Cfhr1 gene deficiency exacerbates Staphylococcus aureus-induced sepsis and acute lung injury through complement alternative pathway hyperactivation.

OBJECTIVE: To explore the role of excessive activation of the complement alternative pathway (AP) in acute lung injury (ALI) and sepsis induced by Staphylococcus aureus. Subsequently, we aimed to define the effects of Cfhr gene deletion on Factor H expression, AP activation, and the development of sepsis-induced ALI. METHODS: A sepsis-induced ALI model was established in Cfhr1-knockout mice by tail vein injection of S. aureus. Sepsis scores, bacterial load in lungs, and cytokine and complement factor levels in blood and lung tissues were evaluated at 6, 12, and 24 h after model establishment. Real-time quantitative PCR and RNA sequencing (RNA-seq) were employed to assess the expression of complement pathway-associated molecules and identify differentially expressed genes (DEGs) related to immune responses. RESULTS: Compared to wild-type mice, Cfhr1-knockout mice exhibited significantly increased C3a formation in lung tissues following S. aureus infection, indicating enhanced terminal complement pathway activation. Notably, these mice also had higher bacterial colony counts in the lungs, suggesting impaired S. aureus clearance. Transcriptome analysis provided further insights into the impact of Cfhr1 deletion on biological processes and signalling pathways involved in immune response regulation. CONCLUSION: Cfhr1 deletion leads to excessive AP activation, exacerbating S. aureus-induced sepsis and ALI.

Fecal Microbiota Transplantation for Severe Infant Botulism, China.

Infant botulism in a 4-month-old boy in China who continued to excrete toxins for over a month despite antitoxin therapy was further treated with fecal microbiota transplantation. After treatment, we noted increased gut microbial diversity and altered fecal metabolites, which may help reduce intestinal pH and enhance anti-inflammatory capabilities.

Dynamics of platelet parameters in children with severe community-acquired pneumonia between viral and bacterial infections.

Background: Changes in platelet parameters may vary according to the different pathogens. However, little is known about the differences in platelet parameters in children with severe community-acquired pneumonia (CAP) children of viral and bacterial infections. Methods: This was a single-center retrospective study that included 156 children with severe CAP. Dynamic changes in platelet parameters, including platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW) and plateletcrit (PCT), were recorded at 24 h, 48 h, 72 h, and day 7 of admission, as well as at discharge. Results: At 72 h of admission, PLT in the viral infection group was significantly lower than that in the bacterial infection and bacterial and viral coinfections group. Meanwhile, the curve of changes in PLT (ΔPLT) in the viral infection group was clearly separated from the other two groups at this time point. Receiver operating characteristic (ROC) analysis showed that PLT at 72 h of admission could assist in distinguishing bacterial and viral infections in severe pneumonia children with the area under curve (AUC) value of 0.683 [95% confidence interval (CI): 0.561-0.805, P=0.007]. However, its sensitivity and specificity were not high, at 68% and 65%, respectively. Conclusions: Although the diagnostic value of platelet parameters in bacterial and viral infection in children with severe CAP is limited, they are still expected to be combined with other indicators to provide a reference for timely treatment.

Effect of Antimicrobial Stewardship 2018 on severe pneumonia with bacterial infection in paediatric intensive care units.

