COVID-19 has spread surprisingly fast worldwide, and new variants continue to emerge. Recently, the World Health Organization acknowledged a new mutant strain “Omicron”, with children were accounting for a growing s...COVID-19 has spread surprisingly fast worldwide, and new variants continue to emerge. Recently, the World Health Organization acknowledged a new mutant strain “Omicron”, with children were accounting for a growing share of COVID-19 cases compared with other mutant strains. However, the clinical and immunological characteristics of convalescent pediatric patients after Omicron infection were lacking. In this study, we comparatively analyzed the clinical data from pediatric patients with adult patients or healthy children and the effects of SARSCoV-2 vaccine on the clinical and immune characteristics in convalescent pediatric patients. Our results indicated that convalescent pediatric patients had unique clinical and immune characteristics different from those of adult patients or healthy children, and SARS-CoV-2 vaccination significantly affected on the clinical and immune characteristics and the prevention of nucleic acid re-detectable positive(RP) in convalescent patients. Our study further deepens the understanding of the impact of Omicron on the long-term health of pediatric patients and provides a valuable reference for the prevention and treatment of children infected with Omicron.展开更多
Atrial fibrillation (AF) increases the risk of stroke. New anticoagulation agents have recently provided alternative and promising approaches. This paper reviews the current state of anticoagulation therapy in AF pati...Atrial fibrillation (AF) increases the risk of stroke. New anticoagulation agents have recently provided alternative and promising approaches. This paper reviews the current state of anticoagulation therapy in AF patients, focusing on various clinical scenarios and on comparisons, where possible, between western and eastern populations.展开更多
Multidrug resistant（MDR） pathogen infections are serious threats to hospitalized patients because of the limited therapeutic options. A novel group of antibiotic candidates, antimicrobial peptides（AMPs）, have rece...Multidrug resistant（MDR） pathogen infections are serious threats to hospitalized patients because of the limited therapeutic options. A novel group of antibiotic candidates, antimicrobial peptides（AMPs）, have recently shown powerful activities against both Gram-negative and Gram-positive bacteria. Unfortunately, the viability of using these AMPs in clinical settings remains to be seen, since most still need to be evaluated prior to clinical trials and not all of AMPs are potent against MDR clinical isolates. To find a connection between the characteristics of several of these AMPs and their effects against MDR pathogens, we selected 14 AMPs of animal origin with typical structures and evaluated their in vitro activities against clinical strains of extensive drugresistant Acinetobacter baumannii, methicillinresistant Staphylococcus aureus, extended spectrum β-lactamase-producing Pseudomonas aeruginosa and extended spectrum β-lactamase-producing Escherichia coli. Our results showed that these peptides＇ hydrophilic/hydrophobic characteristics, rather than their secondary structures, may explain their antibacterial effects on these clinical isolates. Peptides that are amphipathic along the longitudinal direction seemed to be effective against Gramnegative pathogens, while peptides with hydrophilic terminals separated by a hydrophobic intermediate section appeared to be effective against both Gramnegative and Gram-positive pathogens. Among these, cathelicidin-BF was found to inhibit all of the Gram-negative pathogens tested at dosages of no more than 16 mg/L, killing a pandrug-resistant A. baumannii strain within 2 h at 4×MICs and 4 h at 2×MICs. Tachyplesin III was also found capable of inhibiting all Gram-negative and Gram-positive pathogens tested at no more than 16 mg/L, and similarly killed the same A. baumannii strain within 4 h at 4×MICs and 2×MICs. These results suggest that both cathelicidin-BF and tachyplesin III are likely viable targets for the development of AMPs for clinical uses.展开更多
Background: Developing a novel, efficient biomarker for detecting malignant tumors is essential for the early diagnosis of cancers. Our aim was to assess the diagnostic value of a potential plasma tumor marker, thiore...Background: Developing a novel, efficient biomarker for detecting malignant tumors is essential for the early diagnosis of cancers. Our aim was to assess the diagnostic value of a potential plasma tumor marker, thioredoxin reductase (TR), which is expressed in many types of malignant tumor, for the non-invasive detection of cancers. Methods: The plasma activities of TR were measured in 1513 patients with common clinical diseases, 59 patients with benign tumors, and 154 patients with cancers and 586 healthy controls. The area under the ROC curve (AUC) of TR and logistic regression results of different groups were compared by sensitivity, specificity and Youden’s index. Diagnostic cut-offs and clinical reference intervals were established via ROC curve analysis. Results: The logistic regression indicated that TR activity can discriminate between cancers and benign tumors or other common diseases very well (p < 0.0001), with an area under the curve from the receiver-operator characteristics between 0.91 and 0.96. The positive critical value was 2.51 and the cancer critical value was 9.90. The diagnostic gray zone (2.51 - 9.90) may be associated with benign tumors and some common clinical diseases. Conclusions: As a novel potential marker of malignant tumors with quantitative evaluation of proliferation, TR activity detection has an excellent diagnostic potential for early-stage malignant tumors. Impact: The convenient, economical, relatively non-invasive, and reproducible detection method of TR activity makes it suitable for routine clinical practice.展开更多
Pre-mRNA splicing is a fundamental process required for the expression of most metazoan genes. It is carried out by the spliceosome that catalyzes the removal of non-coding intron sequences to ligate exons into mature...Pre-mRNA splicing is a fundamental process required for the expression of most metazoan genes. It is carried out by the spliceosome that catalyzes the removal of non-coding intron sequences to ligate exons into mature mRNA prior to transport and translation. The purpose of our study is to explore whether the in vitro unlabeled pre-mRNA splicing assay could be performed as an alternative method of splicing reaction other than the radiolabeled one. Two different splicing methods in vitro, 32p labeled and unlabeled pre-mRNA as the substrates in the reaction, were investigated. The radiolabeled products were visualized by autoradiography while the unlabeled products were observed by Ethidium Bromide （EB） staining. As a result, although there are more unspecific bands in the EB staining assay than 32p labeled one, the RNA products of in vitro splicing could be observed clearly. This suggests that the unlabeled pre-mRNA splicing assay can be an optional substitution for the isotope-labeled assay.展开更多
Background:Alzheimer's disease(AD)is a progressive neurodegenerative disease with no effective therapies.It is well known that chronic neuroinflammation plays a critical role in the onset and progression of AD.Wel...Background:Alzheimer's disease(AD)is a progressive neurodegenerative disease with no effective therapies.It is well known that chronic neuroinflammation plays a critical role in the onset and progression of AD.Well-balanced neuronal-microglial interactions are essential for brain functions.However,determining the role of microglia—the primary immune cells in the brain—in neuroinflammation in AD and the associated molecular basis has been challenging.Methods:Inflammatory factors in the sera of AD patients were detected and their association with microglia activation was analyzed.The mechanism for microglial inflammation was investigated.IL6 and TNF-α were found to be significantly increased in the AD stage.Results:Our analysis revealed that microglia were extensively activated in AD cerebra,releasing sufficient amounts of cytokines to impair the neural stem cells(NSCs)function.Moreover,the ApoD-induced NLRC4 inflammasome was activated in microglia,which gave rise to the proinflammatory phenotype.Targeting the microglial ApoD promoted NSC self-renewal and inhibited neuron apoptosis.These findings demonstrate the critical role of ApoD in microglial inflammasome activation,and for the first time reveal that microglia-induced inflammation suppresses neuronal proliferation.Conclusion:Our studies establish the cellular basis for microglia activation in AD progression and shed light on cellular interactions important for AD treatment.展开更多
