Age-related cytokine imbalance in the thymus in sudden infant death syndrome (SIDS).

BACKGROUND: Sudden infant death syndrome (SIDS) has been considered to be triggered by a combination of underlying immune dysregulation and infections. The thymus is a crucial lymphatic organ responsible for T cell development in infancy. We hypothesized that an altered thymic immune status may be detectable by intrathymic cytokine profiling in SIDS. METHODS: 27 cytokines in protein lysates of thymus tissue and thymus weights were assessed in 26 SIDS cases and 16 infants who died of other reasons. RESULTS: Seventeen out of 27 cytokines were increased in thymic tissue of SIDS compared to controls without infections, and the most significant discrepancy was in infants younger than 20 weeks. The thymic cytokine profiles in SIDS cases were similar to those in controls with severe infection; however, the magnitude of the cytokine concentration elevation in SIDS was less pronounced, indicating sub-clinical infections in SIDS. In contrast to SIDS, intrathymic cytokine concentrations and thymus weight were increased with age in control children. CONCLUSIONS: Elevated thymic cytokine expression and thymus weight, as well as impaired age-related alterations in SIDS, may be influenced by subclinical infection, which may play a role in initiating SIDS in infants with a compromised immune response. IMPACT STATEMENT: Increased thymic weight and cytokine concentration may suggest possible subclinical infection in SIDS. Elevated thymic weight and cytokine concentration mainly in SIDS cases aged <20 weeks. Age-related impairment in the thymic weight and cytokine expression may be impaired by subclinical infection in SIDS.

Revisiting the association of sudden infant death syndrome (SIDS) with polymorphisms of NHE3 and IL13.

OBJECTIVES: Disturbances of the central nervous system and immune system are thought to play a role in sudden infant death syndrome (SIDS). Dysregulated expression of sodium (Na+)/hydrogen (H+) exchanger 3 (NHE3) in the brainstem and of interleukin 13 (IL13) in the lungs has been observed in SIDS. An association of single-nucleotide polymorphisms (SNPs) in NHE3 and IL13 with SIDS has been proposed, but controversial results were reported. Therefore, there is a need to revisit the association of SNPs in NHE3 and IL13 with SIDS. METHODS: Genotyping of rs71597645 (G1131A) and rs2247114 (C2405T) in NHE3 and rs20541 (+ 4464A/G) in IL13 was performed in 201 SIDS cases and 338 controls. A meta-analysis was performed after merging our data with previously published data (all from European populations). RESULTS: Polymorphisms rs2247114 (NHE3) and rs20541 (IL13) were significantly associated with SIDS overall and in multiple subgroups, but no association was found for rs71597645 (NHE3). After combining our data with previously published data, a fixed-effect meta-analysis showed that rs2247114 in NHE3 retained a significant association with SIDS under a recessive model (OR 2.78, 95%CI 1.53 to 5.06; p = 0.0008). CONCLUSION: Our findings suggest an association of NHE3 variant rs2247114 (C2405T), though not rs71597645 (NHE3), with SIDS. A potential role of rs20541 (IL13) still has to be elucidated. Especially NHE3 seems to be an interesting topic for future SIDS research.

Preliminary findings on diagnostic performance of computed tomography perfusion images for intracranial arterial stenosis: a retrospective study.

