lncRNA SNHG4 inhibits ferroptosis by orchestrating miR-150-5p/c-Myb axis in colorectal cancer.

LncRNAs have shown to regulate ferroptosis in colorectal cancer (CRC), but the mechanism remains largely unknown. This study unveiled the mechanism of SNHG4 underlying ferroptosis in CRC. RNA-seq and RT-PCR assay confirmed SNHG4 was decreased after Erastin treatment in CRC cells. Overexpression of SNHG4 inhibited and silence promoted CRC cells ferroptosis. SNHG4 was positively correlated to c-Myb in CRC tissues and both located in cytoplasm of CRC cells. RIP and RNA pull-down assays verified the interaction between SNHG4 and c-Myb. Silence of c-Myb alleviated the suppressing effect on ferroptosis by SNHG4 in CRC cells. Dual-luciferase reporter assay revealed that SNHG4 sponging miR-150-5p in CRC cells. Overexpression of SNHG4 decreased the miR-150-5p and increased c-Myb expression. c-Myb was a direct target gene of miR-150-5p in CRC cells. Moreover, effect of CDO1 on ferroptosis was regulated transcriptionally by c-Myb, overexpression of c-Myb reduce CDO1 expression and enhance the GPX4 levels. The animal models confirmed that regulatory effect of SNHG4 on miR-150-5p and c-Myb after inducing ferroptosis. We concluded that SNHG4 inhibited Erastin-induce ferroptosis in CRC, this effect is via sponging miR-150-5p to regulate c-Myb expression, and activated CDO1/GPX4 axis. These findings provide insights into the regulatory mechanism of SNHG4 on ferroptosis.

SNHG4-mediated PTEN destabilization confers oxaliplatin resistance in colorectal cancer cells by inhibiting ferroptosis.

Oxaliplatin resistance poses a significant challenge in colorectal cancer (CRC) therapy, necessitating further investigation into the underlying molecular mechanisms. This study aimed to elucidate the regulatory role of SNHG4 in oxaliplatin resistance and ferroptosis in CRC. Our findings revealed that treatment with oxaliplatin led to downregulation of SNHG4 expression in CRC cells, while resistant CRC cells exhibited higher levels of SNHG4 compared to parental cells. Silencing SNHG4 attenuated oxaliplatin resistance and reduced the expression of resistance-related proteins MRD1 and MPR1. Furthermore, induction of ferroptosis effectively diminished oxaliplatin resistance in both parental and resistant CRC cells. Notably, ferroptosis induction resulted in decreased SNHG4 expression, whereas SNHG4 overexpression suppressed ferroptosis. Through FISH, RIP, and RNA pull-down assays, we identified the cytoplasmic localization of both SNHG4 and PTEN, establishing that SNHG4 directly targets PTEN, thereby reducing mRNA stability in CRC cells. Silencing PTEN abrogated the impact of SNHG4 on oxaliplatin resistance and ferroptosis in CRC cells. In vivo experiments further validated the influence of SNHG4 on oxaliplatin resistance and ferroptosis in CRC cells through PTEN regulation. In conclusion, SNHG4 promotes resistance to oxaliplatin in CRC cells by suppressing ferroptosis through instability of PTEN, thus serves as a target for patients with oxaliplatin-base chemoresistance.

Unlocking employee innovative behavior: the role of humble leadership, core self-evaluation, and leader-member exchange.

Humble leadership has gained attention in recent years due to its potential impact on employee performance. This study explores the association between humble leadership and follower innovative behavior by investigating the moderating role of core self-evaluation (CSE) and the mediating role of leader-member exchange (LMX). The study uses data from 328 followers and their immediate leaders to test a mediated moderation model. Results show that there is a favorable association between humble leadership and LMX and followers' innovative behavior, particularly pronounced for followers who possess lower levels of CSE. The findings suggest that humble leaders should focus their development efforts on followers with low CSE to achieve complementarity congruity and improved innovation. This research enhances the existing body of knowledge by emphasizing the significance of comprehending the functions of relational procedures and the psychological resources of followers in determining the effectiveness of humble leadership. These findings have practical implications for organizations seeking to enhance their leadership effectiveness and followers' innovative behavior.

