Mid-term follow-up of reconstruction with liquid nitrogen-inactivated autologous bone graft in patients with diaphyseal malignant tumours / 中华骨科杂志

Objective:To explore the mid-term efficacy of liquid nitrogen-inactivated autologous tumor segment bone replantation for repairing bone defects after resection of malignant tumors in the long bone shaft.Methods:A retrospective analysis was performed on the clinical data of 16 patients treated with liquid nitrogen-inactivated autologous bone graft at Beijing Jishuitan Hospital from July 2015 to June 2017 to repair defects caused by malignant tumour resection of the diaphysis. There were 10 males and 6 females with a mean age of 23.4±11.6 years (range, 8-44 years), including 8 classic osteosarcoma, 2 high-grade surface osteosarcoma, 4 Ewing's sarcoma, 1 periosteal osteosarcoma, and 1 undifferentiated pleomorphic sarcoma. Tumors were located in the humerus in 2 cases, in the femur in 8 cases and in the tibia in 6 cases. The mean length of tumor was 12.4±4.8 cm (range, 5.5-26 cm). Postoperative imaging examination was performed every 6 months, and the healing status of the transplanted bone-host bone was evaluated based on the imaging assessment method of the International Society of Limb Salvage (ISOLS) imaging assessment after allogeneic bone transplantation, and the complications were assessed using the Henderson classification. The five-year survival rate for patients and grafted bone was calculated using the Kaplan-Meier survival curve.Results:The median follow-up was 64 (60.3, 69.8) months. At the end of follow-up, 13 patients were tumour free and 3 patients died of multiple metastases at 19, 20 and 33 months after surgery. There were 32 osteotomy ends in 16 patients, of which 30 healed, including 11 metaphyseal osteotomy ends, and the healing time was 9 (6, 12) months after replantation of the tumour segment with liquid nitrogen-inactivated autologous bone; 19 osteotomy ends in the diaphysis took 13 (9, 21) months to heal, with a statistically significant difference in healing time between different sites ( Z=-2.25, P=0.025). Sixteen patients had six complications, including two cases of non-union at the diaphyseal site, one case of failure of internal fixation due to non-union, three cases of recurrence, and no soft tissue complications or infections. One patient with failed internal fixation was treated with a vascularized tip iliac bone graft that healed 6 months after surgery. Another patient died of multiple metastases with 1 unhealed diaphysis left. Three cases of recurrence were all located in the extracranial soft tissue of the autologous tumor segment inactivated by liquid nitrogen. Among them, one case underwent reoperation and local radiotherapy, and there was still no tumor survival after 65 months of surgery, and two cases died due to multiple metastases. The five-year survival rate of patients was 81% as calculated using the Kaplan-Meier survival curve, and the graft survival rate was 100%. There was no amputation and the limb salvage rate was 100%. Conclusion:The use of liquid nitrogen-inactivated autologous tumor segment bone replantation for reconstruction of bone defects after resection of malignant tumors in the shaft has advantages of higher healing rate, shorter healing time at the metaphyseal end compared to the osteotomy end, fewer complications, and higher survival rate of the replanted bone.

Role of circTmeff-1 in morphine addiction memory of mice / 中国药理学与毒理学杂志

In addition to the essential pharmacologi-cal effects of opioids,situational cues associated with drug addiction memory are key triggers for drug seeking.CircRNAs,an emerging hotspot regulator in crown genet-ics-play an important role in central nervous system-relat-ed diseases.However,the internal mediating mechanism of circRNA in the field of drug reward and addiction mem-ory remains unknown.Here,we trained mice on a condi-tional place preference(CPP)model and collected nucle-us accumbens(NAc)tissues from day 1(T0)and day 8(T1)for high-throughput RNA sequencing.qRT-PCR revealed that circTmeff-1 was highly expressed in the NAc core but not in the NAc shell,suggesting that it plays a role in addiction memory formation.Meanwhile,the reverse regulation of circTmeff-1 by adeno-associated viruses could both inhibit the formation of addiction mem-ory in the NAc core or shell.Subsequently,the GO and KEGG analyses indicated 21 that circTmeff-1 might regu-late the addiction memory via the MAPK and AMPK path-ways.These findings suggest that circTmeff-1 in NAc plays a crucial role in morphine-dependent memory for-mation.

