Progress and prospects of gastric cancer treatment in the 21st century / 中国癌症杂志

Gastric cancer,a malignant tumor with high morbidity and mortality in China,has characteristics such as high heterogeneity and poor prognosis.With the advent of the 21st century,significant progress has been made in gastric cancer diagnosis and treatment due to the rapid development of genomics,laparoscopic minimally invasive techniques,targeted therapy and immunotherapy.This article summarized the important research progress in the field of gastric cancer prevention and treatment since the 21st century,and looked forward to the future.We hope to make greater progress and breakthroughs in early screening,diagnosis and precise treatment of gastric cancer,further improve the overall survival rate of patients,and transform gastric cancer into a controllable"chronic disease".

Mechanism of FTO-mediated and m6A-modified PRKD2 Inhibiting Podocyte Injury in Diabetic Kidney Disease through the SIRT1/HIF-1 Pathway / 现代检验医学杂志

Objective To explore the regulatory role of fat mass and obesity-associated protein(FTO)and serine-threonine kinase protein kinase D2(PRKD2)in progression of diabetic kidney disease(DKD)and its regulatory mechanisms.Methods DKD model in vitro was constructed by podocytes(MPC5 cells)treated with high glucose(HG,35 mmol/L glucose)for 24 h.HG-induced MPC5 cells were transfected with FTO overexpression vector(pcDNA-FTO)and PRKD2 overexpression vector(pcDNA-PRKD2),or empty vector.The overexpression efficiency of FTO and PRKD2 were detected with RT-qPCR.MeRIP was used to detect the N6-methyladenosine(m6A)modification level of PRKD2 mRNA.The activity of Caspase-3 and the secretion of IL-6,TNF-α and monocyte chemotactic protein-1(MCP-1)were detected by ELISA.Cell apoptosis rate was analyzed by flow cytometry.The protein levels of FTO and PRKD2,as well as the key proteins in SIRT1/HIF-1α pathway,were evaluated by Western blot.Pearson analysis was used to analyze the correlation between FTO levels and PRKD2 levels.Results Compared with the control group without HG-induction,the protein expression of FTO(0.51±0.04 vs 1.00±0.03)and PRKD2(0.45±0.03 vs 1.01±0.04)was significantly down-regulated in HG-induced podocytes,and the differences were statistically significant(t=13.17,16.76,all P＜0.001).FTO protein levels were positively correlated with PRKD2 protein levels in HG-induced podocytes(r2=0.705 1,P＜0.001).Compared with the vector group,the m6A levels of PRKD2 mRNA(0.56±0.09 vs 1.01±0.13)in the pcDNA-FTO group were decreased,and the mRNA levels of PRKD2(3.16±0.14 vs 1.03±0.02)were increased,with significant differences(t=51.37,11.82,all P＜0.001).Compared with the control group(IL-6:512.76±61.85 pg/ml,TNF-α:28.17±2.83 pg/ml,MCP-1:157.31±17.69 pg/ml)and the vector group(IL-6:498.41±87.51 pg/ml,TNF-α:26.35±5.47 pg/ml,MCP-1:165.52±16.87 pg/ml),the secretion of IL-6(301.86±21.85 pg/ml),TNF-α(11.06±4.12 pg/ml)and MCP-1(81.45±9.03 pg/ml)were significantly decreased in the pcDNA-PRKD2 group,and the differences were statistically significant(F=7.51,10.47,61.97,all P＜0.01).Compared with the control group(caspase-3 activity:689.65±79.5 U/L,cell apoptosis:22.31%±2.69%)and the vector group(Caspase-3 activity:715.91±113.58 U/L,cell apoptosis:21.07%±3.28%),Caspase-3 activity(437.64±104.76 U/L)and the rate of apoptosis(8.41%±3.15%)were significantly decreased in the pcDNA-PRKD2 group,and the differences were statistically significant(F=2.35,79.13,all P＜0.01).Compared with the control group(SIRT1:1.01±0.05,HIF-1α:1.03±0.07)and the vector group(SIRT1:0.97±0.05,HIF-1α:1.02±0.03),SIRT1 protein levels(3.51±0.15)were increased and HIF-1α protein levels(0.37±0.07)were decreased in the pcDNA-PRKD2 group,and the differences were statistically significant(F=31.54,8.31,all P＜0.01).Conclusion FTO-mediated and m6A-modified PRKD2 suppresses inflammation and apoptosis in HG-induced podocytes through the SIRT1/HIF-1 pathway.

