese National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), and Wanfang Database, and English databases including PubMed and Web of Science. The quality of the included articles was evaluated by the Cochrane Collaboration network bias risk assessment criteria, and meta-analysis was performed using RevMan 5.3 software. 【Results】  A total of 40 articles were finally included. Among the 40 articles, 30 were about in vivo animal experiments and 17 about in vitro cell experiments, and 7 of them included both animal and cell experiments. After analysis, it was found that Sal had significant effects on disease-related indicators of HICD (P < 0.05), such as cerebral infarctsize and brain water content. As to in vivo studies, Sal mainly affects the expressions of apoptotic factors through antiinflammation, anti-oxidation, activation of complement pathway, and regulation of signal transduction and autophagy, thus exerting anti-apoptotic potential in treating HICD. While for in vitro studies, Sal plays the anti-apoptotic role in HICD models mainly through anti-oxidation, anti-inflammation, reduction of Ca2+ overload, regulation of mitochondrial function, signal transduction, and C3 complement. 【Conclusion】  Sal can take anti-apoptotic effects to prevent and treat HICD through mechanisms such as anti-inflammation, anti-oxidation, enhanced autophagy, complement and signal transduction, regulation of mitochondrial membrane potential, and reduction of Ca2 + overload.

Building on the backbone of CD47-based therapy in cancer: Combination strategies, mechanisms, and future perspectives

Described as a "don't eat me" signal, CD47 becomes a vital immune checkpoint in cancer. Its interaction with signal regulatory protein alpha (SIRPα) prevents macrophage phagocytosis. In recent years, a growing body of evidences have unveiled that CD47-based combination therapy exhibits a superior anti-cancer effect. Latest clinical trials about CD47 have adopted the regimen of collaborating with other therapies or developing CD47-directed bispecific antibodies, indicating the combination strategy as a general trend of the future. In this review, clinical and preclinical cases about the current combination strategies targeting CD47 are collected, their underlying mechanisms of action are discussed, and ideas from future perspectives are shared.

Astragaloside IV for Heart Failure: Preclinical Evidence and Possible Mechanisms, A Systematic Review and Meta-Analysis / 中国结合医学杂志

OBJECTIVE@#To explore the cardioprotective effects of astragaloside IV (AS-IV) in heart failure (HF).@*METHODS@#PubMed, Excerpta Medica Database (EMBASE), Cochrane Library, Web of Science, Wanfang Database, Chinese Bio-medical Literature and Retrieval System (SinoMed), China Science and Technology Journal Database (VIP), and China National Knowledge Infrastructure (CNKI) were searched from inception to November 1, 2021 for animal experiments to explore AS-IV in treating HF in rats or mice. The left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic dimension (LVESD), left ventricular weight-to-body weight (LVW/BW) and B-type brain natriuretic peptide (BNP) were recorded. The qualities of included studies were assessed by the risk of bias according to the Cochrane handbook. Meta-analysis was performed using Stata 13.0.@*RESULTS@#Twenty-one articles involving 558 animals were considered. Compared with the control group, AS-IV improved cardiac function, specifically by increasing LVEF (mean difference (MD)=6.97, 95% confidence interval (CI)=5.92 to 8.03, P<0.05; fixed effects model) and LVFS (MD=7.01, 95% CI=5.84 to 8.81, P<0.05; fixed effects model), and decreasing LVEDD (MD=-4.24, 95% CI=-4.74 to -3.76, P<0.05; random effects model) and LVESD (MD=-4.18, 95% CI=-5.26 to -3.10, P<0.05; fixed effects model). In addition, the BNP and LVW/BW levels were decreased in the AS-IV treatment group (MD=-9.18, 95% CI=-14.13 to -4.22, P<0.05; random effects model; MD=-1.91, 95% CI=-2.42 to -1.39, P<0.05; random effects model).@*CONCLUSIONS@#AS-IV is a promising therapeutic agent for HF. However, this conclusion needs to be clinically validated in the future.