Research on the Ethical Dilemmas of Nursing Robots Assisted Home-based Elderly Care: Based on Value Sensitive Design Theory / 中国医学伦理学

With aging population becoming increasingly prominent, more intelligent, integrated, and anthropomorphic nursing robots are becoming an important option for future home-based elderly care. However, a series of ethical dilemmas may arise when nursing robots that provide long-term services participate in the social life of the elderly as social entities. For example, the encroachment of low-level interaction between humans and nursing robots on the high-level interaction between humans, as well as the dispute over the definition of responsibility caused by unclear moral subjects. The value sensitive design theory advocates incorporating value into technical design, and based on its conceptual research, empirical research, and iterative approach, it can be found that the fundamental reason for the above-mentioned ethical dilemma lies in the confusion and dislocation of the ternary nursing relationship among human caregivers, the elderly, and nursing robots. Accordingly, this paper proposed to clarify the user status of the elderly and human caregivers, while nursing robots serve as auxiliary tools to meet the nursing needs of the elderly, protect and enhance the well-being of the elderly.

Discussion on the disposal methods and expiration extending strategy of expired drug in China / 中国药房

China produces about 15 000 tons of expired drugs every year. Standardized destruction of expired drugs consumes a large number of secondary costs， causing huge economic losses. Improper handling will also lead to serious environmental pollution， endanger national health and even endanger public safety. This paper analyzes the hazards， sources and disposal methods， and research status of expired drugs， introduces the Shelf-Life Extension Program of United States， and put forward feasible measures for the recovery， integration and reuse of expired drugs. It is suggested to construct a scientific and reasonable recovery and disposal system of expired drugs in combination with the actual situation in China， explore the strategy of extending the expiration of drugs， and greatly reduce the waste of drug resources.

A real-world study of effectiveness and safety of generic and original clopidogrel in the treatment of acute coronary syndrome / 中国药房

OBJECTIVE To evaluate the clinical effectiveness and safety of domestic generic and imported original clopidogrel for antiplatelet therapy in patients with acute coronary syndrome （ACS）. METHODS The clinical data of ACS patients in Nanjing Drum Tower Hospital of China Pharmaceutical University from January 2020 to June 2021 were retrospectively collected by using electronic medical record system， and the patients were divided into original drug group （321 cases） and generic drug group （328 cases） according to the drug use. Both groups were given dual antiplatelet therapy with clopidogrel and aspirin. The effectiveness and safety outcomes of the two groups were followed up for 12 months and compared， the related influential factors were analyzed. RESULTS Major adverse cardiovascular events （MACE） occurred in 16 and 22 patients in original drug group and generic drug group respectively， including nonfatal myocardial infarction （4 and 5 cases）， stroke （2 and 4 cases）， revascularization （8 and 3 cases）， cardiovascular related death （2 and 4 cases）， and all-cause death （4 and 6 cases）. There were 12 and 7 patients with major bleeding events， 38 and 29 patients with minor bleeding events， and 33 and 21 patients with non-bleeding adverse events. There was no statistically significant difference in the cumulative incidence of related events （P values of Log-Rank tests were all greater than 0.05）. Cox regression analysis showed that the use of generic clopidogrel did not increase the risk of MACE and major bleeding events in ACS patients [hazard ratio of 1.305 and 0.416， 95% confidence interval of （0.678， 2.512） and （0.155， 1.117）， respectively， P＞0.05]， and the combination of proton pump inhibitors （PPI） could reduce the risk of major bleeding events [hazard ratio of 0.196， 95% confidence interval of （0.063， 0.611）， P＜0.05]. CONCLUSIONS Compared with imported original drug， domestic generic clopidogrel has similar clinical effectiveness and good safety. Combined use of PPI may be a beneficial factor to reduce the occurrence of major bleeding events in patients.