Phosphatidic acid-enabled MKL1 contributes to liver regeneration: Translational implication in liver failure

Liver regeneration following injury aids the restoration of liver mass and the recovery of liver function. In the present study we investigated the contribution of megakaryocytic leukemia 1 (MKL1), a transcriptional modulator, to liver regeneration. We report that both MKL1 expression and its nuclear translocation correlated with hepatocyte proliferation in cell and animal models of liver regeneration and in liver failure patients. Mice with MKL1 deletion exhibited defective regenerative response in the liver. Transcriptomic analysis revealed that MKL1 interacted with E2F1 to program pro-regenerative transcription. MAPKAPK2 mediated phosphorylation primed MKL1 for its interaction with E2F1. Of interest, phospholipase d2 promoted MKL1 nuclear accumulation and liver regeneration by catalyzing production of phosphatidic acid (PA). PA administration stimulated hepatocyte proliferation and enhanced survival in a MKL1-dependent manner in a pre-clinical model of liver failure. Finally, PA levels was detected to be positively correlated with expression of pro-regenerative genes and inversely correlated with liver injury in liver failure patients. In conclusion, our data reveal a novel mechanism whereby MKL1 contributes to liver regeneration. Screening for small-molecule compounds boosting MKL1 activity may be considered as a reasonable approach to treat acute liver failure.

Targeting cAMP in D1-MSNs in the nucleus accumbens, a new rapid antidepressant strategy

Studies have suggested that the nucleus accumbens (NAc) is implicated in the pathophysiology of major depression; however, the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated. Here, we identified a specific reduction of cyclic adenosine monophosphate (cAMP) in the subset of dopamine D1 receptor medium spiny neurons (D1-MSNs) in the NAc that promoted stress susceptibility, while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors. Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons (D2-MSNs) of depressed mice, however, the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs. We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration, but not a lower dose. The fast onset property of crocin was verified through multicenter studies. Moreover, crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN. These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc, and provide a potential rapid antidepressant drug candidate, crocin.

CircUBE2D2 regulates HMGB1 through miR-885-5p to promote ovarian cancer malignancy

Abstract Background The newly discovered CircUBE2D2 has been shown to abnormally upregulate and promote cancer progression in a variety of cancers. The present study explored circUBE2D2 (hsa_circ_0005728) in Ovarian Cancer (OC) progression. Methods CircUBE2D2, miR-885-5p, and HMGB1 were examined by RT-qPCR or WB. SKOV-3 cell functions (including cell viability, apoptosis, migration, and invasion) were validated using the CCK-8, flow cytometry, scratch assay, and transwell assay, respectively. The direct relationship between miR-885-5p and circUBE2D2 or HMGB1 was confirmed by a dual-luciferase reporter and RNA pull-down analysis. circUBE2D2′s role in vivo tumor xenograft experiment was further probed. Results OC tissue and cell lines had higher circUBE2D2 and HMGB1 and lower miR-885-5p. Mechanically, CircUBE2D2 shared a binding relation with miR-885-5p, while miR-885-5p can directly target HMGB1. Eliminating circUBE2D2 or miR-885-5p induction inhibited OC cell activities. However, these functions were relieved by down-regulating miR-885-5p or HMGB1 induction. Furthermore, circUBE2D2 knockout reduced tumor growth. Conclusion CircUBE2D2 regulates the expression of HMGB1 by acting as a sponge of ceRNA as miR-885-5p, thereby promoting the control of OC cell proliferation and migration and inhibiting cell apoptosis. Targeting CircUBE2D2 could serve as a new potential treatment strategy for OC.

Comparison of the learning curve of robot -assisted and laparoscopic -assisted gastrectomy / 中南大学学报(医学版)

