Lingnan Fire-needle on Inhibiting Melanocyte Apoptosis in Vitiligo Model Mice by Regulating Hippo-YAP Signaling Pathway / 中山大学学报(医学科学版)

ObjectiveTo observe the effects of fire-needle of Lingnan on the vitiligo model after hydroquinone-induced oxidative stress based on the Hippo-YAP signaling pathway. MethodsC57BL/6 mice were randomly divided into normal group （Control）， model group （HQ）， HQ+fire-needle group （FA）， and positive control group （Halometasone）， with 8 mice in each group. The vitiligo model was prepared by hydroquinone （HQ）. The skin pathological changes were observed by depigmentation score， HE staining and Masson-Fontana. Elisa was used to detect the levels of tyrosinase （TYR）， malondialdehyde （MDA） and monoamine oxidase （MAO）.Western-blot and PCR were used to detect the expression of Yap1 and Tp73 among the groups. ResultsCompared with the control group， the epidermis and dermis were significantly thicker. The number of melanocyte hair follicles， basal melanocytes， epidermal cells containing melanin granules were significantly decreased， and the depigmentation score was significantly reduced（P＜0.01）. The level of TYR decreased， and the levels of MDA and MAO increased after modeling（P＜0.01）. The expression of Yap1 and Tp73 were significantly reduced （P<0.01）. The dermis became thinner in the halometasone and FA group after treatment of 4 weeks. The number of melanocyte hair follicles， basal melanocytes， epidermal cells containing melanin granules increased （P<0.05）. Compared with that of the HQ group， the level of TYR in the halometasone group and FA group was significantly increased （P<0.01）. The levels of MDA and MAO in the FA group were decreased （P<0.05）. The expressions of Yap1 and Tp73 in the FA group were significantly increased （P<0.01）， and their effects were better than those in the Halometasone group （P<0.05）. ConclusionsFire-needle of Lingnan protects melanocytes from oxidative stress by activating the Hippo-YAP pathway. It enhances the synthesis and function of melanocytes and promotes repigmentation by reducing the content and activity of oxidative stress products.

Stereoscopic reconstruction in adults with intermittent exotropia after surgery / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the status of stereoscopic reconstruction in adults with intermittent exotropia after surgery, and analyze related influencing factors.METHODS: A retrospective study was conducted among 196 adults with intermittent exotropia who were admitted to our hospital from January 2019 to January 2021. All patients underwent strabismus surgery, and their preoperative and postoperative data were collected.RESULTS: Near and distal stereo visual function was not found in all the included 196 patients before surgery. The reconstruction rates of near stereo visual function and distal stereo visual function were 52.6%(103/196)and 50.5%(99/196), respectively. There were significant differences in surgical age, age of onset, course of disease, and postoperative level of horizontal strabismus between patients with near stereoscopic reconstruction(103 cases)and those without reconstruction(93 cases; P<0.001). Multivariate Logistic regression analysis showed that age of onset, course of disease, and postoperative level of horizontal strabismus were factors influencing near stereo visual function reconstruction(P<0.05). The receiver operating characteristic(ROC)curve showed that the area under the curve(AUC)values of age of onset, course of disease and postoperative level of horizontal strabismus to predict near stereo visual function reconstruction were 0.757, 0.737 and 0.727, respectively(P<0.001). There were significant differences in surgical age, age of onset, course of disease, and postoperative level of horizontal strabismus between patients with distal stereoscopic reconstruction(99 cases)and those without reconstruction(97 cases; P<0.001). Multivariate Logistic regression analysis showed that age of onset and course of disease were factors influencing distal stereo visual function reconstruction(P<0.05). ROC curve showed that the AUC values of age of onset and course of disease to predict distal stereo visual function reconstruction were 0.672 and 0.821, respectively(P<0.001).CONCLUSION: Stereoscopic reconstruction in adults with intermittent exotropia after surgery is affected by many factors, such as age of onset and course of disease. The influencing factors of near stereo visual function reconstruction and distal stereo visual function reconstruction are different, which deserves attention.