OBJECTIVES: Computed tomographic perfusion (CTP) can play an auxiliary role in the selection of patients with acute ischemic stroke for endovascular treatment. However, data on CTP in non-stroke patients with intracranial arterial stenosis are scarce. We aimed to investigate images in patients with asymptomatic intracranial arterial stenosis to determine the detection accuracy and interpretation time of large/medium-artery stenosis or occlusion when combining computed tomographic angiography (CTA) and CTP images. METHODS: We retrospectively reviewed 39 patients with asymptomatic intracranial arterial stenosis from our hospital database from January 2021 to August 2023 who underwent head CTP, head CTA, and digital subtraction angiography (DSA). Head CTA images were generated from the CTP data, and the diagnostic performance for each artery was assessed. Two readers independently interpreted the CTA images before and after CTP, and the results were analyzed. RESULTS: After adding CTP maps, the accuracy (area under the curve) of diagnosing internal carotid artery (R1: 0.847 vs. 0.907, R2: 0.776 vs. 0.887), middle cerebral artery (R1: 0.934 vs. 0.933, R2: 0.927 vs. 0.981), anterior cerebral artery (R1: 0.625 vs. 0.750, R2: 0.609 vs. 0.750), vertebral artery (R1: 0.743 vs. 0.764, R2: 0.748 vs. 0.846), and posterior cerebral artery (R1: 0.390 vs. 0.575, R2: 0.390 vs. 0.585) occlusions increased for both readers (p < 0.05). Mean interpretation time (R1: 72.4 ± 6.1 s vs. 67.7 ± 6.4 s, R2: 77.7 ± 3.8 s vs. 72.6 ± 4.7 s) decreased when using a combination of both images both readers (p < 0.001). CONCLUSIONS: The addition of CTP images improved the accuracy of interpreting CTA images and reduced the interpretation time in asymptomatic intracranial arterial stenosis. These findings support the use of CTP imaging in patients with asymptomatic intracranial arterial stenosis.

Development of a prediction nomogram for 1-month mortality in neonates with congenital diaphragmatic hernia.

OBJECTIVES: Although many prognostic factors in neonates with congenital diaphragmatic hernia (CDH) have been described, no consensus thus far has been reached on which and how many factors are involved. The aim of this study is to analyze the association of multiple prenatal and postnatal factors with 1-month mortality of neonates with CDH and to construct a nomogram prediction model based on significant factors. METHODS: A retrospective analysis of neonates with CDH at our center from 2013 to 2022 was conducted. The primary outcome was 1-month mortality. All study variables were obtained either prenatally or on the first day of life. Risk for 1-month mortality of CDH was quantified by odds ratio (OR) with 95% confidence interval (CI) in multivariable logistic regression models. RESULTS: After graded multivariable adjustment, six factors were found to be independently and consistently associated with the significant risk of 1-month mortality in neonates with CDH, including gestational age of prenatal diagnosis (OR, 95% CI, P value: 0.845, 0.772 to 0.925, < 0.001), observed-to-expected lung-to-head ratio (0.907, 0.873 to 0.943, < 0.001), liver herniation (3.226, 1.361 to 7.648, 0.008), severity of pulmonary hypertension (6.170, 2.678 to 14.217, < 0.001), diameter of defect (1.560, 1.084 to 2.245, 0.017), and oxygen index (6.298, 3.383 to 11.724, < 0.001). Based on six significant factors identified, a nomogram model was constructed to predict the risk for 1-month mortality in neonates with CDH, and this model had decent prediction accuracy as reflected by the C-index of 94.42%. CONCLUSIONS: Our findings provide evidence for the association of six preoperational and intraoperative factors with the risk of 1-month mortality in neonates with CDH, and this association was reinforced in a nomogram model.

The changed endemic pattern of human adenovirus from species B to C among pediatric patients under the pressure of non-pharmaceutical interventions against COVID-19 in Beijing, China.

