Alternative splicing events in tumors and targeted therapy / 药学学报

Alternative splicing is the key to human gene expression regulation and plays a decisive role in enlarging the diversity of functional proteins. Alternative splicing is an important biomarker in tumor progression, which is closely related to the development of tumors. Tumor cells tend to produce alternative spliceosome that are conducive to their progression. Therefore, targeting regulation of tumor-specific alternative spliceosomes is a potential strategy for tumor therapy. Herein, we provide a brief review of the complex relationship between alternative splicing and tumors. Alternative splicing works by removing non-coding sequences of pre-mRNA and assembling protein-coding fragments in different combinations, ultimately producing proteins with different or even opposite functions. Alternative splicing events can promote the transformation of tumor cells through apoptosis, invasion, metastasis, angiogenesis, and metabolism; they can also influence the effectiveness of cancer immunotherapy by affecting genes that play a key role in the immune pathway. We proposed that direct or indirect targeting of alternative splicing factors and oligonucleotide-based therapies are the main strategies to reverse tumor alternative splicing events. These findings will help us to better understand tumor-related alternative splicing and to develop new strategies for tumor treatment.

Mechanisms and research progress of targeted therapies on regulation of autophagy by natural compounds from traditional Chinese medicine / 药学学报

Autophagy is an important physiological process that can degrade cell components and maintain cell homeostasis, divided into three types including macroautophagy, microautophagy and chaperon-mediated autophagy generally, and macroautophagy is the most common form. Autophagy can affect the progression of a variety of diseases, such as cancer, neurodegenerative diseases, heart-related diseases, and autoimmune diseases, etc. However, autophagy can promote or inhibit diseases in different circumstances because of the dual roles of autophagy. Therefore, targeted regulating autophagy may be a potential treatment plan for diseases in specific stages of disease development. Now, with the development of traditional Chinese medicine (TCM) resources and the deepening of researches on the modern utilization of TCM, many active compounds from TCM have been discovered that can target autophagy to exert pharmacological activity. Most of the natural compounds activate or inhibit autophagy by affecting the classical PI3K/AKT/mTOR autophagy pathway. In addition, some compounds can also affect autophagy through MAPKs signaling pathways such as MEK/ERK, JNK and p38MAPK. These active compounds exert various biological activities by regulating autophagy, including anti-tumor, inhibiting neurodegenerative diseases, protecting cardiomyocytes, and relief of inflammatory response. In this review, we summarized the active compounds in TCM that affect autophagy by targeting different signaling pathways and their mechanisms of regulating autophagy, also introduced the effects of active compounds on diseases after affecting autophagy. Finally, this paper summarized and prospected the development of targeted autophagy for the treatment of diseases by TCM compounds, hoping to provide clues for subsequent exploration and research.

Progress in the research of medial column reconstruction of proximal humerus fractures in the elderly / 中国骨伤

The proximal medial column of the humerus is a continuous cortical region in the inner and lower part of the humerus head, which has attracted more and more attention in clinical and scientific research since it was proposed. It has been shown to increase the stability of internal fixation, maintain the height of the humeral head to prevent varus, and reduce the risk of screw penetration. Biomechanical studies have also shown that the medial column has an outstanding performance in increasing the stiffness, torsion resistance, and shear resistance of the locking plate. Although it has many benefits, there is no unified definition of its concept and specific region, and the existing classification does not include the medial column, therefore more researches are required to provide supporting information. The methods of medial column reconstruction mainly include locking plate combined with talus screw, locking plate combined with bone grafting, internal and external double plate combined support, locking plate combined with bone cement, and humeral cage. These methods have their own characteristics, however they will increase the cost of surgery and bring new complications. How to determine the best way of reconstruction is one of the focuses of future research. In this review, the concept of the proximal medial humerus column, the role of maintaining internal fixation, the role of biomechanics and the reconstruction methods are reviewed.

The question about the numerical value and quantitative data transfer of implant prosthodontics-orom experience guidance to digital guidance / 华西口腔医学杂志

The correct implant site design and placement are the basic clinical techniques that must be known for implant restoration. For a long time, most implants have been placed by free hands, and the choice of site is mostly dependent on the accumulation of long-term experience of the surgeon. The selection of implant site guided by this experience analogy logic is often based on the surgeon's level of experience,which often makes it very easy to produce complications related to the implant restoration of the incorrect site. In contrast, a clinical program using digital guidance and real-time measurable verification has emerged based on the restoration-oriented implantation concept, which marks the formation of an accurate, measurable and verifiable whole-process digital implant prototype. Furthermore, from the perspective of surveying, the numerical requirements that digital implant restoration relies on are actually incomplete to the four elements of measurement, which leading to the doubts about its authenticity. This article will question the numbers in implant restoration, and conduct a preliminary demonstration, and propose a new reliable actual measurement and verification method of the correct location and the numerical requirements of the restoration space and a new clinical program that relies on numbers from the perspective of the evolution of digital restoration, guided implantology and actual measurement technology. And this article further discusses the current mainstream implant restoration technology based on experience analogy which cannot effectively support the whole process of digital implant restoration and provides a new logical cognitive basis for the final realization of the entire process of digital implant restoration.