Bioinformatics analysis of differently expressed genes in osteoblastic sarcoma and screening of key genes / 中华肿瘤杂志

Objective: To screen the different expressed genes between osteosarcoma and normal osteoblasts, and find the key genes for the occurrence and development of osteosarcoma. Methods: The gene expression dataset GSE33382 of normal osteoblasts and osteosarcoma was obtained from Gene Expression Omnibus (GEO) database. The different expressed genes between normal osteoblasts and osteosarcoma were screened by limma package of R language, and the different expressed genes were analyzed by Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. The protein interaction network was constructed by the String database, and the network modules in the interaction network were screened by the molecular complex detection (MCODE) plug-in of Cytoscape software. The different expressed genes contained in the first three main modules screened by MCODE were analyzed by gene ontology (GO) using the BiNGO module of Cytoscape software. The MCC algorithm was used to screen the top 10 key genes in the protein interaction network. The gene expression and survival dataset GSE39055 of osteosarcoma was obtained from GEO database, and the survival analysis was performed by Kaplan-Meier method. The data of 48 patients with osteosarcoma treated in the First Affiliated Hospital of Fujian Medical University from January 2005 to December 2015 were selected for verification. The expression of STC2 protein in osteosarcoma was detected by immunohistochemical method, and the survival analysis was carried out combined with the clinical data of the patients. Results: A total of 874 different expressed genes were identified from GSE33382 dataset, including 402 down-regulated genes and 472 up-regulated genes. KEGG enrichment analysis showed that different expressed genes were mainly related to p53 signal pathway, glutathione metabolism, extracellular matrix receptor interaction, cell adhesion molecules, folate tolerance, and cell senescence. The top 10 key genes in the interaction network were GAS6, IL6, RCN1, MXRA8, STC2, EVA1A, PNPLA2, CYR61, SPARCL1 and FSTL3. STC2 was related to the survival rate of patients with osteosarcoma (P<0.05). The results showed that the expression of STC2 protein was related to tumor size and Enneking stage in 48 cases of osteosarcoma. The median survival time of 25 cases with STC2 high expression was 21.4 months, and that of 23 cases with STC2 low expression was 65.4 months. The survival rate of patients with high expression of STC2 was lower than that of patients with low expression of STC2 (P<0.05). Conclusions: Bioinformatics analysis can effectively screen the different expressed genes between osteosarcoma and normal osteoblasts. STC2 is one of the important predictors for the prognosis of osteosarcoma.

Quality evaluation of Dalbergiae Odoriferae Lignum by HPLC fingerprint and multi-component quantitative analysis / 中国中药杂志

The present study detected the component content in Dalbergiae Odoriferae Lignum by HPLC fingerprint and the multi-component determination method. HPLC analysis was performed on the Agilent ZORBAX SB-C_(18) column(4.6 mm×250 mm, 5 μm). Acetonitrile-0.5% phosphoric acid aqueous solution with gradient elution was employed as the mobile phase. The flow rate was 1.0 mL·min~(-1) and the column temperature was maintained at 30 ℃. The detection wavelength was 210 nm and the sample volume was 10 μL. The similarity of 18 batches of Dalbergiae Odoriferae Lignum was 0.343-0.779, indicating that there were great differences between different batches of Dalbergiae Odoriferae Lignum. Eighteen common peaks were identified, including eight flavonoids such as liquiritigenin and latifolin. The mass fractions of liquiritigenin, luteolin, naringenin, isoliquiritigenin, formononetin, dalbergin, latifolin, and pinocembrin were in the ranges of 0.134 1%-0.495 2%, 0.028 2%-0.167 0%, 0.016 3%-0.591 3%, 0.053 5%-0.188 0%, 0.142 4%-0.640 1%, 0.068 0%-0.590 7%, 0.003 2%-1.980 7%, and 0.009 6%-0.740 2%, respectively. Eighteen batches of Dalbergiae Odoriferae Lignum were divided into three categories by cluster analysis and eight differential components in Dalbergiae Odoriferae Lignum were marked by partial least-squares discriminant analysis(PLS-DA). The cumulative variance contribution rate was 90.5%. The HPLC fingerprint combined with the multi-component determination method for Dalbergiae Odoriferae Lignum is easy in operation and accurate in results, with good repeatability and reliability. The quality of Dalbergiae Odoriferae Lignum can be evaluated and analyzed by the PLS-DA model. This study is expected to provide a reference for the quality control and clinical application of Dalbergiae Odoriferae Lignum.