Hepatic transcriptome delineates the therapeutic effects of Sanren Tang on high-fat diet-induced non-alcoholic fatty liver disease.

OBJECTIVE: To evaluate the effects of Sanren Tang (SRT, ) on a high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) in mice and to investigate the hepatic transcriptome regulated by SRT. METHODS: The primary SRT components were identified using ultra-high-performance liquid chromatography-high-resolution accurate mass spectrometry. The SRT-induced pharmacological effects on HFD-induced NAFLD were evaluated in mice for 16 weeks. Obeticholic acid was used as a control drug. Body weight, food intake, and homeostatic model assessment for insulin resistance (HOMA-IR) index were analysed. Hepatic histological changes were observed in haematoxylin and eosin-stained sections and quantified using the NAFLD activity score (NAS). Serum alanine aminotransferase (ALT) and hepatic triglyceride (TG) levels were measured. Lipids in hepatocytes were visualised by Oil red staining. RNA-sequencing was performed to determine the transcriptome profile of the liver tissue. The differentially expressed genes were validated using real-time polymerase chain reaction and Western blotting. RESULTS: Four principal compounds were identified in the SRT: adenosine, amygdalin, luteoloside, and magnolol. SRT ameliorated hepatic histology and lipid deposition in the NAFLD mice, and decreased HOMA-IR, NAS and ALT, and hepatic TG levels. Hepatic transcriptome analysis revealed 232 HFD-regulated genes that were reversed by SRT simultaneously. Retinol metabolism, cytokine-cytokine receptor interaction, and peroxisome proliferator-activated receptor (PPAR) γ signalling were the top three SRT-regulated pathways in NAFLD. CONCLUSIONS: SRT significantly ameliorated HFD-induced NAFLD, which was correlated with the regulation of genes enriched in the retinol metabolism, cytokine-cytokine receptor interaction, and PPARγ signalling pathways.

Monitoring and management of abandoned, lost and discarded fishing gear (ALDFG) in Penghu Islands, Taiwan.

This study investigated the conditions of abandoned, lost, discarded fishing gear (ALDFG) in natural and artificial reef zones and removed it afterward in Penghu Islands. Various feasible suggestions for improving ALDFG management were proposed for the county government to manage and reduce the generation of ALDFG in the future and maintain the marine ecosystem. This study divided the ocean areas of Penghu into five sub-areas for carrying out research and surveys. 165 boat trips of ALDFG investigation and removal were conducted from July 2018 to October 2019. The results show the ALDFG in natural reef areas is mostly large-mesh gillnets (26 %). The rest are single-layer bottom gillnets (21 %) and multi-layer bottom gillnets (20 %). In line with the recent efforts of the Penghu County Government to address ALDFG, it is recommended that the participation of citizen scientists and the promotion of ocean education can be utilized for fishery co-management in Penghu.

Systematic analyzing a five- miRNA panel and its diagnostic value of plasma expression in colorectal cancer.

BACKGROUND: Aberrant expression of miRNAs have been implicated in cancers, but the role of miRNAs in colorectal cancer (CRC) remains need to be elucidated. This study aimed to identify miRNAs that related to colorectal cancer (CRC) pathogenesis and determine the diagnostic value. METHODS: Three GEO datasets (GSE128449, GSE35602 and GSE49246) with 131 samples were used to screen miRNAs that differential expression between tumor and control tissues. The expression of the identified miRNAs was validated in 50 clinical tissue samples and the GSE35834 dataset. The clinical significance of these miRNAs was analyzed in the TCGA dataset and clinical tissue samples. The expression of miRNAs in tissues and plasma samples were tested by RT-PCR assay in clinical samples, and their diagnostic value was determined. RESULTS: The analysis of three GEO datasets revealed that miR-595 and miR-1237 were upregulated, while miR-126, miR-139, and miR-143 were downregulated in CRC tissues compared to control tissues. The differential expression of the five miRNAs in CRC tissues was confirmed using clinical tissue samples and GEO databases. There was no significant correlation between the TNM stage and tumor stage of CRC and any of the five miRNAs. Plasma expression of the miRNAs differed significantly between CRC and non-cancer patients, and each miRNA had moderate diagnostic value for CRC. Combining the five miRNAs provided better diagnostic potential for CRC than a single miRNA. CONCLUSIONS: This study demonstrated that five miRNAs were related to the pathogenesis of CRC, but independent of the stage of CRC; Plasma expression of these miRNAs have moderate diagnostic value, and combination of these miRNAs showed better diagnostic ability in CRC.