Interarch distance is a target restorative space value: clinical decisionmaking of implant restoration guided by measured value / 华西口腔医学杂志

When design an implant restoration for edentulous patients, many doctors ignore the sufficiency of the interarch distance (vertical distance) or horizontal distance of the patient to accommodate the superstructure and restoration before designing the implant plan. However, the connotation of measuring the interarch distance or horizontal distance has not been clarified in clinical practice. It is often based on visual estimation after operation, and the decision-making path of implant restoration is inverted, resulting in many mistakes regarding the restoration after implantation. The main reason is the lack of standardized paths and practical methods to use before surgery. This article recommended initially establishing a maxillo-mandibular relationship based on natural teeth, old dentures, or new ones and then using the height and horizontal distance or angle of the target restorative space, which was easier to grasp as the measured index. The minimum vertical distance (including the height of the gingival surface and the bone surface) and the horizontal distance (or the angle from the bone or gingival surface to the proposed occlusal plane) should be measured before operation. A decision tree of edentulous jaw restoration guided by the values of the repair space was established based on the measured values. This article clarified the measuring points and planes and thus provided a quantitative relationship basis for the design of implant restoration.

Questions about the numerical value and quantitative data transfer of tooth preparation-from experience guidance to digital guidance / 华西口腔医学杂志

Tooth preparation is a common operation in dental clinical practice. This procedure is irreversible and invasive from the point of view of tooth preservation. Conditions of the abutment tooth, treatment methods, and restoration materials for target restoration affect tooth preparation. To achieve the goals of tooth tissue preservation, dental pulp protection, and periodontal health, dentistry professionals agreed on the importance of minimizing the amount of tooth reduction. The foundations for realizing this consensus are as follows. First, the available restoration materials with improved comprehensive performance need less target restoration space. Next, teeth can be prepared under a digital guide, and the real-time measurement of restoration space can be verified due to the invention of digital technologies for the analysis of the quantity and shape of the prepared tooth and tooth measurement. Moreover, guiding methods for preparation have been developed from freehand operation under the naked eye based on accumulated personal experience to digital-guidance jointing microscope. These innovations indicate the creation of a prototype of guided prosthodontics that is precise and applies real-time measurement throughout the process of tooth preparation. From the perspective of the evolution of digital, guided, and micro prosthodontics, this article raised seven questions about the numerical value and quantitative data transfer of tooth preparation and evaluated the authenticity of existing numerical requirements from the perspective of the four elements of measurement. Identifying unified measuring methods and developing measuring tools with a precision of hundred or ten microns will be the key to solving the problem about the authenticity of numerical measurement. Furthermore, this paper summarizes the methods of how to control tooth reduction and explains in depth why the currently dominant tooth preparation technology, which is based on empiricism, cannot effectively achieve the goals in digital prosthodontics. Therefore, we strongly call for rebuilding the digital foundation of prosthodontic treatment immediately.

Immediate precision of the digital osteotomy template in the digital stackable template: a clinical study / 华西口腔医学杂志

OBJECTIVES@#This study aimed to evaluate the immediate accuracy of the digital osteotomy template in the digital stackable template.@*METHODS@#From November 2018 to January 2020, 4 patients with dentition loss were selected from the Prosthodontics Department, West China Stomatological Hospital. All patients met the conditions for immediate planting and immediate restoration. Owing to the lack of vertical target-restoration space, the implantation plan included intraoperative osteotomy. According to the preoperative cone beam CT (CBCT) data, combined with aesthetic digital smile design (DSD) analysis, virtual wax design, and so on, the ideal bone plane design was performed. According to the virtual osteotomy plane, the virtual implantation plan was designed, and then the digital stackable template assuming osteotomy template, implantation guide, and temporary restoration were made and 3D printed. Osteotomy was performed under the guidance of digital osteotomy template during the operation. The preoperative CBCT and postoperative CBCT of all patients overlapped, the deviation between the actual osteotomy and the ideal osteotomy was calculated, and the angle deviation between the postoperative bone plane and the ideal bone plane was measured.@*RESULTS@#The ave-rage volume deviation between the postoperative design and the ideal one was 492.94 mm³, accounting for 21.21% of the preset osteotomy volume. The average deviation between the postoperative osteotomy and the ideal osteotomy in four patients was 0.024 8 mm. The average angle between the postoperative bone plane and the ideal bone plane was 6.03°.@*CONCLUSIONS@#The displacement deviation of virtual osteotomy design and the actual osteotomy one under the guidance of digital osteotomy template in the digital stackable template are highly consistent with the original design. Thus, this clinical technique is worth popularizing, accurate, and quantifiable.