Comparative study of rat serum pharmacochemistry between Puerariae Lobatae Radix and Puerariae Thomsonii Radix based on UPLC-Q-TOF-MS / 中国中药杂志

UPLC-Q-TOF-MS and serum pharmacochemistry were employed to study the migrating components in rat sera after intragastric administration of the water extracts of Puerariae Lobatae Radix(PLR) and Puerariae Thomsonii Radix(PTR). After the respective intragastric administration of PLR and PTR extracts, blood samples were collected from the orbital vein. The serum samples were treated by protein precipitation method with methanol and acetonitrile at a ratio of 1∶1 and then passed through Agilent ZORBAX RRHD SB-C_(18) column(3 mm×100 mm, 1.8 μm) and Agilent SB-C_(18) pre-column(3 mm×5 mm, 1.8 μm) with 0.1% formic acid aqueous solution(A)-acetonitrile(B) as the mobile phase. The elution was performed at the flow rate of 0.25 mL·min~(-1), the column temperature of 40 ℃, and the injection volume of 2 μL. By comparison of the total ion chromatogram and secondary fragment ion information of PLR and PTR water extracts, PLR-and PTR-containing sera, and blank serum, we found 42 migrating components(including 17 prototype components and 25 metabolites) in the sera of rats treated with PLR and 35 migrating components(including 15 prototype components and 20 metabolites) in the sera of rats treated with PTR. Thirty-three common components were shared by the two treatments, including 13 prototype components and 20 metabolites. The differences of migrating components in the PLR-and PTR-treated rat sera provide a scientific basis for further study of the active components and quality markers of PLR and PTR.

Identification of key genes for neuropathic pain in rats / 中华麻醉学杂志

Objective:To identify the key genes for neuropathic pain in rats.Methods:The genomic data of spinal cord tissues of rats (GSE18803) were downloaded from the Gene Expression Database at the American Center for Biotechnology Information to identify differentially expressed genes associated with neuropathic pain, and key genes were obtained by further analysis of the protein-protein interaction networks.Single-cell localization and expression of the key genes were analyzed by the Tabula Muris database.Results:The protein-protein interaction networks identified 10 hub genes, including Tyrobp, Clec4a3, C1qc, Ptprc, Laptm5, Csf1r, C1qa, C1qb, Fcgr3a, Cd53. Cd53, Laptm5 and Ptprc were mainly expressed in macrophages, B cells, NK cells, monocytes and granulocytes. Clec4a3 and Csf1r were mainly expressed in monocytes, Fcgr3a in monocytes and granulocytes, and Tyrobp in macrophages, monocytes, granulocytes, and pluripotent progenitor cells. Conclusions:Ten target genes associated with neuropathic pain are identified using bioinformatics, and their distribution and expression in immune inflammatory cells are obtained through comprehensive analysis.

Drug therapy and pathological changes of bone microarchitecture in osteoporosis / 中华骨科杂志

Destruction of bone microarchitecture is one of the most important pathological changes of osteoporosis; it will result in the decrease of bone strength and the increase of fracture risk. Imbalance occurring in bone remodeling is the main cause of microarchitecture destruction. Anti-osteoporosis drugs are able to regulate bone remodeling and therefore improve declined bone microarchitecture. So far, there are mainly two types of anti-osteoporosis drugs: antiresorptive agents and anabolic agents. The antiresorptive agents, including bisphosphonates and receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitors, can improve microarchitecture in two ways: (1) preventing further loss of trabecular bone volume, trabecula number and connectivity; and (2) suppressing activation of remodeling, giving the remodeling unit more time to improve bone mineralization. The anabolic agents include teriparatide and abaloparatide, which can stimulate bone remodeling and some extent of bone modeling thus lead to a positive bone metabolism balance. Therefore, anabolic agents can increase the number of trabecula and improve trabecular bone structure. Except for the two types of agents, sclerostin antibodies, a new type of anti-osteoporosis drug, can neutralize sclerostin to bilaterally promote bone formation and inhibit bone resorption, leading to an improvement in microarchitecture in both cortical bone and trabecular bone. Although many studies have proved the efficacy of anti-osteoporosis drugs in the improvement of bone microarchitecture and quality, further research is still needed for specific topics, such as the mechanism of RANKL inhibitor to improve bone modeling and the effect of bisphosphonate on porosity of cortical bone.

