CircRNA Circ_0120051 Inhibits the Fibrotic Phenotype of Myocardial Fibroblasts via Targeting miR-144-3p/IDH2 Axis / 中山大学学报(医学科学版)

ObjectiveTo investigate the regulatory effect of circular RNA circ_0120051 on the fibrotic phenotype of cardiac fibroblasts and the potential mechanism involved. MethodsThe expression of circ_0120051 and its host gene of solute carrier family 8 member A1（SLC8A1） mRNA in the myocardium of healthy organ donors （n=24） and heart failure （HF） patients （n=21） were assessed by real-time quantitative polymerase chain reaction （RT-qPCR） assay. RNA stability of circ_0120051 was identified by RNase R exonuclease digestion assay. The cytoplasmic and nuclear distribution of circ_0120051 in human cardiomyocyte AC16 was detected by RT-qPCR assay. The expression of fibrosis-related genes in mouse cardiac fibroblasts （mCFs） with adenovirus-mediated overexpression of circ_0120051 was detected by RT-qPCR and Western blot assay， respectively. The effect of overexpression of circ_0120051 on the migration activity of mCFs was evaluated by wound-healing assay. RNA co-immunoprecipitation （RIP） was conducted to detect the interaction between circ_0120051 and miR-144-3p. The binding site of miR-144-3p in the 3'-UTR of isocitrate dehydrogenase 2 （Idh2） mRNA was identified by the dual luciferase reporter gene assay. ResultsCirc_0120051 was significantly up-regulated in the myocardium of HF patients， while the mRNA expression of its host gene SLC8A1 was not changed. Circ_0120051 was mainly located in the cytoplasm of human AC16 cells. Results of RNase R exonuclease digestion revealed that circ_0120051 possesses the characteristic stability of circular RNA compared to the linear SLC8A1 mRNA. Overexpression of circ_0120051 could inhibit the expression of fibrosis-related gene in mCFs and mCFs migration. RIP assay confirmed the specific interaction between circ_0120051 and miR-144-3p. Transfection of miR-144-3p mimic could efficiently promote the expression of fibrosis-related genes in mCFs and reverse the inhibitory effect of circ_0120051 on the fibrotic phenotype of mCFs. Results of the dual luciferase reporter gene assay confirmed the interaction between miR-144-3p and the 3'-UTR of Idh2. Transfection of miR-144-3p transcriptionally inhibited Idh2 expression， and overexpression of circ_0120051 enhanced IDH2 expression in mCFs. MiR-144-3p mimic and Idh2 small interfering RNA （siRNA） could consistently reverse the inhibitory effects of circ_0120051 on fibrosis-related genes expression in mCFs and mCFs migration. ConclusionsCirc_0120051 inhibits the fibrotic phenotype of cardiac fibroblasts via sponging miR-144-3p to enhance the target gene of IDH2 expression.

Mechanism of levosimendan in treating hypoxic pulmonary hypertension based on network pharmacology and molecular docking technology / 中国药理学通报

Aim To explore the efficacy of levosimendan on hypoxia pulmonary hypertension through animal experiments, and to further explore the potential mechanism of action using network pharmacological methods and molecular docking technique. Methods The rat model of hypoxia pulmonary hypertension was constructed to detect right heart systolic pressure and right heart remodeling index. HE , Masson, and VG staining were core targets were screened out. GO and KEGG pathway enrichment analysis were performed using the DAVID database. Molecular docking of the core targets was performed with the AutoDock software. Results The results of animal experiments showed that levosimendan had obvious therapeutic effect on hypoxia pulmonary hypertension. The network pharmacology results showed that SRC, HSP90AA1, MAPK1, PIK3R1, AKT1, HRAS, MAPK14, LCK, EGFR and ESR1 used to analyze the changes of rat lung histopathology. Search the Swiss Target Prediction, DrugBank Online, BatMan, Targetnet, SEA, and PharmMapper databases were used to screen for drug targets. Disease targets were retrieved from the GeneCards, OMIM databases. The "drug-target-disease" network was constructed after identification of the two intersection targets. The protein interaction network was constructed and the were the key targets to play a therapeutic role. Molecular docking showed good docking of levosimendan with all the top five core targets with degree values. Conclusions Levosimendan may exert a therapeutic effect on hypoxia-induced pulmonary hypertension through multiple targets.