Treatment of stage Ⅱ-Ⅲ Kümmell disease with robot-assisted bone cement-augmented pedicle screw fixation / 中国骨伤

OBJECTIVE@#To evaluate the early clinical efficacy of robot-assisted percutaneous short-segment bone cement-augmented pedicle screw fixation in the treatment of stageⅡ-Ⅲ Kümmell disease.@*METHODS@#The clinical data of 20 patients with stageⅡ-Ⅲ Kümmell's disease who underwent robot-assisted percutaneous bone cement-augmented pedicle screw fixation between June 2017 and January 2021 were retrospectively analyzed. There were 4 males and 16 females, aged from 60 to 81 years old with an average age of (69.1±8.3) years. There were 9 cases of stageⅡand 11 cases of stage Ⅲ, all of which were single vertebral lesions, including 3 cases of T11, 5 cases of T12, 8 cases of L1, 3 cases of L2, and 1 case of L3. These patients did not exhibit symptoms of spinal cord injury. The operation time, intraoperative blood loss, and complications were recorded. The position of pedicle screws and the filling and leakage of bone cement in gaps were observed using postoperative CT 2D reconstruction. The data of the visual analogue scale (VAS), Oswestry disability index (ODI), kyphosis Cobb angle, wedge angle of the diseased vertebra, and anterior and posterior vertebral height on lateral radiographs were statistically analyzed preoperatively, 1 week postoperatively, and at the final follow-up.@*RESULTS@#Twenty patients were followed up for 10 to 26 months, with an average follow-up of (16.0±5.1) months. All operations were successfully completed. The surgical duration ranged from 98 to 160 minutes, with an average of (122±24) minutes. The intraoperative blood loss ranged from 25 to 95 ml, with an average of (45±20) ml. There were no intraoperative vascular nerve injuries. A total of 120 screws were inserted in this group, including 111 screws at grade A and 9 screws at grade B according to the Gertzbein and Robbins scales. Postoperative CT indicated that the bone cement was well-filled in the diseased vertebra, and cement leakage occurred in 4 cases. Preoperative VAS and ODI were (6.05±0.18) points and (71.10±5.37)%, respectively, (2.05±0.14) points and (18.57±2.77)% at 1 week after operation, and (1.35±0.11) points and (15.71±2.12) % at final follow-up. There were significant differences between postoperative 1 week and preoperative, and between final follow-up and postoperative 1 week(P<0.01). Anterior and posterior vertebral height, kyphosis Cobb angle, and wedge angle of the diseased vertebra were(45.07±1.06)%, (82.02±2.11)%, (19.49±0.77) °, and (17.56±0.94) ° preoperatively, respectively, (77.00±0.99)%, (83.04±2.02)%, (7.34±0.56) °, and (6.15±0.52) ° at 1 week postoperatively, and (75.13±0.86)%, (82.39±0.45)%, (8.38±0.63) °, and (7.09±0.59) ° at the final follow-up.@*CONCLUSION@#Robot-assisted percutaneous short-segment bone cement-augmented pedicle screw fixation demonstrates satisfactory short-term efficacy in treating stageⅡ-Ⅲ Kümmell's disease as an effective minimally invasive alternative. However, longer operation times and strict patient selection criteria are necessary, and long-term follow-up is required to determine its lasting effectiveness.

