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Objective To investigate the effects of Fuzheng Quxie Prescription(mainly with the actions of supporting healthy qi and dispelling pathogens)combined with neoadjuvant chemotherapy on tumor recurrence,serum thymidine kinase 1(TK1)level and immune function in patients with triple-negative breast cancer(TNBC).Methods Eighty patients with TNBC of qi and yin deficiency type were randomly divided into a combination group and a control group,with 40 patients in each group.The control group was treated with AC-T sequential chemotherapy(Doxorubicin combined with Cyclophosphamide plus sequential Docetaxel),and the combination group was treated with Fuzheng Quxie Prescription on the basis of treatment for the control group.One course of treatment covered 21 days,and the two groups were treated for 4 consecutive courses.The changes of traditional Chinese medicine(TCM)syndrome scores,Karnofsky Performance Status(KPS)score,levels of tumor markers of carbohydrate antigen 125(CA125),carbohydrate antigen 153(CA153)and TK1,and T lymphocyte subset levels in the two groups were observed before and after the treatment.Moreover,the clinical efficacy and tumor metastasis and recurrence in the two groups were compared.Results(1)After 4 courses of treatment,the total effective rate of the combination group was 87.50%(35/40),and that of the control group was 67.50%(27/40),and the intergroup comparison(tested by chi-square test)showed that the efficacy of the combination group was significantly superior to that of the control group(P<0.05).(2)After treatment,the TCM syndrome scores in the two groups were significantly decreased compared with those before treatment(P<0.05),and the KPS scores were significantly increased compared with those before treatment(P<0.05),and the decrease of TCM syndrome scores and the increase of KPS scores in the combination group were significantly superior to that in the control group(P<0.05 or P<0.01).(3)After treatment,the serum CA125,CA153 and TK1 levels of patients in the two groups were significantly decreased compared with those before treatment(P<0.05),and the decrease of serum CA125,CA153 and TK1 levels in the combination group was significantly superior to that in the control group(P<0.01).(4)After treatment,the T lymphocyte subset CD3+,CD4+ levels and CD4+/CD8+ ratio in the two groups were significantly increased compared with those before treatment(P<0.05),and the CD8+ level was significantly decreased compared with that before treatment(P<0.05).The post-treatment intergroup comparison showed that the increase of the T lymphocyte subset CD3+,CD4+ levels and CD4+/CD8+ ratio as well as the decrease of the CD8+ level in the combination group was all significantly superior to that in the control group(P<0.05 or P<0.01).(5)The one-year follow-up showed that the tumor recurrence rate and tumor metastasis rate in the combination group were 7.50%(3/40)and 12.50%(5/40)respectively,significantly lower than 25.00%(10/40)and 35.00%(14/40)in the control group,and the differences were statistically significant when comparing between the two groups(P<0.05).Conclusion The combination of neoadjuvant chemotherapy with Fuzheng Quxie Prescription has a better therapeutic effect on TNBC patients with qi and yin deficiency syndrome,which can effectively improve the immune function of the patients,decrease the level of serum tumor markers,improve the quality of life of the patients,and reduce the incidence of tumor recurrence and metastasis.
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BACKGROUND:One-hole split endoscope technique has been widely used in the treatment of lumbar degenerative diseases,but there is no relevant literature on the safety analysis of this technique in the treatment of upper lumbar disc herniation. OBJECTIVE:To observe the position relationship of nerve roots,intervertebral space and bone landmarks in the upper lumbar spine by three-dimensional lumbar CT reconstruction technology,and to provide a basis for the clinical operation of one-hole split endoscope surgery. METHODS:Twenty-six patients with upper lumbar disc herniation underwent a lumbar CT scan.Mimics 17.0 software was imported to measure the related imaging parameters of L1/2 to L3/4 segments:(1)Measurement of vertical distance:In coronal view,the distance(a)from the intersection point of the medial facet of the superior articular process and the superior endplate(N)to the apex of the articular process(S);in the coronal view,the distance(b)from the sagittal intersection(M)of N and the inferior endplate to the apex of the inferior articular process(X).(2)Measured horizontal distance:the distance(c)between the cross-section of N and the lower edge of the outlet nerve root(N2);distance(d)between the cross-section of N and the intersection point of neural tissue(N1);N1 to N2 distance(e);distance(f)between the cross-section of M and the lateral edge of the nerve tissue(M1);M to M cross-section and exit nerve root intersection(M2)distance(g);distance(h)from M1 to M2;distance(i)from M2 to N1;distance(j)from the posterior edge of the articular surface(R)to M2 in sagittal view of the superior articular process. RESULTS AND CONCLUSION:(1)With the decrease of the segment,the distances a and b gradually increased,and the distance j gradually decreased.There was no significant difference between L1/2 and L2/3 segments(P>0.05).(2)With the decrease of the segment,distance d first decreased and then increased;distance f gradually decreased;distances c,e,g,h and i gradually increased;and there was no significant difference between L2/3 and L3/4 segments(P>0.05).(3)Distance i was the shortest distance without pulling nerve roots in the natural state,and the area of the safety zone was between four points M1,M2,N1,and N2.The bone was removed to the upper and lower endplates by biting the bone downward and upward through S and X,respectively,to expose the intervertebral space,and the window of distance g to M2 could be opened outward to avoid injury of the outlet nerve roots.(4)In conclusion,the upper lumbar vertebrae have unique anatomical characteristics.Based on the relevant measurements of nerve roots,spinal dura and intervertebral space,the parameters of the one-hole split endoscope technique are more accurate and safe during operation.