Reappraisals of biological behaviors of PDGFRA mutant gastrointestinal stromal tumor / 中华病理学杂志

Objective: To investigate the biological behavior spectrum of platelet-derived growth factor alpha receptor (PDGFRA)-mutant gastrointestinal stromal tumor (GIST), and to compare the clinical values of the Zhongshan method of benign and malignant evaluation with the modified National Institutes of Health (NIH) risk stratification. Methods: A total of 119 cases of GIST with PDGFRA mutation who underwent surgical resection at Zhongshan Hospital, Fudan University from 2009 to 2020 were collected. The clinicopathological data, follow-up records, and subsequent treatment were reviewed and analyzed statistically. Results: There were 79 males and 40 females. The patients ranged in age from 25 to 80 years, with a median age of 60 years. Among them, 115 patients were followed up for 1-154 months, and 13 patients progressed to disease. The 5-year disease-free survival (DFS) and overall survival (OS) were 90.1% and 94.1%, respectively. According to the modified NIH risk stratification, 8 cases, 32 cases, 38 cases, and 35 cases were very-low risk, low risk, intermediate risk, and high risk, and 5-year DFS were 100.0%, 95.6%, 94.3%, and 80.5%, respectively. There was no significant difference in prognosis among the non-high risk groups, only the difference between high risk and non-high risk groups was significant (P=0.029). However, the 5-year OS was 100.0%, 100.0%, 95.0% and 89.0%, and there was no difference (P=0.221). According to the benign and malignant evaluation Zhongshan method, 43 cases were non-malignant (37.4%), 56 cases were low-grade malignant (48.7%), 9 cases were moderately malignant (7.8%), and 7 cases were highly malignant (6.1%). The 5-year DFS were 100.0%, 91.7%, 77.8%, 38.1%, and the difference was significant (P<0.001). The 5-year OS were 100.0%, 97.5%, 77.8%, 66.7%, the difference was significant (P<0.001). Conclusions: GIST with PDGFRA gene mutation shows a broad range of biological behavior, ranging from benign to highly malignant. According to the Zhongshan method, non-malignant and low-grade malignant tumors are common, the prognosis after surgery is good, while the fewer medium-high malignant tumors showed poor prognosis after surgical resection. The overall biological behavior of this type of GIST is relatively inert, which is due to the low proportion of medium-high malignant GIST. The modified NIH risk stratification may not be effective in risk stratification for PDGFRA mutant GIST.

CircSLC8A1_005 Inhibits the Fibrotic Phenotype of Cardiac Fibroblasts by Encoding Protein / 中山大学学报(医学科学版)

ObjectiveTo investigate the effect of circSLC8A1_005 on the fibrotic phenotype of cardiac fibroblasts and the potential mechanism involved. MethodsThe effect of adenovirus-mediated overexpression of circSLC8A1_005 on the expression of fibrosis-related genes， collagen type I alpha 1 chain （Col1a1）， collagen type Ⅲ alpha 1 chain （Col3a1） and smooth muscle actin alpha 2 （Acta2）， in mouse cardiac fibroblasts （mCFs） were detected. The proliferation and migration activities of mCFs were detected by EdU and wound-healing assay， respectively. Dual luciferase reporter gene assay was performed to detect the activity of potential internal ribozyme entry site （IRES） in circSLC8A1_005. CircSLC8A1_005-translated protein， SLC8A1-605aa， and its intracellular distribution was identified by Western blot assay. The effect of SLC8A1-605aa protein on transcription activity of Sod2 gene was detected by the dual luciferase reporter gene assay. RNA binding protein immunoprecipitation （RIP） was utilized to verify the interaction between SLC8A1-605aa and superoxide dismutase 2 （Sod2） mRNA. Actinomycin D treatment was used to detect the effect of SLC8A1-605aa on Sod2 mRNA stability in mCFs. ResultsAn efficient adenovirus-mediated overexpression of circSLC8A1_005 was achieved in mCFs. The enforced expression of circSLC8A1_005 suppressed proliferation and migration of mCFs， and inhibited the expression of fibrosis-related genes in mCFs. The dual luciferase reporter gene assay revealed the activities of 2 IRES in circSLC8A1_005. Results of Western blot assay showed that circSLC8A1_005 could translate protein SLC8A1-605aa with the prospected molecular weight of 70 ku， which is predominantly distributed in the nucleus. Overexpression of the circSLC8A1_005 and SLC8A1-605aa could consistently inhibit the fibrotic phenotype of mCFs. SLC8A1-605aa could up-regulate superoxide dismutase 2 （Sod2） expression， but not at the transcriptional level. RIP assay indicated that SLC8A1-605aa could specifically interact with Sod2 mRNA， and the results of actinomycin D assay showed that SLC8A1-605aa could enhance the stability of Sod2 mRNA in mCFs. ConclusionCircSLC8A1_005 inhibits the fibrotic phenotype of cardiac fibroblasts via translating SLC8A1-605aa protein， and SLC8A1-605aa may be a potential target for the treatment of myocardial fibrosis.