Chinese expert consensus on emergency surgery for severe trauma and infection prevention during corona virus disease 2019 epidemic (version 2023) / 中华创伤杂志

During coronavirus disease 2019 epidemic, the treatment of severe trauma has been impacted. The Consensus on emergency surgery and infection prevention and control for severe trauma patients with 2019 novel corona virus pneumonia was published online on February 12, 2020, providing a strong guidance for the emergency treatment of severe trauma and the self-protection of medical staffs in the early stage of the epidemic. With the Joint Prevention and Control Mechanism of the State Council renaming "novel coronavirus pneumonia" to "novel coronavirus infection" and the infection being managed with measures against class B infectious diseases since January 8, 2023, the consensus published in 2020 is no longer applicable to the emergency treatment of severe trauma in the new stage of epidemic prevention and control. In this context, led by the Chinese Traumatology Association, Chinese Trauma Surgeon Association, Trauma Medicine Branch of Chinese International Exchange and Promotive Association for Medical and Health Care, and Editorial Board of Chinese Journal of Traumatology, the Chinese expert consensus on emergency surgery for severe trauma and infection prevention during coronavirus disease 2019 epidemic ( version 2023) is formulated to ensure the effectiveness and safety in the treatment of severe trauma in the new stage. Based on the policy of the Joint Prevention and Control Mechanism of the State Council and by using evidence-based medical evidence as well as Delphi expert consultation and voting, 16 recommendations are put forward from the four aspects of the related definitions, infection prevention, preoperative assessment and preparation, emergency operation and postoperative management, hoping to provide a reference for severe trauma care in the new stage of the epidemic prevention and control.

The experience and enlightenment of robotic surgery training course in the University of Pittsburgh Medical Center / 中华医学教育探索杂志

Objective:To introduce the experience of robotic surgery training course in the University of Pittsburgh Medical Center.Methods:The specific process of the training course was introduced in detail, and the results of the training course were summarized and analyzed. A total of 15 surgeons completed the first step of the training (operation table simulation training), 14 (93.3%) completed the second step (pancreatoduodenectomy tissue anastomosis simulation training), and 196 cases of tissue anastomosis simulation training were completed. Statistical analysis was performed using STATA and SPSS software. Wilcoxon rank sum test was used to analyze the data.Results:The average scores of the surface validity Likert scale for anastomosis simulation training were: (15/20) for Pancreaticojejunostomy (PJ), (15/20) for Gastrojejunostomy (GJ), and (17/20) for Hepatocholangiojejunostomy (HJ). In the PJ and GJ simulation training, compared with the gold standard, the error rate and OSATS score were significantly improved ( P > 0.05), and the operation time was not significantly reduced ( P < 0.05). In HJ simulation training, the error rate, OSATS score and operation time did not show significant improvement ( P < 0.05). However, it could be concluded that all the simulation operations performed by the trainees after the training were better than the first time, when linear regression and quadratic fitting models were performed to analyze continuous trainings of the trainees as a group. Conclusion:The training course carried out by the University of Pittsburgh Medical Center is valid and effective, and it can be used for reference to explore a way for the development of robotic surgery fitting to the real conditions of our country.