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BACKGROUND:Cadmium is a common environmental pollutant,which can damage multiple organs and tissues,such as the kidney and bone,but its effect on annulus fibrosus cells in the intervertebral disc has been less reported. OBJECTIVE:To investigate the effect of cadmium chloride on the senescence of annulus fibrosus cells and the role of PI3K/Akt signaling pathway. METHODS:Annulus fibrosus cells from Sprague-Dawley rat intervertebral discs were harvested and passage 3 cells were intervened with different concentrations of cadmium chloride(0,1,5,10,20 μmol/L).Cell viability and proliferation were detected by cell counting kit-8 assay.Transcriptome sequencing and Kyoto Encyclopedia of Genes and Genomes functional enrichment analysis were performed on annulus fibrosus cells with or without cadmium chloride addition.Passage 3 annulus fibrosus cells were divided into control group,cadmium chloride group and LY294002 group.Cell proliferation rate was detected by EdU method,positive cell rate was detected by senescence-associated β-galactosidase staining,and expressions of senescence-associated proteins(p16,p21 and p53)and p-Akt at protein and mRNA levels were measured by western blot,RT-PCR and immunofluorescence. RESULTS AND CONCLUSION:5 μmol/L cadmium chloride could inhibit the proliferation of annulus fibrosus cells.Results from the Kyoto Encyclopedia of Genes and Genomes functional enrichment analysis showed that the main signal transduction pathways included PI3K/Akt,cell cycle and p53 signaling pathways,which were related to cell senescence and proliferation.PI3K/Akt signaling pathways with significant differential expression were selected for validation.Compared with the control group,the EdU-positive rate was significantly decreased in the cadmium chloride group(P<0.05),while the β-galactosidase-positive rate,the expression of senescence-associated proteins(p16,p21 and p53)and p-Akt significantly increased(P<0.05).Compared with the cadmium chloride group,the EdU-positive rate and p-Akt expression were significantly decreased in the LY294002 group(P<0.05),while the β-galactosidase-positive rate and the expression of senescence-associated proteins(p16,p21 and p53)significantly increased(P<0.05).To conclude,cadmium chloride can regulate the senescence of annulus fibrosus cells by activating the PI3K/Akt signaling pathway,thereby inducing the occurrence and progression of intervertebral disc degeneration.