Emphasis on prevention and management of refractures after osteoporotic fractures / 中华骨科杂志

With the aging of society, the incidence of osteoporosis is increasing. Osteoporotic fractures are directly related to osteoporosis. In the context of the gradual increase in osteoporosis, the number of osteoporotic fractures is increasing, and the incidence of refractures is also increasing annually. Refracture after an osteoporotic fracture refers to the occurrence of a new fracture after the initial fracture due to the lack of improvement in bone density and quality and the effect of low-energy external force on the bone. The occurrence of refracture has more harm to the patient's treatment plan, fracture healing, rehabilitation training, self-care ability, psychological expectation, compliance and other clinical indicators. Therefore, the prevention and management of refracture after osteoporotic fracture has gradually become a hot topic at home and abroad. At present, in this field of prevention and treatment, both clinicians and community doctors have problems with insufficient awareness and short-sighted clinical management, such as unclear management standards for refracture prevention, unclear division of labor between doctors at all levels and various types of doctors, and inadequate measures to improve patient's compliance. Focusing on the characteristics of osteoporotic fractures, refractures, and refracture prevention and management, the core points of refracture prevention and management are proposed and elaborated, and the corresponding contents, fixed teams, proprietary databases or proprietary books of refracture prevention and management should be clarified, so as to provide reference for further improving the clinical management of refracture prevention and treatment after osteoporotic fractures.

Effects of the ITGA2B Nonsense Mutation (c.2659C > T, p.Q887X) on Platelet Function in a Mouse Model of Glanzmann's Thrombasthenia Generated with CRISPR/Cas9 Technology / 中国实验血液学杂志

OBJECTIVE@#To construct a mouse model of Glanzmann's thrombasthenia (GT) with ITGA2B c.2659 C>T (p.Q887X) nonsense mutation by CRISPR/Cas9 technology, and then further explore the expression and function of glycoprotein αIIbβ3 on the surface of platelet membrane.@*METHODS@#The donor oligonucleotide and gRNA vector were designed and synthesized according to the ITGA2B gene sequence. The gRNA and Cas9 mRNA were injected into fertilized eggs with donor oligonucleotide and then sent back to the oviduct of surrogate mouse. Positive F0 mice were confirmed by PCR genotyping and sequence analysis after birth. The F1 generation of heterozygous GT mice were obtained by PCR and sequencing from F0 bred with WT mice, and then homozygous GT mice and WT mice were obtained by mating with each other. The phenotype of the model was then further verified by detecting tail hemorrhage time, saphenous vein bleeding time, platelet aggregation, expression and function of αIIbβ3 on the surface of platelet.@*RESULTS@#The bleeding time of GT mice was significantly longer than that of WT mice (P<0.01). Induced by collagen, thrombin, and adenosine diphosphate (ADP), platelet aggregation in GT mice was significantly inhibited (P<0.01, P<0.01, P<0.05). Flow cytometry analysis showed that the expression of αIIbβ3 on the platelet surface of GT mice decreased significantly compared with WT mice (P<0.01), and binding amounts of activated platelets to fibrinogen were significantly reduced after thrombin stimulation (P<0.01). The spreading area of platelet on fibrinogen in GT mice was significantly smaller than that in WT mice (P<0.05).@*CONCLUSION@#A GT mouse model with ITGA2B c.2659 C>T (p.Q887X) nonsense mutation has been established successfully by CRISPR/Cas9 technology. The aggregation function of platelet in this model is defective, which is consistent with GT performance.

Quality control mode based on engineering quality view of Chinese medicine pharmacy / 中国中药杂志

Due to the characteristics of confusing varieties of Chinese medicinal materials, different sources, complex chemical composition, non-standard preparation process, and non-standard pharmaceutical equipment, the quality of Chinese medicinal preparations is difficult to be controlled and evaluated effectively under the current quality control mode and method of Chinese medicinal preparation. The present study proposed an engineering quality view of Chinese medicine pharmacy and a strategy to control the quality of Chinese medicinal preparations based on the current situation. The "overall, dialectical, and dynamic" multi-factor engineering quality view, covering original medicinal materials, preparation technologies, pharmaceutical equipment, and Chinese medicinal preparations, ensures the traceable process, measurable procedures, and feedback quality. The quality control mode of Chinese medicinal preparation with controllable sources, standardized preparation technologies, green pharmaceutical equipment, and intelligent manufacturing is built up.

