Association of congenital heart disease and neurodevelopmental disorders: an observational and Mendelian randomization study.

BACKGROUND: This study aims to thoroughly study the connection between congenital heart disease (CHD) and neurodevelopmental disorders (NDDs) through observational and Mendelian randomization (MR) designs. METHODS: This observational study uses data from the National Survey of Children's Health (2020-2021). Multivariable logistic regression and propensity score matching (PSM) were performed to analyze the association. PSM was used to minimize bias for covariates such as age, race, gender, maternal age, birth weight, concussion or brain injury, preterm birth, cerebral palsy, Down syndrome, and other inherited conditions. In MR analyses, inverse variance-weighted measures, weighted median, and MR-Egger were employed to calculate causal effects. RESULTS: A total of 85,314 children aged 0-17 were analyzed in this study. In regression analysis, CHD (p = 0.04), the current heart condition (p = 0.03), and the severity of current heart condition (p < 0.05) had a suggestive association with speech or language disorders. The severity of current heart condition (p = 0.08) has a potential statistically significant association with attention deficit hyperactivity disorder(ADHD). In PSM samples, ADHD(p = 0.003), intellectual disability(p = 0.012), and speech or language disorders(p < 0.001) were all significantly associated with CHD. The severity of current heart condition (p < 0.001) also had a significant association with autism. MR analysis did not find causality between genetically proxied congenital cardiac malformations and the risk of NDDs. CONCLUSIONS: Our study shows that children with CHD have an increased risk of developing NDDs. Heart conditions currently and severity of current heart conditions were also significantly associated with these NDDs. In the future, we need to try more methods to clarify the causal relationship between CHD and NDDs.

[Expression of CD30 in Patients with Diffuse Large B-Cell Lymphoma and Clinical Significance].

OBJECTIVE: To investigate the expression and clinical significance of CD30 in patients with diffuse large B-cell lymphoma (DLBCL). METHODS: A retrospective analysis was conducted on 124 cases of primary DLBCL diagnosed at Changzhou Second People's Hospital Affiliated with Nanjing Medical University from January 2018 to July 2020. The expression of CD30 in patients with DLBCL was detected by immunohistochemical method, and the clinicopathological characteristics were analyzed and compared between CD30+ and CD30- groups. Kaplan-Meier analysis was used for survival analysis. The relationship between CD30 expression and clinical features and prognosis were analyzed. RESULTS: Among the 124 patients with DLBCL, 19 patients expressed CD30, and the positive rate is 15.32%. The clinico-pathological characteristics of CD30+ in patients with DLBCL were characterized by low age, more common in males, fewer extranodal lesions, lower international prognostic index (IPI), GCB type being more common in Hans subtype, and achieving better therapeutic effects (P < 0.05). However, there were no significant statistical differences in B-symptoms (P =0.323), Ann Arbor staging (P =0.197), Eastern Cooperative Oncology Group (ECOG) score (P =0.479), lactate dehydrogenase (LDH) (P =0.477), and the involvement of bone marrow (P =0.222). There were significant differences in OS and PFS between the CD30+ and CD30- groups (χ2=5.653, P =0.017; χ2＝4.109，P =0.043), the CD30+ group had a better prognosis than that of the CD30- group. The results of subgroup analysis showed that the CD30+ group in the IPI score=1-2, LDH elevated group had a better prognosis (P < 0.05). In the subgroups of Ann Arbor staging III-IV (P =0.055) and non GCB type (P =0.053), the CD30+ group had a good prognosis trend, but the difference was not statistically significant. The results of univariate analysis showed that the good prognosis of DLBCL patients was closely related to CD30+ expression, no B-symptoms, early Ann Arbor staging, low ECOG score, normal LDH, low IPI score, fewer extranodal involvement, and obtaining the best therapeutic effect as CR (all P <0.05). COX multivariate regression analysis showed that the presence of B-symptoms and achieving the best therapeutic effect as Non-CR were independent risk factors affecting the prognosis of DLBCL patients (P < 0.05). CONCLUSION: The CD30+ expression in DLBCL patients indicates a good prognosis and has certain diagnostic value in evaluating the prognosis of DLBCL patients.

The down-regulation of STC2 mRNA may serve as a biomarker for death from mechanical asphyxia.