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BACKGROUND:The distribution of the necrotic area plays an important role in hip preservation treatment.At present,there are few studies on whether the difference in the three-dimensional spatial distribution of osteonecrosis of the femoral head affects the clinical outcome of fibular support. OBJECTIVE:To explore the relationship between the spatial distribution and clinical outcome at the sites of osteonecrosis of the femoral head and fibular support using CT three-dimensional reconstruction so as to provide a basis for optimizing the applicable conditions of fibular support and improving the hip preservation effect of fibular support. METHODS:Eighty patients with osteonecrosis of the femoral head who were treated with fibular support for hip preservation from January 2010 to January 2021 were selected as the study subjects according to the inclusion criteria.They were followed up for at least 2 years.According to the clinical outcome,the patients were divided into the successful hip preservation group(n=55)and the failure hip preservation group(n=25).3D reconstruction was performed according to the preoperative and postoperative CT images of the patients.According to the three-column theory,the femoral head was divided into outer nine areas,middle nine areas and inner nine areas(L1-9,C1-9,and M1-9)to explore the spatial distribution of necrotic area of the femoral head and fibular support area and its relationship with clinical outcome. RESULTS AND CONCLUSION:(1)Before operation,the necrotic area of the femoral head was mainly distributed in L1,L2,L4,L5,C1,C2,C4,and C5(the upper and middle part of the anterior part of the outer ninth area and the middle part of the middle ninth area).After operation,the fibular support area was mainly distributed in L5,L6,C5,and C6(the middle and lower part of the outer ninth area and the middle and lower part of the middle ninth area).(2)There were significant differences in the distribution of osteonecrosis of the femoral head between the successful hip preservation group and the failure hip preservation group in L8(the posterior middle part of the outer ninth area),C3(the anterior lower part of the middle ninth area),C6(the lower middle part of the middle part of the inner ninth area)and M2(the anterior middle part of the inner ninth area)(P<0.05).There was a significant difference in the distribution of fibular support in L5 and L6(middle and lower part of outer nine)(P<0.05).Among them,the L8 region could be used as an independent predictor of hip preservation failure in fibular support surgery.The area under the curve of the L8 single factor prediction model was 0.698[95%CI(0.575,0.822)];the sensitivity was 76%,and the specificity was 63.6%.(3)It turns out,when the necrotic area involves L8,C3,C6,and M2,especially L8,the failure of fibular support may increase,and when the fibular support involves L5 and L6,the effect of hip preservation is often not ideal.
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BACKGROUND:The appearance of the crescent sign in femoral head necrosis is a"turning point"in the progression of the disease,and repairing and stabilizing the bone-cartilage interface is particularly important in preventing further progression and collapse of the femoral head.Tissue engineering offers potential advantages in the simultaneous repair and integration of the bone-cartilage interface. OBJECTIVE:To review potentially suitable techniques addressing the subchondral separation in femoral head necrosis. METHODS:Relevant articles from January 1970 to April 2023 were searched in PubMed,Web of Science,and China National Knowledge Infrastructure(CNKI)using English search terms"femoral head necrosis,avascular necrosis of femoral head,osteonecrosis of femoral head"and Chinese search terms"femoral head necrosis,subchondral bone,cartilage,integration of cartilage and subchondral bone".A total of 114 articles were included for review and analysis. RESULTS AND CONCLUSION:(1)Structural defects,ischemic and hypoxic environment,inflammatory factors,and stress concentration may cause subchondral separation in osteonecrosis of the femoral head.Subchondral bone collapse and failure of hip-preserving surgery may be associated.Integration of tissue engineering scaffolds with the bone-cartilage interface is one potential approach for treating subchondral separation in osteonecrosis of the femoral head.(2)Current literature suggests that multiphase scaffolds,gradient scaffolds,and composite materials have shown improvements in promoting cell adhesion,proliferation,and deposition of bone and cartilage matrix.These advancements aid in the integration of scaffolds with the bone-cartilage interface and have implications for the treatment of subchondral separation in osteonecrosis of the femoral head.(3)Surface modifications of scaffolds can enhance interface integration efficiency,but they have their advantages and disadvantages.Scaffolds providing different environments can induce differentiation of mesenchymal stem cells and facilitate integration between different interfaces.(4)Future scaffolds for subchondral separation in osteonecrosis of the femoral head are expected to be composite materials with gradient and differentiated biomimetic structures.Surface modifications and stem cell loading can promote integration between the bone-cartilage interface and scaffolds for therapeutic purposes,but further experimental verification is still needed.Challenges include synchronizing scaffold degradation rate with repair progress and ensuring stability between different interfaces.