Intervention effect of Qufeng Gutong Cataplasm on myofascial pain syndrome in rats and its mechanism / 中国中药杂志

This paper aims to investigate the intervention effect of Qufeng Gutong Cataplasm(QFGT) on myofascial pain syndrome(MPS) in rats and to preliminarily explain its mechanism from the perspective of improving muscle inflammation and pain. Male SD rats were divided into 6 groups, namely normal group, model group, positive control drug(Huoxue Zhitong Ointment, HXZT) group, and low, medium, and high-dose QFGT groups(75, 150, and 300 mg·d~(-1)). The rat model of MPS was established by striking combined with centrifugation for 8 weeks, during which QFGT and HXZT were used for corresponding intervention. Standard VonFrey fiber was used to evaluate the mechanical pain threshold, and acetone was used to detect the cold pain threshold. The electrophysiological activity of muscle at trigger point was detected, and the electromuscular analysis of trigger point was performed. CatWalk gait analyzer was used to detect pain-induced gait adaptation changes. The hematoxylin-eosin(HE) staining was used to observe the pathological changes in muscle and skin tissues at the trigger point of rats. Immunohistochemistry was used to detect the expression of capsaicin receptor transient receptor potential vanilloid 1(TRPV1) in muscle tissues and interleukin(IL)-33 in skin tissues at the trigger point. The protein expression levels of TRPV1, protein kinase B(Akt), phosphorylated protein kinase B(p-Akt), IL-1β, and tumor necrosis factor-α(TNF-α) in muscle tissues at the trigger point were detected by Western blot. The results showed that as compared with the model group, the mechanical pain threshold and cold pain threshold of rats in other groups were increased after treatment with QFGT. The spontaneous electromyography(EMG) activity was observed in the model group, but QFGT alleviated the EMG activity in a dose-dependent manner. Gait analysis showed that standing duration, average intensity, swing speed, maximum contact point, maximum contact area, paw print length, paw print width, and paw print area were significantly improved in all QFGT groups. Pathological results showed that the disorder of muscle arrangement at the trigger point was decreased, muscle fiber adhesion and atrophy were reduced, and inflammatory cell infiltration was alleviated after treatment with QFGT. In addition, QFGT and HXZT both inhibited the protein expression of TRPV1, PI3K, Akt, p-Akt, IL-1β, and TNF-α in the muscle tissues of rats with MPS. However, there was no significant difference in the pathological structure and expression of IL-33 in the treated skin as compared with the normal group. The related results have proved that QFGT can inhibit the release of inflammatory factors by inhibiting the TRPV1/PI3K/Akt signaling pathway in the muscle trigger point of rats with MPS and finally attenuate the atrophy and adhesion of local muscles and inflammatory infiltration, thereby relieving the muscle pain of rats with MPS, and local administration has no skin irritation.

Mechanism of artesunate on bone destruction in experimental rheumatoid arthritis based on transcriptomics and network pharmacology / 中国中药杂志

The present study investigated the mechanism of artesunate in the treatment of bone destruction in experimental rheumatoid arthritis(RA) based on transcriptomics and network pharmacology. The transcriptome sequencing data of artesunate in the inhibition of osteoclast differentiation were analyzed to obtain differentially expressed genes(DEGs). GraphPad Prism 8 software was used to plot volcano maps and heat maps were plotted through the website of bioinformatics. GeneCards and OMIM were used to collect information on key targets of bone destruction in RA. The DEGs of artesunate in inhibiting osteoclast differentiation and key target genes of bone destruction in RA were intersected by the Venny 2.1.0 platform, and the intersection target genes were analyzed by Gene Ontology(GO)/Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment. Finally, the receptor activator of nuclear factor-κB(RANKL)-induced osteoclast differentiation model and collagen-induced arthritis(CIA) model were established. Quantitative real time polymerase chain reaction(q-PCR), immunofluorescence, and immunohistochemistry were used to verify the pharmacological effect and molecular mechanism of artesunate in the treatment of bone destruction in RA. In this study, the RANKL-induced osteoclast differentiation model in vitro was established and intervened with artesunate, and transcriptome sequencing data were analyzed to obtain 744 DEGs of artesunate in inhibiting osteoclast differentiation. A total of 1 291 major target genes of bone destruction in RA were obtained from GeneCards and OMIM. The target genes of artesunate in inhibiting osteoclast differentiation and the target genes of bone destruction in RA were intersected to obtain 61 target genes of artesunate against bone destruction in RA. The intersected target genes were analyzed by GO/KEGG enrichment. According to the results previously reported, the cytokine-cytokine receptor interaction signaling pathway was selected for experimental verification. Artesunate intervention in the RANKL-induced osteoclast differentiation model showed that artesunate inhibited CC chemokine receptor 3(CCR3), CC chemokine receptor 1(CCR1) and leukemia inhibitory factor(LIF) mRNA expression in osteoclasts in a dose-dependent manner compared with the RANKL-induced group. Meanwhile, the results of immunofluorescence and immunohistochemistry showed that artesunate could dose-dependently reduce the expression of CCR3 in osteoclasts and joint tissues of the CIA rat model in vitro. This study indicated that artesunate regulated the CCR3 in the cytokine-cytokine receptor interaction signaling pathway in the treatment of bone destruction in RA and provided a new target gene for the treatment of bone destruction in RA.