Preclinical study of LMP1-RNAi-based anti-tumor therapy in EBV-positive nasopharyngeal carcinoma

RNA interference (RNAi) treatment has been proven to be an important therapeutic approach in cancer based on downregulation of target-oncogenes, but its clinical efficacy still needs further investigation. LMP1 is usually presented by Epstein-Barr virus (EBV)-positive tumor cells like EBV-associated nasopharyngeal carcinoma (NPC) and acts as an oncogene in tumorigenesis. However, the mechanism of LMP1 as a proto-oncogene in nasopharyngeal carcinoma is still unclear. Two sequence-specific shRNAs 1 and 2 were designed to target the different nucleotide loci of EBV latent antigen LMP1 gene and a series of in vivo and in vitro experiments were performed to investigate the therapeutic effect of sequence-specific shRNAs targeting LMP1 and its related molecular mechanisms in EBV-positive NPC. LMP1-shRNA2 generated a truncated LMP1 mRNA and protein, whereas LMP1-shRNA1 completely blocked LMP1 mRNA and protein expression. Both LMP1-shRNAs inhibited the proliferation and migration of NPC cells overexpressing LMP1 (NPC-LMP1) as well as the NPC-associated myeloid-derived suppressor cell (MDSC) expansion in vitro. However, LMP1-shRNA2 maintained the immunogenicity of NPC-LMP1 cells, which provoked MHC-class I-dependent T cell recognition. LMP1-shRNAs inhibited tumor growth in nude mice but did not reach statistical significance compared to control groups, while the LDH nanoparticle loaded LMP1-shRNAs and the antigen-specific T cells induced by NPC-LMP1 cells treated with LMP1-shRNA2 significantly reduced tumor growth in vivo. LMP1-RNAi-based anti-tumor therapy could be a new hope for the clinical efficacy of RNAi treatment of tumors like NPC.

Anxiety, depression, and memory loss in Chagas disease: a puzzle far beyond neuroinflammation to be unpicked and solved*

Mental disorders such as anxiety, depression, and memory loss have been described in patients with chronic Chagas disease (CD), a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi. Social, psychological, and biological stressors may take part in these processes. There is a consensus on the recognition of an acute nervous form of CD. In chronic CD patients, a neurological form is associated with immunosuppression and neurobehavioural changes as sequelae of stroke. The chronic nervous form of CD has been refuted, based on the absence of histopathological lesions and neuroinflammation; however, computed tomography shows brain atrophy. Overall, in preclinical models of chronic T. cruzi infection in the absence of neuroinflammation, behavioural disorders such as anxiety and depression, and memory loss are related to brain atrophy, parasite persistence, oxidative stress, and cytokine production in the central nervous system. Interferon-gamma (IFNγ)-bearing microglial cells are colocalised with astrocytes carrying T. cruzi amastigote forms. In vitro studies suggest that IFNγ fuels astrocyte infection by T. cruzi and implicate IFNγ-stimulated infected astrocytes as sources of TNF and nitric oxide, which may also contribute to parasite persistence in the brain tissue and promote behavioural and neurocognitive changes. Preclinical trials in chronically infected mice targeting the TNF pathway or the parasite opened paths for therapeutic approaches with a beneficial impact on depression and memory loss. Despite the path taken, replicating aspects of the chronic CD and testing therapeutic schemes in preclinical models, these findings may get lost in translation as the chronic nervous form of CD does not fulfil biomedical model requirements, as the presence of neuroinflammation, to be recognised. It is hoped that brain atrophy and behavioural and neurocognitive changes are sufficient traits to bring the attention of researchers to study the biological and molecular basis of the central nervous system commitment in chronic CD.

Permitted daily exposure from preclinical studies of Ginkgo biloba L. dry extract

Abstract Resolution 658/2022 of the Brazilian Regulatory Agency requires the determination of the permitted daily exposure (PDE) of pharmaceutical agents. Ginkgo biloba L. is used therapeutically to treat memory deficits and other brain diseases. However, published results indicate that more studies are needed to confirm the safety of Ginkgo biloba. This study aimed to evaluate the dry extract of Ginkgo biloba L. leaves PDE as an ingredient in an oral pharmaceutical product in preclinical studies using mice. Acute oral toxicity and repeated dose experiments were performed based on OECD guidelines, as well as genotoxicity tests. The results indicate that Ginkgo biloba L. has low acute toxicity, no liver toxicity, and does not alter blood glucose levels. No changes in weight gain were observed, but food intake decreased in males during the first week of treatment at the highest dose. Hematological parameters were not altered in males, whereas females presented lower leukocyte and lymphocyte counts and higher neutrophil counts at the highest dose. The lipid profile was not altered in males, whereas total cholesterol was increased in females. The estimated PDE was 0.1 mg/day and, when related to the maximum residual concentration, indicates that the cleaning process used is safe and does not require reassessment.