OBJECTIVES@#Da Vinci robot technology is widely used in clinic,with minimally invasive surgery development. This study aims to explore the possible influence of advanced surgical robotics on the surgery learning curve by comparing the initial clinical learning curves of 2 different surgical techniques: robotic-assisted gastrectomy (RAG) and laparoscopic-assisted gastrectomy (LAG).@*METHODS@#From September 2017 to December 2020, a chief surgeon completed a total of 108 cases of radical gastric cancer from the initial stage, including 27 cases of RAG of the Da Vinci Si robotic system (RAG group) and 81 cases of LAG (LAG group). The lymph node of gastric cancer implemented by the Japanese treatment guidelines of gastric cancer. The surgical results, postoperative complications, oncology results and learning curve were analyzed.@*RESULTS@#There was no significant difference in general data, tumor size, pathological grade and clinical stage between the 2 groups (P>0.05). The incidence of serious complications in the RAG group was lower than the LAG group (P=0.003). The intraoperative blood loss in the RAG group was lower than that in the LAG group (P=0.046). The number of lymph nodes cleaned in the RAG group was more (P=0.003), among which there was obvious advantage in lymph node cleaning in the No.9 group (P=0.038) and 11p group (P=0.015). The operation time of the RAG group was significantly longer than the LAG group (P=0.015). The analysis of learning curve found that the cumulative sum analysis (CUSUM) value of the RAG group decreased from the 10th case, while the CUSUM of the LAG group decreased from the 28th case. The learning curve of the RAG group had fewer closing cases than that of the LAG group. The unique design of the surgical robot might help to improve the surgical efficiency and shorten the surgical learning curve.@*CONCLUSIONS@#Advanced robotics helps experienced surgeons quickly learn to master RAG skills. With the help of robotics, RAG are superior to LAG in No.9 and 11p lymph node dissection and surgical trauma reduction. RAG can clear more lymph nodes than LAG, and has better perioperative effect.

The regulatory mechanisms and inhibitors of isocitrate dehydrogenase 1 in cancer

Reprogramming of energy metabolism is one of the basic characteristics of cancer and has been proved to be an important cancer treatment strategy. Isocitrate dehydrogenases (IDHs) are a class of key proteins in energy metabolism, including IDH1, IDH2, and IDH3, which are involved in the oxidative decarboxylation of isocitrate to yield α-ketoglutarate (α-KG). Mutants of IDH1 or IDH2 can produce d-2-hydroxyglutarate (D-2HG) with α-KG as the substrate, and then mediate the occurrence and development of cancer. At present, no IDH3 mutation has been reported. The results of pan-cancer research showed that IDH1 has a higher mutation frequency and involves more cancer types than IDH2, implying IDH1 as a promising anti-cancer target. Therefore, in this review, we summarized the regulatory mechanisms of IDH1 on cancer from four aspects: metabolic reprogramming, epigenetics, immune microenvironment, and phenotypic changes, which will provide guidance for the understanding of IDH1 and exploring leading-edge targeted treatment strategies. In addition, we also reviewed available IDH1 inhibitors so far. The detailed clinical trial results and diverse structures of preclinical candidates illustrated here will provide a deep insight into the research for the treatment of IDH1-related cancers.

Genome sequencing and analysis of BCG strain for vaccine production in China / 上海预防医学

ObjectiveTo conduct the sequencing and preliminarily analysis of the whole genome of BCG Shanghai D2PB302 strain （hereinafter referred to as BCG Shanghai D2 strain）， which has been used exclusively for the vaccine production in China. MethodsThe DNA of of BCG Shanghai D2 strain （D2-JIA12-1） was extracted， and the whole genome was sequenced by Pacbio-RS Ⅱ. The sequence data was assembled by Smrtlink and polished with the illumina data. Genes， tRNA and rRNA were predicted based on the sequence data. The functional annotation of predicted genes was performed through BLASTP. The IVE-TB antigen gene and MTBVAC were selected as the target sequences to be compared with Mycobacterium tuberculosis H37Rv （NC_000962.3）. ResultsThe sequence length of BCG Shanghai D2 strain was 4 045 232 bp， and the GC content was 65.66%. A total of 4 259 protein-encoding genes were predicted， with an average gene size of 933 bp. 2 476 genes had biological functions and others were hypothetical proteins.144 virulence genes were obtained by comparing with the VFDB. There were 29 type Ⅶ secretion system genes and 10 PE/PPE protein family genes. ConclusionThe whole genome sequence of BCG Shanghai D2 strain is clarified. It lays a broad foundation for subsequent detection of the stability of major antigen genes.

The function mechanism of FANCD2 and its research progress in tumors / 中国医师杂志

Fanconi anemia (FA) is an autosomal recessive inherited disease and the most common hereditary bone marrow failure syndrome, which can lead to bone marrow failure, increased risk of cancer, and developmental abnormalities. FANCD2 is a member of the FA gene family and has become the focal point of FA signaling. Research has found that FANCD2 plays an important role in the occurrence and development of tumors and can participate in regulating ferroptosis as a related gene. This article reviews the mechanism of action of FANCD2 and its research progress in tumors, in order to provide new directions and ideas for the diagnosis and treatment of diseases.