BACKGROUND: Under the pressure of non-pharmaceutical interventions (NPIs) targeting severe acute respiratory syndrome coronavirus 2, the prevalence of human adenovirus (HAdV) was monitored before and after NPIs launched on Jan 24, 2020 in pediatric patients in Beijing, China. METHODS: Respiratory samples collected from children hospitalized with acute respiratory infections from Jan 2015 to Dec 2021 were screened by direct immunofluorescence test or capillary electrophoresis-based multiplex PCR assay. The hexon, penton base, and fiber genes were amplified from HAdV positive specimens, then sequenced. For HAdV typing, phylogenetic trees were built by MEGA X. Then clinical data of HAdV positive cases were collected. All data were evaluated using SPSS Statistics 22.0 software. RESULTS: A total of 16,097 children were enrolled and 466 (2.89%, 466/16,097) were HAdV-positive. The positive rates of HAdV varied, ranging from 4.39% (151/3,438) in 2018 to1.25% (26/2,081) in 2021, dropped from 3.19% (428/13,408) to 1.41% (38/2,689) from before to after NPIs launched (P < 0.001). There were 350 cases typed into nine types of species B, C, or E and 34 recorded as undetermined. Among them, HAdV-B3 (51.56%, 198/384) was the most prevalent types from 2015 to 2017, and HAdV-B7 (29.17%, 112/384) co-circulated with HAdV-B3 from 2018 to 2019. After NPIs launched, HAdV-B3 and B7 decreased sharply with HAdV-B7 undetected in 2021, while HAdV-C1 became the dominant one and the undetermined were more. CONCLUSIONS: The endemic pattern of HAdV changed in Beijing because of the NPIs launched for COVID-19. Especially, the dominant types changed from HAdV-B to HAdV-C.

Pulmonary immune profiling of SIDS: impaired immune maturation and age-related cytokine imbalance.

BACKGROUND: For sudden infant death syndrome (SIDS), an impaired immunocompetence has been discussed for a long time. Cytokines and chemokines are soluble immune mediators (SIM) whose balance is essential for the immune status. We hypothesized that an imbalanced immune response might contribute to the etiology of SIDS. METHODS: We investigated 27 cytokines, chemokines, and growth factors in protein lysates of lungs derived from 29 SIDS cases and 15 control children deceased for other reasons. RESULTS: Except for the CCL5, no significant differences were detected in the lungs between SIDS cases with and without mild upper respiratory tract infections. In contrast, IL-1RA, IL-7, IL-13, and G-CSF were decreased in the merged SIDS cases compared to control cases without evidence of infection. Plotting SIM concentrations against infant age resulted in increasing concentrations in control but not in SIDS lungs, indicating a disturbed immune maturation. Moreover, an age-dependent shift towards a Th2-related pattern was observed in SIDS. CONCLUSIONS: Our findings suggest that an impaired maturation of the immune system, an insufficient response to respiratory pathogens, and an immune response modulated by Th1/Th2 imbalance might play a possible role in triggering SIDS. These findings might in part be explained by chronic stress. IMPACT: Maturation of the cytokine and chemokine network may be impaired in SIDS. An imbalance between Th1- and Th2-related cytokines, which may reflect a state of chronic stress causing a more Th2 shift. An impaired immune maturation, an insufficient response to respiratory pathogens, and an immune response modulated by Th1/Th2 imbalance might play a possible role in SIDS.

Post-mortem genetic analysis of sudden unexplained death in a young cohort: a whole-exome sequencing study.

Sudden unexplained death (SUD) constitutes a considerable portion of unexpected sudden death in the young. Molecular autopsy has proved to be an efficient diagnostic tool in the multidisciplinary management of SUD. Yet, many cases remain undiagnosed using the widely adopted targeted genetic screening strategies. Here, we investigated the genetic substrates of a young SUD cohort (18-40 years old) from China using whole-exome sequencing (WES), with the primary aim to identify novel SUD susceptibility genes. Within 255 previously acknowledged SUD-associated genes, 21 variants with likely functional effects (pathogenic/likely pathogenic) were identified in 51.9% of the SUD cases. More importantly, a set of 33 candidate genes associated with myopathy were identified to be novel susceptibility genes for SUD. Comparative analysis of the cumulative PHRED-scaled CADD score and polygenetic burden score showed that the amount and deleteriousness of variants in the 255 SUD-associated genes and the 33 candidate genes identified by this study were significantly higher compared with 289 randomly selected genes. A significantly higher genetic burden of rare variants (MAF < 0.1%) in the 33 candidate genes also highlighted putative roles of these genes in SUD. After incorporating these novel genes, the genetic testing yields of the current SUD cohort elevated from 51.9 to 66.7%. Our study expands understanding of the genetic variants underlying SUD and presents insights that improve the utility of genetic screenings.