Professor LIN Guo-hua's clinical experience in staging treatment for post-stroke dysphagia / 中国针灸

The paper summarizes professor LIN Guo-hua's clinical experience in staging treatment for post-stroke dysphagia. Professor LIN Guo-hua adheres to "essence and marrow deficiency and primary yang decline" as the pathogenesis and "conducting yin from yang " as the treating principle. By regulating the conception vessel and the governor vessel and focusing on yang meridians, in association with meridian differentiation and the location differentiation, professor LIN provides the staging treatment for post-stroke dysphagia. At the oral phase, yangming is dysfunction, manifested as facial paralysis and flaccid tongue. In treatment, reducing method is predominated at yangming meridian specially. At the pharyngeal phase, shaoyang is invaded by pathogens, manifested as pivoting dysfunction. The treatment focuses on communicating the exterior with the interior and promoting shaoyang meridian. At the esophageal phase, yangming meridian is deficiency and the turbid qi fails to descend, thus the reinforcing method is dominated to promote and tonify yangming. Additionally, the kinesiotherapy of acupuncture is assisted and the Lingnan fire needling therapy is used particularly. All of the summaries above provide the reference for the clinical treatment of post-stroke dysphagia.

Current status of research on the role of fibronectin in the progression of posterior capsular opacification fibrosis / 国际眼科杂志(Guoji Yanke Zazhi)

Posterior cataract opacification(PCO)is the epithelial-mesenchymal transformation(EMT)of residual lens epithelial cells(LECs)after cataract surgery, resulting in opaque scar which is one of the main complications of cataract surgery. A large amount of fibronectin(FN)produced by LECs after cataract surgery binds to a variety of cell surface receptors, matrix components and growth factors to regulate cell behavior. The purpose of this article is to review the literatures on the treatment of PCO targeting fibronectin and provide references for clinical treatment of PCO. In this paper, the research status of fibronectin in PCO in recent years is reviewed.

The imminent risk of osteoporotic fracture in Chinese elderly population / 中华内分泌代谢杂志

With the aging of the population, the incidence of osteoporotic fractures is increasing year by year, which leads to a heavy burden to society and families. Preventing osteoporotic fractures and re-fractures are critical issues and current challenges in our country. At present, most patients with high risk of osteoporotic fractures are identified in hospitals after fractures. Due to lack of proper understanding of osteoporotic fractures and a comprehensive management system, clinicians only focus on to the treatment of the fracture itself, and pay less attention to the prevention of long-term fractures. Epidemiological data show that in patients with high risk of osteoporotic fracture or those having first fractures, the risk of reoccurring fractures within 2 years is significantly increased, and the risk of death also continues to increase. This is defined as imminent fracture risk, and it is one of the pressing areas that we can and should start to take action in clinic. Taking into considecation of national conditions, this article analyzes current gaps in the risk management of osteoporotic fractures and proposes strategies from aspects of high-risk population identification, treatment, and multidisciplinary cooperation.

Three cases of cerebraltendinous xanthomatosis caused by compound heterozygous mutation of CYP27A1 gene / 中华神经科杂志

Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive genetic disease caused by mutation of CYP27A1 gene. This article reported three cases with clinical phenotypes of CTX and CYP27A1 gene mutation and analyzed the pedigree with a literature review. All the three CTX cases had c.379C>T (p.Arg127Trp) missense mutation on exon 2 of CYP27A1 gene. They all had compound heterozygous mutation and two cases had new type of exon and intron compound mutation. This article enriched the types of CYP27A1 gene mutations in CTX patients. The primers of CYP27A1 gene should also cover more gene sequences including intron regions.