Research progress in targeting autophagy of traditional Chinese medicine and natural compounds to regulate atherosclerosis / 中国中药杂志

Atherosclerosis(AS) is the common pathological basis of many ischemic cardiovascular diseases, and its formation process involves various aspects such as vascular endothelial injury and platelet activation. Vascular endothelial injury is the initiating factor of AS plaque. Monocytes are recruited to differentiate into macrophages at the damaged endothelial cells, which absorb oxidized low-density lipoprotein(ox-LDL) and slowly transform into foam cells. Smooth muscle cells(SMCs) proliferate and migrate continuously. As the only cell producing interstitial collagen fibers in the fibrous cap, SMCs largely determine whether the plaque ruptured or not. The amplifying inflammatory response during the formation of AS recruits platelets to adhere to the damaged area of vascular endothelium and stimulates excessive platelet aggregation. Autophagy activity is associated with vascular lesions and abnormal platelet activation, and excessive autophagy is considered to be a negative factor for plaque stability. Therefore, precise regulation of different types of vascular autophagy and platelet autophagy to treat AS may provide a new therapeutic perspective for the prevention and treatment of atherosclerotic ischemic cardiovascular disease. Currently, treatment strategies for AS still focus on lowering lipid levels with high-intensity statins, which often cause significant side effects. Therefore, the development of safer and more effective drugs and treatment modes is the focus of current research. Traditional Chinese medicine and natural compounds have the potential to treat AS by targeted autophagy, and have been playing an increasingly important role in the prevention and treatment of cardiovascular diseases in China. This paper summarizes the experimental studies on different vascular cell types and platelet autophagy in AS, and sums up the published research results on targeted autophagy of traditional Chinese medicine and natural plant compounds to regulate AS, providing new ideas for further research.

Management of liver transplantation perioperative period in acute-on-chronic liver failure / 中华肝脏病杂志

Acute-on-chronic liver failure (ACLF) is a potentially reversible entity that occurs in patients with chronic liver disease accompanied with or without cirrhosis and is characterized by extrahepatic organ failure and high short-term mortality. Currently, the most effective treatment method for patients with ACLF is liver transplantation; therefore, admission timing and contraindications must be emphasized. The function of vital organs such as the heart, brain, lungs, and kidneys should be actively supported and protected during the liver transplantation perioperative period in patients with ACLF. Focusing on the anesthesia management level during anesthesia selection, intraoperative monitoring, three-stage management, prevention and treatment of post-perfusion syndrome, monitoring and management of coagulation function, volume monitoring and management, and body temperature monitoring management for liver transplantation should strengthen anesthesia management. Additionally, standard postoperative intensive care treatment should be recommended, and grafts and other vital organ functions should be monitored throughout the perioperative period to promote early postoperative recovery in patients with ACLF.