Analysis of Internal Transcribed Spacer (ITS) region and D1/D2 domain coupled with Random Amplified Polymorphic DNA (RAPD) reveal the inter- and intraspecific relationships of Diutina rugosa and Diutina mesorugosa isolated from Malaysian patients

Aims@#This study was aimed to characterise nine clinical isolates in our culture collection that were categorized as Diutina species based on their molecular genetic profiles. D. rugosa is a species complex comprising four taxa., i.e., D. rugosa sensu stricto, D. pseudorugosa, D. neorugosa and D. mesorugosa. The most commonly used phenotypic identification methods for yeasts often lead to the misidentification of this species complex. @*Methodology and results@#The Diutina isolates were received from two local referral hospitals as pure cultures. Species confirmation was performed using conventional phenotypic methods; CHROMagar and RapID Yeast Plus Kit. To study the inter- and intraspecific relationships among the clinical isolates, ITS region, D1/D2 domain and random amplified polymorphic DNA (RAPD) analyses were performed. The results were further validated using the housekeeping gene sequence similarity technique coupled with pairwise sequence alignment. The results from phenotypic methods results were ambiguous and inconclusive. The sequence analyses of ITS regions and D1/D2 domains revealed that the samples consisted of three yeast species; D. rugosa complex: D. rugosa (n=1), D. mesorugosa (n=6), Candida pararugosa (n=1) and Meyerozyma guilliermondii (n=1). The RAPD analysis with random primers, OPG4, OPG11 and OPA18, demonstrated good banding patterns that could distinguish between the Diutina isolates. The pairwise sequence alignment revealed that the Diutina isolates were genetically similar to D. rugosa ATCC 10571.@*Conclusion, significance and impact of study@#The molecular methods, D1/D2 domain, ITS1 and ITS4 region, and RAPD analyses have proven helpful for accurately identifying the yeasts, especially closely related species; D. rugosa and D. mesorugosa.

Application value of the aortic dissection detection risk score plus D-dimer for the early diagnosis of acute aortic dissection / 中国基层医药

Objective:To investigate the application value of aortic dissection detection risk score (ADD-RS) combined with D-dimer (DD) in the early diagnosis of acute aortic dissection (AAD).Methods:The clinical data of 70 patients with suspected aortic dissection detection admitted to The Second Hospital of Jiaxing from August 2019 to April 2020 were collected. All patients were scored using the ADD-RS, and grouped according to the scoring results. The sensitivity and specificity of ADD-RS plus DD in the early diagnosis of AAD were calculated. The areas under the receiver operating characteristic (ROC) curves that were plotted for drADD-RS plus DD versus DD alone to screen AAD were compared to evaluate efficacy. Results:CT angiography results showed that among 70 patients with suspected AAD, 29 patients had AAD and 41 patients had no AAD. A total of 21 patients were scored 0, 41 patients were scored > 1, and 8 patients were scored > 0. ADD-RS > 0 had an overall sensitivity of 79.31% and a specificity of 36.59% for AAD diagnosis. DD test results had an overall sensitivity of 86.20% and a specificity of 36.50% for AAD diagnosis. The area under the ROC curve of ADD-RS = 0 plus DD-negative result and the area under the ROC curve of DD-negative result alone in ruling out AAD were 0.885 with 95% CI (0.786-0.949) and 0.787 with 95% CI (0.673-0.876), respectively. The difference between the two groups was statistically significant ( P = 0.024). Conclusion:Compared with DD-negative result alone, the ADD-RS = 0 plus DD-negative result strategy offers greater specificity to rule out AAD. The combined strategy has a greater efficacy in ruling out AAD. However, a multi-center study involving a large sample is required for in-depth evaluation.

Influential factors of hypoalbuminemia in patients with preeclampsia and observation of pregnancy outcomes / 中国基层医药

