The GG genotype of rs743572 in CYP17A1 gene regulating the decrease of T/E ratio can be an independent risk factor for MetS-BPH: a retrospective cohort study.

PURPOSE: To confirm if the CYP17A1 gene regulates the ratio of T/E leading to MetS-BPH. METHODS: 824 men, aged 47-88 years, were recruited into this study through consecutive routine physical examination programs and long-term outpatient screening. Several parameters, including SNPs of CYP17A1 gene, total testosterone, estradiol, and the ratio of total testosterone to estradiol (T/E) were obtained for each participant. Based on the diagnosis of BPH, MetS, and MetS-BPH, the participants were divided into BPH and non-BPH groups, MetS and non-MetS groups, and MetS-BPH and non-MetS-BPH groups. Values of the obtained parameters were evaluated using one-way analysis of variance, Student's t-test, Chi-squared test, and logistic regression analysis. RESULTS: SNPs of the CYP17A1 gene, including the rs743572 genotypes (GG, GA, and AA), rs3781287 genotypes (GG, GT, TT), and rs4919686 genotypes (CC, CA, and AA), were present in every group. Only the GG genotype of rs743572 was independently associated with BPH (OR = 5.868, 95% CI: 3.363-7.974, P < 0.001), MetS (OR = 7.228, 95% CI: 3.925-11.331, P < 0.001), and MetS-BPH (OR = 3.417, 95% CI: 1.783-5.266, P < 0.001) after adjusting for age. In the population of genotype GG of rs743572, the decrease in T/E ratio was an independent risk factor for BPH (OR = 839.756, 95% CI: 36.978-1334.263, P = 0.001), MetS (OR = 376.988, 95% CI: 12.980-488.976, P < 0.003), and MetS-BPH (OR = 388.236, 95% CI: 24.869-495.363, P = 0.003). CONCLUSION: The GG genotype of rs743572 in CYP17A1 gene regulating the decrease of T/E ratio can be an independent risk factor for MetS-BPH populations. TRIAL REGISTRATION NUMBER: ChiCTR2200057632 "retrospectively registered". DATE OF REGISTRATION: March 15, 2022 "retrospectively registered".

Molecular Phylogenetics and the Evolution of Morphological Complexity in Aytoniaceae (Marchantiophyta).

Aytoniaceae are one of the largest families of complex thalloid liverworts (Marchantiopsida), consisting of about 70 species, with most species being distributed in temperate areas. However, the phylogeny and evolution of the morphological character of Aytoniaceae are still poorly understood. Here, we employed two chloroplast loci, specifically, rbcL and trnL-F, along with a 26S nuclear ribosomal sequence to reconstruct the phylogeny and track the morphological evolution of Aytoniaceae. Our results reveal that Aytoniaceae are monophyletic, and five monophyletic clades were recovered (i.e., Asterellopsis-Cryptomitrium, Calasterella, Mannia, Reboulia-Plagiochasma, and Asterella). Asterella was divided into five clades (i.e., Asterella lindenbergiana, subg. Saccatae, subg. Phragmoblepharis, subg. Wallichianae, and subg. Asterella), except for Asterella palmeri, which is the sister of Asterellopsis grollei. Bayesian molecular clock dating indicates that the five primary clades within Aytoniaceae underwent divergence events in the Cretaceous period. Asterellopsis differentiated during the early Upper Cretaceous (c. 84.2 Ma), and Calasterella originated from the late Lower Cretaceous (c. 143.0 Ma). The ancestral Aytoniaceae plant is reconstructed as the absence of a pseudoperianth, lacking equatorial apertures, and having both male and female reproductive organs on the main thallus. At present, Asterellopsis consists of two species known in Asia and America with the new transfer of Asterella palmeri to Asterellopsis. A new subgenus, Asterella subg. Lindenbergianae, is proposed.

Exploring the role of pyroptosis and immune infiltration in sepsis based on bioinformatic analysis.