HIV-1 Transmission among Injecting Drug Users is Principally Derived from Local Circulating Strains in Guangxi, China / 生物医学与环境科学（英文）

OBJECTIVE@#The mode of human immunodeficiency virus (HIV) transmission via injection drug use (IDU) still exists, and the recent shift in IDU-related transmission of HIV infection is largely unknown. The purpose of this study was to analyze the spatiotemporal sources and dynamics of HIV-1 transmission through IDU in Guangxi.@*METHODS@#We performed a molecular epidemiological investigation of infections across Guangxi from 2009 to 2019. Phylogenetic and Bayesian time-geographic analyses of HIV-1 sequences were performed to confirm the characteristics of transmission between IDUs in combination with epidemiological data.@*RESULTS@#Among the 535 subjects, CRF08_BC (57.4%), CRF01_AE (28.4%), and CRF07_BC (10.7%) were the top 3 HIV strains; 72.6% of infections were linked to other provinces in the transmission network; 93.6% of sequence-transmitted strains were locally endemic, with the rest coming from other provinces, predominantly Guangdong and Yunnan; 92.1% of the HIV transmission among people who inject drugs tended to be transmitted between HIV-positive IDUs.@*CONCLUSION@#HIV recombinants were high diversity, and circulating local strains were the transmission sources among IDUs in Guangxi. However, there were still cases of IDUs linked to other provinces. Coverage of traditional prevention strategies should be expanded, and inter-provincial collaboration between Guangxi, Yunnan, and Guangdong provinces should be strengthened.

A glass micropipette vacuum technique of cerebrospinal fluid sampling in C57BL/6 mice / 生理学报

The purpose of this study was to establish a suitable method for extracting cerebrospinal fluid (CSF) from C57BL/6 mice. A patch clamp electrode puller was used to draw a glass micropipette, and a brain stereotaxic device was used to fix the mouse's head at an angle of 135° from the body. Under a stereoscopic microscope, the skin and muscle tissue on the back of the mouse's head were separated, and the dura mater at the cerebellomedullary cistern was exposed. The glass micropipette (with an angle of 20° to 30° from the dura mater) was used to puncture at a point 1 mm inboard of Y-shaped dorsal vertebral artery for CSF sampling. After the first extraction, the glass micropipette was connected with a 1 mL sterile syringe to form a negative pressure device for the second extraction. The results showed that the successful rate of CSF extraction was 83.33% (30/36). Average CSF extraction amount was (7.16 ± 0.43) μL per mouse. In addition, C57BL/6 mice were given intranasally ferric ammonium citrate (FAC) to establish a model of brain iron accumulation, and the CSF extraction technique established in the present study was used for sampling. The results showed that iron content in the CSF from the normal saline control group was not detected, while the iron content in the CSF from FAC-treated group was (76.24 ± 38.53) μmol/L, and the difference was significant. These results suggest that glass micropipette vacuum technique of CSF sampling established in the present study has the advantages of simplicity, high success rate, large extraction volume, and low bleeding rate, and is suitable for the research on C57BL/6 mouse neurological disease models.

Acupuncture for glaucoma-induced optic atrophy: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the clinical effect of acupuncture for glaucoma-induced optic atrophy.@*METHODS@#A total of 70 patients (89 affected eyes) with glaucoma-induced optic atrophy were randomized into an observation group and a control group, 35 cases in each group. The control group was given basic western medicine treatment. In the observation group, on the basis of the treatment in the control group, acupuncture was applied at main acupoints i.e. Baihui (GV 20), Shangjingming (Extra), Chengqi (ST 1), Fengchi (GB 20), Zusanli (ST 36), combined with supplementary acupoints based on syndrome differentiation, once every three days, twice a week. The treatment for 3 months was required in both groups. Before treatment, after treatment and in follow-up of 6 months after treatment, the best corrected visual acuity (BCVA), intraocular pressure (IOP), indexes of visual field (visual field index [VFI], mean deviation [MD], pattern standard deviation [PSD]) and mean thickness of retinal nerve fiber layer (RNFL) were observed in the two groups.@*RESULTS@#Compared before treatment, BCVA was decreased after treatment and in follow-up in the control group (P<0.05); in the follow-up, BCVA in the observation group was higher than that in the control group (P<0.05). On each time point before and after treatment, there was no significant difference within or between the two groups (P>0.05). After treatment and in the follow-up, the mean thickness of RNFL was larger than the control group (P<0.05).@*CONCLUSION@#On the basis of the basic western medicine treatment, acupuncture can delay the decline of vision and the thinning of retinal nerve fiber layer in patients with glaucoma-induced optic atrophy.