Recent advances in mass spectrometry imaging and its application in drug research / 中国药科大学学报

@#Mass spectrometry imaging (MSI), a label-free molecular imaging technique, has been applied widely in the spatial localization of small molecule metabolites, lipids, peptides, and proteins, with its unique advantage of high spatial resolving power compared to traditional liquid chromatography-mass spectrometry (LC-MS).With the nonstop advancement of its achievable sensitivity and spatial resolution, MSI technique has been providing novel perspectives into the preclinical studies of drugs, such as in vivo localization of drugs and their metabolites, visualization of drug metabolism, and drug delivery tracking.This review introduces the basics of MSI techniques, including basic principles, key features, technical advantages, and limitations, with particular highlight of the recent applications of MSI in drug efficacy and safety evaluation, drug distribution research, drug delivery research, and analysis of Chinese medicine from recent publications, aiming to promote the utilization and further expansion of MSI in the research and development of drugs.

Transgenic Rodent Models in Toxicological and Environmental Research: Future Perspectives

The coexistence of humans and animals has existed for centuries. Over the past decade, animal research has played a critical role in drug development and discovery. More and more diverse animals, including transgenic animals, are used in basic research than in applied research. Transgenic animals are generated using molecular genetic techniques to add functional genes, alter gene products, delete genes, insert reporter genes into regulatory sequences, replace or repair genes, and make changes in gene expression. These genetically engineered animals are unique tools for studying a wide range of biomedical issues, allowing the exhibition of specific genetic alterations in various biological systems. Over the past two decades, transgenic animal models have played a critical role in improving our understanding of gene regulation and function in biological systems and human disease. This review article aims to highlight the role of transgenic animals in pharmacological, toxicological, and environmental research. The review accounts for various types of transgenic animals and their appropriateness in multiple types of studies.

Anxiolytic-like activity of Aloysia virgatavar. platyphylla leaves extract in mice / Actividad ansiolítica del extracto de hojas de Aloysia virgatavar. platyphylla en ratones

Background: Medicinal plants are part of traditional medicine and should be considered a therapeutic alternative for mental diseases. Several plants belonging to the Verbenaceae family have proved useful in treating general anxiety disorders, the most prevalent psychiatric disorders. Objective: This research aimed to verify the extract's safety, the effect on general behavior, and the effect on sleeping time, as well as to evaluate the anxiolytic-like effect of the methanol extract of Aloysia virgata var. platyphylla (Avp), in mice. Methodology: The toxicity test was done according to the OECD guide (mice groups n=5), and general behavior was observed during the assay. Sleeping time was assessed using the pentobarbital-induced hypnosis method (n=8). Male Swiss albino mice (n=6) were treated with 50 to 400 mg/kg of Avp extract and diazepam as a control. The anxiolytic-like effect was tested through the hole board and elevated plus-maze test. Results: The Avp extract has no side effects in tested doses, and no central nervous system depressant activity was noted. A. virgatavar. platyphyllaincreased exploration (number and time) in the hole board. In the elevated plus-maze, increased number and time into open arms were evidenced compared to the control group. Conclusion: With all these results, we concluded that the Avp extract is safe and has a potential anxiolytic-like activity in the animal model used

Antecedentes: Las plantas medicinales forman parte de la medicina tradicional y deben ser consideradas una alternativa terapéutica para las enfermedades mentales. Varias plantas pertenecientes a la familia Verbenaceae han demostrado su utilidad en el tratamiento de los trastornos de ansiedad, uno de los trastornos psiquiátricos más prevalentes. Objetivo: Esta investigación tuvo como objetivo verificar la seguridad del extracto, el efecto sobre el comportamiento general y el efecto sobre el tiempo de sueño, así como evaluar el efecto tipo ansiolítico del extracto metanólico de Aloysia virgata var. platyphylla(Avp), en ratones. Metodología: La prueba de toxicidad se realizó de acuerdo con la guía de la OCDE (grupos de ratones n=5), y se observó el comportamiento general durante el ensayo. El tiempo de sueño se evaluó mediante el método de hipnosis inducida por pentobarbital (n=8). Se trataron ratones albinos suizos macho (n=6) con 50 a 400 mg/kg de extracto de Avp y diazepam como control. El efecto ansiolítico se probó a través de la placa perforada y prueba del laberinto en cruz elevado. Resultados: El extracto de Avp no tiene efectos secundarios en las dosis probadas y no se observó actividad depresora del sistema nervioso central. A. virgata var. platyphylla aumentó la exploración (número y tiempo) en el tablero de agujeros. En el laberinto en cruz elevado, se evidenció un mayor número y tiempo en los brazos abiertos en comparación con el grupo de control. Conclusión: Con todos estos resultados, concluimos que el extracto de Avp es seguro y tiene una potencial actividad ansiolítica en el modelo animal utilizado