PURPOSE: Sepsis is a disease that is typically treated in intensive care units with high mortality and morbidity. Pyroptosis is a newly identified type of programmed cell death and is characterized by inflammatory cytokine secretion. However, the role of pyroptosis in sepsis remains unclear. METHODS: GSE28750 and GSE134347 datasets were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed pyroptosis genes (DEPGs) were identified between sepsis and healthy controls. Machine learning was used to further narrow the gene range. Receiver operating curves (ROC) were generated to estimate the diagnostic efficacy. Immune infiltration levels were estimated via single-sample gene set enrichment analysis (ssGSEA). A network database was used to predict the upstream transcription factors and miRNAs of DEPGs. Finally, the expression of the genes was validated by qRT-PCR between sepsis patients and healthy controls. RESULTS: We found that the pyroptosis pathway was enriched and activated in sepsis. 8 DEPGs were identified. A heatmap showed that the genes, NLRC4, NAIP, IL-18, AIM2 and ELANE, were abundant in the sepsis samples, and the genes, NLRP1, CHMP7 and TP53, were abundant in the healthy control samples. The ssGSEA results showed that the abundances of activated dendritic cells, MDSC, macrophage, plasmacytoid dendritic cells, regulatory T-cells, and Th17-cells were significantly higher, while the activated B-cell, activated CD8 T-cell, CD56 dim tural killer cell, immature B-cell, monocyte, and T follicular helper cell abundances were lower in sepsis samples compared to healthy controls. The qRT-PCR results showed that the expression levels of NAIP, IL-18, TP53, CHMP7, NLRC4, ELANE and NLRP1 were consistant with the bioinformatic analyses, while the expression level of AIM2 has no significant difference. CONCLUSION: Our study identified seven potential pyroptosis-related genes, NAIP, IL-18, TP53, CHMP7, NLRC4, ELANE and NLRP1. This study revealed that pyroptosis may promote sepsis development by activating the immune response.

Schistosoma-related molecules as a new strategy to combat type 1 diabetes through immune regulation.

The study of immune regulation mechanisms induced by parasites may help develop new treatment methods for inflammatory diseases including type 1 diabetes, which is related to type 1 immune responses. The negative correlation between schistosomiasis infection and type 1 diabetes has been confirmed, and the mechanism of Schistosoma-mediated prevention of type 1 diabetes may be related to the adaptive and innate immune systems. Schistosoma-related molecules affect immune cell composition and macrophage polarization and stimulate an increase in natural killer T cells. Furthermore, Schistosoma-related molecules can regulate the adaptive immune responses related to the prevention of type 1 diabetes and change the Th1/Th2 and Th17/Treg axis. Our previous review showed the role of regulatory T cells in the protective of type 1 diabetes mediated by Schistosoma. Here, we aim to review the other mechanisms of schistosomiasis infection and Schistosoma-related products in regulating the immune response associated with the treatment of type 1 diabetes.

Dysfunction of duplicated pair rice histone acetyltransferases causes segregation distortion and an interspecific reproductive barrier.

Postzygotic reproductive isolation, which results in the irreversible divergence of species, is commonly accompanied by hybrid sterility, necrosis/weakness, or lethality in the F1 or other offspring generations. Here we show that the loss of function of HWS1 and HWS2, a couple of duplicated paralogs, together confer complete interspecific incompatibility between Asian and African rice. Both of these non-Mendelian determinants encode the putative Esa1-associated factor 6 (EAF6) protein, which functions as a characteristic subunit of the histone H4 acetyltransferase complex regulating transcriptional activation via genome-wide histone modification. The proliferating tapetum and inappropriate polar nuclei arrangement cause defective pollen and seeds in F2 hybrid offspring due to the recombinant HWS1/2-mediated misregulation of vitamin (biotin and thiamine) metabolism and lipid synthesis. Evolutionary analysis of HWS1/2 suggests that this gene pair has undergone incomplete lineage sorting (ILS) and multiple gene duplication events during speciation. Our findings have not only uncovered a pair of speciation genes that control hybrid breakdown but also illustrate a passive mechanism that could be scaled up and used in the guidance and optimization of hybrid breeding applications for distant hybridization.

Research progress of virtual reality and augmented reality technology in colorectal surgery / 中国医学装备

With the rapid development of artificial intelligence and deep learning,virtual reality(VR)and augmented reality(AR)technologies have been widely used in the medical field with their unique advantages.Despite the rapid advances of techniques in colorectal surgery,the risk of colorectal surgery remained high due to the complexity of colorectal anatomy,and the burden of postoperative symptoms remained high.VR and AR technologies can help overcome some of these challenges.The application of VR and AR in colorectal surgery was reviewed,including education and training,surgical assistance,patient education,symptom management,etc.,in order to provide references for clinical application of VR and AR in colorectal surgery.