Objective:To analyze the influential factors of hypoalbuminemia in patients with preeclampsia and observe the pregnancy outcomes.Methods:The clinical data of 237 pregnant women with preeclampsia who received treatment in The Sixth Affiliated Hospital of Guangzhou Medical University (Qingyuan People's Hospital) from July 2018 to December 2020 were retrospectively collected and analyzed. These patients were divided into hypoproteinemia (observation group) and no hypoproteinemia (control group) groups according to whether they had hypoproteinemia. The general situation, clinical data, and adverse maternal and infant outcomes were statistically analyzed. Risk factors of hypoalbuminemia were analyzed using a logistic regression model. The predictive efficacy was evaluated using the receiver operating characteristic curve.Results:There were no significant differences in general data between the two groups (all P > 0.05). Multivariate analysis showed that D-dimer ( OR = 1.25, P = 0.004), 24-hour urinary protein ( OR = 1.29, P < 0.001), and total bile acid ( OR = 1.08, P = 0.010) were the independent risk factors for hypoproteinemia in preeclampsia. The predictive efficacy of these three indicators (area under the receiver operating characteristic curve = 0.855, P < 0.001) was greater than that of a single indicator. The incidences of adverse maternal and infant outcomes including placental abruption (9.4%, P = 0.019), liver and kidney dysfunction (34.4%, P < 0.001), pleural and ascitic fluid (28.1%, P = 0.001), fetal intrauterine growth restriction (50.0%, P = 0.001), fundus lesions (6.2%, P = 0.018), HELLP syndrome (9.4%, P = 0.019), mild neonatal asphyxia (15.6%, P = 0.022), severe asphyxia (6.2%, P = 0.049), metabolic acidosis (12.5%, P = 0.001), intrauterine infection (12.5%, P = 0.004), and neonatal hospitalization for more than 20 days (37.5%, P < 0.001) were greater in the observation group compared with the control group. There were no significant differences in postpartum hemorrhage, eclampsia, respiratory distress syndrome, fetal loss, and neonatal death between the two groups (all P > 0.05). Conclusion:D-dimer, 24-hour urinary protein, and total bile acid are independent risk factors for hypoproteinemia in preeclampsia. Patients with preeclampsia complicated by hypoproteinemia have a high risk of adverse maternal and infant outcomes.

Comparison of unilateral medial forebrain bundle and unilateral striatum lesioned by 6-hydroxydopamine at early lesioned stage in rat model / 安徽医科大学学报

Objective@#To compare the functional changes of neurotransmitters in the dopamine ( DA) system of rats lesioned by 6-hydroxydopamine in unilateral medial forebrain bundle ( MFB) and unilateral striatum after 4 weeks of modeling．@*Methods @#Adult male Sprague-Dawley rats (n = 62) were divided randomly into four groups : single-site model ( one site striatal lesion model，n = 18) ，four-site model ( four sites striatal lesion model，n = 18) ，MFB model (MFB lesion model，n = 18) and a sham operated control group (n = 8) ．Immunohistochemical tyrosine hydroxylase (TH) staining was used to calculate the loss rate of positive DA neurons．The functional changes of dopamine transporters(DAT) and D2 receptors in rat models of four groups were detected by radioligand-receptor binding assay in vitro，behavioral test and small-animal PET. @*Results @# Immunohistochemical staining results of TH at 1-lesion，4-lesion and MFB model showed that the TH-positive cell loss rates of the lesion side in three models were 19. 1% ，84. 7% and 97. 1% ，respectively，indicating that the model was successfully constructed. The results of DAT / D2 receptor functions in the three models showed that，compared with the sham operated control group，the DAT binding ratio of radioactivity on the lesion side of 1-lesion，4-lesion and MFB model significantly decreased (P＜0. 05，P＜0. 05 and P＜0. 01) ．The DAT binding ratio of radioactivity on the lesion side was compared among 1，4 lesion and MFB model．It was found that the decrease degree of MFB model was significantly higher than that of the previous two models (P＜0. 01) ，and the decrease degree of 4-lesion model was significantly higher than that of 1-lesion model (P＜0. 05) ．Compared with the sham operated control group，the D2 receptor binding ratio of radioactivity on the lesion side of 1-lesion and 4-lesion model significantly decreased (P＜0. 05) ， and there was no significant difference in the degree of decrease between the two models，but the D2 receptor binding ratio of radioactivity on the lesion side of MFB model significantly increased (P＜0. 05) ．There was no difference in the distribution of DAT / D2 receptor on the lesion side and the normal side of the sham operated control group．Methamphetamine caused ipsilateral rotations to the lesion side in all models． There were no significant differences in methamphetamine-induced rotation among 1-lesion，4-lesion and MFB models．Bromocriptine caused ipsilateral rotations to the lesion side in 1-lesion and 4-lesion models but contralateral rotations in MFB model. There were no significant differences in bromocriptine-induced rotation between 1-lesion and 4-lesion models．The results of stepping test showed the motion initiation time of the lesion side was significantly longer than that of the normal side，the stepping length of the lesion side was significantly shorter than that of the normal side，and the adjusting steps of the lesion side was significantly less than that of the normal side (P＜0. 001) ，but there was no significant difference of the lesion side in the initiation time ，stepping length ，and adjusting steps among the three groups of models． @*Conclusion@#The striatal lesion and MFB lesion models showed different pathophysiological processes in terms of DA neurotransmitter functions and behavior．The MFB lesion model can mimic primary Parkinson's disease，while the striatal lesion model is similar to some Parkinson syndromes.