Proteína tau como biomarcador en Alzheimer preclínico / Tau protein as a biomarker in preclinical Alzheimer's disease

El desarrollo de biomarcadores de la proteína tau para el diagnóstico temprano de la enfermedad de Alzheimer (EA) emerge como un desafío fundamental, pudiendo mejorar la efectividad de un tratamiento preventivo o que enlentezca la progresión de la enfermedad. Esta revisión analiza las evidencias que justificarían el uso de la proteína tau como biomarcador en Alzheimer preclínico. Para esto se seleccionaron artículos científicos (2011-2021) que incluyeran a la proteína tau en plasma y plaquetas como biomarcador. La presencia de la proteína tau fosforilada en el líquido cefalorraquídeo presenta limitaciones por su carácter invasivo mientras que las técnicas de imagen son costosas. La medición de tau en plaquetas se correlaciona con la severidad de la demencia, y sería útil en el seguimiento de la EA. Sin embargo, la pertinencia de su uso en la detección temprana de EA se mantiene en discusión. La presencia de proteína tau fosforilada en plasma correspondería al biomarcador con mayor nivel de desarrollo, respecto de beta amiloide. La proteína tau plasmática detecta la EA con gran precisión en casos de demencia y ha sido validada por estudios neuropatológicos. p-tau217 plasmática medida por primera vez junto a técnicas de imagen, fue importante en la etapa preclínica de EA pudiendo predecir la formación de ovillos neurofibrilares. La correlación entre especies fosforiladas de tau en plasma y EA preclínica ha sido bien establecida, por lo que su uso como biomarcador podría ser de utilidad para la comprensión del proceso fisiopatológico de la neurodegeneración y la detección temprana de EA

The development of tau protein biomarkers for the early diagnosis of Alzheimer's disease (AD) emerges as a fundamental challenge, which may improve the effectiveness of preventive treatment or slow the progression of the disease. This review analyzes the evidence that would justify the use of tau protein as a biomarker in preclinical Alzheimer's disease. For this purpose, we selected scientific articles (2011-2021) that included tau protein in plasma and platelets as a biomarker. Phosphorylated tau protein in cerebrospinal fluid has limitations due to its invasiveness, while imaging techniques are expensive. The tau measurement in platelets correlates with the severity of dementia and would be helpful in the follow-up of AD. However, the relevance of its use in the early detection of AD remains under discussion. Plasma phosphorylated tau protein would correspond to the biomarker with the highest level of development for beta-amyloid. Plasma tau protein detects AD with high accuracy in cases of dementia, and neuropathological studies validate its use. Plasma p-tau217 measured for the first time with imaging techniques was important in preclinical AD and could predict the formation of neurofibrillary tangles. The correlation between plasma phosphorylated tau species and preclinical AD is well-established, so its use as a biomarker would help understand the pathophysiological process of neurodegeneration and early AD detection.

