Objective:To explore the clinicopathological and genetic characteristics of sporadic medullary thyroid carcinoma (MTC) and new therapeutic targets for sporadic MTC.Methods:Based on family and personal disease history, we identified 32 sporadic MTC who underwent surgical resection from Jan 2010 to Dec 2022. Clinicopathological and immunohistochemical features were analyzed in all patients, while 6 of them were subject to the whole exome sequencing (WES).Results:Compared with those of low-grade sporadic MTC, patients with high-grade tumors were more likely to have lymph node metastasis at presentation ( χ2=4.428, P=0.040); less likely to be cured by biochemical treatment ( χ2=4.072, P=0.044). Pathological grading scheme, biochemical cure, and TNM stage were independent risk factors of disease free survival. WES was performed on 6 pairs of normal tissues. We screened RET and RAS as driver mutations, and the mutation ratio was 3/6 respectively. Patients with RET or RAS mutations had no recurrence. In addition, we detected PDGFRA somatic mutation, with a mutation ratio of 1/6. Conclusions:For sporadic MTC cases, the pathological grading system has important prognostic value, and RET and RAS somatic mutations are the main driver mutations. PDGFRA are potential therapeutic targets for sporadic MTC.

Bone substitute material implantation has become an important treatment strategy for the repair of oral and maxillofacial bone defects. Recent studies have shown that appropriate inflammatory and immune cells are essential factors in the process of osteoinduction of bone substitute materials. Previous studies have mainly focused on innate immune cells such as macrophages. In our previous work, we found that T lymphocytes, as adaptive immune cells, are also essential in the osteoinduction procedure. As the most important antigen-presenting cell, whether dendritic cells (DCs) can recognize non-antigen biomaterials and participate in osteoinduction was still unclear. In this study, we found that surgical trauma associated with materials implantation induces necrocytosis, and this causes the release of high mobility group protein-1 (HMGB1), which is adsorbed on the surface of bone substitute materials. Subsequently, HMGB1-adsorbed materials were recognized by the TLR4-MYD88-NFκB signal axis of dendritic cells, and the inflammatory response was activated. Finally, activated DCs release regeneration-related chemokines, recruit mesenchymal stem cells, and initiate the osteoinduction process. This study sheds light on the immune-regeneration process after bone substitute materials implantation, points out a potential direction for the development of bone substitute materials, and provides guidance for the development of clinical surgical methods.
Biocompatible Materials/metabolism* ; HMGB1 Protein/metabolism* ; Myeloid Differentiation Factor 88/metabolism* ; Bone Substitutes/metabolism* ; Dendritic Cells/metabolism*

Objective:To analyze the data of critical care related literatures published in Web of Science core set by knowledge map visualizing technology, and summarize the research status and hotspots of critical care.Methods:The core set database of Web of Science from January 2011 to December 2020 was searched, the extracted information was standardized and analyzed by knowledge map visualizing technology.Results:A total of 783 articles in the field of critical care were included, and the number of literatures increased year by year, among which the number of articles published in the American Journal of Critical Care(305) was the most. The United States (437) was the country with the most published literatures, and Australia was the country with the highest centrality (centrality=0.67). The number and centrality of articles published from China were at the lower middle level. There was cooperation among countries, but not close cooperation. The cooperation among authors was in the state of small aggregation and large dispersion. Cluster analysis and keyword emergence analysis showed that many aspects in the field of intensive care had been the research hotspots, among which "post intensive care syndrome" and "children′s intensive care" were the research hotspots in recent years.Conclusions:The research field of intensive care is still in the rising stage of development, and post intensive care syndrome and children's intensive care are the latest hotspots in intensive care research.