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BACKGROUND:Bone has bioelectric effects.However,bone defects can lead to loss of endogenous bioelectricity in bone.The implantation of bone tissue engineering scaffolds with bioelectric effect into bone defects will replenish the missing electrical signals and accelerate the repair of bone defects. OBJECTIVE:To introduce the bioelectric effect of bone tissue and expound the repair effect of electrical stimulation on bone defects,summarize the research progress of bioelectric effect applied to bone tissue engineering,in order to provide new ideas for the research of bone tissue engineering. METHODS:Relevant articles were searched on CNKI,WanFang,PubMed,Web of Science and ScienceDirect databases,using"bioelectrical effect,bioelectrical materials,electrical stimulation,bone tissue engineering,bone scaffold,bone defect,bone repair,osteogenesis"as the English and Chinese search terms.Finally,87 articles were included for analysis. RESULTS AND CONCLUSION:(1)Bioelectrical effect combined with ex vivo electrical stimulation to design bone tissue engineering scaffolds is an ideal and feasible approach,and the main materials involved include metallic materials,graphene materials,natural bio-derived materials,and synthetic biomaterial.At present,the most widely used conductive material is graphene material,which benefits from its super conductivity,large specific surface area,good biocompatibility with cells and bones,and excellent mechanical properties.(2)Graphene materials are mainly introduced into the scaffold as modified materials to enhance the conductivity of the overall scaffold,while its large surface area and rich functional groups can promote the loading and release of bioactive substances.(3)However,there are still some major challenges to overcome for bioelectrically effective bone tissue engineering scaffolds:not only electrical conductivity but also the overall performance of the bracket needs to be considered;lack of uniform,standardized preparation of bioelectrically effective bone tissue engineering scaffolds;extracorporeal electrical stimulation intervention systems are not yet mature enough;lack of individualized guidance on stent selection to enable the selection and design of the most appropriate stent for patients with different pathologies.(4)When designing conductive scaffolds,researchers have to deeply consider the comprehensive effects of the scaffolds,such as biocompatibility,mechanical properties,and biodegradability.This combination of properties can be achieved by combining multiple materials.(5)Beyond that,clinical translation should be the ultimate consideration for conductive stent design.On the basis of evaluating the safe current threshold for electrical stimulation to act on the human body and facilitate the repair of bone defects,animal experiments as well as basic experiments are designed and then applied to the clinic to achieve the ultimate goal of applying bioelectrical effect bone tissue engineering scaffolds in the clinic.
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BACKGROUND:Minipigs are often used in research fields such as skin injury,vascular trauma and cosmetic medicine because they are highly similar to human beings in terms of skin tissue structure and cardiovascular system.Hydrogel as a wound repair drug possesses a variety of excellent physicochemical properties such as strong water retention and adhesion,which can provide isolation moisturization and drug release for wounds. OBJECTIVE:To summarize and conclude the progress of the application of trauma models for different experimental purposes of hydrogel therapy for minipigs,to reveal the development status of various types of minipig trauma models,to analyze the deficiencies of minipig trauma models at the present stage. METHODS:The relevant articles published in Web of Science database and CNKI database from the establishment of each database to 2023 were checked,using"piglet,miniature pig,minipig,miniature pig;gel,hydrogel;trauma,injury,wound,lesion,incision"as Chinese search terms and"Miniature Swine,Miniature pig,minipig;gel,hydrogel;injury,wound,lesion,incision"as English search terms.A total of 438 Chinese and English documents were retrieved,and 59 documents were included in the study through the inclusion and exclusion criteria. RESULTS AND CONCLUSION:(1)At present,the main models used clinically for trauma repair are large animal species(dogs and pigs),rabbits,and rodents(rats and mice).Because the skin structure of the minipig is more like that of humans,the minipig is the most ideal animal model for trauma repair.(2)In the in-vitro skin injury model,skin defect model is the basic wound model,which can be divided into full skin defect model and medium-thickness skin defect model according to the depth of the wound defect.Burn wound model and infected wound model are multidimensional models with hot metal scald and bacterial culture imposed on the basis of the skin defect model,which have the advantages of high safety coefficient and low operation difficulty.(3)In the in-vivo trauma repair model,mini-pigs are used as esophageal cricothyrotomy model which is more in line with the pathological state of clinical diseases.Mini-pigs are used in the gastric perforation and vascular hemostasis model,which can visually demonstrate the stronger organ adhesion,hemostatic properties and tissue regeneration-promoting effects of the hydrogel.(4)The specific parts of the pig also has the corresponding mode of use:pig ear is usually used to evaluate the hydrogel drug delayed-release effect.Porcine cellular proteins and pig skin collagen are mostly used to prepare composite hydrogels of tissue origin.