Clinical Value of Translocator Protein Gene in Evaluating the Efficacy of FLT3-ITD/DNMT3A R882 Double-Mutated Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To observe the clinical significance of translocator proteins (TSPO) gene in the treatment of FLT3-ITD/DNMT3A R882 double-mutated acute myeloid leukemia (AML).@*METHODS@#Seventy-six patients with AML hospitalized in the Department of Hematology of the Affiliated People's Hospital of Ningbo University from June 2018 to June 2020 were selected, including 34 patients with FLT3-ITD mutation, 27 patients with DNMT3A R882 mutation, 15 patients with FLT3-ITD/DNMT3A R882 double mutation, as well as 19 patients with immune thrombocytopenia (ITP) hospitalized during the same period as control group. RNA was routinely extracted from 3 ml bone marrow retained during bone puncture, and TSPO gene expression was detected by transcriptome sequencing (using 2-deltadeltaCt calculation).@*RESULTS@#The expression of TSPO gene in FLT3-ITD group and DNMT3A R882 group at first diagnosis was 2.02±1.04 and 1.85±0.76, respectively, which were both higher than 1.00±0.06 in control group, but the differences were not statistically significant (P=0.671, P=0.821). The expression of TSPO gene in the FLT3-ITD/DNMT3A R882 group was 3.98±1.07, wich was significantly higher than that in the FLT3-ITD group and DNMT3A R882 group, the differences were statistically significant (P=0.032, P=0.021). The expression of TSPO gene in patients who achieved complete response after chemotherapy in the FLT3-ITD/DNMT3A R882 group was 1.19±0.87, which was significantly lower than that at first diagnosis, and the difference was statistically significant (P=0.011).@*CONCLUSION@#TSPO gene may be used as an indicator of efficacy in FLT3-ITD /DNMT3A R882 double-mutated AML.

Clinical and pathological characteristics of immune-mediated liver injury caused by immune checkpoint inhibitors / 中华内科杂志

Objective: Cancer immunotherapy can lead to various side effects, termed immune-related adverse events (irAE). This study summarized and analyzed the clinical and pathological characteristics of immune-mediated liver injury caused by immune checkpoint inhibitors (ILICI). Methods: This is a retrospective case series study involving 11 patients diagnosed with ILICI at the Peking Union Medical College Hospital from November 2019 to November 2021. Patient demographic information and clinical data, including gender, age, ILICI onset, clinical and radiological manifestations, pathological features, treatment, and resumption of ICI were retrospectively collected and analyzed. Results: The patients were primarily males (9/11) with a median age of 65 (range: 32-73) years. ICI mainly resulted in either partial remission (4/11) or stable disease (3/11). ILICI occurred after a median of two cycles of anti-programmed cell death-1 (PD-1) therapy, with a median time from the initial and last anti-PD-1 therapy to ILICI onset of 57 days and 17 days, respectively. ILICI was mostly severe (3/11) or very severe (6/11). While the clinical and radiological manifestations were non-specific, the pathological features were active lobular hepatitis and portal inflammation, with prominent CD8+T lymphocyte infiltration. The basic treatment was hepatoprotective drugs (10/11). Glucocorticoids were used as the primary therapy (9/11) but were ineffective in 4 of 9 cases. Of these, 3 of 9 cases received combined treatment with mycophenolate mofetil (MMF), only one of whom achieved remission. By the end of the study, 2 of 11 cases had resumed ICI and neither had experienced an ILICI relapse. Conclusion: The ILICI patients in this study had a corresponding history of ICI treatment and pathological features. The main treatment included hepatoprotective drugs and glucocorticoids. Immunosuppressive drugs were added for some cases but had poor efficacy.

Microdeletions and vertical transmission of the Y-chromosome azoospermia factor region / 亚洲男科学杂志(英文版)

Spermatogenesis is regulated by several Y chromosome-specific genes located in a specific region of the long arm of the Y chromosome, the azoospermia factor region (AZF). AZF microdeletions are the main structural chromosomal abnormalities that cause male infertility. Assisted reproductive technology (ART) has been used to overcome natural fertilization barriers, allowing infertile couples to have children. However, these techniques increase the risk of vertical transmission of genetic defects. Despite widespread awareness of AZF microdeletions, the occurrence of de novo deletions and overexpression, as well as the expansion of AZF microdeletion vertical transmission, remains unknown. This review summarizes the mechanism of AZF microdeletion and the function of the candidate genes in the AZF region and their corresponding clinical phenotypes. Moreover, vertical transmission cases of AZF microdeletions, the impact of vertical inheritance on male fertility, and the prospective direction of research in this field are also outlined.