Death from mechanical asphyxia (DMA) is a common cause of death in forensic pathology. However, due to the lack of biomarkers, the authentication of DMA now relies on a series of non-specific signs, which may cause troubles in the judicial trials, especially when the criminal scene is not fully elucidated. To search for the potential biomarkers for DMA, brain samples of DMA and craniocerebral injury groups were screened by microarray. The obtained mRNAs were validated by animal and human samples. Primary cell culture was conducted to explore the biochemical changes under hypoxia. 415 differentially expressed mRNAs between two groups were discovered. Ten mRNAs were examined in both human and animal samples died of different causes of death. Stanniocalcin-2 (STC2) showed significant down-regulation in DMA samples compared to other groups, regardless of PMI, age, or temperature. Cellular experiments indicated that ROS level peaked after 15-min-hypoxic culture, when the expression level of STC2 was significant down-regulated simultaneously. The ER-stress-related proteins also showed potential connection with STC2. In general, it is indicated that the down-regulation of STC2 may serve as a biomarker for DMA.

Serum amyloid A as a biomarker for immunoglobulin resistance in Kawasaki disease.

BACKGROUND: Intravenous immunoglobulin (IVIG) resistance is of prime importance in Kawasaki disease (KD). In this study, we examined the value and mechanism of serum amyloid A (SAA) level in predicting IVIG resistance in patients with KD. METHODS: SAA levels were measured in 497 consecutive patients with KD before IVIG therapy in the training set. The patients were divided into two groups (IVIG-responsive and IVIG-resistant) according to the American Heart Association (AHA) definition of IVIG resistance. Demographic, echocardiographic, and laboratory data were also retrospectively analyzed and tabulated to predict IVIG resistance. The predictive value of SAA was validated on test sets of prospective data. Cytokine microarrays were analyzed from 4 patients with resistant to IVIG, 4 patients with responsive to IVIG and 4 healthy volunteers. RESULTS: During the training set, 409 patients with KD were enrolled, of whom 43 (10.5%) were resistant to initial IVIG treatment and 47 (11.49%) had coronary artery lesions (CALs). Serum levels of SAA were higher in the IVIG resistant group compared to the IVIG responsive group, (380.00 [204.40-547.25] vs 230.85 [105.40-490.00] mg/L; p = .008). The values of total bilirubin, C-reactive protein, neutrophils, alanine aminotransferase, aspartate aminotransferase, interleukin-6(IL-6), and procalcitonin were significantly higher in the IVIG-resistant group than in the IVIG-responsive group (p < .05); however, the lymphocytes, platelets, serum sodium levels, and duration of fever before IVIG therapy were significantly lower (p < .05). There was no significant difference in SAA levels between patients with KD with and without CALs. Binary logistic regression analysis showed that SAA (p = .008), neutrophils (p < .001), total bilirubin (p = .001), platelet count (p = .004), and serum sodium level (p = .019) were independent factors influencing IVIG resistance. The optimal cutoff value of SAA for IVIG resistance prediction was 252.45 mg/L, with a corresponding clinical sensitivity of 69.8% and specificity of 54.4%. Based on receiver operating characteristic (ROC) curve analyses, the area under the curve (AUC) of combined detection with these five indicators was 0.800, clinical sensitivity was 69.8%, and specificity was 76.2%. In the prospective data, the sensitivity, specificity, and accuracy of SAA for identifying IVIG resistance KD were 77.8%,69.0%, and 70.0%, respectively. Compared with IVIG- responsive group and healthy children, the levels of IL-6 was upregulated significantly in IVIG-resistant group through cytokine microarrays. CONCLUSIONS: SAA may be a potential biomarker for predicting IVIG responsiveness to KD, Combined detection of SAA levels, total bilirubin, neutrophil count, platelet count, and serum sodium levels is superior to that of any other single indicator for predicting IVIG resistance in KD. And elevated SAA may accompany with IL-6 in KD patients, its use in clinical practice may be helpful for treatment management.

Predictive and prognostic role of early apolipoprotein A-I alteration in recurrent or metastatic nasopharyngeal carcinoma patients treated with anti-PD-1 therapy.