Clinical characteristics of subjective cognitive decline in patients with Parkinson′s disease and its relationship with affective symptoms: a preliminary study / 中华神经科杂志

Objective:To investigate the characteristics and clinical related factors of Parkinson′s disease (PD) patients with subjective cognitive decline (SCD).Methods:Ninety-nine PD patients with normal cognitive function enrolled in Beijing Hospital from January to December 2018 were collected for the study. Patients with PD were divided into groups with ( n=57) and without ( n=42) SCD using the first question in Part 1 of the Unified Parkinson′s Disease Rating Scale (UPDRS). All patients were assessed by Montreal Cognitive Assessment (MoCA), modified Hoehn-Yahr grading, UPDRS, Hamilton Rating Scale for Depression (HAMD), Hamilton Rating Scale for Anxiety (HAMA), Parkinson′s Disease Sleep Scale, Ability of Daily Living Scale and 39-item Parkinson′s Disease Questionnaire (PDQ-39). Levodopa equivalent dose conversion was performed for patients taking anti-PD drugs. Patients′ self-reported years of formal education were collected. Results:The proportion of PD with SCD in this group was 57.58% (57/99). There were statistically significant differences in MoCA [28.00 (27.00, 29.00) vs 28.00 (27.00, 29.00) ,Z=-2.28, P=0.023], HAMD [6.00 (5.00, 8.50) vs 5.00 (2.00, 8.00), Z=-2.23, P=0.026], HAMA [7.00 (6.00, 11.00) vs 6.00 (3.00, 8.25) , Z=-2.70, P=0.007], PDQ-39-emotional health [2.00 (0, 5.00) vs 1.00 (0, 3.00), Z=-2.03, P=0.042] and PDQ-39-cognitive scores [4.00 (2.00, 5.00) vs 2.00 (0, 4.00), Z=-3.42, P=0.001] between PD with and without SCD groups. SCD was correlated with MoCA ( r=-0.23, P=0.022), HAMD ( r=0.23, P=0.025) and HAMA ( r=0.27, P=0.006) scores to varying degrees. When controlling for HAMD and HAMA scores, the correlation between SCD and MoCA scores ( r′=-0.18, P=0.084) was no longer existed. Conclusions:SCD is common in PD patients with normal cognitive function and is associated with poorer cognitive performance and more severe symptoms of depression and anxiety. In this group of patients, the relationship between SCD and affective symptoms may be greater than that of objective overall cognitive function, which is worthy of further studies.

Feasibility study on developing clinical pediatrics curriculum for medical students engaged in long schooling system in the pre-clinical stage / 中华医学教育探索杂志

Objective:To analyze the feasibility of developing clinical pediatrics curriculum for pediatric students at the pre-clinical stage, and to provide a basis for the subsequent curriculum construction.Methods:A total of 90 pediatric medical students were enrolled, including pre-clinical group (G1, third semester of the second year, n=47) and the clinical clerkship group (G2, seventh semester of the fourth year, n=43). A questionnaire survey was conducted to compare the two groups from three aspects: clinical interest, learning methods and learning ability. And 24 and 20 students were randomly selected from the two groups to participate a clinical course respectively. Both of the formative evaluation and in-class test were carried out to compare the learning performance and learning effect between G1 and G2. SPSS 22.0 was used for data analysis. The counting data were described by case number and rate, and the frequency between groups was compared by chi-square test. When the chi-square test condition is not met, Fisher's exact test was performed. Normal distribution test was carried out for measurement data. Two independent sample t test was conducted for the comparison between groups of normal distribution data and Mann-Whitney U test for the comparison between groups of skewed distribution respectively. Results:There was no significant difference in clinical interest and pre-clinical interest between the two groups (Fisher's exact probability method, P=0.252, 1.000). There were partial differences in learning methods: G1 spent more time learning after class ( Z=-2.36, P=0.018), learned more in spare time ( Z=2.53, P=0.011), learned more on the homework ( P=0.020), and had a higher preview rate ( Z=-5.07, P < 0.001). There were also partial differences in learning ability: G2 had better literature retrieval ability ( χ2=10.57, P=0.001); G2 had higher scores on class and extended class performance ( t=-3.18, P=0.004; t=-10.14, P<0.001). In terms of learning effect, G2 scored higher scores on only one multiple choice question ( t=-2.46, P=0.022). Conclusion:The pediatrics students at the pre-clinical stage have certain interest and ability to receive clinical pediatrics courses. Sufficient pre-class preparation and appropriate curriculum design are helpful to the early cultivation of student's clinical thinking.