Serum-integrated omics reveal the host response landscape for severe pediatric community-acquired pneumonia.

OBJECTIVE: Community-acquired pneumonia (CAP) is the primary cause of death for children under five years of age globally. Hence, it is essential to investigate new early biomarkers and potential mechanisms involved in disease severity. METHODS: Proteomics combined with metabolomics was performed to identify biomarkers suitable for early diagnosis of severe CAP. In the training cohort, proteomics and metabolomics were performed on serum samples obtained from 20 severe CAPs (S-CAPs), 15 non-severe CAPs (NS-CAPs) and 15 healthy controls (CONs). In the verification cohort, selected biomarkers and their combinations were validated using ELISA and metabolomics in an independent cohort of 129 subjects. Finally, a combined proteomics and metabolomics analysis was performed to understand the major pathological features and reasons for severity of CAP. RESULTS: The proteomic and metabolic signature was markedly different between S-CAPs, NS-CAPs and CONs. A new serum biomarker panel including 2 proteins [C-reactive protein (CRP), lipopolysaccharide (LBP)] and 3 metabolites [Fasciculol C, PE (14:0/16:1(19Z)), PS (20:0/22:6(4Z, 7Z, 10Z, 13Z, 16Z, 19Z))] was developed to identify CAP and to distinguish severe pneumonia. Pathway analysis of changes revealed activation of the cell death pathway, a dysregulated complement system, coagulation cascade and platelet function, and the inflammatory responses as contributors to tissue damage in children with CAP. Additionally, activation of glycolysis and higher levels of nucleotides led to imbalanced deoxyribonucleotide pools contributing to the development of severe CAP. Finally, dysregulated lipid metabolism was also identified as a potential pathological mechanism for severe progression of CAP. CONCLUSION: The integrated analysis of the proteome and metabolome might open up new ways in diagnosing and uncovering the complexity of severity of CAP.

The clinical significance of renal resistance index (RRI) and renal oxygen saturation (RrSO2) in critically ill children with AKI: a prospective cohort study.

OBJECTIVE: The purpose of this study was to look into the clinical significance of the renal resistance index (RRI) and renal oxygen saturation (RrSO2) in predicting the development of acute kidney injury (AKI) in critically ill children. A new non-invasive method for the early detection and prediction of AKI needs to develop. METHODS: Patients admitted to the pediatric intensive care unit (PICU) affiliated with the capital institute of pediatrics from December 2020 to March 2021 were enrolled consecutively. Data of clinical information, renal Doppler ultrasound, RrSO2, and hemodynamic index within 24 h of admission were prospectively collected. Patients were divided into two groups: the study group was AKI occurred within 72 h, while the control group did not. SPSS (version 25.0) was used to analyze the data, and P < 0.05 was considered a statistical difference. RESULTS: 1) A total of 66 patients were included in this study, and the incidence of AKI was 19.70% (13/66). The presence of risk factors (shock, tumor, severe infection) increased the incidence of AKI by three times. 2) Univariate analysis showed significant differences in length of hospitalization, white blood cells (WBC), C-reactive protein (CRP), renal resistance index (RRI), and ejection fraction (EF) between the study and control groups (P < 0.05). There were no significant differences in renal perfusion semi-quantitative score (P = 0.053), pulsatility index (P = 0.051), pediatric critical illness score (PCIS), and peripheral vascular resistance index (P > 0.05). 3) Receiver operating characteristic (ROC) curve showed that if RRI > 0.635, the sensitivity, specificity, and AUC for predicting AKI were 0.889, 0.552, and 0.751, respectively; if RrSO2 < 43.95%, the values were 0.615, 0.719 and 0.609, respectively; if RRI and RrSO2 were united, they were 0.889, 0.552, and 0.766, respectively. CONCLUSIONS: The incidence of AKI is high in PICU patients. And infection, RRI, and EF are risk factors for AKI in PICU patients. RRI and RrSO2 have certain clinical significance in the early prediction of AKI and may provide a new non-invasive method for early diagnosis and prediction of AKI.