Erratum: Author correction to 'Protective effects of VMY-2-95 on corticosterone-induced injuries in mice and cellular models' Acta Pharmaceutica Sinica B 11(2021) 1903-1913

[This corrects the article DOI: 10.1016/j.apsb.2021.03.002.].

Application of triangle stability mechanical model in the layer separation of transanal total mesorectal excision / 中华胃肠外科杂志

Transanal total mesorectal resection (taTME) has come a long way since it was first used in the clinic in 2010.The learning curve of this procedure is long due to different surgical approaches, different perspectives and different anatomical positions. Many surgeons experience complications during this procedure. Although the advantages and problems of this procedure have been reported in much literature, the anatomy and operation methods of taTME introduced in literatures and training centers are too complicated, which makes many surgeons encounter difficulties in carrying out taTME surgery. According to the author's experience in learning and carrying out this operation, spatial expansion process of ultralow rectal cancer was divided into three stages. At each stage, according to different pulling forces, three different schemes of triangular stability mechanics model were adopted for separation. From point to line, from line to plane, the model can protect the safety of peripheral blood vessels and nerves while ensuring total mesorectal excision . This model simplifies the complex surgical process and is convenient for beginners to master taTME surgical separation skills.

Clinicopathological features and prognostic factors of gastric intermediate-risk gastrointestinal stromal tumor after surgical resection: a retrospective study / 中华病理学杂志

Objective: To investigate the clinicopathological features, treatment and prognosis of gastric intermediate-risk gastrointestinal stromal tumor (GIST), so as to provide a reference for clinical management and further research. Methods: A retrospective observational study of patients with gastric intermediate-risk GIST, who underwent surgical resection between January 1996 and December 2019 at Zhongshan Hospital of Fudan University, was carried out. Results: Totally, 360 patients with a median age of 59 years were included. There were 190 males and 170 females with median tumor diameter of 5.9 cm. Routine genetic testing was performed in 247 cases (68.6%, 247/360), and 198 cases (80.2%) showed KIT mutation, 26 cases (10.5%) showed PDGFRA mutation, and 23 cases were wild-type GIST. According to "Zhongshan Method"(including 12 parameters), there were 121 malignant and 239 non-malignant cases. Complete follow-up data were available in 241 patients; 55 patients (22.8%) received imatinib therapy, 10 patients (4.1%) experienced tumor progression, and one patient (PDGFRA mutation, 0.4%) died. Disease-free survival (DFS) and overall survival rate at 5 years was 96.0% and 99.6%, respectively. Among the intermediate-risk GIST, there was no difference in DFS between the overall population, KIT mutation, PDGFRA mutation, wild-type, non-malignant and malignant subgroups (all P>0.05). However, the non-malignancy/malignancy analysis showed that there were significant differences in DFS among the overall population (P<0.01), imatinib treatment group (P=0.044) and no imatinib treatment group (P<0.01). Adjuvant imatinib resulted in potential survival benefit for KIT mutated malignant and intermediate-risk GIST in DFS (P=0.241). Conclusions: Gastric intermediate-risk GIST shows a heterogeneous biologic behavior spectrum from benign to highly malignant. It can be further classified into benign and malignant, mainly nonmalignant and low-grade malignant. The overall disease progression rate after surgical resection is low, and real-world data show that there is no significant benefit from imatinib treatment after surgery. However, adjuvant imatinib potentially improves DFS of intermediate-risk patients with tumors harboring KIT mutation in the malignant group. Therefore, a comprehensive analysis of gene mutations in benign/malignant GIST will facilitate improvements in therapeutic decision-making.

Hydnocarpin inhibits malignant progression of triple negative breast cancer via CNOT4-mediated ubiquitination and degradation of YAP / 中国中药杂志