Research progress of 5-HT / 中国药理学通报

The serotonin 2A receptor(5-HT

The Dynamics of Dopamine D2 Receptor-Expressing Striatal Neurons and the Downstream Circuit Underlying L-Dopa-Induced Dyskinesia in Rats / 神经科学通报·英文版

L-dopa (l-3,4-dihydroxyphenylalanine)-induced dyskinesia (LID) is a debilitating complication of dopamine replacement therapy for Parkinson's disease. The potential contribution of striatal D2 receptor (D2R)-positive neurons and downstream circuits in the pathophysiology of LID remains unclear. In this study, we investigated the role of striatal D2R+ neurons and downstream globus pallidus externa (GPe) neurons in a rat model of LID. Intrastriatal administration of raclopride, a D2R antagonist, significantly inhibited dyskinetic behavior, while intrastriatal administration of pramipexole, a D2-like receptor agonist, yielded aggravation of dyskinesia in LID rats. Fiber photometry revealed the overinhibition of striatal D2R+ neurons and hyperactivity of downstream GPe neurons during the dyskinetic phase of LID rats. In contrast, the striatal D2R+ neurons showed intermittent synchronized overactivity in the decay phase of dyskinesia. Consistent with the above findings, optogenetic activation of striatal D2R+ neurons or their projections in the GPe was adequate to suppress most of the dyskinetic behaviors of LID rats. Our data demonstrate that the aberrant activity of striatal D2R+ neurons and downstream GPe neurons is a decisive mechanism mediating dyskinetic symptoms in LID rats.

Histopathological and immunohistochemical clues to the illusive diagnosis of follicular dendritic cell sarcoma: A clinicopathological masquerader

Follicular dendritic cell sarcoma is a rare histiocytic and dendritic neoplasm mainly involving the lymph nodes and selective extranodal sites. They are often misdiagnosed due to nonspecific clinical, radiological, and morphological findings in addition to their rarity. Four cases described below had variable age of presentation, site of involvement, size of the lesion, and histopathological features. Application of an extensive immunohistochemical panel, including a combination of >1 dendritic cell marker, clinched the diagnosis. A combination of D2-40 and Cluster of differentiation 21 (CD21) worked best in establishing a definite role in the current series. Programmed death-ligand 1 (PD-L1) analysis was positive in two of the three cases where it could be performed. However, none of our cases had received immunotherapy. Prompt recognition of the described histopathology features and incorporation of novel immunohistochemical markers can translate to timely initiation of therapy for this aggressive disease

La relación entre el biomarcador índice digital D2:D4 y el diagnóstico psicopedagógico de TDAH. Datos de un estudio / The relationship between the biomarker ratio D2:D4 and the psycho-pedagogical diagnosis of ADHD. Data from a study

Resumen La hipótesis organizacional sostiene que el índice digital D2:D4 (obtenido de la división entre la longitud de los dedos índice y anular) es un biomarcador que informa de la sobreexposición a la testosterona a nivel prenatal (Myers et al., 2018). El objetivo del presente trabajo fue determinar si el índice digital podría ser útil en el diagnóstico psicopedagógico del trastorno por déficit de atención con hiperactividad (TDAH), dado que los trabajos previos no son concluyentes en este punto (Stevenson et al., 2007; Wang et al., 2017). La muestra estudiada estuvo conformada por 82 estudiantes de ambos sexos (Medad = 11.77 años, DE = 2.97) de la región de Andalucía (España), igualada en edad, sexo y nivel cognitivo. La mitad de los participantes tenía diagnóstico de TDAH, la otra mitad, no. Los resultados reflejan menor índice digital en participantes del grupo con diagnóstico de TDAH (.945) versus el grupo control (.995), y estas diferencias son significativas (p = .000), independientemente del sexo. Además, la presencia de determinados comportamientos en el entorno doméstico (medidos con la Escala Conners) correlaciona positivamente con un bajo valor del índice digital (r = .47; p = .001) y con el diagnóstico psicopedagógico de TDAH.