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BACKGROUND:Quercetin plays an important role in the proliferation and differentiation of bone marrow mesenchymal stem cells,but less research has been done on its mechanism of promoting the migration of bone marrow mesenchymal stem cells. OBJECTIVE:To study the effect of quercetin on the migration of human bone marrow mesenchymal stem cells through in vitro experiments,and to explore the regulatory role of CCR1 and CXCR4. METHODS:Human bone marrow mesenchymal stem cells were selected as experimental subjects.CCK8 assay was used to detect the effect of quercetin on the proliferative activity of human bone marrow mesenchymal stem cells.Cell scratch assay and Transwell assay were used to detect the in vitro invasive and migratory abilities of human bone marrow mesenchymal stem cells after quercetin treatment,respectively.The role of quercetin in relation to CCR1 and CXCR4 was demonstrated with the help of molecular docking technology.Western blot assay and real-time fluorescence quantitative PCR were used to detect the migration-related chemokine expression after quercetin treatment. RESULTS AND CONCLUSION:(1)5 and 10 μmol/L quercetin could significantly promote the proliferation of human bone marrow mesenchymal stem cells,and the drug concentration of 10 μmol/L resulted in the highest cell proliferation efficiency.(2)To better explore the dose-effect relationship of quercetin affecting the migration of human bone marrow mesenchymal stem cells,5 and 10 μmol/L quercetin were selected for the subsequent experiments,and ligustrazine was used as the positive control drug,and the experiments were divided into blank control group,5 μmol/L quercetin group,10 μmol/L quercetin group,and 100 μmol/L ligustrazine group.(3)In vitro migration and invasion ability of human bone marrow mesenchymal stem cells were elevated in a concentration-dependent manner after quercetin treatment,and the migration effect of 10 μmol/L quercetin group was better than that of ligustrazine group.(4)The molecular docking results suggested that there was a strong interaction between quercetin and CCR1 and CXCR4.(5)Quercetin could up-regulate the expression of CCR1 and CXCR4 proteins and mRNA.(6)This study confirmed at the cellular level that quercetin could promote the migration of human bone marrow mesenchymal stem cells by targeting CCR1 and CXCR4.
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Objective To systematically evaluate the influencing factors for pulmonary infection after cardiac sur-gery.Methods Literatures were retrieved from PubMed,Embase,Web of Science,the Cochrane Library,CBM,Wanfang,CNKI and VIP databases.The retrieval time was from the establishment of databases to November 22,2022.Meta-analysis was performed with RevMan 5.4 and Stata 15.0 softwares.Results A total of 20 literatures were included in the analysis.Meta-analysis showed that age(≥65 years),mechanical ventilation time(≥5 days),smoking,acute renal damage,perioperative blood transfusion,operation time(≥240 minutes),secondary thora-cotomy,and oxygenation index(PaO2/FiO2≤300 mmHg)were risk factors for postoperative pulmonary infection.Conclusion The existing evidence shows that all of the above 8 factors are risk factors for pulmonary infection after cardiac surgery,which can provide a theoretical basis for health care workers to prevent and treat infection.
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Ovarian cancer has become the most lethal gynecological tumor due to the difficulty in early diagnosis,the late stage when diagnosed and the high recurrence rate.Resistance to platinum-based anti-tumor chemotherapy drugs is an important reason for the poor prognosis of ovarian cancer.circular RNA(circRNA)is more stable than mRNA in cells due to its special structure,and it is involved in the regulation of the occurrence,development and chemotherapy resistance of a variety of tumors.circRNA can be used as a competing endogenous RNA(ceRNA)of miRNA to bind to proteins,and regulates the phenotypic polarization of macrophages,it can also be used as an exosomal circRNA to regulate the sensitivity of platinum resistance in ovarian cancer.circRNA is expected to be a new marker of platinum resistance and a new target for the treatment of platinum resistance.In order to further explore the relationship between circRNA and platinum resistance in ovarian cancer,this article summarizes the recent literature related to circRNA and platinum resistance in ovarian cancer.
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With the increasing proportion of laboratory projects in the revenue of public hospitals,how to adjust the prices of labo-ratory projects and improve the income structure of public hospitals has become one of the important contents of China's medical re-form.It is based on a systematic introduction and summary of the pricing methods for inspection projects in British Columbia,Canada,the US,and WHO.Combining with China's national conditions,it proposes three policy recommendations:establishing a cost cal-culation system and cost calculation tools for inspection projects,adopting differentiated pricing strategies based on social medical secu-rity levels,and regularly reviewing and updating the prices of inspection projects.
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It summarizes the practical experience of medical insurance payment methods for medical services provided by Canadian medical staff,covering payment methods for medical services and alternative payment methods.Taking into account the current situation and conditions of the medical insurance payment method for medical services provided by medical personnel in China,it proposes policy recommendations for exploring diversified payment models,introducing direct settlement of health insurance,optimizing payment methods,considering regional differences,and ensuring the long-term sustainability of healthcare personnel health insurance payment methods.