Malignant melanoma,characterized by its high metastatic potential and resistance to conventional therapies,presents a major challenge in oncology.This review explores the current status and advancements in tumor vacci...Malignant melanoma,characterized by its high metastatic potential and resistance to conventional therapies,presents a major challenge in oncology.This review explores the current status and advancements in tumor vaccines for melanoma,focusing on peptide,DNA/RNA,dendritic cell,tumor cell,and neoantigen-based vaccines.Despite promising results,significant challenges remain,including the immunosuppressive tumor microenvironment,patient heterogeneity,and the need for more effective antigen presentation.Recent strategies,such as combining vaccines with immune checkpoint inhibitors(ICIs),aim to counteract immune evasion and enhance T cell responses.Emerging approaches,including personalized neoantigen vaccines and the use of self-amplifying RNA platforms,hold promise for overcoming tumor heterogeneity and improving vaccine efficacy.Additionally,optimizing vaccine delivery systems through nanotechnology and genetic modifications is essential for increasing stability and scalability.This review highlights the potential of these innovative strategies to address current limitations,with a focus on how future research can refine and combine these approaches to improve melanoma treatment outcomes.展开更多
Hemorrhagic shock is a common clinical emergency that can aggravate cell injury after resuscitation.Astrocytes are crucial for the survival of neurons because they regulate the surrounding ionic microenvironment of ne...Hemorrhagic shock is a common clinical emergency that can aggravate cell injury after resuscitation.Astrocytes are crucial for the survival of neurons because they regulate the surrounding ionic microenvironment of neurons.Although hemorrhagic shock and resuscitation(HSR)injury can impair cognition,it remains unclear how this insult directly affects astrocytes.In this study,we established an HSR model by bleeding and re-transfusion in mice.The social interaction test and new object recognition test were applied to evaluate post-operative cognitive changes,and the results suggest that mice experience cognitive impairment following exposure to HSR.In the HSR group,the power spectral density ofβandγoscillations decreased,and the coupling of theθoscillation phase andγoscillation amplitude was abnormal,which indicated abnormal neuronal oscillation and cognitive impairment after HSR exposure.In brief,cognitive impairment in mice is strongly correlated with Ca^(2+)signal strength in lateral septum astrocytes following HSR.展开更多
Background Atrial fibrillation （AF） is associated with inflammation and endothelial dysfunction. However, the association between inflammation （as indexed by high-sensitivity C-reactive protein, hs-CRP） and endoth...Background Atrial fibrillation （AF） is associated with inflammation and endothelial dysfunction. However, the association between inflammation （as indexed by high-sensitivity C-reactive protein, hs-CRP） and endothelial function [as indexed by big endothelin-1 （ET-1）] in AF patients remains unclear. Methods We enrolled 128 patients with lone AF, among which 83 had paroxysmal AF, and 45 had persistent AF. Eighty-two age- and gender-matched controls of paroxysmal supraventricular tachycardia without AF history were evaluated. Plasma hs-CRP, big ET-1 levels and other clinical characteristics were compared among the groups. Results Patients with persistent AF had higher hs-CRP concentrations than those with paroxysmal AF （P 〈 0.05）, both groups had higher hs-CRP level than controls （P 〈 0.05）. Patients with persistent AF had higher big ET-1 level than those with paroxysmal AF, although the difference did not reach the statistical significance （P 〉 0.05）, and both groups had higher big ET-1 levels than controls （P 〈 0.05）. Multiple regression analyses revealed hs-CRP as an inde- pendent determinant of AF （P 〈 0.001）. Further adjusted for big ET-1, both big ET-1 and hs-CRP were independent predictors for AF （P 〈 0.001）, but the odds ratio for hs-CRP in predicting AF attenuated from 8.043 to 3.241. There was a positive relation between hs-CRP level and big ET-1 level in paroxysmal AF patients （r = 0.563, P 〈 0.05）, however, the relationship in persistent AF patients was poor （r = 0.094, P 〈 0.05）. Conclusions Both plasma hs-CRP and big ET-1 levels are elevated in lone AF patients, and are associated with AF. In paroxysmal lone AF patients, there were significant positive correlations between plasma hs-CRP level and big ET- 1 level.展开更多
Objective To describe the clinical characteristics of idiopathic ventricular fibrillation （IVF） with fragmented QRS complex （f-QRS） and J wave in resting electrocardiogram. Methods We reviewed data from 21 case su...Objective To describe the clinical characteristics of idiopathic ventricular fibrillation （IVF） with fragmented QRS complex （f-QRS） and J wave in resting electrocardiogram. Methods We reviewed data from 21 case subjects in our hospital who were resuscitated after cardiac arrest due to IVF and assessed the prevalence of f-QRS and J wave in resting electrocardiogram （ECG）. All the case subjects were classified among three groups based on the electrocardiographic morphology： group I, both f-QRS and J wave were observed （n = 6）, group II, only J wave was observed （n = 9）, group III, neither f-QRS nor J wave was observed （n = 6）. Population characteristics, history of syncope or sudden cardiac arrest, incidence of ventricular fibrillation （VF）, and circumstance of VF were evaluated among the three groups. Results The incidence of index events （syncope, survived cardiac arrest and VF episodes recorded in implantable cardioverter defibrillator （ICD） or pacemakers） was 13.4 ~ 5.6 per-year in group I, 10.8 ~ 3.9 per-year in group II, and 9.8 -4- 4.2 per-year in group HI. There were significant differences in incidences among the three groups, the most frequent index events were observed in group I. The hazard ratio for incidence was 3.2 （95%CI, 1.1-7.9; P = 0.01）. The history and circumstance of the index events were different among the groups. In group I, all the index events occurred during sleep in early morning. In group II, four subjects suffered VF during strenuous physical activities or agitation state, two during sleep in early morning, three in usual activity. In group III, one subject suffered VF during sleep in early morning, one in agitation state, four in usual activity. Conclusions This study suggests that the IVF patients with the combined appearance of f-QRS and J wave in the resting ECG suffer an increased risk of VF, this subgroup of IVF patients has a unique clinical feature.展开更多