Abstract The digital ratio D2:D4 (length of the index finger between the length of the ring finger) is a biomarker that reports the presence of high levels of testosterone during the prenatal period. A differential digital pattern (D2 < D4) has been found in several disorders (ASD or Klinefelter's syndrome) although data for Attention Deficit Hyperactivity Disorder (ADHD) are not conclusive (Stevenson et al., 2007; Wang et al., 2017). The aim of this paper was to determine whether digital ratio can be used as an indicator in the psychoeducational diagnosis of ADHD. A sample of 82 students of both sexes aged between 6 and 16 years (M = 11.77, SD = 2.97) from the Andalusian Community was taken. Among the members of the sample there were no differences in terms of sex, age, or cognitive level. The sample was divided into two groups, the group with a psycho-pedagogical diagnosis of ADHD and the control or undiagnosed group. The group with ADHD consisted of 42 subjects and the control group consisted of 46 subjects. All sessions were conducted individually for each of the subjects and their families following these guidelines: the session began with the parent signing a consent form that allowed the therapist to proceed with the intervention. After that, the TONI-2 non-verbal intelligence test was given to the child by the therapist in a quiet room. At the same time, the parents responded to the Conners Scale questions on behaviour at home to verify the existence or not of behavioural symptoms compatible with the presence of ADHD. For parents of children with ADHD diagnosis, an interview was conducted to learn about the course of the disease to have a general profile of the patient and his or her disorder. Finally, the participants' right hand was scanned at the same school with an HP DeskJet 2630 scanner printer. Using the scanner and the Adobe Photoshop® tool, the length of the index and ring fingers was measured [(from proximal line of the finger to the end of the distal phalanx of the index (D2) and ring (D4) fingers]. The digital measurements from the scanned images were taken by the two researchers who signed the work, and there was more than 90 % agreement on the measurements. The results show a lower digital index in participants in the ADHD group (.945) versus the control group (.995), these differences being significant (p = 0.000), regardless of gender. In addition, the presence of certain behaviours in the home environment (measured with the Conners Scale) correlates positively with a low value of the digital index (r = .47; p = .001) and with the psycho-pedagogical diagnosis of ADHD. Significant differences have been shown in this study. Subjects with a psychopedagogical diagnosis of ADHD have been exposed to higher levels of testosterone during pregnancy since they present a lower D2:D4 ratio compared to the participants in the control group (without a diagnosis of ADHD), in line with the work of Martel et al. (2008) and Wang et al. (2017). In addition, this study has found that the group with psychopedagogical diagnosis of ADHD has a shorter index finger than the ring finger in both boys and girls, while for the control group the digital pattern is reversed or there is no difference between the two fingers. Therefore, we consider that the digital ratio biomarker (D2:D4) may be an additional useful criterion for the psychopedagogical diagnosis of ADHD or at least as a screening method.

The importance of optimal 25-hydroxyvitamin D levels in the glycemic control of older adults with type 2 Diabetes Mellitus: Data from the study on aging and longevity EELO

INTRODUCTION: Optimal serum levels of vitamin D are of great importance, especially in populations with comorbidities such as Diabetes Mellitus (DM). OBJECTIVE: The study evaluated the relationship between hypovitaminosis D and glycemic control in older adults with type 2 DM. METHODS: Cross-sectional and prospective study, part of the EELO project (Study on Aging and Longevity), conducted in Southern Brazil. Glycated hemoglobin (diabetes ≥6.5%) and serum levels of vitamin D (25(OH)D) were evaluated. Hypovitaminosis D was determined using cutoff points <20 and <30 ng/mL). Multivariate logistic regression was used to assess the risk of having uncontrolled DM. RESULTS: Of the 120 older adults included in the study, aged between 60 and 87 years, 74.2% were women, 66.7% used hypoglycemic medications and 75.8% exhibited uncontrolled diabetes. An inverse correlation was observed between the levels of 25(OH) D and glycated hemoglobin (rS=-0.19, p=0.037), suggesting that low levels of vitamin D are associated with poor glycemic control in diabetic individuals. The prevalence of hypovitaminosis D when using the cutoff points of <20 and <30 ng/mL were 34.2% and 75.0%, respectively. The odds ratio (OR) analysis showed that individuals with 25(OH)D<20ng/mL have almost 4 times more risk of having uncontrolled DM (OR:3.94; CI95%:1.25-12.46, p=0.02) when compared to the older adults with sufficient levels of vitamin D. CONCLUSION: The results indicate that the optimal serum levels currently recommended for 25(OH)D should preferably be 30 ng/mL or higher to contribute to better glycemic control in older adults with type 2 DM.