Chinese multidisciplinary expert consensus on the management of adverse drug reactions associated with savolitinib / 中华肿瘤杂志

MET gene is a proto-oncogene, which encodes MET protein with tyrosine kinase activity. After binding to its ligand, hepatocyte growth factor, MET protein can induce MET dimerization and activate downstream signaling pathways, which plays a crucial role in tumor formation and metastasis. Savolitinib, as a specific tyrosine kinase inhibitor (TKI) targeting MET, selectively inhibits the phosphorylation of MET kinase with a significant inhibitory effect on tumors with MET abnormalities. Based on its significant efficacy shown in the registration studies, savolitinib was approved for marketing in China on June 22, 2021 for the treatment of advanced non-small cell lung cancer with MET 14 exon skipping mutations. In addition, many studies have shown that MET TKIs are equally effective in patients with advanced solid tumors with MET gene amplification or MET protein overexpression, and relevant registration clinical studies are ongoing. The most common adverse reactions during treatment with savolitinib include nausea, vomiting, peripheral edema, pyrexia, and hepatotoxicity. Based on two rounds of extensive nationwide investigations to guide clinicians, the consensus is compiled to use savolitinib rationally, prevent and treat various adverse reactions scientifically, and improve the clinical benefits and quality of life of patients. This consensus was prepared under the guidance of multidisciplinary experts, especially including the whole-process participation and valuable suggestions of experts in Traditional Chinese Medicine, thus reflecting the clinical treatment concept of integrated Chinese and western medicines.

Short-term effectiveness of orthopedic robot-assisted resection for osteoid osteoma / 中国修复重建外科杂志

OBJECTIVE@#To investigate short-term effectiveness and clinical application advantages of orthopedic robot-assisted resection for osteoid osteoma compared with traditional open surgery.@*METHODS@#A retrospective analysis was conducted on clinical data of 48 osteoid osteoma patients who met the selection criteria between July 2022 and April 2023. Among them, 23 patients underwent orthopedic robot-assisted resection (robot-assisted surgery group), and 25 patients received traditional open surgery (traditional surgery group). There was no significant difference ( P>0.05) in gender, age, disease duration, lesion location and size, and preoperative visual analogue scale (VAS) score, and musculoskeletal tumor society (MSTS) score between the two groups. The surgical time, intraoperative blood loss, intraoperative lesion localization time, initial localization success rate, infection, and recurrence were recorded and compared. VAS scores before surgery and at 24 hours, 1, 3, 6, and 9 months after surgery and MSTS score before surgery and at 3 months after surgery were assessed.@*RESULTS@#All patients completed the surgery successfully, with no significant difference in surgical time between the two groups ( P>0.05). Compared to the traditional surgery group, the robot-assisted surgery group had less intraoperative blood loss, shorter lesion localization time, and shorter hospitalization time, with significant differences ( P<0.05). The initial localization success rate was higher in the robot-assisted surgery group than in the traditional surgery group, but the difference between the two groups was not significant ( P>0.05). All patients in both groups were followed up, with the follow-up time of 3-12 months in the robot-assisted surgery group (median, 6 months) and 3-14 months in the traditional surgery group (median, 6 months). The postoperative MSTS scores of both groups improved significantly when compared to those before surgery ( P<0.05), but there was no significant difference in the changes in MSTS scores between the two groups ( P>0.05). The postoperative VAS scores of both groups showed a gradually decreasing trend over time ( P<0.05), but there was no significant difference between the two groups after surgery ( P>0.05). During follow-up, except for 1 case of postoperative infection in the traditional surgery group, there was no infections or recurrences in other cases. There was no significant difference in the incidence of postoperative infection between the two groups ( P>0.05).@*CONCLUSION@#Orthopedic robot-assisted osteoid osteoma resection achieves similar short-term effectiveness when compared to traditional open surgery, with shorter lesion localization time.

Self-management of older adults at high risk of stroke / 国际脑血管病杂志

Stroke in the elderly has a high incidence rate and great harm. Strengthening the management of high-risk populations is the key to primary stroke prevention. Disease self-management has a better cost-effectiveness ratio. This article reviews the self-management of the elderly at high risk of stroke from the aspects of current situation, content and influencing factors of self-management.