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Objective:To evaluate the clinical efficacy of a single-session implantation of spinal cord electrical stimulation with neurophysiological monitoring a spinal cord electrical stimulator under general anesthesia with neurophysiological monitoring for the treatment of high-risk diabetic foot.Methods:The clinical data of seven patients with high-risk diabetic foot who underwent spinal cord electrical stimulation in neurosurgery ward nine of Tianjin Huanhu Hospital from May 2022 to May 2023 were collected. The operation was performed under general anesthesia with the "C" arm X ray machine guidance and neurophysiological monitoring. The arterial diameter and peak flow rate of lower extremity, lower extremity skin temperature (calf skin temperature, foot skin temperature), visual analog scale (VAS), continuous distance of movement, blood glucose level and toe wound were compared between patients before and after surgery.Results:A total of seven patients with high-risk diabetic foot were included. The diameters and peak flow rates of femoral artery, popliteal artery, anterior tibial artery, posterior tibial artery and dorsal foot artery in both lower limbs were significantly improved after surgery. All patients had different degrees of lower limb pain before operation. After operation, VAS score decreased significantly (1.1±0.9 vs. 6.8±3.4), the pain was significantly relieved, and the calf skin temperature and foot skin temperature were significantly higher than those before surgery [calf skin temperature (℃): 33.3±0.9 vs. 30.9±0.7, foot skin temperature (℃): 31.4±0.8 vs. 29.1±0.6], fasting blood glucose and postprandial blood glucose were significantly lower than those before surgery [fasting blood glucose (mmol/L): 7.6±1.4 vs. 10.5±1.2, postprandial blood glucose (mmol/L): 9.3±2.3 vs. 13.5±1.1], the differences were statistically significant (all P < 0.01). The lower limb movement of all seven patients was significantly improved after surgery, including one patient who needed wheelchair travel before surgery, and one patient who had intermittent claudication before surgery. Among them, one patient needed wheelchair travel and one patient had intermittent claudication before surgery. All patients could walk normally at 2 weeks after operation. Among the seven patients, two patients had the diabetic foot wound ulceration before surgery, which could not heal for a long time. One month after surgery, blood flow around the foot wound recovered and the healing was accelerated. The wound was dry and crusted around the wound, and the wound healed well. Conclusion:For diabetic high-risk foot patients who are intolerant to diabetic peripheral neuralgia and local anesthesia spinal cord electrical stimulation test, one-time implantation of spinal cord electrical stimulator under general anesthesia under neurophysiological monitoring can effectively alleviate peripheral neuralgia and other diabetic foot related symptoms, improve lower limb blood supply, and reduce the risk of toe amputation. Clinical practice has proved the effectiveness of this technique, especially for the early treatment of diabetic high-risk foot patients.
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High-precision radiotherapy represented by stereotactic body radiation therapy(SBRT)plays an important role in every stage of lung cancer treatment.The development of medical imaging technology,more accurate dose calculation methods,and the application of advanced imaging and dose verification algorithms provide guarantee for the realization of high-precision radiotherapy.Four-dimensional computed tomography(4D CT)can better display the individualized motion of tumors affected by respiration.Four-dimensional cone beam computed tomography(4D-CBCT)is an image-guided technology to delineate and obtain the internal target volume(ITV),which Can provide guarantee for precise treatment.The combination of the two technologies can correct the displacement error,monitor the range of tumor motion,and ensure that the moving target is within the irradiation range,which is the guarantee of stereotactic radiotherapy.From the perspective of image-guided radiation technology in the application of precise radiotherapy for lung cancer,the clinical application value of 4D CT combined with 4D-CBCT in SBRT of tumors was reviewed,aiming to provide reference for clinical radiotherapy of lung cancer.
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Objective This study aims to sort out the rare disease drugs in the China′s Second List of Rare Diseases, to provide reference for the management of rare disease drug treatment. Methods Up to December 31, 2023, based on the China′s Second List of Rare Diseases, we sorted out the drugs approved in China with the drug label, or approved by the U.S. Food and Drug Administration(FDA) and the European Medicines Agency (EMA) for the treatment of the above diseases, and developed the second batch of rare disease drug catalog in China. The accessibility, localization and coverage of the national medical insurance were also analyzed. Results From the point of view of diseases, a total of 37 diseases in the China′s Second List of Rare Diseases have drug indications approved in China, and 10 diseases have drugs listed by the U.S. FDA/EMA and approved in China, but for off-label use. From the point of view of drugs, there are 55 drug indications approved for the treatment of the China′s Second List of Rare Diseases, and 22 drugs listed in the U.S. FDA/EMA and approved in the China, but for off-label use. Among the above-mentioned drugs with domestic approved rare disease indications or approved numbers, 39 drugs have at least one domestic approval number for a dosage form, covering 30 rare diseases; 37 drugs used for at least one rare disease are included in the national medical insurance catalog and are covered by reimbursement, covering 29 rare diseases. Conclusions The list of rare disease drugs in the China′s Second List of Rare Diseases was established. The number of rare disease drugs and covered diseases approved by China and the U.S. FDA/EMA has increased, and the number of rare disease drugs and covered diseases that are localized and included in the medical insurance catalog has also continued to increase.