Focusing on the treatments for delayed cerebral ischemia in neurocritical ill patients / 中国实用内科杂志

Delayed cerebral ischemia(DCI)is a disease that seriously threatens the lives of critically ill patients,which is a primary cause of disability and death in patients after subarachnoid hemorrhage(SAH).However,due to severe neurological damage and clinical manifestations being not obvious,and diagnosis being difficult,DCI is not paid attention to by clinicians.The basis for understanding DCI is the transition from emphasizing macroscopic(vasospasm) to microscopic(microcirculation disfunction,impaired autonomic regulation)in pathophysiological processes.Early diagnosis and effective treatment are the key to prevention and treatment of DCI.Through reviewing literatures,this article elaborates on the definition of DCI,monitoring techniques,and treatment methods,and discusses the integrated prevention and treatment strategies of DCI.

Dose-related effects of dexmedetomidine on immunomodulation and mortality to septic shock in rats / 世界急诊医学杂志（英文）

BACKGROUND:Dexmedetomidine has already been used in septic patients as a new sedative agent, few studies have examined its effects on immunomodulation. Therefore, the authors have designed a control ed experimental study to characterize the immunomodulation effects of dexmedetomidine in the cecal ligation and puncture (CLP) model in rats. METHODS:After CLP, 48 Wistar rats were randomly allocated into four groups:(1) CLP group;(2) small-dose treatment group (2.5 μg·kg-1·h-1); (3) medium-dose treatment group (5.0 μg·kg-1· h-1);and (4) large-dose treatment group (10.0 μg·kg-1·h-1). HLA-DR and plasma cytokine (IL-4, IL-6, IL-10 and TNF-α) levels were measured, and the mean arterial blood pressure (MAP), heart rate (HR), arterial blood gases, lactate concentrations and mortality were also documented. RESULTS:The HLA-DR level, inflammatory mediator levels, MAP and HR had no obvious changes among Dexmedetomidine treatment groups (DEX groups). Compared with the CLP group, the DEX groups exhibited decreased HLA-DR levels (Pgroup=0.0202) and increased IL-6 production, which was increased at 3 h (P= 0.0113) and was then attenuated at 5 h; additionally, the DEX groups exhibited decreased HR (P<0.001) while maintaining MAP (Pgroup=0.1238), and remarkably improving lactate (P<0.0001). All of these factors led to a significant decrease in the mortality, with observed rates of 91.7％, 66.7％, 25％ and 18％ for the CLP, DEX2.5, DEX5.0, DEX10.0 groups, respectively. CONCLUSION:Dexmedetomidine treatment in the setting of a CLP sepsis rat model has partially induced immunomodulation that was initiated within 5 h, causing a decreased HR while maintaining MAP, remarkably improving metabolic acidosis and improving mortality dose-dependently.

Modulating Effects and Mechanisms of p53-miR-34a-SIRT1 Feedback Loop on Reproductive Senescence of Vascular Endothelial Progenitor Cells / 中国循环杂志

Objectives: To explore the modulating effects and related mechanisms of p53-miR-34a-SIRT1 feedback loop in the process of replication senescence of vascular endothelial progenitor cells (EPC). Methods: EPC derived from umbilical cord blood were cultured and identified. Differences on senescence, cell apoptosis, cell cycle and blood tube formation were observed in EPC of 3rdand 6thgeneration. Protein expression of p53, Acetyl-p53, and SIRT1 was also detected by Western blotting in EPC of 3rdand 6thgeneration. The miR-34a inhibitor lentiviral vector was constructed and used to identify whether miR-34a inhibitor can protect 6thgeneration EPC from apoptosis. Results: EPC derived from umbilical cord blood were successfully cultured. The cells senescence rate and apoptosis rate of the 6thgeneration EPC were significantly higher than those of the 3rdgeneration EPC. The cell cycle of 6thgeneration EPC was mainly arrested at G0/G1 phase. The protein expression level of p53 was significantly higher, while the protein expression of acetyl-p53 and SIRT1 was significantly lower in the 6thgeneration EPC than in the 3rdgeneration EPC, all P<0.05. The senescence was significantly attenuated, and late apoptotic cells were significantly reduced, while angiogenesis ability was significantly enhanced in the 6thgeneration EPC transfected with lentiviral vector carrying miR-34a inhibitor. Conclusions: p53-miR-34a-SIRT1 is an important feedback mechanism in the process of EPC replication senescence. The miR-34a inhibitor may be the potential target of delaying EPC senescence.