An investigation of the microstructure and mechanical properties of dental zirconia manufactured by digital light processing 3D printing / 华西口腔医学杂志

OBJECTIVES@#This study was performed to investigate the microstructure and mechanical properties of dental zirconia manufactured by digital light processing (DLP) 3D printing and the clinical application prospects of this material.@*METHODS@#The experiment (DLP) group was zirconia manufactured by DLP 3D printing, and the control (MILL) group was milled zirconia. The density, grain size, and phase composition were measured to study the microstructure. Flexural strength was measured by using three-point bending tests, while Vickers hardness was determined through a Vickers hardness tester. Fracture toughness was tested using the single-edge V-notched beam method.@*RESULTS@#Zirconia density of the DLP group was (6.019 8±0.021 3) g·cm@*CONCLUSIONS@#Zirconia manufactured by DLP 3D printing had microstructure and mechanical properties similar to those of the milled zirconia. Only the flexural strength and the Vickers hardness of the experimental zirconia were slightly lower than those of the milled zirconia. Therefore, DLP-manufactured zirconia has a promising future for clinical use.

Traditional Chinese Medicine Intervention on Th17/Treg Balance in Chronic Obstructive Pulmonary Disease： A Review / 中国实验方剂学杂志

Chronic obstructive pulmonary disease （COPD）， a common clinical chronic respiratory disease， has a long course and is intractable. It is closely related to many factors， such as immune imbalance. Helper T cell 17 （Th17）， an immune-promoting cell， and regulatory T cell （Treg）， an immunosuppressive cell， maintain the balance of the immune microenvironment together. In the course of COPD， the proportion of Th17 cells usually increases， while the proportion of Tregs that inhibit Th17 activity decreases. Their coordination and balance are critical in the inflammatory and immune processes of COPD. At present， COPD is mainly treated with nasal inhalation preparations and oral drugs by western medicine. In spite of a certain therapeutic effect， side effects of drugs and heavy economic burden are becoming increasingly prominent. Modern research shows that traditional Chinese medicine （TCM） has the characteristics of few side effects， stable curative effect， and multi-target regulation， and it is advantageous and promising in the prevention and treatment of COPD. In recent years， a large number of TCM clinical and experimental trials on the intervention of Th17/Treg balance in COPD have been launched. Substantial pieces of evidence confirm that the intervention of Th17/Treg balance is an important potential target of TCM in the treatment of COPD. This study reviewed the previous research on the intervention effect of single Chinese medicine， effective components of Chinese medicine， and Chinese medicinal compound on Th17/Treg balance in COPD to comprehensively reveal the potential target of Th17/Treg balance in COPD for clinicians and scientific researchers， promote relevant research， and provide references for the rational application of TCM in the prevention and treatment of COPD.

Precise tooth preparation technique guided by 3D printing guide plate with quantitative hole / 华西口腔医学杂志

The minimum amount of tooth preparation that can be fully controlled is crucial in achieving long-term, stable, and effective aesthetic restoration, which is also a major difficulty in aesthetic restoration. The tooth preparation can be imple-mented efficiently and accurately through digital technology based on the fixed-deep hole guiding technology. Prior the actual tooth preparation, the technology first designs the virtual contour, layering, and virtual occlusion of the prosthesis on the computer. Then, virtual tooth preparation is carried out by cutting back according to the virtual prosthesis. Next, the virtual drilling operation plan is designed according to the shape of the virtual tooth preparation and the contour of the abutment tooth. Finally, the tooth preparation guide plate is designed and printed in 3D. It realizes the whole process of quantitative and precise guidance of dental preparation, visualizes the restoration space, reduces the clinical operation time, and guarantees the quality of dental preparation. It also promotes the improvement of the teaching quality of digital practical exercises.