A 4D Proteome Investigation of the Potential Mechanisms of SA in Triggering Resistance in Kiwifruit to Pseudomonas syringae pv. actinidiae.

Kiwifruit bacterial cankers caused by Pseudomonas syringae pv. actinidiae (Psa) are a serious threat to the kiwifruit industry. Salicylic acid (SA) regulates plant defense responses and was previously found to enhance kiwifruit's resistance to Psa. However, the underlying mechanisms of this process remain unclear. In this study, we used 4D proteomics to investigate how SA enhances kiwifruit's resistance to Psa and found that both SA treatment and Psa infection induced dramatic changes in the proteomic pattern of kiwifruit. Psa infection triggered the activation of numerous resistance events, including the MAPK cascade, phenylpropanoid biosynthesis, and hormone signaling transduction. In most cases, the differential expression of a number of genes involved in the SA signaling pathway played a significant role in kiwifruit's responses to Psa. Moreover, SA treatment upregulated numerous resistance-related proteins, which functioned in defense responses to Psa, including phenylpropanoid biosynthesis, the MAPK cascade, and the upregulation of pathogenesis-related proteins. We also found that SA treatment could facilitate timely defense responses to Psa infection and enhance the activation of defense responses that were downregulated in kiwifruit during infection with Psa. Thus, our research deciphered the potential mechanisms of SA in promoting Psa resistance in kiwifruit and can provide a basis for the use of SA to enhance kiwifruit resistance and effectively control the occurrence of kiwifruit bacterial cankers.

The MdBBX22-miR858-MdMYB9/11/12 module regulates proanthocyanidin biosynthesis in apple peel.

Proanthocyanidins (PAs) have antioxidant properties and are beneficial to human health. The fruit of apple (Malus × domestica Borkh.), especially the peel, is rich in various flavonoids, such as PAs, and thus is an important source of dietary antioxidants. Previous research on the regulation of PAs in apple has mainly focussed on the transcription level, whereas studies conducted at the post-transcriptional level are relatively rare. In this study, we investigated the function of mdm-miR858, a miRNA with multiple functions in plant development, in the peel of apple fruit. We showed that mdm-miR858 negatively regulated PA accumulation by targeting MdMYB9/11/12 in the peel. During fruit development, mdm-miR858 expression was negatively correlated with MdMYB9/11/12 expression and PA accumulation. A 5'-RACE experiment, GUS staining assays and transient luminescent assays indicated that mdm-miR858 cleaved and inhibited the expression of MdMYB9/11/12. Overexpression of mdm-miR858 in apple calli, tobacco and Arabidopsis reduced the accumulation of PAs induced by overexpression of MdMYB9/11/12. Furthermore, we found that MdBBX22 bound to the mdm-miR858 promoter and induced its expression. Overexpression of MdBBX22 induced the expression of mdm-miR858 to inhibit the accumulation of PAs in apple calli overexpressing MdMYB9/11/12. Under light stress, MdBBX22 induced mdm-miR858 expression to inhibit PA accumulation and thereby indirectly enhanced anthocyanin synthesis in the peel. The present results revealed that the MdBBX22-miR858-MdMYB9/11/12 module regulates PA accumulation in apple. The findings provide a reference for further studies of the regulatory mechanism of PA accumulation and the relationship between PAs and anthocyanins.