Clinical and genetic analyses of Joubert syndrome in children / 中国当代儿科杂志

OBJECTIVES@#To study the clinical and genetic features of Joubert syndrome (JS) in children.@*METHODS@#A retrospective analysis was performed on the clinical data, genetic data, and follow-up data of 20 children who were diagnosed with JS in the Department of Children's Rehabilitation, the Third Affiliated Hospital of Zhengzhou University, from January 2017 to July 2022.@*RESULTS@#Among the 20 children with JS, there were 11 boys and 9 girls. The common clinical manifestations were developmental delay (20 children, 100%), abnormal eye movement (19 children, 95%), and hypotonia (16 children, 80%), followed by abnormal respiratory rhythm in 5 children (25%) and unusual facies (including prominent forehead, low-set ears, and triangular mouth) in 3 children (15%), and no limb deformity was observed. All 20 children (100%) had the typical "molar tooth sign" and "midline cleft syndrome" on head images, and 6 children (30%) had abnormal eye examination results. Genetic testing was performed on 7 children and revealed 6 pathogenic genes, i.e., the CPLANE1, RPGRIP1L, MKS1, CC2D2A, CEP120, and AHI1 genes.@*CONCLUSIONS@#For children with developmental delay, especially those with abnormal eye movement and hypotonia, it is recommended to perform a head imaging examination to determine the presence or absence of "molar tooth sign" and "midline cleft syndrome", so as to screen for JS to avoid missed diagnosis and misdiagnosis. There are many pathogenic genes for JS, and whole-exome sequencing can assist in the diagnosis of JS.

Effect of SAM junctional tourniquet on respiration when applied in the axilla: A swine model / 中华创伤杂志(英文版)

PURPOSE@#SAM junctional tourniquet (SJT) has been applied to control junctional hemorrhage. However, there is limited information about its safety and efficacy when applied in the axilla. This study aims to investigate the effect of SJT on respiration when used in the axilla in a swine model.@*METHODS@#Eighteen male Yorkshire swines, aged 6-month-old and weighing 55 - 72 kg, were randomized into 3 groups, with 6 in each. An axillary hemorrhage model was established by cutting a 2 mm transverse incision in the axillary artery. Hemorrhagic shock was induced by exsanguinating through the left carotid artery to achieve a controlled volume reduction of 30% of total blood volume. Vascular blocking bands were used to temporarily control axillary hemorrhage before SJT was applied. In Group I, the swine spontaneously breathed, while SJT was applied for 2 h with a pressure of 210 mmHg. In Group II, the swine were mechanically ventilated, and SJT was applied for the same duration and pressure as Group I. In Group III, the swine spontaneously breathed, but the axillary hemorrhage was controlled using vascular blocking bands without SJT compression. The amount of free blood loss was calculated in the axillary wound during the 2 h of hemostasis by SJT application or vascular blocking bands. After then, a temporary vascular shunt was performed in the 3 groups to achieve resuscitation. Pathophysiologic state of each swine was monitored for 1 h with an infusion of 400 mL of autologous whole blood and 500 mL of lactated ringer solution. Tb and T0 represent the time points before and immediate after the 30% volume-controlled hemorrhagic shock, respectively. T30, T60, T90 and T120, denote 30, 60, 90, and 120 min after T0 (hemostasis period), while T150, and T180 denote 150 and 180 min after T0 (resuscitation period). The mean arterial pressure and heart rate were monitored through the right carotid artery catheter. Blood samples were collected at each time point for the analysis of blood gas, complete cell count, serum chemistry, standard coagulation tests, etc., and thromboelastography was conducted subsequently. Movement of the left hemidiaphragm was measured by ultrasonography at Tb and T0 to assess respiration. Data were presented as mean ± standard deviation and analyzed using repeated measures of two-way analysis of variance with pairwise comparisons adjusted using the Bonferroni method. All statistical analyses were processed using GraphPad Prism software.@*RESULTS@#Compared to Tb, a statistically significant increase in the left hemidiaphragm movement at T0 was observed in Groups I and II (both p < 0.001). In Group III, the left hemidiaphragm movement remained unchanged (p = 0.660). Compared to Group I, mechanical ventilation in Group II significantly alleviated the effect of SJT application on the left hemidiaphragm movement (p < 0.001). Blood pressure and heart rate rapidly increased at T0 in all three groups. Respiratory arrest suddenly occurred in Group I after T120, which required immediate manual respiratory assistance. PaO2 in Group I decreased significantly at T120, accompanied by an increase in PaCO2 (both p < 0.001 vs. Groups II and III). Other biochemical metabolic changes were similar among groups. However, in all 3 groups, lactate and potassium increased immediately after 1 min of resuscitation concurrent with a drop in pH. The swine in Group I exhibited the most severe hyperkalemia and metabolic acidosis. The coagulation function test did not show statistically significant differences among three groups at any time point. However, D-dimer levels showed a more than 16-fold increase from T120 to T180 in all groups.@*CONCLUSION@#In the swine model, SJT is effective in controlling axillary hemorrhage during both spontaneous breathing and mechanical ventilation. Mechanical ventilation is found to alleviate the restrictive effect of SJT on thoracic movement without affecting hemostatic efficiency. Therefore, mechanical ventilation could be necessary before SJT removal.