OBJECTIVES: Antimicrobial Stewardship 2018 (ASP 18) in China emphasizes the hierarchical control of antimicrobial drugs and the management of physicians' prescribing authority, especially in children. The purpose of this study was to assess the effect of implementation of ASP 2018 on antibiotic consumption, resistance, and treatment outcomes in children with severe pneumonia from bacterial infections. METHODS: A single center, retrospective study was conducted on 287 children with severe bacterial pneumonia, including 165 patients before intervention (May 2016-April 2018) and 122 patients after intervention (May 2018-April 2020). The antimicrobial resistance rates, antibiotic consumption, and clinical outcomes of the two periods were compared. RESULTS: After the implementation of ASP 2018, Staphylococcus aureus (17.9%) became the predominant Gram-positive bacterium. The resistance of Streptococcus pneumoniae to clindamycin, erythromycin, and tetracycline was significantly reduced (P < 0.001), and Staphylococcus aureus to tetracycline also decreased (P = 0.034). In addition, Klebsiella pneumoniae (18.4%) replaced Pseudomonas aeruginosa (9.5%) as the most common Gram-negative bacterium. The resistance rates of Klebsiella pneumoniae to amoxicillin/clavulanic acid (AMC) and trimethoprim/sulfamethoxazole (SXT), and Acinetobacter baumannii to cefotaxime and SXT decreased significantly (P < 0.02). Total consumption (DDD/100 patient-days) of five antibiotics (cephalosporins, carbapenems, macrolides, antifungal agents, and linezolid) showed a decreasing trend, and the decrease in antifungal agents and linezolid was the most significant (27.4% and 25.6%, P < 0.001). The isolation rate of multidrug-resistant (MDR) strains decreased significantly from the highest, 16.8%, before intervention to 6.7% after intervention (P < 0.001). CONCLUSION: Our data indicate that the implementation of antimicrobial management strategies has significantly reduced the consumption of antibiotics and the occurrence of antimicrobial resistance in children with severe bacterial pneumonia in PICU.

Multilevel omics for the discovery of biomarkers in pediatric sepsis.

Severe sepsis causes organ dysfunction and continues to be the leading reason for pediatric death worldwide. Early recognition of sepsis could substantially promote precision treatment and reduce the risk of pediatric death. The host cellular response to infection during sepsis between adults and pediatrics could be significantly different. A growing body of studies focused on finding markers in pediatric sepsis in recent years using multi-omics approaches. This narrative review summarized the progress in studying pediatric sepsis biomarkers from genome, transcript, protein, and metabolite levels according to the omics technique that has been applied for biomarker screening. It is most likely not a single biomarker could work for precision diagnosis of sepsis, but a panel of markers and probably a combination of markers detected at multi-levels. Importantly, we emphasize the importance of group distinction of infectious agents in sepsis patients for biomarker identification, because the host response to infection of bacteria, virus, or fungus could be substantially different and thus the results of biomarker screening. Further studies on the investigation of sepsis biomarkers that were caused by a specific group of infectious agents should be encouraged in the future, which will better improve the clinical execution of personalized medicine for pediatric sepsis.

Fatal methanol poisoning with different clinical and autopsy findings: Case report and literature review.

Methanol poisoning is responsible for high morbidity and mortality, and the elevated concentration of methanol in the body is the major criteria for forensic diagnosis of methanol poisoning. However, in cases with lower methanol concentrations, diagnosis is mainly dependent on highly variable postmortem manifestations.Herein, we report a fatal methanol poisoning cases that two subjects ingested the same amount of methanol simultaneously, yet the subject one presented only non-specific gastrointestinal and mild central nervous system symptoms, while the other subject exhibited typical toxic manifestations with the exception of visual compromise. In autopsy, subject number 1 did not show typical pathological changes caused by methanol poisoning, except for the elevated levels of methanol in body fluids. On the contrary, bilateral basal ganglia hemorrhage and necrosis caused by methanol-induced brain lesion was observed in case number 2. Due to the complex and multifactorial process of methanol intoxication, many factors, including comprehensive autopsy, quantitative detection of methanol and formic acid, and genotype analysis, participate in its metabolism and toxicity, and can impact the clinical symptoms, prognosis and postmortem manifestations. Therefore, a combination of multiple diagnosis methods may more accurately contribute to the forensic diagnosis of methanol poisoning and should be tailored on an individual basis. This case report also reviews forensic diagnosis literature on methanol poisoning to provide a reference for forensic pathologists.

Sudden cardiac death of Duchenne muscular dystrophy with NT-proBNP in pericardial fluid as a useful biomarker for diagnosis of the cause of death: a case report.