Analysis of chemical constituents in Liujing Toutong Tablets by HPLC-Q-TOF/MS / 中草药

Objective To separate and identify the chemical constituents in Liujing Toutong Tablets (LTT) by HPLC-Q-TOF/MS. Methods The main components were separated by using the gradient elution method with RP-HPLC, Diamonsil C18 (250 mm × 4.6 μm, 5 μm). The positive and negative electro spray ionization (ESI) source was adopted for determine the chromatographic effluent, the main chromatographic peaks are assigned and distinguished by Q-TOF. These components were further analyzed by accurately relative molecular mass of compounds, and Combined with Positive and negative ions MS information and related literature data. Results According to the MS principle, the corresponding reference substances and literature datas, Ninety-five compounds of LTT were identified, mainly including isoflavones, coumarins, iridoids and phthalides. Furthermore, all of the constituents were surveyed and classified according to their medicinal materials derivation. Conclusion In this study, the main components in LTT were elucidated completely by HPLC-Q-TOF/MS. The results could provide the evidence for the research on active constituents and quality control of LTT.

Diagnostic value of procalcitonin, erythrocyte sedimentation rate, and C-reactive protein in intracranial infection after craniocerebral surgery in patients in intensive care unit / 中国感染控制杂志

Objective To explore the diagnostic value and clinical significance of serum procalcitonin (PCT),erythrocyte sedimentation rate(ESR),and C-reactive protein(CRP) in intracranial infection after craniocerebral surgery in patients in intensive care unit(ICU).Methods 21 patients who were admitted to the ICU in a hospital between June 2011 and January 2016 were as infection group,42 patients without intracranial infection after craniocerebral surgery during the same period were as control group.Levels of PCT,ESR,and CRP in two groups were detected and analyzed statistically.Results Differences in age,gender,average body mass index,types of craniocerebral diseases,and postoperative indwelling drainage between infection group and control group were all not statistically significant (all P＞0.05).Patients with elevated serum PCT,ESR,and CRP in infection group accounted for 95.24％,80.95％ and 90.48％ respectively,in control group were 4.76％,14.29％,and 4.76％ respectively;the average concentrations of serum PCT,ESR,and CRP between two groups were compared respectively,differences were all significant(all P＜0.05).The sensitivity of PCT,ESR,CRP,and PCT + ESR + CRP in the diagnosis of intracranial infection after craniocerebral surgery in ICU patients were 95.24％,80.95％,90.47％,and 95.61 ％respectively;specificity were 95.23％,85.71％,95.23％,and 89.37％ respectively.Conclusion The combined detection of PCT,ESR,and CRP is helpful for the diagnosis of intracranial infection after craniocerebral surgery in ICU patients,it has important guiding significance for the rational use of antimicrobial agents in early stage.

Effects of traditional Tibetan drug Liu Tea on proliferation and chemotherapeutic sensitivity of drug-resistant human gastric cancer cell BGC823/5-FU / 中国中药杂志

To investigate the effects of Liu Tea extracts(LTE) on proliferation, apoptosis and drug sensitivity of drug-resistant gastric cancer cell BGC823/5-FU. MTT assay was used to analyze effect of LTE on cell growth and sensitivity chemotherapeutic drugs, and synergistic effect of the combination of LTE with 5-FU on BGC823/5-FU cells. Combination index (CI) was calculated by CompuSyn. Cell apoptosis was measured by flow cytometry (FCM). Protein expressions of P-gp, Bcl-2, Bax and Caspase-3 (17KD) were detected by Western blot at different concentrations of LTE in BGC823/5-FU cells (100, 200, 400 mg•L⁻¹). The results showed that LTE had an inhibitory effect on growth of BGC823/5-FU cell in a dose-time-dependent manner and significantly reduced IC₅₀ of 5-FU, CDDP, PTX and ADM to BGC823/5-FU cells(P<0.05), indicating it could reverse tolerance of drug resistant cells to chemotherapeutic drugs, with reversion multiples of 2.35, 1.68, 1.96, 0.52. The combination of LTE with 5-FU had positive synergistic effect on the BGC-823 cell line. FCM assay suggested that LTE could induce BGC823/5-FU apoptosis. The apoptosis rate was up to 46.2% when the cells were treated with 800 mg•L⁻¹ LTE after 24 h(P<0.01). According to the protein detection results, with the increase in concentration of LTE, the protein expression of Bcl-2 was gradually decreased(P<0.01), the expression of Bax and Caspase-3 were extremely increased(P<0.01), with statistical significance in difference(P<0.01) but no difference in the expression of P-gp between experiment group and control group. LTE can inhibit the growth of drug-resistant human gastric cancer cell BGC823/5-FU and reverse its chemotherapeutic tolerance to some extent. Inhibition of antiapoptotic proteins, activation of proapoptotic proteins and induction of apoptosis of resistant cells may be its main mechanisms.