Background Metabolic syndrome is known to be a prothrombotic state. We undertook this study to examine a hypothesis that aspirin resistance may be associated with metabolic syndrome, and to assess other potential dete...Background Metabolic syndrome is known to be a prothrombotic state. We undertook this study to examine a hypothesis that aspirin resistance may be associated with metabolic syndrome, and to assess other potential determinants of aspirin resistance in patients with cardiovascular disease （CVD）. Methods A total of 469 elderly patients with CVD were recruited. One hundred and seventy-two patients with metabolic syndrome and 297 without metabolic syndrome （control group） received daily aspirin therapy （〉 75 mg） over one month. Platelet aggregation was measured by light transmission aggregometry （LTA）. Aspirin resistance was defined as 〉 20% arachidonic acid （AA）- and 〉 70% adenosine diphosphate （ADP）-induced aggregation according to LTA. Aspirin semi-responders were defined as meeting one （but not both） of these criteria. Results By LTA, 38 of 469 （8.1%） patients were aspirin resistant. The prevalence of aspirin resistance was higher in the metabolic syndrome group compared with the control group [11.6 % vs. 6.6%, odds ratio （OR） = 2.039; 95% confidence interval （CI）： 1.047-3.973]. In the multivariate logistic regression analysis, metabolic syndrome （OR = 4.951, 95% CI： 1.440-17.019, P = 0.011） was a significant risk factor for aspirin resistance. Conclusions A significant number of patients with CVD and metabolic syndrome are resistant to aspirin therapy. This might further increase the risk of cardiovascular morbidity and mortality in these patients.展开更多
As a group of nonspecific inflammatory diseases affecting the intestine,inflammatory bowel disease(IBD)exhibits the characteristics of chronic recurring inflammation,and was proven to be increasing in incidence(Kaplan...As a group of nonspecific inflammatory diseases affecting the intestine,inflammatory bowel disease(IBD)exhibits the characteristics of chronic recurring inflammation,and was proven to be increasing in incidence(Kaplan,2015).IBD induced by genetic background,environmental changes,immune functions,microbial composition,and toxin exposures(Sasson et al.,2021)primarily includes ulcerative colitis(UC)and Crohn's disease(CD)with complicated clinical symptoms featured by abdominal pain,diarrhea,and even blood in stools(Fan et al.,2021;Huang et al.,2021).展开更多
It has been reported that Ethaselen shows inhibitory effects on thioredoxin reductase（TrxR） activity and human tumor cell growth. In order to find an efficient way to reverse cisplatin resistance, we investigated th...It has been reported that Ethaselen shows inhibitory effects on thioredoxin reductase（TrxR） activity and human tumor cell growth. In order to find an efficient way to reverse cisplatin resistance, we investigated the reversal effects of Ethaselen on cisplatin resistance in K562/cisplatin（CDDP） cells that were established by pulse-inducing human erythrocyte leukemic cell line K562, which are fivefold more resistant to cisplatin compared to K562 cells. The morphology and growth showed that the adhesion of K562/CDDP further decreased while the cell volume increased. The proliferation of K562/CDDP is strengthened. The antitumor activities in vitro were assessed by MTT（3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide） assay and combination index（CI）, showing the significant synergic effects of cisplatin and Ethaselen. Focusing on apoptosis, a series of comparisons was made between K562 and K562/CDDP. Cisplatin induced higher reactive oxygen species（ROS） generation in K562 and subsequently induced the formation of mitochondrial permeability transition pores（PTPs）. In addition, cisplatin increased the ratio of Bax to Bcl-2 in K562, which can influence the mitochondrial membrane permeability. PTP formation and mitochondrial membrane permeabilization eventually resulted in the release of cytochrome c and activation of the Caspase pathway. However, these effects were not clearly seen in K562/CDDP, which may be the reason for the acquired CDDP resistance. However, Ethaselen can induce a high level of ROS in K562/CDDP by TrxR activity inhibition and increased ratio of Bax to Bcl-2 in K562/CDDP by nuclear factor κB（NF-κB） suppression, which subsequently induces the release of cytochrome c in K562/CDDP. This response is partly responsible for the reversal of the cisplatin resistance in K562/CDDP cells.展开更多
BACKGROUND Hemolymphangioma of the jejunum is rare and lacks clinical specificity,and can manifest as gastrointestinal bleeding,abdominal pain,and intestinal obstruction.Computed tomography,magnetic resonance imaging,...BACKGROUND Hemolymphangioma of the jejunum is rare and lacks clinical specificity,and can manifest as gastrointestinal bleeding,abdominal pain,and intestinal obstruction.Computed tomography,magnetic resonance imaging,and other examinations show certain characteristics of the disease,but lack accuracy.Although capsule endoscopy and enteroscopy make up for this deficiency,the diagnosis also still re-quires pathology.CASE SUMMARY A male patient was admitted to the hospital due to abdominal distension and abdominal pain,but a specific diagnosis by computed tomography examination was not obtained.Partial resection of the small intestine was performed by robotic surgery,and postoperative pathological biopsy confirmed the diagnosis of hemo-lymphangioma.No recurrence in the follow-up examination was observed.CONCLUSION Robotic surgery is an effective way to treat hemolymphangioma through minima-lly invasive techniques under the concept of rapid rehabilitation.展开更多
Our study was to investigate the epidemiological characteristics of M.tuberculosis from a national tuberculosis referral center in China. All strains isolated from TB patients, were genotyped by the RD105 deletion, 8 ...Our study was to investigate the epidemiological characteristics of M.tuberculosis from a national tuberculosis referral center in China. All strains isolated from TB patients, were genotyped by the RD105 deletion, 8 and 51 SNP loci and VNTR. The high differentiation SNPs of modern Beijing strains were analyzed for protein function and structure. 413 M. tuberculosis were included. Of 379 Beijing lineage M. tuberculosis, ＇modern＇ and ＇ancient＇ strains respectively represented 85.5% （324/379） and 14.5% （55/379）. Rv2494 （V48A） and Rv0245 （Sl03F） were confirmed as high differentiation SNPs associated with modern strains. In a word, Modern Beijing lineage M.tuberculosis was dominant and the structural models suggested that modern sub-lineage may more easily survive in ＇extreme＇ host condition.展开更多
Objective:FGFR is considered an important driver gene of lung squamous cell carcinoma(LSCC).Thus,identification of the biological events downstream of FGFR is important for the treatment of this malignancy.Our previou...Objective:FGFR is considered an important driver gene of lung squamous cell carcinoma(LSCC).Thus,identification of the biological events downstream of FGFR is important for the treatment of this malignancy.Our previous study has shown that the FGFR/RACK1 complex interacts with PKM2 and consequently promotes glycolysis in LSCC cells.However,the biological functions of the FGFR/RACK1 complex remain poorly understood.Methods:Anchorage-independent assays and in vivo tumorigenesis assays were performed to evaluate cancer cell malignancy.Distant seeding assays were performed to evaluate cancer cell metastasis.β-gal staining was used to examine cell senescence,and immunoprecipitation assays were performed to examine the interactions among FGFR,RACK1,and MDM2.Results:FGFR/RACK1 was found to regulate the senescence of LSCC cells.Treatment with PD166866,an inhibitor of FGFR,or knockdown of RACK1 induced senescence in LSCC cells(P<0.01).A molecular mechanistic study showed that FGFR/RACK1/MDM2 form a complex that promotes the degradation of p53 and thus inhibits cell senescence.PD166866 and RG7112,an MDM2/p53 inhibitor,cooperatively inhibited the colony formation and distal seeding of LSCC cells(P<0.01),and upregulated the expression of p53 and p21.Conclusions:Together,our findings revealed the regulatory roles and mechanisms of FGFR/RACK1 in cell senescence.This understanding should be important in the treatment of LSCC.展开更多