Objective:To investigate the effect of using extended trans-dome onlay graft(eTDOG) made of costal cartilage combined with nasal vestibule V-Y advancement flap for correction of alar retraction.Methods:Clinical data of patients diagnosed with alar retraction at Chongqing Huamei Plastic Surgery Hospital between July 2019 and October 2020 were retrospectively analyzed. The 6th or 7th right costal cartilage was harvested, cut into pieces for grafts, including a laminar trans-dome onlay graft, made from cortex part of the rib. Then a V-shaped flap was designed on the vestibular skin. At the end of the rhinoplasty, a pocket was created along the alar rim, and the eTDOG was inserted into the pocket to push down the alar rim. Nasal vestibule V-Y advancement flap provides extra soft tissue for alar retraction correction. Splints were applied to hold the eTDOG and flap in place. Assessment of therapeutic effect was made from three aspects. First of all, therapeutic satisfaction assessment, which was made based on the visual analogue scale(VAS). VAS scoring was conducted by patients and two surgeons who were not involved in surgery. Results were divided into three categories, total satisfaction with scoring 9 or 10, partly satisfaction with scoring 7 or 8, and dissatisfaction with scoring 0-6. Subsequently, the percentage of satisfaction indeed in the total number of cases was counted. Alar symmetry assessment was also included. The percentage of cases with alar symmetry in the total number of cases. Third, the ratio (a/b) of the distance between the line defined by bilateral highest points of alar retraction and the line determined by tip-defining points (a) to that between the line determined by bilateral highest points of alar retraction and the horizontal line defined by the turning point of columella lobule (b) was calculated on frontal view. The value of a and b was measured using Image J, and a/b<1 represented absence of alar retraction. The statistical analysis was performed using SPSS version 20.0. Chi-square test was used to compare the symmetry of alae pre- and post-operation. Values of a/b were expressed as Mean±SD, and was compared using t-test. SNK were used for comparison among and between groups of different types, respectively. P-value less than 0.05 considered to be statistically significant. Results:Forty-three cases were included in this study, including 5 men and 38 women, with mean age of 27.3 years (18-45 yars). Among them, medial, central and lateral type of alar retraction was comprised of 17, 22 and 4 cases, respectively. The median follow-up time was 4 months (range, 1-24 months). During the follow-up, no complications like avascular necrosis of ala, step like deformity or alar contracture were observed, so was the recurrence of alar retraction. A total of 5 complications were observed, including 4 cases of hypertrophic scar at the incision which were improved after injection of Triamcinolone and 1 case of remaining alar asymmetry which was corrected by reoperation. The VAS score of patient was 8.93±1.12, and patients with satisfaction indeed accounted for 81.4% (35/43). The mean VAS score of the two operation-non-participated surgeons was 8.93±1.04; and cases assessed to be satisfaction indeed accounted for 81.4% (70/86). The proportion of symmetric alae significantly improved from 58.1% (25/43) to 93.0% (40/43) ( P<0.01). The ratio of a/b decreased from 0.79±0.06 pre-operation to 1.00±0.04 post-operation( P<0.01). While no significance was found among groups neither pre- nor post-operation ( P>0.05). Conclusions:eTDOG made of costal cartilage combining nasal vestibule V-Y advancement flap is an effective method for correction of all types of alar retraction and improvement of alar symmetry, with high satisfaction of patients and surgeons.