Sudden infant death syndrome revisited: serotonin transporter gene, polymorphisms and promoter methylation.

BACKGROUND: Based on findings in the brain stems of SIDS victims, the serotonin transporter (5-HTT) gene has been discussed to be associated with SIDS. METHODS: In the largest study to date, we investigated the promoter length (5-HTTLPR) and intron 2 VNTR polymorphisms in 274 cases and 264 controls and the Ile425Val polymorphism in 65 cases and 64 controls. Moreover, the methylation of the internal promoter region was investigated in 35 cases and 14 controls. RESULTS: For 5-HTTLPR, we observed a trend towards an association of allele L (58.8% vs. 53.4%) with SIDS and significant results were observed after stratifying for age, season at death, and prone position. Nevertheless, when pooling all published data, a significant association of allele L with SIDS is confirmed (p: 0.001). For the intron 2 VNTR polymorphism, no significant differences were observed. After pooling, a significant accumulation of the rare allele 9 was observed in SIDS (2.1% vs. 0.6%; p: 0.018). For the Ile425Val polymorphism, no differences were observed. CONCLUSION: We conclude that genetic variation at this gene might be of some importance in SIDS. Epigenetic analysis of the internal promoter, however, revealed no influence on the relative risk to succumb to SIDS. IMPACT: This is the largest study published up to now on 5-HTT gene polymorphisms and SIDS. Polymorphisms in the 5-HTT gene appear to contribute (although to a small degree) to the risk to die from SIDS. There is no evidence that a methylation of the promoter region is of impact for the etiology of SIDS.

Variants in genes encoding the SUR1-TRPM4 non-selective cation channel and sudden infant death syndrome (SIDS): potentially increased risk for cerebral edema.

Increasing evidence suggests that brain edema might play an important role in the pathogenesis of sudden infant death syndrome (SIDS) and that variants of genes for cerebral water channels might be associated with SIDS. The role of the sulfonylurea receptor 1 (SUR1)-transient receptor potential melastatin 4 (TRPM4) non-selective cation channel in cerebral edema was demonstrated by extensive studies. Therefore, we hypothesized that variants at genes of the SUR1-TRPM4 channel complex might be linked to SIDS. Twenty-four polymorphisms in candidate genes involved in the SUR1-TRPM4 non-selective cation channel were investigated in 185 SIDS cases and 339 controls. One (rs11667393 in TRPM4) of these analyzed SNPs reached nominal significance regarding an association with SIDS in the overall analysis (additive model: p = 0.015, OR = 1.438, 95% CI = 1.074-1.925; dominant model: p = 0.036; OR = 1.468, 95% CI = 1.024-2.106). In the stratified analysis, further 8 variants in ABCC8 (encoding SUR1) or TRPM4 showed pronounced associations. However, none of the results remained significant after correction for multiple testing. This preliminary study has provided the first evidence for a genetic role of the SUR1-TRPM4 complex in the etiology of SIDS, and we suggest that our initial results should be evaluated by further studies.

Extrarenal Wilms tumor with hypertension and dilated cardiomyopathy in an infant: A report of an unusual case.

While Wilms tumors are the most frequently detected kidney cancer type in children, extrarenal Wilms tumors (ERWTs) remain rare. This report is the first to describe hypertension and dilated cardiomyopathy in a patient with an ERWT. A 6-month-old male infant presented with an abdominal mass and paroxysmal hypertension; echocardiography revealed dilated cardiomyopathy with an ejection fraction of 34%, as well as substantially increased plasma renin activity. Pathology yielded a definitive diagnosis of ERWT. Cardiac function and blood pressure gradually returned to normal after tumorectomy. The early diagnosis of such a tumor together with efficient oncologic treatment are vital to optimal patient outcomes.

Anti-epileptic/pro-epileptic effects of sodium channel modulators from Buthus martensii Karsch.