Objective:To study the differential lncRNA/mRNA expression profiles of placental tissues in patients with gestational hypertension,analyze their possible mechanisms of action,and explore their target genes and small m...Objective:To study the differential lncRNA/mRNA expression profiles of placental tissues in patients with gestational hypertension,analyze their possible mechanisms of action,and explore their target genes and small molecule drug-related lncRNAs.Methods:Three patients with gestational hypertension who were treated in our hospital from May 2018 to May 2019 were selected as the research subjects and three healthy pregnant women who underwent a prenatal examination in the same hospital were selected as the control group.The placental tissues were taken from the patients.RNA-sequencing was performed to construct lncRNA/mRNA differential expression profiles;screening differentially expressed lncRNAs were used to predict target genes,and GO and KEGG enrichment analysis predicted the biological functions of target genes and the enriched signal pathways,respectively.Protein-protein interaction network,lncRNA-miRNAmRNA network,and differentially expressed genesmall molecule drug association networks were constructed.Results:RNA-seq analysis revealed 19 differentially expressed lncRNA(4 up-regulated;15 down-regulated)(P<0.05).Moreover,423 differentially expressed genes(DEGs)(84 up-regulated;339 downregulated)(P<0.05).GO and KEGG enrichment analysis found that gestational hypertension is mainly related to endothelial cell damage,inflammatory response,abnormal immune regulation,and abnormal trophoblast invasion.The PPI network and lncRNA-miRNA-mRNA network were constructed.Differentially expressed gene-drug small molecule prediction results found 19 pairs of differentially gene-small drug relationship pairs,mainly including antibody,inhibitor et al.Conclusion:Differently expressed lncRNAs in the placenta of patients with gestational hypertension can participate in the regulation of multiple biological functional levelrelated signal pathways through targeted regulation of their target genes,and play an important role in the occurrence and development of gestational hypertension.The predicted small molecule drug can be used as a reference for clinical treatment.展开更多
AIM: To make an electrophysiological demonstration of a possible jaw muscle afferents-oculomotor neural pathway that was proposed by our previous works on rats, which substantiates an early "release hypothesis&qu...AIM: To make an electrophysiological demonstration of a possible jaw muscle afferents-oculomotor neural pathway that was proposed by our previous works on rats, which substantiates an early "release hypothesis" on pathogenesis of human Marcus Gunn Syndrome(MGS). METHODS: Extracellular unit discharge recording was applied and both orthodromic and spontaneous unitary firing were recorded in the oculomotor nucleus(III), and the complex of pre-oculomotor interstitial nucleus of Cajal and Darkschewitsch nucleus(INC/DN), following electric stimulation of the ipsilateral masseter nerve(MN) in rats. RESULTS: Extracellular orthodromic unit discharges, with latencies of 3.7±1.3 and 4.7±2.9 ms, were recorded unilaterally in the III, and the INC/DN neurons, respectively. Spontaneous unit discharges were also recorded mostly in the INC/DN and less frequently in the III. Train stimulation could prompt either facilitation or inhibition on those spontaneous unit discharges. The inhibition pattern of train stimulation on the spontaneous discharging was rather different in the III and INC/DN. A slow inhibitory pattern in which spontaneous firing rate decreased further and further following repeated train stimulation was observed in the III. While, some high spontaneous firing rate units, responding promptly to the train stimuli with a short-term inhibition and recovered quickly when stimuli are off, were recorded in the INC/DN. However, orthodromic unit discharge was not recorded in the III and INC/DN in a considerable number of experiment animals. CONCLUSION: A residual neuronal circuit might exist in mammals for the primitive jaw-eyelid reflex observed in amphibians, which might not be well-developed in all experimental mammals in current study. Nonetheless, this pathway can be still considered as a neuroanatomic substrate for development of MGS in some cases among all MGS with different kind of etiology.展开更多
BACKGROUND Kallmann syndrome(KS)is a hypogonadotropic hypogonadism accompanied by anosmia or hyposmia.It is associated with the low secretion of gonadotropins which can lead to other abnormal endocrine metabolism diso...BACKGROUND Kallmann syndrome(KS)is a hypogonadotropic hypogonadism accompanied by anosmia or hyposmia.It is associated with the low secretion of gonadotropins which can lead to other abnormal endocrine metabolism disorders such as diabetes.Through genetic and molecular biological methods,more than 10 KS pathogenic genes have been found.AIM To identify the existing mutation sites of KS with diabetes and reveal the relationship between genotype and phenotype.METHODS We studied KS pathogenesis through high-throughput exome sequencing on four diabetes’patients with KS for screening the potential pathogenic sites and exploring the genotype-phenotype correlation.Clinical data and peripheral blood samples were collected from the patients.White blood cells were separated and genomic DNA was extracted.High-throughput sequencing of all exons in the candidate pathogenic genes of probands was performed,and the results obtained were analyzed.RESULTS Sequencing revealed mutations in the KLB p.T313M,ANOS1 p.C172F,and IGSF10 gene(p.Lys1819Arg and p.Arg1035Thr)at different sites,which may have been associated with disease onset.CONCLUSION The diagnosis of KS is challenging,especially in early puberty,and the clinical manifestations reflect physical delays in development and puberty.Timely diagnosis and treatment can induce puberty,thereby improving sexual,bone,metabolic and mental health.展开更多
Implantation of implantable cardioverter defibrillators （ICD） has widely been accepted for secondary prevention of sudden cardiac death （SCD） in cardiac arrest survivors.1 Currently there are increasing interests ...Implantation of implantable cardioverter defibrillators （ICD） has widely been accepted for secondary prevention of sudden cardiac death （SCD） in cardiac arrest survivors.1 Currently there are increasing interests in primary preven- tion of SCD in selected high risk patients who have not experienced cardiac arrest.~ Despite extensive investigation for risk stratification, our current ability to accurately iden- tify patients at high risk for SCD remains very poor. The primary reason is probably due to our limited understand- ing of the mechanisms underlying the pathogenesis of ven- trieular tachy-arrhythmias and sudden cardiac death （Fig. 1）.展开更多
基金supported by Tianjin Municipal Health Commission Science and Technology Project (TJWJ2021QN016)Tianjin Key Medical Discipline (Specialty) Construction Project
文摘COVID-19 has spread surprisingly fast worldwide, and new variants continue to emerge. Recently, the World Health Organization acknowledged a new mutant strain “Omicron”, with children were accounting for a growing share of COVID-19 cases compared with other mutant strains. However, the clinical and immunological characteristics of convalescent pediatric patients after Omicron infection were lacking. In this study, we comparatively analyzed the clinical data from pediatric patients with adult patients or healthy children and the effects of SARSCoV-2 vaccine on the clinical and immune characteristics in convalescent pediatric patients. Our results indicated that convalescent pediatric patients had unique clinical and immune characteristics different from those of adult patients or healthy children, and SARS-CoV-2 vaccination significantly affected on the clinical and immune characteristics and the prevention of nucleic acid re-detectable positive(RP) in convalescent patients. Our study further deepens the understanding of the impact of Omicron on the long-term health of pediatric patients and provides a valuable reference for the prevention and treatment of children infected with Omicron.