A technique to design the framework of removable partial denture by multi-stage expert system / 华西口腔医学杂志

This study aims to apply a new expert system to design removable partial denture (RPD) framework. The RPD design is completed in three steps, namely, "selecting missing teeth", "selecting abutment condition", and "selecting personalized clasp". The system can help auxiliary dentists develop personalized treatment plans to reduce their clinical workload. It can also generate a dental preparation guideline for clinical preparation, which can prevent tooth preparation mistakes. By generating the standard electronic drawings of the framework design, the system can reduce the inconvenience caused by manual drawing, thereby facilitating dentist-technician communication and reducing the rate of remade.

Precise implant insertion technology for measuring dental implant placement / 华西口腔医学杂志

Identifying the ideal implantation site is important for the long-term stability and effectiveness of follow-up restorations. Implant surgical guide and navigation are used to determine the implantation site in clinic and improve the precision of implantation. However, due to difficulties in digital methods, such as multiple procedures, high cost, and actual accuracy of more than 1 mm, many physicians still prefer to operate with free hand. In preoperative, intraoperative, and postoperative procedures, time-saving and practical methods for implant site evaluation are lacking. In many cases, oral physicians found that the position deviates only by cone beam CT, which was costly to modify the position. In this article, we presented a precise implantation insertion technology that is guided by a measurable technique throughout the implantation application for all implant systems. This method was guided by a dynamic control measuring ruler, which functions together with the measuring and intraoperative locating rulers. The 3D space of the operative area was measured by a measuring ruler prior to operation, and the implant plan and quantitative guidance design were conducted according to the measured and cone beam CT data. The whole implantation process was guided by the dynamic control measuring ruler, and measuring verification results were also considered. This method can realize the quantification of the entire preoperative space analysis, intraoperative precise implantation guidance, and postoperative site measurement and evaluation. This practical technique also helps to adjust the position, improve the implantation accuracy and is suitable in generalizing dental implantation.

Clinical pathway and preparation method of high-precision tooth shoulder platform / 华西口腔医学杂志

A clear shoulder platform that can be easily identified by doctors and technicians or machines (mouth scan and warehouse scan) is important to obtaining a good long-term and stable fixed prosthesis treatment effect. At present, the pre-paration of the shoulder platform is usually based on free hands, and the practical operation is mainly guided by experience. Moreover, no comprehensive and objective preoperative design, intraoperative verification, and final test are available. Thus, the accuracy of shoulder platform preparation needs to be improved. In this study, the clinical pathway of "three determination, three selection, and three steps" with high accuracy of preparation and the precise shoulder preparation method of "bur-tip guidance" are proposed in detail.

Observation of Effect of Qianjin Weijingtang on Differentiation of Th17/Treg and Expressions of Related Cytokines in Lung Tissues of Model Rats Exposed to Cigarette Smoke / 中国实验方剂学杂志

Objective:The present study was to observe the effect of Qianjin Weijingtang on the differentiation of helper T cells 17 （Th17）/T regulatory cell （Treg） and the expressions of related cytokines in the lung tissues of the model rats exposed to cigarette smoke. Method:Totolly 60 male rats were randomly assigned into six groups （control group， model group， acetylcysteine group and Qianjin Weijingtang high， moddle and low dose groups）， with 10 rats in each group. After 30 day's modeling and 30 day's intervention， rats were killed peacefully with their tissues collected. Real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） was used to detect the expression of retinoic acid associated orphan receptor （ROR-γt） and forkhead/pterygoid helix transcription factor 3 （Foxp3） mRNA， enzyme-linked immunosorbent assay （ELISA） was used to check the concentration of interleukin-17（IL-17）， IL-6， IL-10 and transforming growth factor-β1（TGF-β1）. Htoxylin eosin （HE） staining was used to observe the pathological changes of lung tissues， while flow cytometry was used to detect Treg（Foxp3+CD25+）， Th17（CD4+IL-17+） and Treg/Th17 ratio. Result:As compared with the control group， the ROR-γt mRNA expression in model group was higher（P<0.01）. As compared with the model group， various doses of Qianjin Weijingtang down-regulated the expression（P<0.05，P<0.01）. As compared with the control group， the expression of the Foxp3 mRNA was down-regulated in model group（P<0.05）， but was up-regulated in Qianjin Weijingtang middle and low dose groups（P<0.05）. Compared with the control group， the concentration of IL-17 and IL-6 in the model group were significantly increased， while the concentration of IL-10 and TGF-β1 in the model group were significantly decreased（P<0.05，P<0.01）. As compared with the model group， intervention with various doses of Qianjin Weijingtang could help to decrease the concentration of IL-17 and IL-6 in lung tissues， and increase the concentration of IL-10（P<0.05）， which were consistent with those of Real-time PCR results. Flow cytometry examination showed that the Th17（CD4+IL-17+） proportion decreased and Treg/Th17 ratio increased after Qianjin Weijing Tang middle and low dose intervention（P<0.05，P<0.01）. Conclusion:Qianjin Weijingtang could regulate Treg/Th17 ratio and help to achieve Th17/Treg balance.