Application of the preclinical education integrated with clinical medicine in the teaching of clinical anatomy / 中华医学教育探索杂志

This project starts with the teaching of clinical anatomy for eight-year medical students, selects specialists to enter the courses according to the content of clinical anatomy, and explores the deep integration of basic and clinical education. This study used the self-made questionnaire to evaluate the effect of the integrated teaching model, and Likert scale was used to score. Meanwhile, the correlation between the scores of each question and total points was analyzed with the item analysis. Moreover, we assessed the principal components through the exploratory factor analysis. The results showed that more than 95% questioned students thought the preclinical education integrated with clinical medicine teaching model is necessary and practical, which can assist medical students in the anatomical structure learning combined with clinical disease, and meanwhile cultivate students' clinical thinking. Only fewer than 10% thought it can connect the basic knowledge and clinical cases effectively, and over 35% thought there are difficulties. Additionally, more than half students (54%) hold the negative attitude which clinicians can't completely replace basic teachers in teaching. Our finding suggests that the integrated teaching model is attractive and feasible. Nonetheless, clinicians can’t replace preclinical teachers completely in the clinical anatomy education yet.

Advances in research based on primary human hepatocytes in vitro / 中华肝胆外科杂志

Due to the special functions of liver, the topic of liver physiological function and pathophysiological changes has always been the main issue in life science area. Human liver is composed of multiple types of cells, among which the hepatocyte is the most essential one. Primary human hepatocytes are considered as the gold standard model in vitro for the liver study and the ideal cell for hepatocyte transplantation and bioartificial liver. Nowadays, primary human hepatocytes play a vital role in the field of basic science research and applied research. Therefore, we presented recent advances in research based on primary human hepatocytes in vitro.

Determination of paclitaxel prodrug in SD rat plasma by LC-MS/MS and its application in preclinical pharmacokinetic studies / 药学学报

A fast and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of prodrug of paclitaxel (Pro-PTX) and paclitaxel (PTX) in rat plasma was developed. The plasma samples were subjected to protein precipitation with acetonitrile (0.1% formic acid), and then separated by LC with an Ultimate AQ-C18 column (50 mm × 3.0 mm, 3 μm) and acetonitrile-1 mmol·L-1 ammonium formate (containing 0.1% formic acid) as the mobile phase. Multiple reaction monitoring (MRM) scanning mode was used to detect the ion responses m/z 983.4→415.2 (Pro-PTX), m/z 854.4→286.1 (PTX) and m/z 808.3→527.2 (Docetaxel, internal standard) by using a triple quadrupole tandem mass spectrometer with electrospray ionization source and positive ion mode. The method validation results show that the linear ranges of Pro-PTX and PTX in plasma were 2.00-500 ng·mL-1 (r > 0.99) and 4.00-1 000 ng·mL-1 (r > 0.99), the lower limit of quantification was 2.00 ng·mL-1 and 4.00 ng·mL-1, respectively; the quality control samples with low, medium and high concentrations of Pro-PTX and PTX were within the batch, the relative standard deviation (RSD) between batches were all less than 9%; the relative deviation (RE) was within the range of ± 9%; In the stability test, both Pro-PTX and PTX in plasma were stable under various storage conditions. The method was sensitive, specific, and reproducible, and was suitable for the pharmacokinetic study of Pro-PTX in rats. Animal experiments were approved by the Ethics Committee of Laboratory Animal Management and Animal Welfare, Institute of Materia Medica, Chinese Academy of Medical Sciences (No.: 00003552).

Progress in preclinical study of combination of PARP inhibitors against tumor / 中国药房

Poly（ADP-ribose）polymerase（PARP）is a kind of DNA damage repair enzyme. PARP inhibitors include Olaparib （AZD2281），Niraparib（MK-4827），Rucaparib，Veliparib（ABT-888），Fluzoparib and Talazoparib （BMN-673），etc. This article reviews the preclinical research on the combined application of PARP inhibitors against tumor by searching the relevant literatures. Through the synthetic lethal mode ，PARP inhibitors have a strong killing effect on tumor cells with homologous recombination repair defects. However ，for tumor cells with intact DNA damage repair function ，PARP inhibitors often need to be combined with radiotherapy or other drugs to play a role. Combined application drugs include antiangiogenic drugs ，heat shock protein 90 inhibitors，cyclin-dependent kinase 12 inhibitors，immune checkpoint inhibitors ，histone deacetylase inhibitors ，etc. The combined application of PARP inhibitors is expected to enhance the efficacy of anti-tumor drugs and achieve the goals of sensitization ， synergism and reversal of drug resistance ，which is worthy of further in-depth research and exploration of new combined treatment schemes.