Advances on the microbial synthesis of plant-derived diterpenoids / 生物工程学报

Natural plant-derived diterpenoids are a class of compounds with diverse structures and functions. These compounds are widely used in pharmaceuticals, cosmetics and food additives industries because of their pharmacological properties such as anticancer, anti-inflammatory and antibacterial activities. In recent years, with the gradual discovery of functional genes in the biosynthetic pathway of plant-derived diterpenoids and the development of synthetic biotechnology, great efforts have been made to construct a variety of diterpenoid microbial cell factories through metabolic engineering and synthetic biology, resulting in gram-level production of many compounds. This article summarizes the construction of plant-derived diterpenoid microbial cell factories through synthetic biotechnology, followed by introducing the metabolic engineering strategies applied to improve plant-derived diterpenoids production, with the aim to provide a reference for the construction of high-yield plant-derived diterpenoid microbial cell factories and the industrial production of diterpenoids.

Clinical guideline on first aid for blast injury of the chest (2022 edition) / 中华创伤杂志

Blast injury of the chest injury is the most common wound in modern war trauma and terrorist attacks, and is also the most fatal type of whole body explosion injury. Most patients with severe blast injury of the chest die in the early stage before hospitalization or during transportation, so first aid is critically important. At present, there exist widespread problems such as non-standard treatment and large difference in curative effect, while there lacks clinical treatment standards for blast injury of the chest. According to the principles of scientificity, practicality and advancement, the Trauma Society of Chinese Medical Association has formulated the guidance of classification, pre-hospital first aid, in-hospital treatment and major injury management strategies for blast injury of the chest, aiming to provide reference for clinical diagnosis and treatment.

Experimental observation on a new chimney shaped mechanical valve completely implanted above mitral annulus in animals / 中华胸心血管外科杂志