Duchenne muscular dystrophy (DMD) is one of the most common and severest muscular dystrophies. Although it can be a cause of death when associated with cardiac muscle and/or respiratory muscles, no cases of sudden deaths in the setting of undiagnosed DMD with cardiac involvement have been reported in the literatures. Previous studies showed that N-terminal-proBNP (NT-proBNP) was a robust laboratory biomarker to diagnose and monitor cardiac failure in clinical situations, suggesting that it may be used as an auxiliary indicator for diagnosis on left ventricular dysfunction in sudden cardiac deaths in forensic settings. Here, we reported a case of 29-year-old man who died suddenly. Autopsy revealed that muscles of the body were almost replaced by fatty and fibrotic tissues. The heart was enlarged with disarray and degeneration of cardiomyocytes in cardiac muscle. Total absence of dystrophin was detected by immunohistochemical staining, which confirmed DMD. Postmortem biochemical test of pericardial fluid revealed a high level of NT-proBNP, indicating dysfunction of the left ventricle before death. The cause of death was certified as an early dilated cardiomyopathy (DCM)/dysfunction of the left ventricle secondary to DMD, suggesting that sudden cardiac death with cardiac dysfunction could be identified by immunohistochemical method in combination with pericardial fluid NT-proBNP determination after systemic autopsy.

A retrospective study of poisoning deaths from forensic autopsy cases in northeast China (Liaoning).

Acute poisoning is a public health threat that leads to morbidity and mortality worldwide. In this retrospective study, we evaluated autopsies from deaths caused by acute poisoning from 2008 to 2017 at the School of Forensic Medicine, China Medical University (SFMCMU) in the Liaoning Province, northeast China. A total of 140 poisoning deaths were investigated and the demographic characteristics, causes and manner of death, toxics category were analyzed. The number of poisoning deaths gradually increased during the study period. The majority of poisoning deaths were accidents (66.43%), followed by suicides (27.86%), and homicides (3.57%). Of the 140 cases, 47 (33.57%) were caused by drugs, 38 (27.14%) by agrochemicals (mainly organophosphate pesticides, n = 16), 37 (26.43%) by respiratory dysfunction toxics (mainly carbon monoxide, n = 21), and 9 (6.43%) by poisonous plants and animals. Alcohol/methanol (5, 3.57%) and other chemicals (4, 2.86%) accounted for the remaining cases. The present study provides poisoning distribution in the Liaoning province and highlights implications for public health policy and prevention efforts in northeast China.

Long non-coding RNA HOTAIR acts as a competing endogenous RNA to promote malignant melanoma progression by sponging miR-152-3p.

HOX transcript antisense RNA (HOTAIR) is associated with the growth and metastasis of many human tumors, but its biological roles in malignant melanoma remain unclear. In this study, we show that HOTAIR is overexpressed in melanoma tissues and cells, especially in metastatic melanoma. High HOTAIR levels correlate with poor prognosis in melanoma patients. We also determined that HOTAIR functions as a competing endogenous RNA (ceRNA) for miR-152-3p. miR-152-3p was decreased and acted as a tumor suppressor in melanoma, and c-MET was the functional target of miR-152-3p. Furthermore, HOTAIR promotes the growth and metastasis of melanoma cells by competitively binding miR-152-3p, which functionally liberates c-MET mRNA and results in the activation of the downstream PI3k/Akt/mTOR signaling pathway. We determined that HOTAIR acts as a ceRNA to promote malignant melanoma progression by sponging miR-152-3p. This finding elucidates a new mechanism for HOTAIR in melanoma development and provides a potential therapeutic target for melanoma patients.

A fatal case of hypothermia caused by dog bites.