This study aims to investigate the effect and mechanism of hydnocarpin(HC) in treating triple negative breast cancer(TNBC). Cell counting kit-8(CCK-8), xCELLigence real-time cellular analysis(RTCA), and colony formation assay were employed to determine the effects of HC on the proliferation of two TNBC cell lines: MDA-MB-231 and MDA-MB-436. The effects of HC on the migration and invasion of TNBC cells were detected by high-content analysis, wound-healing assay, and Transwell assay. The changes in the epithelial-mesenchymal transition(EMT) and the expression of invasion-and migration-associated proteins [E-cadherin, vimentin, Snail, matrix metalloproteinase-2(MMP-2), and MMP-9] were detected by Western blot. Western blot and RT-qPCR were employed to determine the protein and mRNA levels of Yes-associated protein(YAP) and downstream targets(CTGF and Cyr61). TNBC cells were transfected with Flag-YAP for the overexpression of YAP, and the role of YAP as a key target for HC to inhibit TNBC malignant progression was examined by CCK-8 assay, Transwell assay, and wound-healing assay. The pathway of HC-induced YAP degradation was detected by the co-treatment of proteasome inhibitor with HC and ubiquitination assay. The binding of HC to YAP and the E3 ubiquitin ligase Ccr4-not transcription complex subunit 4(CNOT4) was detected by microscale thermophoresis(MST) assay and drug affinity responsive target stability(DARTS) assay. The results showed that HC significantly inhibited the proliferation, colony formation, invasion, and EMT of TNBC cells. HC down-regulated the protein and mRNA levels of CTGF and Cyr61. HC down-regulated the total protein level of YAP, while it had no effect on the mRNA level of YAP. The overexpression of YAP antagonized the inhibitory effects of HC on the proliferation, migration, and invasion of TNBC cells. HC promoted the degradation of YAP through the proteasome pathway and up-regulated the ubiquitination level of YAP. The results of MST and DARTS demonstrated direct binding between HC, YAP, and CNOT4. The above results indicated that HC inhibited the malignant progression of TNBC via CNOT4-mediated degradation and ubiquitination of YAP.

Clinical characteristics of in-hospital cardiac arrest in emergency patients in Kashgar area and analysis of influencing factors on success rate of cardiopulmonary resuscitation / 中华危重病急救医学

OBJECTIVE@#To analyze the clinical characteristics of patients with emergency in-hospital cardiac arrest (IHCA) in Kashgar, Xinjiang Uygur Autonomous Region and the factors affecting the success rate of cardiopulmonary resuscitation.@*METHODS@#Retrospectively selected patients who had cardiac arrest and cardiopulmonary resuscitation in the emergency department of the People's Hospital of 6 counties and cities in Kashgar area from January 2019 to January 2022. The clinical data of all patients were collected, including gender, age, major underlying diseases, the beginning and duration of resuscitation, the number of electric defibrillation acute physiology and chronic health evaluation II (APACHE II). According to whether the resuscitation was successful, all patients were divided into successful resuscitation group and failed resuscitation group. The clinical characteristics of the two groups were compared. Then, the influencing factors of the success rate of cardiopulmonary resuscitation in IHCA patients were analyzed by binary Logistic regression.@*RESULTS@#A total of 1 376 patients were enrolled, including 1 117 cases of failed resuscitation and 259 cases of successful resuscitation. The success rate of resuscitation was 18.82%. Compared with the resuscitation failure group, the patients in the successful resuscitation group were younger (age: 49.10±20.99 vs. 58.44±18.32), the resuscitation start time was earlier [resuscitation start time ≤ 5 minutes: 76.45% (198/259) vs. 66.61% (744/1 117)], the proportion of cardiovascular and cerebrovascular diseases was lower [cardiovascular disease: 49.42% (128/259) vs. 58.19% (650/1 117), cerebrovascular disease: 17.37% (45/259) vs. 21.58% (241/1 117)], the number of electric defibrillation was lower [times: 0 (0, 2) vs. 1 (0, 1)], the proportion of endotracheal intubation was more [80.31% (208/259) vs. 55.60% (621/1 117)], APACHE II score was lower (13.75±8.03 vs. 17.90±4.63), and the difference was statistically significant (all P < 0.01). Binary Logistic regression analysis showed that age, start time of resuscitation, ventilation mode and APACHE II score were protective factors affecting the success rate of cardiopulmonary resuscitation in patients with emergency IHCA [age: odds ratio (OR) = 0.982, 95% confidence interval (95%CI) was 0.973-0.991, P < 0.001; resuscitation start time ≤ 5 minutes: OR = 0.629, 95%CI was 0.409-0.966, P = 0.034; tracheal intubation assisted ventilation: OR = 0.243, 95%CI was 0.149-0.397, P < 0.001; low APACHE II score: OR = 0.871, 95%CI was 0.836-0.907, P < 0.001], while underlying diseases (cardiovascular diseases) are a risk factor affecting the success rate of cardiopulmonary resuscitation (OR = 1.190, 95%CI was 1.015-1.395, P = 0.036).@*CONCLUSIONS@#Age, resuscitation start time, ventilation mode, APACHE II score and major underlying diseases (cardiovascular diseases) have a greater impact on the success rate of resuscitation in IHCA patients. The above factors are conducive to improving or formulating more effective rescue strategies for IHCA patients, so as to achieve the purpose of improving the success rate of clinical treatment.