Objective:To investigate the effect of using extended trans-dome onlay graft(eTDOG) made of costal cartilage combined with nasal vestibule V-Y advancement flap for correction of alar retraction.Methods:Clinical data of patients diagnosed with alar retraction at Chongqing Huamei Plastic Surgery Hospital between July 2019 and October 2020 were retrospectively analyzed. The 6th or 7th right costal cartilage was harvested, cut into pieces for grafts, including a laminar trans-dome onlay graft, made from cortex part of the rib. Then a V-shaped flap was designed on the vestibular skin. At the end of the rhinoplasty, a pocket was created along the alar rim, and the eTDOG was inserted into the pocket to push down the alar rim. Nasal vestibule V-Y advancement flap provides extra soft tissue for alar retraction correction. Splints were applied to hold the eTDOG and flap in place. Assessment of therapeutic effect was made from three aspects. First of all, therapeutic satisfaction assessment, which was made based on the visual analogue scale(VAS). VAS scoring was conducted by patients and two surgeons who were not involved in surgery. Results were divided into three categories, total satisfaction with scoring 9 or 10, partly satisfaction with scoring 7 or 8, and dissatisfaction with scoring 0-6. Subsequently, the percentage of satisfaction indeed in the total number of cases was counted. Alar symmetry assessment was also included. The percentage of cases with alar symmetry in the total number of cases. Third, the ratio (a/b) of the distance between the line defined by bilateral highest points of alar retraction and the line determined by tip-defining points (a) to that between the line determined by bilateral highest points of alar retraction and the horizontal line defined by the turning point of columella lobule (b) was calculated on frontal view. The value of a and b was measured using Image J, and a/b<1 represented absence of alar retraction. The statistical analysis was performed using SPSS version 20.0. Chi-square test was used to compare the symmetry of alae pre- and post-operation. Values of a/b were expressed as Mean±SD, and was compared using t-test. SNK were used for comparison among and between groups of different types, respectively. P-value less than 0.05 considered to be statistically significant. Results:Forty-three cases were included in this study, including 5 men and 38 women, with mean age of 27.3 years (18-45 yars). Among them, medial, central and lateral type of alar retraction was comprised of 17, 22 and 4 cases, respectively. The median follow-up time was 4 months (range, 1-24 months). During the follow-up, no complications like avascular necrosis of ala, step like deformity or alar contracture were observed, so was the recurrence of alar retraction. A total of 5 complications were observed, including 4 cases of hypertrophic scar at the incision which were improved after injection of Triamcinolone and 1 case of remaining alar asymmetry which was corrected by reoperation. The VAS score of patient was 8.93±1.12, and patients with satisfaction indeed accounted for 81.4% (35/43). The mean VAS score of the two operation-non-participated surgeons was 8.93±1.04; and cases assessed to be satisfaction indeed accounted for 81.4% (70/86). The proportion of symmetric alae significantly improved from 58.1% (25/43) to 93.0% (40/43) ( P<0.01). The ratio of a/b decreased from 0.79±0.06 pre-operation to 1.00±0.04 post-operation( P<0.01). While no significance was found among groups neither pre- nor post-operation ( P>0.05). Conclusions:eTDOG made of costal cartilage combining nasal vestibule V-Y advancement flap is an effective method for correction of all types of alar retraction and improvement of alar symmetry, with high satisfaction of patients and surgeons.

COVID-19 pandemic caused by SARS-CoV-2 infection severely threatens global health and economic development. No effective antiviral drug is currently available to treat COVID-19 and any other human coronavirus infections. We report herein that a macrolide antibiotic, carrimycin, potently inhibited the cytopathic effects (CPE) and reduced the levels of viral protein and RNA in multiple cell types infected by human coronavirus 229E, OC43, and SARS-CoV-2. Time-of-addition and pseudotype virus infection studies indicated that carrimycin inhibited one or multiple post-entry replication events of human coronavirus infection. In support of this notion, metabolic labelling studies showed that carrimycin significantly inhibited the synthesis of viral RNA. Our studies thus strongly suggest that carrimycin is an antiviral agent against a broad-spectrum of human coronaviruses and its therapeutic efficacy to COVID-19 is currently under clinical investigation.