Death from hypothermia usually *We presented a fatal case of hypothermia after being bitten by dog in this article. occurs among people exposed to cold and humid environmental conditions when they are homeless, aged, suffering from natural or psychiatric diseases and drug or alcohol intoxication. A normal healthy person dying from hypothermia due to dog bites is unusual and rare. Here, we present a fatal case of hypothermia following dog bites causing blood loss and multiple wounds on the body. A 56-year-old man was found dead in a remote roadside puddle of a small village, early in the morning. He was naked, and his body trunk and limbs had multiple irregular wounds. Gray animal hairs could be seen in parts of the wound cavities and surrounding areas. In addition, there was a kennel near the scene. Family members argued that the deceased was bitten to death by a dog. However, autopsy revealed several findings which were strongly supportive of fatal hypothermia. Moreover, we saw no obvious changes caused by blood loss, either on the body surface or internal organs. Accordingly, we concluded the true cause of his death was fatal hypothermia; bites from a dog was a necessary causative factor.

[Progress on Hypoxic-ischemic Brain Damage Associated with CCR2 and CCL2].

Hypoxic-ischemic brain damage (HIBD) is referred to a common type of cerebral damage, which is caused by injury, leading to shallow bleeding in the cortex with intact cerebral pia mater. In recent years, studies show that a various kinds of immune cells and immune cellular factors are involved in the occurrence of HIBD. CC chemokine receptor 2 (CCR2) is a representative of CC chemokine receptor, and is widely distributed in cerebral neuron, astrocyte, and microglial cells, and is the main chemo-tactic factor receptor in brain tissue. CC chemokine ligand 2 (CCL2) is a kind of basophilic protein and the ligand of CCR2, and plays an important role in inflammation. In order to provide evidence for correlational studies in HIBD, this review will introduce the biological characteristics of CCR2 and CCL2, and illustrate the relationship between the immunoreactivity and HIBD.

[Progress on Correlation between the Expression of CDK5 and Brain Injury Time].

Cyclin-dependent kinase 5 (CDK5) is a member of cyclin-dependent kinase family, which does not directly regulate cell cycle. Through phosphorylation of target protein, CDK5 plays an irreplaceable role in the development, reparation and degeneration of neurons. Brain injury refers to the organic injury of brain tissue caused by external force hit on the head. Owing to the stress and repair system activated by our body itself after injury, various proteins and enzymes of the brain tissues are changed quantitatively, which can be used as indicators for estimating the time of injury. This review summarizes the progress on the distribution, the activity mechanism and the physiological effects of CDK5 after brain injury and its corresponding potential served as a marker for brain injury determination.

[Expression of p35 and p25 after Focal Cerebral Contusion in Rat].

OBJECTIVE: To study the expression of p35 and p25 in rat after focal cerebral contusion and to provide experimental data for estimating brain injury time. METHODS: Fifty adult male SD rats were randomly divided into 0 h, 6 h, 12 h, 24 h, 3 d, 5 d, 7 d, 10 d after focal cerebral contusion, control and sham-operated groups (5 rats each group). The focal cerebral contusion rat model was established. The expression of p35 and p25 protein of the damage peripheral zone in brain were detected by HE staining, immunohistochemistry and Western blotting at different injury time. RESULTS: A large number of p35 protein and a small amount of p25 protein were expressed in control group and sham-operated group. After focal cerebral contusion, p35 presented unimodal change with time and p25 presented bimodal changes with time. CONCLUSION: Expression of p35 and p25 showed different regularity with good time correlation, which could help to estimate the brain injury time.

[Progress of the recovery mechanism of brain injury associated with the gene polymorphism of apolipoproteins E].

Brain injury is a kind of wound by violence on head, which is a mechanical distortion of skull, meninx, cerebral vascular and brain tissue due to outside force acting on head. Apolipoproteins E (ApoE) is a major kind of apolipoproteins, participating in the metabolism of lipid and regulating balance of cholesterol. Some recent investigations show that gene polymorphism of ApoE is associated with various kinds of diseases. Also its immunoreactivity is changed regularly with brain injury. In addition, ApoE has remarkable effect in neurological normal growth and reparative process after brain injury. This article reviews the biological characteristics and mechanism of ApoE in the repair of brain injury and application prospect in forensic medicine, which may be able to provide new ideas for estimation of the brain injury time and related experimental research.