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Objective To summarize and analyze what the listing in market of orphan drugs in China, the United States, the European Union, and Japan in 2023, and to provide empirical reference to Chinese pharmaceutical enterprises, pharmaceutical management, and new drug research and development departments. Methods Collect the 2023 drug market data released by official drug regulatory agencies in four countries and international organization-China, the United States, the European Union, and Japan categorize the market of rare disease drugs and and their indications, approval dates, R&D status in China, component therapeutic areas, and special review and approval pathways were analyzed. Results Findings in 2023, 28 orphan drugs were listed in the United States, mostly anti-tumor related, accounting for 32.1% (9 out of 28); 17 orphan drugs were listed in the European Union, anti-tumor related accounting for 47.0% (8 of 17); 22 listed in Japan; and 45 listed in China. In 2023, over 70% orphan drugs listed in the European Union and Japan entered the phase of clinical trials/marketing and applications/approved clinical applications in China (86.4% from Japan and 70.6% from European Union). Conclusions Currently, there is no qualification accreditation mechanism for orphan drugs in China. However, in 2023, the number of rare disease drugs listed in China was the greatest among the four countries/international organization. It reflects that China′s Catalog for Rare Diseases played a guiding role in drug research and development. Meanwhile, the reform of drug approval and review in China and the issue of rare disease catalogs took place in a short period of time, so the review and approval, as well as research and development of rare disease drugs are still in the catching up stage.
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Objective To analyze the effectiveness and safety of bisphosphonates in the treatment of patients with calcification defense. Methods PubMed, Embase databases, CNKI and Wanfang were searched to collect the case reports and clinical studies of bisphosphonates for calcification defense. Then, the relevant information of patients was extracted for statistical analysis. Results A total of 18 case reports were selected involving 20 patients. Thirteen patients (65.0%) were treated with pamidronate, four (20.0%) were treated with etidronate, two (10.0%) were treated with alendronate, and one (5.0%) was treated with zoledronic acid. Thirteen patients (65.0%) recovered completely, the recovery time of whom ranged from half month to nine months. The tolerance of bisphosphonates in most patients(90.0%)was good, while one patient who did not tolerate pamidronate recovered after the frequency of administration was adjusted and one patient with high dosage of etidronate returned to normal after the discontinuation of the usage. Conclusions Bisphosphonates, an inhibitor of bone resorption, is effective and safe in the treatment of patients with calcification defense.
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We studied the patients diagnosed with X-linked hypophosphatemicrickets(XLH) and treated with burosumab in Peking Union Medical College Hospital from January 2021 to December 2022. In addition, we described the clinical characteristics of the patients, the changes of clinical indexes before and after burosumab treatment, and the adverse drug reactions during treatment. We also evaluated the efficacy and safety of burosumab for XLH. The results showed that three children XLH patients and one adult XLH patients received burosumab treatment. After treatment, the serum phosphorus level of all patients increased; the serum phosphorus of 3 children patients increased above the lower limit of the reference value range; the serum alkaline phosphatase(ALP) of all patients was lower than that of before treatment; the serum ALP of one adult patient was close to the normal range after 2.5 years of treatment. One child patient showed small crystals in kidney through ultrasound 48 weeks after treatment; one child and one adult showed increased serum parathyroid hormone(PTH)level before treatment and serum PTH continued increasing after treatment. Finally, it may be concluded that burosumab increased serum phosphorus levels in XLH patients, kept the level relatively stable, and reduced serum ALP levels. No serious adverse reactions occurred during treatment, in order to provide reference for the use of burosumab in patients with XLH.