The value of radiomics for individualized prophylactic cranial irradiation in limited-stage small cell lung cancer / 中华放射肿瘤学杂志

Objective:To investigate the predictive value of enhanced CT-based radiomics for brain metastasis (BM) and selective use of prophylactic cranial irradiation (PCI) in limited-stage small cell lung cancer (LS-SCLC).Methods:Clinical data of 97 patients diagnosed with LS-SCLC confirmed by pathological and imaging examination in Shanxi Provincial Cancer Hospital from January 2012 to December 2018 were retrospectively analyzed. The least absolute shrinkage and selection operator (LASSO) Cox and Spearman correlation tests were used to select the radiomics features significantly associated with the incidence of BM and calculate the radiomics score. The calibration curve, the area under the receiver operating characteristic (ROC) curve (AUC), 5-fold cross-validation, decision curve analysis (DCA), and integrated Brier score (IBS) were employed to evaluate the predictive power and clinical benefits of the radiomics score. Kaplan-Meier method and log-rank test were adopted to draw survival curves and assess differences between two groups.Results:A total of 1272 radiomics features were extracted from enhanced CT. After the LASSO Cox regression and Spearman correlation tests, 8 radiomics features associated with the incidence of BM were used to calculate the radiomics score. The AUCs of radiomics scores to predict 1-year and 2-year BM were 0.845 (95% CI=0.746-0.943) and 0.878 (95% CI=0.774-0.983), respectively. The 5-fold cross validation, calibration curve, DCA and IBS also demonstrated that the radiomics model yielded good predictive performance and net clinical benefit. Patients were divided into the high-risk and low-risk cohorts based on the radiomics score. For patients at high risk, the 1-year and 2-year cumulative incidence rates of BM were 0% and 18.2% in the PCI group, and 61.8% and 75.4% in the non-PCI group, respectively ( P<0.001). In the PCI group, the 1-year and 2-year overall survival rates were 92.9% and 78.6%, and 85.3% and 36.8% in the non-PCI group, respectively ( P=0.023). For patients at low risk, the 1-year and 2-year cumulative incidence rates of BM were 0% and 0% in the PCI group, and 10.0% and 20.2% in the non-PCI group, respectively ( P=0.062). In the PCI group, the 1-year and 2-year overall survival rates were 100% and 77.0%, and 96.7% and 79.3% in the non-PCI group, respectively ( P=0.670). Conclusion:The radiomics model based on enhanced CT images yields excellent performance for predicting BM and individualized PCI.

A Brief Analysis of Equivalence Demonstration Techniques for Clinical Evaluation of Medical Devices / 中国医疗器械杂志

This study overviewed equivalence demonstration, the principles for the selection of comparative devices, the difficulties in equivalence demonstration, and the equivalence demonstration of special medical devices. In addition, the concept of equivalence demonstration was adopted for the products exempted from clinical evaluation, and there were many confusion in actual use. The operation points and difficult points of equivalence demonstration for the products exempted from clinical evaluation were introduced in order to provide reference for medical device colleagues.

The Ubiquitin Ligase SMURF1 Catalyzes the Polyubiquitination of ADAR1 / 中国生物化学与分子生物学报

It is known that SMAD specific E3 ubiquitin protein ligase 1 (SMURF1) mediates autophagy through its E3 ubiquitin ligase activity, but the ubiquitinated substrates of SMURF1 need to be further explored. In this paper, the interacting proteins of SMURF1 in THP-1 cells were captured and identified by co-immunoprecipitation (Co-IP) combined with mass spectrometry. It was found that SMURF1 could physically bind to 222 proteins in THP-1 cells, and Adenosine deaminase acting on RNA 1 (ADAR1) had a higher peptide binding score. SMURF1 overexpression vectors were constructed and transfected into HEK-293T cells, then Co-IP and Western blotting assays verified the interaction between exogenous SMURF1 and endogenous ADAR1. qRT-PCR and Western blotting assays were carried out after transfecting SMURF1 overexpression vectors in HEK-293T cells, which identified that overexpression of SMURF1 attenuated the protein levels of ADAR1 (P<0. 05). However, there was no significant difference in the mRNA level of ADAR1. HEK-293T cells with normal and overexpressing SMURF1 were treated with cycloheximide (CHX), respectively, and Western blotting assays showed a shortened half-life of ADAR1 after overexpression of SMURF1 (P < 0. 05). Furthermore, overexpression of SMURF1 increased the polyubiquitination level of ADAR1 as detected by Co-IP and Western blot (P<0. 05). After the proteasome inhibitor (MG132) treatment, the Western blotting assay was performed to demonstrate that the negative regulatory effect of SMURF1 on ADAR1 was weakened after the proteasome degradation pathway was attenuated (P<0. 05). This study shows that SMURF1 interacts with ADAR1, catalyzes the polyubiquitination of ADAR1 and mediates its degradation through the proteasome pathway, which provides a theoretical basis for exploring the various biological functions of SMURF1 by affecting the stability of ADAR1.