The East Asian scorpion Buthus martensii Karsch (BmK) is one of the classical traditional Chinese medicines for treating epilepsy for over a thousand years. Neurotoxins purified from BmK venom are considered as the main active ingredients, acting on membrane ion channels. Voltage-gated sodium channels (VGSCs) play a crucial role in the occurrence of epilepsy, which make them become important drug targets for epilepsy. Long chain toxins of BmK, composed of 60-70 amino acid residues, could specifically recognize VGSCs. Among them, α-like neurotoxins, binding to the receptor site-3 of VGSC, induce epilepsy in rodents and can be used to establish seizure models. The ß or ß-like neurotoxins, binding to the receptor site-4 of VGSC, have significant anticonvulsant effects in epileptic models. This review aims to illuminate the anticonvulsant/convulsant effects of BmK polypeptides by acting on VGSCs, and provide potential frameworks for the anti-epileptic drug-design.

High-throughput 16S rDNA sequencing assisting in the detection of bacterial pathogen candidates: a fatal case of necrotizing fasciitis in a child.

Postmortem detection of pathogens in infectious deaths is quite important for diagnosing the cause of death and public health. However, it is difficult to detect possible bacterial pathogens in forensic practice using conventional methods like bacterial culture, especially in cases with putrefaction and antibiotic treatment. We report a fatal case caused by necrotizing fasciitis due to bacterial infection. An 8-year-old girl was found dead during sleep 4 days after a minor trauma to her left knee. The gross autopsy suggested that bacterial soft tissue infection might be the cause of death, and the microscopic examination confirmed the diagnosis. The slight putrefaction found at gross autopsy might interfere through postmortem bacterial translocation and reproduction with bacterial culture. High-throughput 16S rDNA sequencing was employed to identify possible pathogens. Bacterial DNA sequencing results suggested Streptococcus pyogenes and Staphylococcus, typical pathogens of necrotizing fasciitis in the tissue. 16S rDNA sequencing might thus be a useful tool for accurate detection of pathogens in forensic practice.

Might life-threatening acute pulmonary edema occur after using recombinant tissue plasminogen activator? A case report.

BACKGROUND: Recombinant tissue plasminogen activator (rt-pa) is the first-line drug for the treatment of acute ischemic stroke, and can lead to some complications.There were rare reports of death due to acute pulmonary edema during rt-pa thrombolysis treatment. CASE PRESENTATION: This study reports a 30-year-old man was diagnosed with acute ischemic stroke and underwent rt-pa thrombolytic therapy. Finally he died despite active rescue. CONCLUSIONS: The autopsy revealed that he died of acute pulmonary edema. This case suggests that it is necessary to pay close attention to the changes of vital signs during thrombolysis and be aware of possibility of pulmonary edema during thrombolysis.

Rarely fatal bilateral re-expansion pulmonary edema after inserting a chest tube for unilateral spontaneous pneumothorax: a case report.

We describe a case of a 32-year-old man who died due to bilateral re-expansion pulmonary edema (RPE) following the insertion a chest tube for unilateral spontaneous pneumothorax. Fifteen minutes after inserting the chest tube, the patient with right spontaneous pneumothorax was diagnosed with right re-expansion edema by chest radiograph. Although multiple treatments were administered, the patient died. However, the findings from autopsy showed bilateral RPE existed in the decedent but not unilateral RPE. Autopsy, microscopic examination, and clinical records concluded that the cause of death was acute cardiac and respiratory failure due to bilateral re-expansion pulmonary edema following unilateral spontaneous pneumothorax. Bilateral RPE due to a unilateral pneumothorax is quite rare in clinical and forensic practice. To the best of our knowledge, this is the first time that the pathological changes of RPE have been described by gross and microscopic examinations. This case is reported to provide histopathologic references for diagnosis of RPE and indicate that combining death investigation, pathological findings and clinical courses plays a vital role in diagnosis of RPE in forensic pathology.