基金Project (No. 200902001) supported by the Research on Monitoring,Prevention, Early-Warning, Diagnosis,and Therapy of Cardiovascular Diseases Part Ⅱ:Community Based Approach for Atrial Fibrillation and Sudden Cardiac Death, China
文摘Atrial fibrillation (AF) increases the risk of stroke. New anticoagulation agents have recently provided alternative and promising approaches. This paper reviews the current state of anticoagulation therapy in AF patients, focusing on various clinical scenarios and on comparisons, where possible, between western and eastern populations.
基金This study was supported by the Peking Union Medical College （PUMC） Youth Fund and the Fundamental Research Funds for the Central Universities, China （333203084）
文摘Multidrug resistant（MDR） pathogen infections are serious threats to hospitalized patients because of the limited therapeutic options. A novel group of antibiotic candidates, antimicrobial peptides（AMPs）, have recently shown powerful activities against both Gram-negative and Gram-positive bacteria. Unfortunately, the viability of using these AMPs in clinical settings remains to be seen, since most still need to be evaluated prior to clinical trials and not all of AMPs are potent against MDR clinical isolates. To find a connection between the characteristics of several of these AMPs and their effects against MDR pathogens, we selected 14 AMPs of animal origin with typical structures and evaluated their in vitro activities against clinical strains of extensive drugresistant Acinetobacter baumannii, methicillinresistant Staphylococcus aureus, extended spectrum β-lactamase-producing Pseudomonas aeruginosa and extended spectrum β-lactamase-producing Escherichia coli. Our results showed that these peptides＇ hydrophilic/hydrophobic characteristics, rather than their secondary structures, may explain their antibacterial effects on these clinical isolates. Peptides that are amphipathic along the longitudinal direction seemed to be effective against Gramnegative pathogens, while peptides with hydrophilic terminals separated by a hydrophobic intermediate section appeared to be effective against both Gramnegative and Gram-positive pathogens. Among these, cathelicidin-BF was found to inhibit all of the Gram-negative pathogens tested at dosages of no more than 16 mg/L, killing a pandrug-resistant A. baumannii strain within 2 h at 4×MICs and 4 h at 2×MICs. Tachyplesin III was also found capable of inhibiting all Gram-negative and Gram-positive pathogens tested at no more than 16 mg/L, and similarly killed the same A. baumannii strain within 4 h at 4×MICs and 2×MICs. These results suggest that both cathelicidin-BF and tachyplesin III are likely viable targets for the development of AMPs for clinical uses.
文摘Background: Developing a novel, efficient biomarker for detecting malignant tumors is essential for the early diagnosis of cancers. Our aim was to assess the diagnostic value of a potential plasma tumor marker, thioredoxin reductase (TR), which is expressed in many types of malignant tumor, for the non-invasive detection of cancers. Methods: The plasma activities of TR were measured in 1513 patients with common clinical diseases, 59 patients with benign tumors, and 154 patients with cancers and 586 healthy controls. The area under the ROC curve (AUC) of TR and logistic regression results of different groups were compared by sensitivity, specificity and Youden’s index. Diagnostic cut-offs and clinical reference intervals were established via ROC curve analysis. Results: The logistic regression indicated that TR activity can discriminate between cancers and benign tumors or other common diseases very well (p < 0.0001), with an area under the curve from the receiver-operator characteristics between 0.91 and 0.96. The positive critical value was 2.51 and the cancer critical value was 9.90. The diagnostic gray zone (2.51 - 9.90) may be associated with benign tumors and some common clinical diseases. Conclusions: As a novel potential marker of malignant tumors with quantitative evaluation of proliferation, TR activity detection has an excellent diagnostic potential for early-stage malignant tumors. Impact: The convenient, economical, relatively non-invasive, and reproducible detection method of TR activity makes it suitable for routine clinical practice.
基金We thank Hao Zhang for technical assistance, Dr. Robin Reed for providing AdML plasmids. The work was supported by grants from National Natural Science Foundation of China （30670441, 30300070）Program for New Century Excellent Talents in University （NCET-04-0245）+1 种基金 Specialized Fund for the Doctoral Program of Higher Education （20040062003）Tianjin Municipal Science and Technology Commission （043802811）.
文摘Pre-mRNA splicing is a fundamental process required for the expression of most metazoan genes. It is carried out by the spliceosome that catalyzes the removal of non-coding intron sequences to ligate exons into mature mRNA prior to transport and translation. The purpose of our study is to explore whether the in vitro unlabeled pre-mRNA splicing assay could be performed as an alternative method of splicing reaction other than the radiolabeled one. Two different splicing methods in vitro, 32p labeled and unlabeled pre-mRNA as the substrates in the reaction, were investigated. The radiolabeled products were visualized by autoradiography while the unlabeled products were observed by Ethidium Bromide （EB） staining. As a result, although there are more unspecific bands in the EB staining assay than 32p labeled one, the RNA products of in vitro splicing could be observed clearly. This suggests that the unlabeled pre-mRNA splicing assay can be an optional substitution for the isotope-labeled assay.