Application of DRGs in clinical blood management / 中国输血杂志

【Objective】 To explore the application of the indicator system of disease diagnosis related groups (DRGs) on the management of clinical blood use in hospitals. 【Methods】 Statistics information on clinical blood use as well as DRGs indexes including case mixed index (CMI), DRG grouping and corresponding weights among patients discharged during 2017 to 2019 from a hospital were recorded. RBC usage per 100 discharged patients after CMI adjustment and DRGs with a larger number of annual blood use cases were compared to make recommendations on the management of clinical blood use in the hospital. 【Results】 From 2017 to 2019, the number of blood users and patients discharged from our hospital kept growing, while the total blood use, RBC usage per 100 discharged patients after CMI adjustment showed a decreasing trend. There were 6 DRGs with the top five blood users from 2017 to 2019, and the top five DRGs accounted for 0.79%(5/629)in 2019, involving 1 611 blood use cases, accounted for 37.49%(1 611/4 297)of all cases of blood use in the year. 【Conclusion】 The application of the indicator system of DRGs to evaluate the clinical use of blood in hospitals is conductive to improve the rationality of clinical blood use, and can provide recommendations for the management of clinical blood use.

Antiplatelet therapy of patients with intracranial aneurysms undergoing stent-assisted coil embolization / 国际脑血管病杂志

Stent-assisted coil embolization is a common endovascular treatment for ruptured/unruptured intracranial aneurysms. Stent implantation process can damage vascular endothelium, activate platelet and coagulation cascade, and then increase the risk of thrombosis. In order to reduce the risk of postoperative embolism, antiplatelet therapy is required. Among them, aspirin combined with clopidogrel dual antiplatelet therapy is a commonly used strategy. For patients with low response to clopidogrel, tigrelol or cilostazol can be used as an alternative drug. Although the scheme has been considered to be effective and safe, it is still controversial.

Evaluation of the skill ，adherence and effectiveness of medication in asthma patients from a pharmacist perspective / 中国药房

OBJECTIVE To analyze th e evaluation methods of the skill ，adherence and effectiveness of medication in bronchial asthma （hereinafter referred to as “asthma”）patients from a pharmacist perspective ，and to provide reference for pharmacists to carry out clinical intervention researches and management of asthma patients. METHODS Referring to diagnosis and treatment guidelines ，evidence-based medicine literature and clinical practice experience ，the evaluation methods of asthma patients ’ medication with clinical value were expounded from three aspects including medication skill （inhalation technology ），adherence and effectiveness. RESULTS Inhalation technique rating form was an important evaluation method of medication skills in asthma patients. Medication adherence could be evaluated by Morisky Medication Adherence Scale or the Medication Adherence Report Scale for Asthma. Effectiveness evaluation methods contained direct evaluation indexes （such as clinical manifestations ，situation of acute exacerbation and relieving medication ，examination indexes such as pulmonary function indexes and fractional concentration of exhaled nitric oxide ）and indirect evaluation tools （i.e. various scales ，including Asthma Control Test ，Children-Asthma Control Test，the Test for Respiratory and Asthma Control in Kids ，asthma related quality of life scales ，etc.）CONCLUSIONS The combination of the evaluation methods of medication skill ， adherence and effectiveness contributes to assessing the pharmacotherapy effect of asthma patients. Pharmacists should apply and perfect these evaluation methods in practice ，so as to conduct better pharmaceutical intervention on asthma patients.