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@#Objective To explore the prevention and treatment of vasovagal reflex during and after operation in diseases of urinary system.Methods From February 2020 to April 2023,1436 patients who completed inpatient surgery in Department of Urology,Songshan Hospital,Qingdao University Medical College were selected to analyze the emergency management measures of vasovagal reflex during and after operation and summarize the diagnosis and treatment experience.Results Among 1436 patients,vasovagal reflex occurred in 4 cases during operation and 14 cases after operation,with an incidence of 1.25%.Most patients showed simultaneous decrease in blood pressure and heart rate.After intravenous injection of atropine and dopamine,blood pressure and heart rate returned to normal,and various concomitant symptoms disappeared,and no death cases were reported.Conclusion Urological specialists should pay attention to vasovagal reflex,sum up experience,do early identification,timely treatment to ensure the safety of patients.
ABSTRACT
Methamphetamine (METH) is a powerful stimulant drug that can cause addiction and serious health problems. It is one of the most widely abused drugs in the world. However, the mechanisms of how METH affects the brain and leads to addiction are still unclear, and there are no effective treatments for METH addiction in clinical practice. Therefore, it is important to explore the new addiction mechanisms and treatment strategies of METH. METH addiction is a complex and chronic brain disorder that involves multiple brain regions and neurotransmitter systems. Neurotransmitters are chemical messengers that transmit signals between neurons (nerve cells) in the brain. Some of the main neurotransmitters involved in METH addiction are dopamine (DA), glutamate (Glu), norepinephrine (NE), and serotonin (SNRIS). These neurotransmitters regulate various aspects of brain function, such as reward, reinforcement, motivation, cognition, emotion, and behavior. When a person takes METH, it causes a surge of these neurotransmitters in the brain, especially in the prefrontal cortex (mPFC), ventral tegmental area (VTA), and nucleus accumbens (NAc). These brain regions form a circuit called the mesocorticolimbic system, which is responsible for mediating the rewarding and reinforcing effects of drugs and natural stimuli. The increased levels of neurotransmitters in this circuit make the person feel euphoric, alert, confident, and energetic. However, repeated or chronic use of METH can also cause negative effects, such as anxiety, paranoia, psychosis, depression, and cognitive impairment. The effects of METH on the brain are not only due to the changes in neurotransmitter levels, but also to the changes in gene expression. Gene expression is the process by which genes are turned on or off to produce proteins that perform various functions in the cells. Gene expression can be influenced by environmental factors, such as drugs, stress, diet, etc. One way that environmental factors can affect gene expression is through epigenetic mechanisms. Epigenetics is a branch of genetics that studies the heritable changes in gene expression that are not caused by changes in DNA sequence. Epigenetic mechanisms include histone modifications, DNA methylation, and non-coding RNA regulation. These mechanisms can modulate the chromatin structure and accessibility, thereby affecting the transcriptional activity of genes. Chromatin is a complex of DNA and proteins that forms the chromosomes in the nucleus of the cell. The chromatin structure can be altered by adding or removing chemical groups to histones (proteins that wrap around DNA) or DNA itself. These chemical groups can either activate or repress gene expression by changing the affinity of transcription factors (proteins that bind to DNA and initiate transcription) or other regulatory molecules. Non-coding RNAs are RNA molecules that do not code for proteins but can regulate gene expression by interacting with DNA, RNA, or proteins. Epigenetic mechanisms provide a link between environmental stimuli and gene expression, and play an important role in various physiological and pathological processes, including drug addiction. Recent studies have shown that epigenetic mechanisms are involved in the regulation of neurotransmitter systems and neural plasticity in response to METH exposure. Neural plasticity is the ability of neurons to change their structure and function in response to experience or injury. Neural plasticity is essential for learning, memory, adaptation, and recovery. The expression of some genes related to METH addiction is altered by epigenetic modifications, such as histone acetylation, methylation, ubiquitination, and non-coding RNA regulation. These epigenetic changes may affect the synaptic function and morphology, neuronal connectivity, and circuitry formation in the brain regions implicated in METH addiction. Moreover, some epigenetic modifications may persist for a long time after METH withdrawal, suggesting that they may contribute to the development and maintenance of METH addiction. In this article, we review the current literature on the epigenetic mechanisms of METH addiction. We will first introduce METH and its pharmacological effects, and then discuss the epigenetic regulation of neurotransmitter systems and neural plasticity by METH. We will focus on the changes of histone, DNA, and RNA during METH addiction, and the possible causes and consequences of their relationship with METH addiction. We will also provide some perspectives on the potential applications of epigenetic interventions for METH addiction treatment.