基金supported by the Guiding Science and Technology Development Grant in the Social Sector of Luoyang(2101083A)。
文摘Background:Alzheimer's disease(AD)is a progressive neurodegenerative disease with no effective therapies.It is well known that chronic neuroinflammation plays a critical role in the onset and progression of AD.Well-balanced neuronal-microglial interactions are essential for brain functions.However,determining the role of microglia—the primary immune cells in the brain—in neuroinflammation in AD and the associated molecular basis has been challenging.Methods:Inflammatory factors in the sera of AD patients were detected and their association with microglia activation was analyzed.The mechanism for microglial inflammation was investigated.IL6 and TNF-α were found to be significantly increased in the AD stage.Results:Our analysis revealed that microglia were extensively activated in AD cerebra,releasing sufficient amounts of cytokines to impair the neural stem cells(NSCs)function.Moreover,the ApoD-induced NLRC4 inflammasome was activated in microglia,which gave rise to the proinflammatory phenotype.Targeting the microglial ApoD promoted NSC self-renewal and inhibited neuron apoptosis.These findings demonstrate the critical role of ApoD in microglial inflammasome activation,and for the first time reveal that microglia-induced inflammation suppresses neuronal proliferation.Conclusion:Our studies establish the cellular basis for microglia activation in AD progression and shed light on cellular interactions important for AD treatment.
文摘Malignant melanoma,characterized by its high metastatic potential and resistance to conventional therapies,presents a major challenge in oncology.This review explores the current status and advancements in tumor vaccines for melanoma,focusing on peptide,DNA/RNA,dendritic cell,tumor cell,and neoantigen-based vaccines.Despite promising results,significant challenges remain,including the immunosuppressive tumor microenvironment,patient heterogeneity,and the need for more effective antigen presentation.Recent strategies,such as combining vaccines with immune checkpoint inhibitors(ICIs),aim to counteract immune evasion and enhance T cell responses.Emerging approaches,including personalized neoantigen vaccines and the use of self-amplifying RNA platforms,hold promise for overcoming tumor heterogeneity and improving vaccine efficacy.Additionally,optimizing vaccine delivery systems through nanotechnology and genetic modifications is essential for increasing stability and scalability.This review highlights the potential of these innovative strategies to address current limitations,with a focus on how future research can refine and combine these approaches to improve melanoma treatment outcomes.
基金supported by the National Natural Science Foundation of China(82171455).
文摘Hemorrhagic shock is a common clinical emergency that can aggravate cell injury after resuscitation.Astrocytes are crucial for the survival of neurons because they regulate the surrounding ionic microenvironment of neurons.Although hemorrhagic shock and resuscitation(HSR)injury can impair cognition,it remains unclear how this insult directly affects astrocytes.In this study,we established an HSR model by bleeding and re-transfusion in mice.The social interaction test and new object recognition test were applied to evaluate post-operative cognitive changes,and the results suggest that mice experience cognitive impairment following exposure to HSR.In the HSR group,the power spectral density ofβandγoscillations decreased,and the coupling of theθoscillation phase andγoscillation amplitude was abnormal,which indicated abnormal neuronal oscillation and cognitive impairment after HSR exposure.In brief,cognitive impairment in mice is strongly correlated with Ca^(2+)signal strength in lateral septum astrocytes following HSR.
文摘Background Atrial fibrillation （AF） is associated with inflammation and endothelial dysfunction. However, the association between inflammation （as indexed by high-sensitivity C-reactive protein, hs-CRP） and endothelial function [as indexed by big endothelin-1 （ET-1）] in AF patients remains unclear. Methods We enrolled 128 patients with lone AF, among which 83 had paroxysmal AF, and 45 had persistent AF. Eighty-two age- and gender-matched controls of paroxysmal supraventricular tachycardia without AF history were evaluated. Plasma hs-CRP, big ET-1 levels and other clinical characteristics were compared among the groups. Results Patients with persistent AF had higher hs-CRP concentrations than those with paroxysmal AF （P 〈 0.05）, both groups had higher hs-CRP level than controls （P 〈 0.05）. Patients with persistent AF had higher big ET-1 level than those with paroxysmal AF, although the difference did not reach the statistical significance （P 〉 0.05）, and both groups had higher big ET-1 levels than controls （P 〈 0.05）. Multiple regression analyses revealed hs-CRP as an inde- pendent determinant of AF （P 〈 0.001）. Further adjusted for big ET-1, both big ET-1 and hs-CRP were independent predictors for AF （P 〈 0.001）, but the odds ratio for hs-CRP in predicting AF attenuated from 8.043 to 3.241. There was a positive relation between hs-CRP level and big ET-1 level in paroxysmal AF patients （r = 0.563, P 〈 0.05）, however, the relationship in persistent AF patients was poor （r = 0.094, P 〈 0.05）. Conclusions Both plasma hs-CRP and big ET-1 levels are elevated in lone AF patients, and are associated with AF. In paroxysmal lone AF patients, there were significant positive correlations between plasma hs-CRP level and big ET- 1 level.
文摘Objective To describe the clinical characteristics of idiopathic ventricular fibrillation （IVF） with fragmented QRS complex （f-QRS） and J wave in resting electrocardiogram. Methods We reviewed data from 21 case subjects in our hospital who were resuscitated after cardiac arrest due to IVF and assessed the prevalence of f-QRS and J wave in resting electrocardiogram （ECG）. All the case subjects were classified among three groups based on the electrocardiographic morphology： group I, both f-QRS and J wave were observed （n = 6）, group II, only J wave was observed （n = 9）, group III, neither f-QRS nor J wave was observed （n = 6）. Population characteristics, history of syncope or sudden cardiac arrest, incidence of ventricular fibrillation （VF）, and circumstance of VF were evaluated among the three groups. Results The incidence of index events （syncope, survived cardiac arrest and VF episodes recorded in implantable cardioverter defibrillator （ICD） or pacemakers） was 13.4 ~ 5.6 per-year in group I, 10.8 ~ 3.9 per-year in group II, and 9.8 -4- 4.2 per-year in group HI. There were significant differences in incidences among the three groups, the most frequent index events were observed in group I. The hazard ratio for incidence was 3.2 （95%CI, 1.1-7.9; P = 0.01）. The history and circumstance of the index events were different among the groups. In group I, all the index events occurred during sleep in early morning. In group II, four subjects suffered VF during strenuous physical activities or agitation state, two during sleep in early morning, three in usual activity. In group III, one subject suffered VF during sleep in early morning, one in agitation state, four in usual activity. Conclusions This study suggests that the IVF patients with the combined appearance of f-QRS and J wave in the resting ECG suffer an increased risk of VF, this subgroup of IVF patients has a unique clinical feature.