Objective:To fundamentally solve the problems of valve dysfunction caused by limited size of artificial valve, high requirements for implantation technology, destruction of subvalvular structure and proliferation of fibrous endothelial tissue. We have developed a prosthetic valve with zero left ventricular occupancy. The valve frame is appropriately higher than the existing products, slightly chimney shaped, fully accommodates the movement of the valve leaves in the valve frame, and completely supraannular surgical implantation. This study uses this valve for preclinical animal test.Methods:Seven sheep underwent the replacement of the artificial valve under the direct vision of cardiopulmonary bypass. Warfarin was used for anticoagulation for 6 months 24 hours after operation. The blood biochemistry, anticoagulation and cardiac color Doppler ultrasound were detected after operation. The sheep were killed 180 days later for autopsy to observe whether the artificial valve caused thromboembolism. The efficacy and safety of valve were observed.Results:Two of the seven sheep died within 24 hours after operation, and five survived for a long time. Later, they were killed at 180 days. The mechanical properties of the artificial valve were good, and there was no thromboembolism around the artificial valve and important organs. The tissue layer of suture ring has been completely organized and endothelial cells, and the thickness of tissue layer is about 0.6-1.0 mm. The mitral valve of experimental animals can be opened and closed freely, with smooth surface and no abnormal echo. The follow-up of color Doppler ultrasound showed that the left ventricular ejection fraction was normal (0.60-0.70) before and 6 months after operation. The results of cross valve pressure difference and blood flow velocity of artificial valve were good (vmean was far lower than 5 mmHg(1 mmHg=0.133 kPa) and pmean was lower than 1 m/s) , suggesting that the hemodynamic performance of artificial valve was good. Left ventricular retrograde angiography showed that the artificial valve was completely located in the left atrium with good position and normal opening and closing. There was no obvious perivalvular leakage and other abnormalities. Within 7 days of blood test, the indexes of surgical stress were more abnormal than those before operation. At 12 and 24 weeks, there were no obvious abnormalities in blood routine test, liver and kidney function and other blood test indexes of animals in each group.Conclusion:The new chimney shaped mechanical valve implanted completely above the mitral annulus has good wear resistance, histocompatibility, antithrombotic and hemodynamic performance.

Analysis of different fixation devices in precision radiotherapy for prostate cancer under bowel and bladder preparation protocol / 中华放射肿瘤学杂志

Objective:To provide evidence for the selection of fixation devices and CTV to PTV margins (M ptv) in precision radiotherapy for pelvic tumors by analyzing three fixation devices in precision radiotherapy for prostate cancer. Methods:From April 2015 to December 2020, 133 prostate cancer patients treated with pelvic drainage area irradiation in our center were retrospectively analyzed. The patients were fixed with 1.2m vacuum bag (n=39), 1.8m vacuum bag (n=44) and personalized prone plate by our center (n=50). Each patient was asked to complete our bowel and bladder preparation process before positioning and radiotherapy. The registration of CBCT to planned CT before each treatment adopted the same registration box and algorithm. Setup errors in the SI, LR and AP directions under qualified bowel and bladder conditions were recorded. Setup errors in three directions under three fixation devices and corresponding M ptv values were analyzed. The correlation between setup errors with age and body mass index (BMI) was analyzed. Results:Analysis of 3333 setup errors data showed: in the SI and LR directions, the mean setup errors of 1.2m vacuum bag (3.26mm, 2.34mm) were greater than those of 1.8m vacuum bag (2.51mm, P<0.001; 1.90mm, P<0.001), and personalized prone plate (3.07mm, P=0.066; 2.10 mm, P=0.009). In the AP direction, the mean setup errors of 1.2m vacuum bag (supine)(2.20mm) were smaller than those of 1.8m vacuum bag (3.33mm, P<0.001) and personalized prone plate (3.61mm, P<0.001). The setup errors of 1.8m vacuum bag in all directions were smaller than those of personalized prone plate (P≤0.028). According to Van Herk's expansion formula, the M ptv of 1.2m vacuum bag in three directions was approximately 4 mm. The M ptv of 1.8m vacuum bag and personalized prone plate in the SI and LR directions was approximately 3 mm, and more than 5 mm in the AP direction. The setup errors were not correlated with age or BMI. Conclusions:From the setup errors results of three devices, 1.8m vacuum bag is the best, followed by personalized prone plate. And supine position is better than prone position in the AP direction.

Analysis of safety and efficacy of laparoscopic distal pancreatectomy in the treatment of left pancreatic malignant tumors.