Erratum: Author correction to 'Protective effects of VMY-2-95 on corticosterone-induced injuries in mice and cellular models' Acta Pharmaceutica Sinica B 11 (2021) 1903-1913

[This corrects the article DOI: 10.1016/j.apsb.2021.03.002.].

Clinical significance of pathological diagnosis and genetic abnormalities detection in gastrointestinal stromal tumor using endoscopic biopsy / 中华病理学杂志

Objective: To investigate the clinical significance of pathological diagnosis and genetic abnormalities detection of gastrointestinal stromal tumor (GIST) using endoscopic biopsy. Methods: Patients with GIST diagnosed by endoscopic biopsy (from January 1st, 2016 to August 1st, 2018, at Zhongshan Hospital, Fudan University) were included in this study. This retrospective study evaluated the histopathologic and immunohistochemical (IHC) features, genetic abnormalities of the tumors and the treatment and clinical course of the patients. Results: Totally 4 095 cases of GIST were collected, among which 67 patients (67/4 095, 1.6%) underwent endoscopic biopsy. Forty-eight patients (71.6%) were male and 19 (28.4%) were female, with a mean age of 61 years (range 31-90 years). Fifty-nine lesions were located in stomach and eight in duodenum. Of all the 67 cases, 47 were spindle type, 14 were epithelioid type, and 6 mixed type. IHC staining showed the positive rates were 100.0% (64/64) for DOG1, 98.4% (62/63) for CD117, 87.5% (56/64) for CD34, 3.6% (2/56) for S-100 protein, 12.1% (7/58) for α-SMA, 12.3% (7/57) for desmin and 4.0% (2/50) for CKpan. Morphologically, 34 cases were malignant; three cases (all epithelioid type) were originally misdiagnosed as poorly differentiated carcinoma; missed-diagnosis were found in four cases (spindle type) due to the insufficient diagnostic tumor cells. The genetic abnormality detection rate in the biopsy tissue was 38.8% (26/67),among them two patients were lost to follow up after biopsy, 33 patients received surgical resection, 16 cases underwent operation after neoadjuvant therapy and 16 patients with advanced disease underwent continuous imatinib therapy, with the genetic testing rate of 6.1% (2/33), 10/16 and 14/16, respectively. Conclusions: Endoscopic biopsy is a useful but rare method for the preoperative diagnosis of GIST. For majority of biopsy, accurate pathological diagnosis and auxiliary examination can be completed to guide clinical treatment. A thorough history in combination with endoscopic finding is essential to avoid misdiagnosis (epithelioid type) and missed diagnosis (spindle type) in suspicious cases. Genetic testing should be recommended in patients who will undergo targeted therapy after endoscopic biopsy, and it can provide valuable information and guidance for clinical treatment.

Microvascular perfusion and cardiac function after revascularization assessed by myocardial contrast echocardiography in patients with acute ST-segment elevation myocardial infarction / 中华心血管病杂志