Objective To evaluate the inductive effect of interferon-γ(IFN-γ) combined with tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) on programmed necrosis of the human immortalized keratinocyte cell line HaCaT,and to explore its mechanisms.Methods In vitro cultured HaCaT cells were divided into several groups:negative control group receiving no treatment,IFN-γ group treated with 50 μg/L IFN-γ,TRAIL group treated with 4 μg/L TRAIL,and cytokine combination group treated with 50 μg/L IFN-γ and 4 μg/L TRAIL or zVAD combination group pretreated with 40 μmo/L zVAD for 1 hour followed by the treatment with 50 μg/L IFN-γand 4 μg/L TRAIL.After 48-hour treatment,the morphology of HaCaT cells were observed under a light microscope,methyl-thiazolyl-tetrazolium assay was performed to evaluate the inhibitory effect of the treatment on the proliferation of HaCaT cells,and double staining flow cytometry to detect the necrosis of HaCaT cells.Meanwhile,real-time fluorescence-based quantitative PCR (qPCR) was conducted to determine the mRNA expression of receptor interaction protein kinase 3 (RIP3) and mixed lineage kinase domain-like protein (MLKL),Western blot analysis to determine the expression of RIP1,RIP3,MLKL proteins and their phosphorylated forms (pRIP1,pRIP3,pMLKL),immunofluorescent staining to observe the distribution of pRIP3 and pMLKL in HaCaT cells,and the level of reactive oxygen species (ROS) in HaCaT cells in the above groups was detected by the fluorescence probe DCFH-DA.Statistical analysis was carried out with SPSS 22 software by using one-way analysis of variance (ANOVA) for comparing indices among different groups,and least significant difference (LSD)-t test for multiple comparisons.Results After 48-hour treatment,HaCaT cells in the cytokine combination group and zVAD combination group showed necrosis-like morphologic features.Methyl-thiazolyl-tetrazoliumassay revealed significant differences in the survival rate of HaCaT cells among the IFN-γgroup,TRAIL group,cytokine combination group,zVAD combination group and negative control group (73.16％ ± 5.71％,81.46％ ± 4.68％,72.18％ ± 2.93％,69.67％ ± 3.24％ and 100％,respectively;F =24.34,P ＜ 0.001).The necrosis rate of HaCaT cells was notably higher in the cytokine combination group and zVAD combination group (9.86％ ± 1.31％,10.33％ ± 2.16％,respectively) than in the negative control group (5.26％ ± 0.91％,t =4.61,5.07,respectively,both P ＜ 0.05).qPCR revealed that the mRNA expression of RIP3 and MLKL significantly increased in the cytokine combination group and zVAD combination group compared with the negative control group (tRIP3 =0.99,1.84,tMLKL =1.51,2.17,respectively,all P ＜ 0.05).Western blot analysis suggested that the protein expression of RIP1,RIP3,MLKL,pRIP1,pRIP3 and pMLKL significantly increased in the cytokine combination group compared with the negative control group (all P ＜ 0.05),and the zVAD combination group showed significantly decreased caspase 8 expression and increased expression of the above proteins compared with the cytokine combination group.Fluorescence microscopy showed that enhanced green dot-like or clump-like fluorescent spots (representing pRIP3) could be observed in the cytoplasm,and red fluorescent spots (representing pMLKL) could be seen on the cell membrane in the cytokine combination group.The average fluorescence intensity of ROS was significantly higher in the cytokine combination group than in the negative control group (t =702.00,P ＜ 0.05).Conclusion IFN-γcombined with TRAIL can induce the programmed necrosis of HaCaT cells with increased level of ROS.