OBJECTIVE: Distal pancreatectomy is the most extensive operation to treat malignant tumors of the left pancreas; however, malignant pancreatic tumors are prone to early invasion and metastasis. METHODS: The clinical data of 80 patients undergoing surgical treatment for malignant tumors of the pancreatic body or tail from January 2013 to December 2017 were retrospectively analyzed. The main clinical variables were compared between patients undergoing laparoscopic distal pancreatectomy (LDP) vs. open distal pancreatectomy (ODP). RESULTS: There were no significant differences in general patient characteristics, complications, and postoperative survival (χ2 = 0.09) between the groups. The operation time in the LDP group was significantly longer than that in the ODP group; however, the LDP group was superior to the ODP group regarding the length of postoperative hospital stay, diet recovery, and rectal exhaust and ambulation times. CONCLUSION: LDP is a safe and feasible treatment for left pancreatic malignancies, with the same surgical efficacy as ODP. LDP also has the advantages of minimally invasive surgery, such as minimal trauma and enhanced recovery after surgery.

CD147 antibody specifically and effectively inhibits infection and cytokine storm of SARS-CoV-2 variants

SARS-CoV-2 and its variants are raging worldwide. Unfortunately, the global vaccination is not efficient enough to attain a vaccine-based herd-immunity and yet no special and effective drug is developed to contain the spread of the disease. Previously we have identified CD147 as a novel receptor for SARS-CoV-2 infection. Here, we demonstrated that CD147 antibody effectively inhibits infection and cytokine storm caused by SARS-CoV-2 variants. In CD147KO VeroE6 cells, infections of SARS-CoV-2, its variants (B.1.1.7, B.1.351) and pseudovirus mutants (B.1.1.7, B.1.351, B.1.525, B.1.526 (S477N), B.1.526 (E484K), P.1, P.2, B.1.617.1, B.1.617.2) were decreased. Meanwhile, CD147 antibody effectively blocked the entry of variants and pseudomutants in VeroE6 cells, and inhibited the expression of cytokines. A model of SARS-CoV-2-infected hCD147 transgenic mice was constructed, which recapitulated the features of exudative diffuse alveolar damage and dynamic immune responses of COVID-19. CD147 antibody could effectively clear the virus and alveolar exudation, resolving the pneumonia. We found the elevated level of cyclophilin A (CyPA) in plasma of severe/critical cases, and identified CyPA as the most important proinflammatory intermediate causing cytokine storm. Mechanistically, spike protein of SARS-CoV-2 bound to CD147 and initiated the JAK-STAT pathway, which induced expression of CyPA. CyPA reciprocally bound to CD147, triggered MAPK pathway and consequently mediated the expression of cytokine and chemokine. In conclusion, CD147 is a critical target for SARS-CoV-2 variants and CD147 antibody is a promising drug to control the new wave of COVID-19 epidemic.

Efficacy evaluation of nilotinib treatment in different genomic subtypes of gastrointestinal stromal tumors: A meta-analysis and systematic review.

Nilotinib has been used as a third-line drug for gastrointestinal stromal tumors (GISTs) after a failure of sunitinib. In this study, we aimed to evaluate the efficacy of nilotinib in different genomic subtypes of GISTs. We searched the English articles through EMBASE, Cochrane Library and PubMed Database regarding to the use of nilotinib on GISTs, which published up to February 15, 2019. Inclusion criteria were: GISTs patients received nilotinib in a clinical trial and had detailed genetic subtype records (such as KIT exon 9, KIT exon 11, or PDGFRA mutations, or wild-type). The clinical benefit rate was used to assess the efficacy of nilotinib. A total of 3 studies involving 218 GISTs were included in this meta-analysis. The overall OR (KIT group vs WT group) was 3.26 (95% CI: 1.14-9.28; P = 0.027, Pheterogeneity = 0.613). The overall OR in KIT exon 11 group vs WT group was 5.30 (95% CI: 1.79-15.68; P = 0.003, Pheterogeneity = 0.409). The overall OR in KIT exon 9 group vs WT group was 0.13 (95% CI: 0.02-0.86; P = 0.035, Pheterogeneity = 0.229). The overall OR in KIT exon 11 group vs exon 9 group was 9.96 (95% CI: 0.39-254.66; P < 0.0001, Pheterogeneity = 0.024). Different genotypes of GISTs showed different responses to nilotinib, and KIT exon 11-mutant GISTs mostly benefited from nilotinib, followed by KIT exon 9-mutant or WT one.