INTRODUÇÃO: Os níveis séricos ideais de vitamina D são de grande importância, especialmente na população com comorbidades como o Diabetes Mellitus (DM). OBJETIVO: O estudo avaliou a relação entre hipovitaminose D e controle glicêmico em idosos com DM tipo 2. MÉTODOS: Estudo transversal e prospectivo, parte do projeto EELO (Estudo sobre Envelhecimento e Longevidade), no Sul do Brasil. A hemoglobina glicada (diabetes ≥6,5%) e os níveis séricos de vitamina D (25(OH)D) foram avaliados. Hipovitaminose D foi determinada usando ponto de corte <20 e <30 ng/mL. Regressão logística multivariada foi utilizada para avaliar o risco de ter DM descompensado. RESULTADOS: Dos 120 idosos incluídos no estudo, idade entre 60 a 87 anos, 74,2% eram mulheres, 66,7% faziam uso de medicamentos hipoglicemiantes e 75,8% apresentavam diabetes descompensada. Uma correlação inversa foi observada entre os níveis de 25(OH)D e hemoglobina glicada (rS=-0,19; p=0.037), sugerindo que baixos níveis de vitamina D está associado a um pior controle glicêmico em diabéticos. A prevalência de hipovitaminose D quando se utiliza ponto de corte <20 e <30 ng/mL foi de 34,2% e 75,0%, respectivamente. A análise Odds ratio (OR) mostrou que indivíduos com 25(OH)D<20 ng/mL tem quase 4 vezes mais risco de ter DM descompensado (OR:3,94; IC95%:1,25­12,46; p=0,02) quando comparado aos idosos com níveis suficientes de vitamina D. CONCLUSÃO: Os resultados indicam que os níveis sérios ideais atualmente recomendados para 25(OH)D maior ou igual a 30 ng/ml contribuem para o melhor controle glicêmico na população idosa com DM tipo 2.

Interpretation of 2021 China Chest Pain Center Quality Control Report / 中国胸心血管外科临床杂志

@#The Medical Administration and Hospital Administration of the National Health Commission released the "2021 China Chest Pain Center Quality Control Report" in January 2022. This report analyzes the construction ratio of chest pain centers in the second-level and above medical institutions nationwide in 2021 and the construction of standard and basic chest pain centers, mainly from the way of coming to the hospital, symptom onset to first medical contact time, door to wire time, reperfusion therapy ratio, in-hospital mortality, proportion of discharges with medication recommended by the guidelines and average length and cost of hospital stay of ST-segment elevation myocardial infarction patients to comprehensively describe the current status of the construction of the national chest pain centers. This article interprets the report in detail by reviewing relevant literature.

Metabolomics study of rat tail vibration model / 环境与职业医学

Background The metabolites and metabolic pathways of hand-arm vibration syndrome have not yet been elucidated. Objective To investigate the effect of local vibration on endogenous metabolites in rat serum by metabolomic analysis, to preliminarily explore the potential metabolic pathway of endogenous metabolites, so as to provide evidence for further research on the mechanism of hand-arm vibration syndrome. Methods Thirty-two SPF male SD rats, (211.3±11.1) g, 7−8 weeks of age, were selected and randomly divided into three groups: control group (14 rats, without vibration), 7 d vibration group (9 rats, continuously vibration for 7 d), and 14 d vibration group (9 rats, continuous vibration for 14 d). The vibration rats were vibrated every day for 4 h, the frequency weighted acceleration was 4.9 m·s−2, the vibration frequency was 125 Hz, and the vibration direction was one-way vertical vibration. The control group had the same conditions except not contacting vibration. After the vibration exposure, the blood samples taken from the abnormal aorta of rats were collected, and the changes of rat serum metabolome were analyzed by ultra-performance liquid chromatography-tandem time-of-flight mass spectrometry. Principal components analysis (PCA) was used to explore changes in rat serum metabolic profile, and orthogonal partial least squares-discriminant analysis (OPLS-DA) was used to screen out differential metabolites. Combined with online databases, a metabolic pathway enrichment analysis of differential metabolites was performed. Results The PCA analysis showed that compared with the control group, the rat serum metabolic profiles in the 7 d group and the 14 d group were clearly differentiated, and the rat serum metabolic profiles in the 7 d group and the 14 d group partially overlapped. The OPLS-DA analysis showed significant differences between groups. The main parameters were: model interpretation rate R2Y=0.914, model predictive ability Q2=0.58. The OPLS-DA analysis screened out 26 and 119 differential metabolites from the 7 d group and the 14 d group respectively, and there were 24 common differential metabolites between the 7 d group and the 14 d group. The metabolomic pathway analysis showed that local vibration-induced changes in rat serum metabolism were mainly related to arachidonic acid metabolism in the 14 d group, among which the metabolites with significant effects were arachidonic acid, prostaglandin E2, and prostaglandin D2. Conclusion Local vibration could affect the normal metabolism in rats, and the metabolic pathway with significant influence is arachidonic acid metabolism after a 14 d exposure and the involved metabolites are arachidonic acid, prostaglandin E2, and prostaglandin D2.