Objectives: To evaluate microvascular perfusion and left ventricular function in patients with acute ST-segment elevation myocardial infarction after revascularization using myocardial contrast echocardiography (MCE), and to explore clinical influencing factors of abnormal microvascular perfusion in these patients. Methods: This is a cross-sectional study. The analysis was performed among patients admitted to Peking University People's Hospital for acute ST-segment elevation myocardial infarction (STEMI) from June 2018 to July 2021. All patients underwent percutaneous coronary intervention (PCI) and completed MCE within 48 hours after PCI. Patients were divided into normal myocardial perfusion group and abnormal perfusion group according to the myocardial perfusion score. The echocardiographic indexes within 48 hours after PCI, including peak mitral valve flow velocity (E), mean value of early diastolic velocity of left ventricular septum and lateral mitral annulus (Em), left ventricular global longitudinal strain (GLS) and so on, were analyzed and compared between the two groups. Multivariate logistic regression analysis was used to evaluate the influencing factors of myocardial perfusion abnormalities. Results: A total of 123 STEMI patients, aged 59±13 years with 93 (75.6%) males, were enrolled. There were 50 cases in the normal myocardial perfusion group, and 73 cases in the abnormal myocardial perfusion group. The incidence of abnormal myocardial perfusion was 59.3% (73/123). The left ventricular volume index ((62.3±18.4)ml/m2 vs. (55.1±15.2)ml/m2, P=0.018), wall motion score index (WMSI) (1.59 (1.44, 2.00) vs. 1.24(1.00, 1.47), P<0.001) and mitral E/Em (17.8(12.0, 24.3) vs. 12.2(9.2, 15.7), P<0.001) were significantly higher whereas left ventricular global longitudinal strain (GLS) ((-10.8±3.4)% vs. (-13.8±3.5)%, P<0.001) was significantly lower in the abnormal myocardial perfusion group than those in the normal myocardial perfusion group. Multivariate logistic regression analysis showed that left anterior descending (LAD) as culprit vessel (OR=3.733, 95%CI 1.282-10.873, P=0.016), intraoperative no/low-reflow (OR=6.125, 95%CI 1.299-28.872, P=0.022), and peak troponin I (TnI) (OR=1.018, 95%CI 1.008-1.029, P=0.001) were independent risk factors of abnormal myocardial perfusion. As for ultrasonic indexes, deceleration time of mitral E wave (OR=0.979, 95%CI 0.965-0.993, P=0.003), mitral E/Em (OR=1.100, 95%CI 1.014-1.194, P=0.022) and WMSI (OR=7.470, 95%CI 2.630-21.222, P<0.001) were independently related to abnormal myocardial perfusion. Conclusions: The incidence of abnormal myocardial perfusion after PCI is high in patients with acute STEMI. Abnormal myocardial perfusion is related to worse left ventricular systolic and diastolic function. LAD as culprit vessel, intraoperative no/low-reflow and peak TnI are independent risk factors of abnormal myocardial perfusion.

Research progress of exosome delivery vehicles in tumor phototherapy / 药学学报

Exosome is a self-secreted phospholipid bilayer nanovesicles, and has shown great potential in drug delivery field due to the important advantages of low immunogenicity and homologous targeting. Phototherapy, mainly includes photodynamic therapy (PDT) and photothermal therapy (PTT), utilize light to activate photoactive drug for tumor cell killing. The advanced therapeutic strategy shows low toxic side-effect and non-invasion precise advantages, and thus has made great progress in tumor treatment over the past few years. Therefore, using exosomes as a drug delivery system to deliver phototherapeutic agents can improve therapeutic performances with a reduced side-effect, and further enhance their application potential for clinical tumor therapy. This review focus on the rising cross-subjects field involving exosomes and phototherapy, and mainly introduce the research progress and relative case of exosomes-based delivery system for cancer phototherapy. Additionally, the advantages and challenges of exosome-based phototherapy are also discussed and proposed.

HIV-1 Subtype Diversity and Factors Affecting Drug Resistance among Patients with Virologic Failure in Antiretroviral Therapy in Hainan Province, China, 2014-2020 / 生物医学与环境科学（英文）

OBJECTIVE@#This study aimed to determine the HIV-1 subtype distribution and HIV drug resistance (HIVDR) in patients with ART failure from 2014 to 2020 in Hainan, China.@*METHODS@#A 7-year cross-sectional study was conducted among HIV/AIDS patients with ART failure in Hainan. We used online subtyping tools and the maximum likelihood phylogenetic tree to confirm the HIV subtypes with pol sequences. Drug resistance mutations (DRMs) were analyzed using the Stanford University HIV Drug Resistance Database.@*RESULTS@#A total of 307 HIV-infected patients with ART failure were included, and 241 available pol sequences were obtained. Among 241 patients, CRF01_AE accounted for 68.88%, followed by CRF07_BC (17.00%) and eight other subtypes (14.12%). The overall prevalence of HIVDR was 61.41%, and the HIVDR against non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) were 59.75%, 45.64%, and 2.49%, respectively. Unemployed patients, hypoimmunity or opportunistic infections in individuals, and samples from 2017 to 2020 increased the odd ratios of HIVDR. Also, HIVDR was less likely to affect female patients. The common DRMs to NNRTIs were K103N (21.99%) and Y181C (20.33%), and M184V (28.21%) and K65R (19.09%) were the main DRMs against NRTIs.@*CONCLUSION@#The present study highlights the HIV-1 subtype diversity in Hainan and the importance of HIVDR surveillance over a long period.