Promising efficacy of SHR-1210, a novel anti-programmed cell death 1 antibody, in patients with advanced gastric and gastroesophageal junction cancer in China.

BACKGROUND: The clinical response to anti-programmed cell death 1 (PD-1) antibodies in patients with advanced gastric and gastroesophageal junction (GEJ) cancer in China has not been reported. METHODS: This study evaluated the efficacy and safety of SHR-1210, an anti-PD-1 antibody, in patients with advanced gastric/GEJ cancer in a phase 1 trial. The associations between candidate biomarkers (programmed death ligand 1 [PD-L1] expression, mismatch repair status, tumor mutation load, and lactate dehydrogenase [LDH] levels) and the efficacy of SHR-1210 were also explored. RESULTS: Thirty patients with recurrent or metastatic gastric/GEJ adenocarcinoma who were refractory or intolerant to previous chemotherapy were enrolled between June 2, 2016, and June 8, 2017. Seven patients (23.3%) demonstrated objective responses, including 1 complete response. The objective response rates for patients with PD-L1-positive and PD-L1-negative tumors were 23.1% (3 of 13) and 26.7% (4 of 15), respectively (P = 1.000). Two treatment-related grade 3 or higher adverse events were reported: one was grade 3 pruritus, and the other (3.3%) was grade 5 interstitial lung disease. All 20 patients tested for the mismatch repair status had mismatch repair-proficient tumors, and the response rate was 30.0% (95% confidence interval, 11.9%-54.3%). Patients with a higher mutation load (4 of 10) tended to have better responses than those with fewer mutations (2 of 10), but the difference was not significant (P = .628). Patients with a >10% relative increase from the baseline LDH level were more likely to experience disease progression (90% [9 of 10]) than patients with a ≤10% change (40% [8 of 20]; P = .017). CONCLUSIONS: Anti-PD-1 antibody SHR-1210 shows encouraging efficacy in patients with advanced gastric/GEJ cancer in China, including mismatch repair-proficient subgroups.

Genetic diversity of diazotrophs and total bacteria in the phyllosphere of Pyrus serotina, Prunus armeniaca, Prunus avium, and Vitis vinifera.

The phyllosphere, which supports a large number of microorganisms, represents the interface between the aboveground parts of plants and air. In this study, four nifH clone libraries were constructed from the phyllosphere of Pyrus serotina (L), Vitis vinifera (P), Prunus armeniaca (X), and Prunus avium (Y). Clones related to Skermanella (L, 12.1%; X, 15.6%; Y, 62.5%; P 70.8%), Bradyrhizobium (X, 2.1%; P, 15.1%; L, 63.7%), Erwinia (X, 68.8%), Pseudomonas (L, 3.3%; P, 7.6%), and Chroococcidiopsis (P, 0.9%; L, 4.4%, X; 5.2%, Y; 19.6%) were present at high percentages, highlighting their critical role in contributing nitrogen to the phyllosphere ecosystem. The 16S rDNA sequence analysis suggested that phyllosphere-associated bacteria were affiliated with a wide range of taxa, encompassing members from Alphaproteobacteria, Betaproteobacteria, Gammaproteobacteria, Deltaproteobacteria, Actinobacteria, Bacteroidetes, Firmicutes, Cyanobacteria, Tenericutes, and Deinococcus-Thermus. Additionally, the abundance of the nifH gene and 16S rDNA was assessed with quantitative PCR. The number of copies of nifH and 16S rDNA ranged from 1.14 × 103 to 1.49 × 104 and from 3.72 × 106 to 7.02 × 107 copies/g fresh leaf sample, respectively. In conclusion, our work sheds light on the microbial communities of the phyllosphere that are important for plant growth. Moreover, we observed a unique composition of nitrogen-fixing bacteria in each phyllosphere sample, suggesting the existence of specific interactions between these functional microorganism and plants, which may provide information or be a reference for the development of bacterial fertilizers.