To explore the effects of extract of selenium-enriched Astragalus membranaceus(ESAM)on insulin resistance(IR)in streptozotocin(STZ)diabetic rats. In this study, type 2 diabetes mellitus(T2DM)was established; ESAM and pioglitazone were used to intervene T2DM model rats; the general condition of rats in each group was observed, and body weight and fasting blood glucose(FBG)were recorded before modeling and after modeling. At the end of the fourth week, the blood and liver tissues of each group were collected. The total cholesterol(CHOL), triglyceride(TG), high-density lipoprotein(HDL), low-density lipoprotein(LDL)in blood were detected by biochemical detector; ELISA was used to detected content changes of blood fasting insulin(FINS), tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), C-reactive protein(CRP), interleukin-1β(IL-1β); Western blotting was used for the detection of insulin receptor substrate protein 1(IRS1), phosphorylated IRS1(p-IRS1), nuclear factor κB inhibitor kinase β(IKKβ), phosphorylated IKKβ(p-IKKβ), c -Jun N-terminal kinase(JNK), phosphorylated JNK(p-JNK)protein changes. Results showed that compared with the blank group, the body weight of the model group was significantly decreased. FBG, CHOL, TG, LDL, TNF-α, IL-6, CRP, IL-1β in the blood and p-IRS1, p-IKKβ, p-JNK in the liver was increased significantly; after intervention, pioglitazone, ESAM can reverse the body weight of the model rats and the changes of the above cytokines and proteins. In conclusion, ESAM can reduce the expression of inflammatory cytokines in T2DM rats, inhibit the increase of free fatty acids(FFA), decrease the activation of IKKβ and JNK phosphorylation in surrounding tissues, activate insulin pathway and improve the IR effect of T2DM.

BACKGROUND:It is unclear whether short-term high-intensity interval training (HIT) can be used to protect against myocardium injury after acute myocardial infarction, as wel as the underlying mechanism.
OBJECTIVE:To observe the effects of short-term HIT on the ventricular remodeling and mitochondrial content after acute myocardial infarction, and the biological effect of mitochondrial biogenesis and autophagy in this process.
METHODS:Male Sprague-Dawley rats were modeled into acute myocardial infarction by ligating coronary artery. One week later, HIT was performed:each interval consisted of 4-minute high-intensity running (80%of maximal oxygen consumption) and 3-minute active recovery (40%of maximal oxygen consumption), for 4 consecutive weeks of 5 days each week, repeated 7 cycles.
RESULTS AND CONCLUSION:Four-week HIT after acute myocardial infarction could markedly enhance left ventricular pump function and mitochondrial content, improve mitochondrial membrane potential and ATP synthetic activity, inhibit mitochondrial reactive oxygen species generation, up-regulate PGC-1α/Tfam induced mitochondrial biogenesis and Bnip3/Beclin-1 induced autophagy. These results indicate that short-term HIT can improve normal mitochondrial content after acute myocardial infarction, which in turn ameliorates myocardial systolic property and energy metabolism. As a cardiac rehabilitation method, HIT exhibits fine timeliness.

Objective To investigated the different effect of moderate-intensity continuous training (MCT) and high-intensity interval exercise training (HIT) on ventricular remodeling and mitochondrial homeostasis after acute myocardial infarction (AMI).Methods The AMI rat model was achieved by ligating coronary artery.The AMI and sham operation rats were randomly (random number) divided into four groups:sham operation group (Sham),AMI control group (AMI),AMI MCT group (AMI + M),and AMI HIT group (AMI + H).Animals in the AMI + M and AMI + H groups underwent 4 weeks MCT and HIT respectively.Five weeks after AMI,hemodynamic changes,mitochondrial bioenergetics,and PINK1,Beclinl,Mfn2,Drp1,Tfam,COXⅣ,PGC-1α were detected.Results Comparing with AMI group,in AMI + M and AMI + H groups,Beclin1,PINK1,Mfn2 and PGC-1α expression elevated significantly (P ＜0.05 or P ＜0.01),whereas ROS generation and Drp1 expression showed dramatic decrease (P ＜ 0.05 or P＜0.01).In addition,in AMI + H group,±dp/dt max,mitochondrial membrane potential,ATP synthesis activity,Tfam and COXⅣ expression improved significantly (P ＜ 0.05).Comparing with AMI + M group,in AMI + H group,± dp/dt max,PGC-1α,Tfam and COX Ⅳ expression improved significantly (P ＜ 0.05).Conclusions HIT is superior to MCT for ameliorating ventricular remodeling and mitochondrial homeostasis after AMI.