[Metallothionein-I/II in brain injury repair mechanism and its application in forensic medicine].

Metallothionein (MT) is a kind of metal binding protein. As an important member in metallothionein family, MT-I/II regulates metabolism and detoxication of brain metal ion and scavenges free radicals. It is capable of anti-inflammatory response and anti-oxidative stress so as to protect the brain tissue. During the repair process of brain injury, the latest study showed that MT-I/II could stimulate brain anti-inflammatory factors, growth factors, neurotrophic factors and the expression of the receptor, and promote the extension of axon of neuron, which makes contribution to the regeneration of neuron and has important effect on the recovery of brain injury. Based on the findings, this article reviews the structure, expression, distribution, adjustion, function, mechanism in the repair of brain injury of MT-I/II and its application prospect in forensic medicine. It could provide a new approach for the design and manufacture of brain injury drugs as well as for age estimation of the brain injury.

[Twenty autopsy cases of anaphylactic shock induced by cephalosporins].

OBJECTIVE: To explore the characteristics of autopsy cases of anaphylactic shock induced by cephalosporins and provide the evidences in forensic medicine. METHODS: Twenty cases of anaphylactic shock induced by cephalosporins were collected from April 2005 to August 2009 in judicial expertise center of China Medical University, and the characteristics of the cases were analyzed retrospectively. RESULTS: The age of decedents ranged from 40 to 60 years. Ninety percent of cases were from local medical centers and private clinics. The symptoms of the shock appeared 30 s-150 min after the administration of the drug, and death occurred 10 min-210 min after the appearance of the shock symptoms. In all cases, various degrees of eosinophil infiltration were observed in trachea and the lungs. Serum IgE detected by ELISA method was normal value in 14 cases. CONCLUSION: In fatal anaphylactic cases, little specific findings are detected during postmortem and microscope examination. For this reason, the determination of cause of death in these cases requires comprehensive analysis combined with clinic information and excludes other diseases leading to the sudden death.

[Homer protein expression after focal brain contusion in rats].

OBJECTIVE: To investigate Homer protein expression after focal brain contusion and explore the relationship between expression and injury time. METHODS: Focal brain contusion in rats was established and Homer protein expression in brain at different injury intervals after contusion was detected by immunohistochemistry and Western blotting. RESULTS: A small amount of Homer positive expression cells were detected in control group, sham operated group and experimental group (0.5 h after contusion). The amount of Homer positive expression cells increased after 3 h and reached peak 12 h after contusion. The amount of positive cells continued to decrease 1 d after contusion and to the base level 7 d after contusion. Homer protein expression based on immunohistochemistry and Western blotting had statistical difference among adjacent groups. CONCLUSION: Expression of Homer protein near the focal contusion area shows time dependence after brain contusion in rats.

[Expression of matrix metalloproteinase-3 after brain contusion in rats].

OBJECTIVE: To investigate the expression of matrix metalloproteinase-3 after brain contusion and its applicability for estimating the age of brain contusion. METHODS: Rats had been divided into three groups: control group, sham operation group and brain contusion group. The expression of matrix metalloproteinase-3 at different time was detected by immunohistochemistry and Western blot. RESULTS: By the immunohistochemistry, no staining was observed in control and sham operation groups. The positive staining of MMP-3 appeared 6 hours after contusion, increased gradually in 24 hours and peaked 5 days after contusion, then started to decrease, 14 days after contusion still could be observed. By the Western blot analysis, no expression of MMP-3 was detected in control and sham groups. The positive staining of MMP-3 appeared 6 hours after contusion, increased gradually and maximized 5 days after contusion, then started to decrease, 14 days after contusion still could be found. CONCLUSION: Time-order expression of MMP-3 could be used for estimating the age of brain contusion in forensic pathology.