N-containing compounds from seeds of Paganum harmala / 中国中药杂志

To investigate the N-containing compounds in the seeds of Paganum harmala,fourteen compounds were finally isolated from the 95% Et OH extract of P. harmala seeds by using various chromatographic techniques including silica gel,MCI resin,and ODS column chromatography as well as the semi-preparative HPLC. Depending on spectroscopic techniques and comparison with the reported data in the literatures,the structures of all compounds were identified as N-[3-(2-amino-4-methoxyphenyl)-3-oxopropyl]acetamide(1),dehydroharmalacidine(2),harmalacidine(3),harmine N-oxide(4),harmine(5),tetrahydroharmine(6),demethylharmalacidine(7),harmol(8),tetrahydroharmol(9),harmindol β-D-glucopyranoside(10),tryptophyl β-D-glucopyranoside(11),pegamineβ-D-glucopyranoside(12),vasicol(13) and vasicinone(14). Among them,1 was a new compound,and 2 and 10 were obtained as natural products for the first time.

Expert consensus on biomechanical research of dental implant / 华西口腔医学杂志

Current biomechanical research of dental implants focuses on the mechanical damage and enhancement mechanism of the implant-abutment interface as well as how to obtain better mechanical strength and longer fatigue life of dental implants. The mechanical properties of implants can be comprehensively evaluated by strain gauge analysis, photo elastic stress analysis, digital image correlation, finite element analysis, implant bone bonding strength test, and measurement of mechanical properties. Finite element analysis is the most common method for evaluating stress distribution in dental implants, and static pressure and fatigue tests are commonly used in mechanical strength test. This article reviews biomechanical research methods and evaluation indices of dental implants. Results provide methodology guidelines in the field of biomechanics by introducing principles, ranges of application, advantages, and limitations, thereby benefitting researchers in selecting suitable methods. The influencing factors of the experimental results are presented and discussed to provide implant design ideas for researchers.

Advances in titanium dental implant surface modification / 华西口腔医学杂志

Titanium dental implants have wide clinical application due to their many advantages, including comfort, aesthetics, lack of damage to adjacent teeth, and significant clinical effects. However, the failure of osseointegration, bone resorption, and peri-implantitis limits their application. Physical-chemical and bioactive coatings on the surface of titanium implants could improve the successful rate of dental implants and meet the clinical application requirements. This paper reviews the characteristics of surface modification of titanium implants from the aspects of physics, chemistry, and biology. Results provide information for research and clinical application of dental implant materials.

Minimal invasive microscopic tooth preparation based on endodontic, periodontal and functional health / 华西口腔医学杂志

Tooth preparation is the primary and core operation technique for dental esthetic restoration treatment, due to its effect of providing restoration space, bonding interfaces and marginal lines for dental rehabilitation after tooth tissue reduction. The concept of microscopic minimal invasive dentistry put forward the issue of conducting high-quality tooth preparation, conserve tooth-structure, protect vital pulp and periodontal tissue simultaneously. This study reviewed the concepts, physiology background, design and minimal invasive microscopic tooth preparation, and in the meantime, individualized strategies and the two core elements of tooth preparation (quantity and shape) are listed.

Criteria for success in dental implants / 华西口腔医学杂志

With the comprehensive application and development of implant dentistry in recent years, multi-institutional data have supported a large number of clinical research findings. A consensus was gradually reached on the evaluation of the state and effect of implants and types of indicators that were selected after restoration. This study aims to examine the frequently used criteria to define treatment success in implant dentistry.

A review of peri-implant microbiology / 华西口腔医学杂志

Dental implants represent the majority of treatment strategies used to replace missing teeth. However, peri-implant diseases caused by disturbance in peri-implant microbiological balance are among the reasons for implant failure. Since the 1980s, peri-implant microorganisms have been a hot research topic in dental microbiology. The bacterial ecology between the disease and health largely differs, which directly or indirectly increases the risk of peri-implant diseases. Accordingly, the determination of the 'core microbiome' of peri-implantitis and peri-implant mucositis is a key point of recent research.