Role of NOD2 in dorsal root ganglion in development of neuropathic pain in rats / 中华麻醉学杂志

Objective:To evaluate the role of nucleotide-binding oligomerization domain-2 (NOD2) in dorsal root ganglion in the development of neuropathic pain (NP) in rats.Methods:Thirty-two adult male SPF Sprague-Dawley rats, weighing 240-260 g, aged 2-3 months, were divided into 4 groups ( n=8 each) using a random number table method: control group (group C), NP group (group S), negative control siRAN group (group N), and NOD2-siRNA group (group R). In N and R groups, 1×10 8 IFU/ml negative control siRNA and NOD2-siRNA 10 μl were intrathecally injected, respectively, once a day for 3 consecutive days.Normal saline 10 μl was intrathecally injected once a day for 3 consecutive days in C and S groups.The model of NP was established using spared nerve injury (SNI) at 2 weeks after intrathecal injection.The mechanical paw withdrawal threshold (MWT) was measured at 1 day before surgery and 1, 3, 7, 10, 14 and 28 days after SNI.Animals were sacrificed after measuring pain threshold on day 28, and the dorsal root ganglions (DRGs) of the lumbar segment (L 4-6) were removed for determination of the expression of NOD2 (by Western blot) and expression of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), IL-6 and NOD2 mRNA (using quantitative real-time polymerase chain reaction). Results:Compared with group C, MWT was significantly decreased at each time point after SNI, and the expression of NOD2 protein and mRNA and TNF-α, IL-1β and IL-6 mRNA in DRGs was up-regulated in group NP ( P<0.01). Compared with group NP, MWT was significantly increased at each time point after SNI, and the expression of NOD2 protein and mRNA and TNF-α, IL-1β and IL-6 mRNA in DRGs was down-regulated in group R ( P<0.01), and no significant change was found in the parameters mentioned above in group N ( P>0.05). Conclusion:The mechanism underlying the development of NP may be related to the up-regulation of NOD2 expression in DRGs, thus further promoting the expression of pro-inflammatory factors in rats.

Effect of anticoagulation timing on perioperative deep venous thrombosis in elderly patients with hip fracture / 中华创伤骨科杂志

Objective:To study the influence of anticoagulation timing on incidence of perioperative deep venous thrombosis (DVT) in elderly patients with hip fracture.Methods:A retrospective analysis was made of the 179 elderly patients with hip fracture who had been admitted to Department of Orthopedics and Traumaology, Hong-Hui Hospital from July 2017 to December 2018. They were 78 males and 101 females, aged from 62 to 91 years (mean, 79.5 years). There were 79 femoral neck fractures and 100 intertrochanteric fractures, 109 of which were treated by internal fixation and 70 by hip replacement. The patients were divided into 3 groups depending on the timing of anticoagulation after injury. In group 1 of 74 cases, anticoagulation started <24 h after injury; in group 2 of 36 cases, anticoagulation started 24 to 48 h after injury; in group 3 of 69 cases, anticoagulation started >48 h after injury. Anticoagulation continued until 12 h before surgery in all patients but was resumed 8 to 12 h after surgery. The 3 groups were compared in incidence of perioperative DVT.Results:The 3 groups were comparable due to insignificant differences between them in their pre-operative general data ( P>0.05). DVT occurred perioperatively in 84 patients, yielding an incidence of 46.9% (84/179). The incidences of perioperative DVT were 27.0% (20/74), 47.2% (17/36) and 68.1% (47/69) in groups 1, 2 and 3, respectively, showing significant differences ( χ2=24.206, P<0.001), between any 2 groups ( P<0.05). Conclusion:Since the earlier anticoagulation starts after injury the lower incidence of perioperative DVT in elderly patients with hip fracture, early standardized prophylactic anticoagulation after injury can effectively reduce incidence of perioperative DVT.

Discovery of a subtype-selective, covalent inhibitor against palmitoylation pocket of TEAD3

The TEA domain (TEAD) family proteins (TEAD1‒4) are essential transcription factors that control cell differentiation and organ size in the Hippo pathway. Although the sequences and structures of TEAD family proteins are highly conserved, each TEAD isoform has unique physiological and pathological functions. Therefore, the development and discovery of subtype selective inhibitors for TEAD protein will provide important chemical probes for the TEAD-related function studies in development and diseases. Here, we identified a novel TEAD1/3 covalent inhibitor (DC-TEADin1072) with biochemical IC

Downregulation of hsa_circ_0000936 sensitizes resistant glioma cells to temozolomide by sponging miR-1294