Value of Kidney Disease Improving Global Outcomes Urine Output Criteria in Critically Ill Patients: A Secondary Analysis of a Multicenter Prospective Cohort Study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Urine output (UO) is an essential criterion of the Kidney Disease Improving Global Outcomes (KDIGO) definition and classification system for acute kidney injury (AKI), of which the diagnostic value has not been extensively studied. We aimed to determine whether AKI based on KDIGO UO criteria (KDIGOUO) could improve the diagnostic and prognostic accuracy, compared with KDIGO serum creatinine criteria (KDIGOSCr).</p><p><b>METHODS</b>We conducted a secondary analysis of the database of a previous study conducted by China Critical Care Clinical Trial Group (CCCCTG), which was a 2-month prospective cohort study (July 1, 2009 to August 31, 2009) involving 3063 patients in 22 tertiary Intensive Care Units in Mainland of China. AKI was diagnosed and classified separately based on KDIGOUOand KDIGOSCr. Hospital mortality of patients with more severe AKI classification based on KDIGOUOwas compared with other patients by univariate and multivariate regression analyses.</p><p><b>RESULTS</b>The prevalence of AKI increased from 52.4% based on KDIGOSCrto 55.4% based on KDIGOSCrcombined with KDIGOUO. KDIGOUOalso resulted in an upgrade of AKI classification in 7.3% of patients, representing those with more severe AKI classification based on KDIGOUO. Compared with non-AKI patients or those with maximum AKI classification by KDIGOSCr, those with maximum AKI classification by KDIGOUOhad a significantly higher hospital mortality of 58.4% (odds ratio [OR]: 7.580, 95% confidence interval [CI]: 4.141-13.873, P< 0.001). In a multivariate logistic regression analysis, AKI based on KDIGOUO (OR: 2.891, 95% CI: 1.964-4.254, P< 0.001), but not based on KDIGOSCr (OR: 1.322, 95% CI: 0.902-1.939, P = 0.152), was an independent risk factor for hospital mortality.</p><p><b>CONCLUSION</b>UO was a criterion with additional value beyond creatinine criterion for AKI diagnosis and classification, which can help identify a group of patients with high risk of death.</p>

Prevalence, risk factors, clinical course, and outcome of acute kidney injury in Chinese intensive care units: a prospective cohort study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Acute kidney injury (AKI) has been recognized as a major healthcare problem affecting millions of patients worldwide. However, epidemiologic data concerning AKI in China are still lacking. The objectives of this study were to characterize AKI defined by RIFLE criteria, assess the association with hospital mortality, and evaluate the impact of AKI in the context of other risk factors.</p><p><b>METHODS</b>This prospective multicenter observational study enrolled 3,063 consecutive patients from 1 July 2009 to 31 August 2009 in 22 ICUs across mainland China. We excluded patients who were admitted for less than 24 hours (n = 1623), younger than 18 years (n = 127), receiving chronic hemodialysis (n = 29), receiving renal transplantation (n = 1) and unknown reasons (n = 28). There were 1255 patients in the final analysis. AKI was diagnosed and classified according to RIFLE criteria.</p><p><b>RESULTS</b>There were 396 patients (31.6%) who had AKI, with RIFLE maximum class R, I, and F in 126 (10.0%), 91 (7.3%), and 179 (14.3%) patients, respectively. Renal function deteriorated in 206 patients (16.4%). In comparison with non AKI patients, patients in the risk class on ICU admission were more likely to progress to the injury class (odds ratio (OR) 3.564, 95% confidence interval (CI) 1.706 - 7.443, P = 0.001], while patients in the risk class (OR 5.215, 95% CI 2.798-9.719, P < 0.001) and injury class (OR 13.316, 95% CI 7.507-23.622, P < 0.001) had a significantly higher probability of deteriorating into failure class. The adjusted hazard ratios for 90-day mortality were 1.884 for the risk group, 3.401 for the injury group, and 5.306 for the failure group.</p><p><b>CONCLUSIONS</b>The prevalence of AKI was high among critically ill patients in Chinese ICUs. In comparison with non-AKI patients, patients with RIFLE class R or class I on ICU admission were more susceptibility to progression to class I or class F. The RIFLE criteria were robust and correlated well with clinical deterioration and mortality.</p>