Analysis of m / 中国生物化学与分子生物学报

In this study, we performed high-throughput sequencing technology methylated RNA immunoprecipitation sequencing (MeRIP-seq), transcriptome sequencing (RNA-seq) and bioinformatics to analyze the differentially m6A-methylated and differentially expressed profile of circular RNA (circRNA) in middle cerebral artery occlusion/reperfusion (MCAO/R) model, which provided some scientific evidences for revealing the relationship between RNA epigenetic modification and cerebral ischemia reperfusion injury. The neurological deficit scores of mice were evaluated by the Longa score standard. TTC staining was used to detect cerebral infarction volumes, and dot blot was used for the quantification of m

Generation of Kidney Directed Differentiation Platform from Human Pluripotent Stem Cells / 中国生物化学与分子生物学报

Kidney is an essential organ in human body with multiple physiological functions. However, there is 10 % population worldwide with renal disease. It is urgent to generate a model which is more similar with kidney at structural and functional level to study renal disease. The rise of in vitro differentiation technology from pluripotent stem cells gives regeneration medicine and precise medicine new energy. This study mimics kidney development in vitro by inducing human pluripotent stem cells including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) into kidney progenitor cells, and further forming nephrons, which is the structure and function unit in kidney. Human pluripotent stem cells were differentiated into primitive streak through activating WNT pathway while inhibiting TGF-(B signaling. Afterward, the primitive streak spontaneously differentiated into intermediate mesoderm. Then, we induced intermediate mesoderm cells into kidney progenitor cells through FGF pathway. The FACS analysis data indicated kidney progenitor cells were up to 51. 5%-61. 9% in total cell population. Immuno-stai-ning results showed these structures contained podocytes of glomerulus, proximal tubule, and distal tubule. This kidney differentiation protocol is stable, high-efficient, and well repeatable. This research provides a novel platform for early human kidney development study, kidney disease modeling, and drug screening.

Investigation of metabolites of synthetic cannabinoid 4CN-MDMB-BUTINAC in vitro by liquid-chromatography-quadruple/orbitrap mass spectrometry / 药学学报

To investigate the metabolites of a new synthetic cannabinoid 3,3-dimethyl-2-[1-(4-cyanobutyl)indazole-3-formamimino]methyl butyrate (4CN-MDMB-BUTINACA) in vitro, a human liver microsome incubation model was established to analyze the metabolic biotransformation of synthetic cannabinoids using ultra-high performance liquid chromatography coupled to quadrupole-orbitrap high-resolution mass spectrometry. Nontarget metabolomic results showed that the metabolites of 4CN-MDMB-BUTINACA included hydroxylation, ester hydrolysis, ester hydrolysis with hydroxylation reaction, pentane oxidation and ester hydrolysis with pentane oxidation reaction, among which M1-a, M2 and M4 were potential metabolic markers. The research results provide a theoretical basis and technical support for the biomonitoring and metabolic characterisation of the cannabinoid 4CN-MDMB-BUTINACA.

Revision for Aseptic Loosening of Tumor Prosthesis in Lower Limbs / 肿瘤防治研究

Objective To determine the prosthesis survival and limb function after revision of global modular replacement system (GMRS) tumor prosthesis. Methods We retrospectively analyzed the clinical data of 16 patients who developed aseptic loosening of lower extremity tumor prosthesis and subsequently received revision with GMRS from 2009 to 2012. Kaplan-Meier method was used to calculate the 5- and 8-year survival rates of the prosthesis. The MSTS function scale was used to evaluate the functional outcomes. Results The average follow-up time was 90 months (52-118 months). The 5- and 8-year survival rates of GMRS prosthesis were both 94%. After revision, two patients failed, including one case of infection and one case of repeated aseptic loosening. The average interval between the first joint replacement and revision surgery was 81 months (27-187 months). Until the last follow-up, 93.3%(14/15) of the patients did not develop repeated aseptic loosening, 85.7%(12/14) of the patients who underwent GMRS revision had a longer loosening-free survival than those with the primary joint replacement (90.6±19.3 vs. 43.4±29.7 months, P=0.001). The average MSTS functional score was 27.7(24-30). Conclusion The incidence of repeated aseptic loosening for GMRS prosthesis is low and the limb function is good. The reported technique is satisfactory in the middle and long term.