Glioma is one of the most aggressive forms of brain tumor and is hallmarked by high rate of mortality,metastasis and drug resistance. Herein, we explore the role of circular RNA (circRNA) hsa_circ_0000936 inthe resistance of glioma cells to temozolomide (TMZ). In this study, Relative changes in gene expression levelswere compared using qRT-PCR. The role of hsa_circ_0000936 was characterized by cell count kit -8 assay andflow cytometry. Luciferase reporter assay was carried out for target validation.We found that hsa_circ_0000936was upregulated in glioma tissues as compared to their adjacent normal tissues. Increased expression ofhsa_circ_0000936 was found in the glioma tissues of patients showing resistance to TMZ compared with thatof patients showing sensitivity to TMZ. The upregulation of hsa_circ_0000936 was also confirmed in TMZresistant glioma cells. miR-1294 was downregulated in TMZ-resistant glioma cells and identified as a directtarget of hsa_circ_0000936. Downregulation of hsa_circ_0000936 increased the sensitivity of TMZ-resistantglioma cells towards TMZ. Moreover, restoration of miR-1294 could abrogate the promoting effect ofhsa_circ_0000936 on TMZ resistance in TMZ-resistant glioma cells. In conclusion, downregulation ofhsa_circ_0000936 sensitizes TMZ-resistant glioma cells to TMZ by sponging miR-1294, suggesting thathsa_circ_0000936 may be a potential target for overcoming the resistance of glioma cells to TMZ.

Correlation between serum phosphorus levels and outcomes of weaning from mechanical ventilation in elderly chronic obstructive pulmonary disease patients with type Ⅱ respiratory failure / 中华老年医学杂志

Objective:To investigate the correlation between serum phosphorus levels and outcomes of weaning from mechanical ventilation in elderly chronic obstructive pulmonary disease(COPD)patients with type Ⅱ respiratory failure.Methods:A total of 142 hospitalized elderly COPD patients with type Ⅱ respiratory failure receiving mechanical ventilation in our hospital from August 2016 to December 2018 were retrospectively enrolled.Patients were divided into the successful weaning group(n=101)and the unsuccessful weaning group(n=41)based on weaning outcomes.General data, blood phosphorus levels on admission and before spontaneous breathing trials(SBT)and the incidence of hypophosphatemia were compared between the two groups.The logistic regression equation was used to analyze the related factors for the unsuccessful weaning, and the receiver operating characteristics(ROC)curve was drawn to analyze the value of serum phosphorus levels in predicting the failure of weaning.Methods:Compared with the successful weaning group, Acute Physiology and Chronic Health evaluation Ⅱ(APACHEⅡ)scores, rapid shallow breathing index(RSBI), and serum creatinine(Cr), C-reactive protein(CRP)levels were higher, while the oxygenation index(PaO 2/FiO 2), serum albumin(ALB)and magnesium levels were lower in the unsuccessful weaning group than in the successful weaning group( P<0.05). The incidences of hypophosphatemia on admission and before SBT were higher in the unsuccessful weaning group than in the successful weaning group(34.2% or 34/41 vs.17.8% or 18/101, 46.3% or 19/41 vs.25.7% or 26/101, χ2=4.452 and 5.716, P<0.05). Serum phosphorus levels on admission and before SBT were lower in the unsuccessful weaning group than in the successful weaning group[(0.82±0.21) mmol/L vs.(1.05±0.23) mmol/L, (0.71±0.19) mmol/L vs.(1.02±0.22) mmol/L, t=5.171 and 7.646, P<0.05)]. Multivariate logistic regression analysis showed that hypophosphatemia on admission or before SBT was an independent risk factor for unsuccessful weaning in elderly COPD patients with type Ⅱ respiratory failure( P<0.05). The areas under the ROC curve(AUC)of hypophosphatemia on admission and before SBT for predicting the failure of weaning was 0.657 and 0.776, respectively, and with 0.84 mmol/L and 0.76 mmol/L as the respective optimal threshold values, the sensitivity and specificity were 67.3% and 68.3% for AUC on admission and 76.5% and 85.6% for AUC before SBT, respectively.AUC of the serum phosphorus level was higher before SBT than on admission( Z=3.142, P<0.05). Conclusions:The decrease of blood phosphorus levels is common in elderly COPD patients with type Ⅱ respiratory failure, and hypophosphatemia has a high incidence and may be an independent risk factor for the failure of weaning.Blood phosphorus levels should be closely monitored in order to guide clinical weaning.