文摘Background Metabolic syndrome is known to be a prothrombotic state. We undertook this study to examine a hypothesis that aspirin resistance may be associated with metabolic syndrome, and to assess other potential determinants of aspirin resistance in patients with cardiovascular disease （CVD）. Methods A total of 469 elderly patients with CVD were recruited. One hundred and seventy-two patients with metabolic syndrome and 297 without metabolic syndrome （control group） received daily aspirin therapy （〉 75 mg） over one month. Platelet aggregation was measured by light transmission aggregometry （LTA）. Aspirin resistance was defined as 〉 20% arachidonic acid （AA）- and 〉 70% adenosine diphosphate （ADP）-induced aggregation according to LTA. Aspirin semi-responders were defined as meeting one （but not both） of these criteria. Results By LTA, 38 of 469 （8.1%） patients were aspirin resistant. The prevalence of aspirin resistance was higher in the metabolic syndrome group compared with the control group [11.6 % vs. 6.6%, odds ratio （OR） = 2.039; 95% confidence interval （CI）： 1.047-3.973]. In the multivariate logistic regression analysis, metabolic syndrome （OR = 4.951, 95% CI： 1.440-17.019, P = 0.011） was a significant risk factor for aspirin resistance. Conclusions A significant number of patients with CVD and metabolic syndrome are resistant to aspirin therapy. This might further increase the risk of cardiovascular morbidity and mortality in these patients.
基金supported by the Zhenjiang Key Research and Development Plan(Social Development)(No.SH2021066)the Clinical Medical Science and Technology Development Fund Project of Jiangsu University in 2018(No.JLY20180031)the Taicang Science and Technology Planning Project(No.TC2020JCYL17),China。
文摘As a group of nonspecific inflammatory diseases affecting the intestine,inflammatory bowel disease(IBD)exhibits the characteristics of chronic recurring inflammation,and was proven to be increasing in incidence(Kaplan,2015).IBD induced by genetic background,environmental changes,immune functions,microbial composition,and toxin exposures(Sasson et al.,2021)primarily includes ulcerative colitis(UC)and Crohn's disease(CD)with complicated clinical symptoms featured by abdominal pain,diarrhea,and even blood in stools(Fan et al.,2021;Huang et al.,2021).
基金supported in part by the National Natural Science Foundation of China(No.81372266)the National Science and Technology Major Project of the Ministry of Science and Technology of China(No.2011zx09101-001-03)
文摘It has been reported that Ethaselen shows inhibitory effects on thioredoxin reductase（TrxR） activity and human tumor cell growth. In order to find an efficient way to reverse cisplatin resistance, we investigated the reversal effects of Ethaselen on cisplatin resistance in K562/cisplatin（CDDP） cells that were established by pulse-inducing human erythrocyte leukemic cell line K562, which are fivefold more resistant to cisplatin compared to K562 cells. The morphology and growth showed that the adhesion of K562/CDDP further decreased while the cell volume increased. The proliferation of K562/CDDP is strengthened. The antitumor activities in vitro were assessed by MTT（3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide） assay and combination index（CI）, showing the significant synergic effects of cisplatin and Ethaselen. Focusing on apoptosis, a series of comparisons was made between K562 and K562/CDDP. Cisplatin induced higher reactive oxygen species（ROS） generation in K562 and subsequently induced the formation of mitochondrial permeability transition pores（PTPs）. In addition, cisplatin increased the ratio of Bax to Bcl-2 in K562, which can influence the mitochondrial membrane permeability. PTP formation and mitochondrial membrane permeabilization eventually resulted in the release of cytochrome c and activation of the Caspase pathway. However, these effects were not clearly seen in K562/CDDP, which may be the reason for the acquired CDDP resistance. However, Ethaselen can induce a high level of ROS in K562/CDDP by TrxR activity inhibition and increased ratio of Bax to Bcl-2 in K562/CDDP by nuclear factor κB（NF-κB） suppression, which subsequently induces the release of cytochrome c in K562/CDDP. This response is partly responsible for the reversal of the cisplatin resistance in K562/CDDP cells.
基金Supported by Tianjin Key Medical Discipline(Specialty)Construction Project,No.TJYXZDXK-015A and No.TJYXZDXK-058B.
文摘BACKGROUND Hemolymphangioma of the jejunum is rare and lacks clinical specificity,and can manifest as gastrointestinal bleeding,abdominal pain,and intestinal obstruction.Computed tomography,magnetic resonance imaging,and other examinations show certain characteristics of the disease,but lack accuracy.Although capsule endoscopy and enteroscopy make up for this deficiency,the diagnosis also still re-quires pathology.CASE SUMMARY A male patient was admitted to the hospital due to abdominal distension and abdominal pain,but a specific diagnosis by computed tomography examination was not obtained.Partial resection of the small intestine was performed by robotic surgery,and postoperative pathological biopsy confirmed the diagnosis of hemo-lymphangioma.No recurrence in the follow-up examination was observed.CONCLUSION Robotic surgery is an effective way to treat hemolymphangioma through minima-lly invasive techniques under the concept of rapid rehabilitation.
基金supported by the National Natural Science Foundation of China(No.81273144)Beijing Natural Science Foundation Program and Scientific Research Key Program of Beijing Municipal Commission of Education(KZ201510025024)Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support(ZYLX201304)
文摘Our study was to investigate the epidemiological characteristics of M.tuberculosis from a national tuberculosis referral center in China. All strains isolated from TB patients, were genotyped by the RD105 deletion, 8 and 51 SNP loci and VNTR. The high differentiation SNPs of modern Beijing strains were analyzed for protein function and structure. 413 M. tuberculosis were included. Of 379 Beijing lineage M. tuberculosis, ＇modern＇ and ＇ancient＇ strains respectively represented 85.5% （324/379） and 14.5% （55/379）. Rv2494 （V48A） and Rv0245 （Sl03F） were confirmed as high differentiation SNPs associated with modern strains. In a word, Modern Beijing lineage M.tuberculosis was dominant and the structural models suggested that modern sub-lineage may more easily survive in ＇extreme＇ host condition.
基金supported by grants from the National Natural Science Foundation of China(Grant No.81972163)the Guangdong Provincial Department of Science and Technology(Grant No.2019A1515010947)+3 种基金the State Key Lab of Respiratory Disease(Grant Nos.SKLRDQN201702,SKLRD-OP-202003)the Guangdong High Level University Clinical Cultivation Project(Grant No.2017-21020)the Wu Jieping Medical Foundation(Grant Nos.320.6750.18125,320.6750.19088-8)the Nonprofit Central Research Institute Fund of the Chinese Academy of Medical Sciences(Grant No.2019PT320003)。
文摘Objective:FGFR is considered an important driver gene of lung squamous cell carcinoma(LSCC).Thus,identification of the biological events downstream of FGFR is important for the treatment of this malignancy.Our previous study has shown that the FGFR/RACK1 complex interacts with PKM2 and consequently promotes glycolysis in LSCC cells.However,the biological functions of the FGFR/RACK1 complex remain poorly understood.Methods:Anchorage-independent assays and in vivo tumorigenesis assays were performed to evaluate cancer cell malignancy.Distant seeding assays were performed to evaluate cancer cell metastasis.β-gal staining was used to examine cell senescence,and immunoprecipitation assays were performed to examine the interactions among FGFR,RACK1,and MDM2.Results:FGFR/RACK1 was found to regulate the senescence of LSCC cells.Treatment with PD166866,an inhibitor of FGFR,or knockdown of RACK1 induced senescence in LSCC cells(P<0.01).A molecular mechanistic study showed that FGFR/RACK1/MDM2 form a complex that promotes the degradation of p53 and thus inhibits cell senescence.PD166866 and RG7112,an MDM2/p53 inhibitor,cooperatively inhibited the colony formation and distal seeding of LSCC cells(P<0.01),and upregulated the expression of p53 and p21.Conclusions:Together,our findings revealed the regulatory roles and mechanisms of FGFR/RACK1 in cell senescence.This understanding should be important in the treatment of LSCC.
基金Medical and health science and Technology Development Plan of Shandong Province(No:2018WS090)Weifang Science and Technology Development Program(No:2018YX035).
文摘Objective:To study the differential lncRNA/mRNA expression profiles of placental tissues in patients with gestational hypertension,analyze their possible mechanisms of action,and explore their target genes and small molecule drug-related lncRNAs.Methods:Three patients with gestational hypertension who were treated in our hospital from May 2018 to May 2019 were selected as the research subjects and three healthy pregnant women who underwent a prenatal examination in the same hospital were selected as the control group.The placental tissues were taken from the patients.RNA-sequencing was performed to construct lncRNA/mRNA differential expression profiles;screening differentially expressed lncRNAs were used to predict target genes,and GO and KEGG enrichment analysis predicted the biological functions of target genes and the enriched signal pathways,respectively.Protein-protein interaction network,lncRNA-miRNAmRNA network,and differentially expressed genesmall molecule drug association networks were constructed.Results:RNA-seq analysis revealed 19 differentially expressed lncRNA(4 up-regulated;15 down-regulated)(P<0.05).Moreover,423 differentially expressed genes(DEGs)(84 up-regulated;339 downregulated)(P<0.05).GO and KEGG enrichment analysis found that gestational hypertension is mainly related to endothelial cell damage,inflammatory response,abnormal immune regulation,and abnormal trophoblast invasion.The PPI network and lncRNA-miRNA-mRNA network were constructed.Differentially expressed gene-drug small molecule prediction results found 19 pairs of differentially gene-small drug relationship pairs,mainly including antibody,inhibitor et al.Conclusion:Differently expressed lncRNAs in the placenta of patients with gestational hypertension can participate in the regulation of multiple biological functional levelrelated signal pathways through targeted regulation of their target genes,and play an important role in the occurrence and development of gestational hypertension.The predicted small molecule drug can be used as a reference for clinical treatment.
基金Supported by Natural Sciences Research Funding from Shaanxi Province(No.2009K01-74)
文摘AIM: To make an electrophysiological demonstration of a possible jaw muscle afferents-oculomotor neural pathway that was proposed by our previous works on rats, which substantiates an early "release hypothesis" on pathogenesis of human Marcus Gunn Syndrome(MGS). METHODS: Extracellular unit discharge recording was applied and both orthodromic and spontaneous unitary firing were recorded in the oculomotor nucleus(III), and the complex of pre-oculomotor interstitial nucleus of Cajal and Darkschewitsch nucleus(INC/DN), following electric stimulation of the ipsilateral masseter nerve(MN) in rats. RESULTS: Extracellular orthodromic unit discharges, with latencies of 3.7±1.3 and 4.7±2.9 ms, were recorded unilaterally in the III, and the INC/DN neurons, respectively. Spontaneous unit discharges were also recorded mostly in the INC/DN and less frequently in the III. Train stimulation could prompt either facilitation or inhibition on those spontaneous unit discharges. The inhibition pattern of train stimulation on the spontaneous discharging was rather different in the III and INC/DN. A slow inhibitory pattern in which spontaneous firing rate decreased further and further following repeated train stimulation was observed in the III. While, some high spontaneous firing rate units, responding promptly to the train stimuli with a short-term inhibition and recovered quickly when stimuli are off, were recorded in the INC/DN. However, orthodromic unit discharge was not recorded in the III and INC/DN in a considerable number of experiment animals. CONCLUSION: A residual neuronal circuit might exist in mammals for the primitive jaw-eyelid reflex observed in amphibians, which might not be well-developed in all experimental mammals in current study. Nonetheless, this pathway can be still considered as a neuroanatomic substrate for development of MGS in some cases among all MGS with different kind of etiology.
文摘BACKGROUND Kallmann syndrome(KS)is a hypogonadotropic hypogonadism accompanied by anosmia or hyposmia.It is associated with the low secretion of gonadotropins which can lead to other abnormal endocrine metabolism disorders such as diabetes.Through genetic and molecular biological methods,more than 10 KS pathogenic genes have been found.AIM To identify the existing mutation sites of KS with diabetes and reveal the relationship between genotype and phenotype.METHODS We studied KS pathogenesis through high-throughput exome sequencing on four diabetes’patients with KS for screening the potential pathogenic sites and exploring the genotype-phenotype correlation.Clinical data and peripheral blood samples were collected from the patients.White blood cells were separated and genomic DNA was extracted.High-throughput sequencing of all exons in the candidate pathogenic genes of probands was performed,and the results obtained were analyzed.RESULTS Sequencing revealed mutations in the KLB p.T313M,ANOS1 p.C172F,and IGSF10 gene(p.Lys1819Arg and p.Arg1035Thr)at different sites,which may have been associated with disease onset.CONCLUSION The diagnosis of KS is challenging,especially in early puberty,and the clinical manifestations reflect physical delays in development and puberty.Timely diagnosis and treatment can induce puberty,thereby improving sexual,bone,metabolic and mental health.
文摘Implantation of implantable cardioverter defibrillators （ICD） has widely been accepted for secondary prevention of sudden cardiac death （SCD） in cardiac arrest survivors.1 Currently there are increasing interests in primary preven- tion of SCD in selected high risk patients who have not experienced cardiac arrest.~ Despite extensive investigation for risk stratification, our current ability to accurately iden- tify patients at high risk for SCD remains very poor. The primary reason is probably due to our limited understand- ing of the mechanisms underlying the pathogenesis of ven- trieular tachy-arrhythmias and sudden cardiac death （Fig. 1）.