BACKGROUND: The primary objective of this study was to evaluate the predictive and prognostic value of serum lipids in recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) patients received anti-PD-1 therapy. MATERIALS AND METHODS: Patients treated with anti-PD-1 therapy (monotherapy or combined with chemotherapy) from two clinical trials (CAPTAIN and CAPTAIN-1st study) were included. Serum lipids were measured at baseline and after two cycles of treatment. We examined the impact of both baseline and post-treatment lipid levels on objective response rate (ORR), progression-free survival (PFS), and duration of response (DOR). RESULTS: Of 106 patients, 89 patients (84%) were male. The patients' median age was 49 years. An early elevated (after two cycles of treatment) cholesterol (CHO), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A-I (ApoA-I), and apolipoprotein B (ApoB) were significantly associated with better ORR. Moreover, early elevated CHO, LDL-C, and ApoA-I were also positively correlated with DOR and PFS. Further multivariate analysis showed that only early change in ApoA-I could independently predict PFS (HR, 2.27; 95% CI, 1.11-4.61; p = 0.034). The median PFS for patients with early elevated and reduced ApoA-I was 11.43 and 1.89 months, respectively. However, baseline lipids levels do not play a significant role in the prognosis and prediction of patients with anti-PD-1 treatment. CONCLUSION: Collectively, an early elevation in ApoA-I was correlated with better outcomes for anti-PD-1 therapy in patients with R/M NPC, suggesting that clinicians should consider the early alteration of ApoA-I as a useful marker in treating R/M NPC patients with anti-PD-1.

Development of Henoch-Schoenlein purpura in a child with idiopathic hypereosinophilia syndrome with multiple thrombotic onset: A case report.

BACKGROUND: The incidence of pulmonary embolism (PE) in children is low, but its mortality is high. Hypereosinophilic syndrome (HES) is a group of diseases caused by an abnormal increase in eosinophilic granulocytes resulting in multiple-organ dysfunction. The urgent event of thromboembolism in the pulmonary region provoked by eosinophils in idiopathic HES (IHES) is relatively unusual. This article reports a case of IHES with multiple PEs and left leg venous thrombosis as the first manifestation. One month later, the patient developed Henoch-Schonlein purpura (HSP), which is very rare. CASE SUMMARY: We report the case of a 12-year-old boy who was admitted to the hospital with dyspnea, left leg pain, and aggravation. He had bilateral PE and left leg venous embolism with mild eosinophilia. Low-molecular-weight heparin and urokinase were given. At the same time, the interventional department was contacted about filter implantation, followed by urokinase thrombolysis. The left leg thrombus was aspirated under ultrasound guidance. He was discharged from the hospital on rivaroxaban. One month later, he developed a rash on both legs and ankle pain consistent with HSP, with severe eosinophilia and motor and sensory disturbances. The patient was diagnosed with IHES with multiple embolisms complicated by HSP after excluding other causes of the eosinophil elevation. After glucocorticoid treatment, the symptoms were relieved, but the patient later developed purpura nephritis. CONCLUSION: We report a rare and life-threatening case of IHES with multiple embolisms associated with HSP. A mild elevation of eosinophils early in the disease leads to difficulties in diagnosis and delayed treatment.

Gastric Mucosa Pathology in Rats with Precancerous Lesions of Gastric Cancer with Spleen Deficiency and Blood Stasis.

Objective: This research aimed at better understanding the histopathological development of precancerous lesions of gastric cancer (PLGC) and organelle ultrastructure changes. Methods: Sprague-Dawley rats were randomly assigned to the model and control groups. Model rats drank N-methyl-N'-nitro-N-nitrosoguanidine solution, while control rats drank pure water ad libitum. At 1, 3, 5, 6, and 8 months after the start of feeding, eight rats were randomly chosen from each group, and gastric mucosa tissues were removed for histopathological analysis. H&E staining was applied to analyze the pathological histological structure of the rat gastric mucosa via a light microscope, and the ultrastructural changes were observed via a transmission electron microscope. Results: Gastric mucosal pathologies of model rats such as mucosal atrophy, intestinal metaplasia, inflammatory lesions, and even intraepithelial neoplasia deteriorated over time. The endoplasmic reticulum gap widened, the mitochondrial endothelial cristae were disrupted, the nuclear membrane thickened, and chromatin condensed with heterotypic alterations in the main and parietal cells. Additionally, endothelial cell enlargement and thickening of the microvascular intima were seen. Conclusion: Our research showed that the PLGC progression of rats is correlated with the pathological alteration axis of "normal gastric mucosa-gastric mucosa inflammatory changes-intestinal metaplasia with mild dysplasia-moderate to severe dysplasia." Ultrastructure analysis of model rats is compatible with the structural changes in the gastric mucosa with spleen deficiency and blood stasis. The pathological evolutionary axis and ultrastructural analysis are helpful for evaluating potential novel herbal therapies for PLGC.

Effects of Plasma Exchange Combined with Immunoglobulin Therapy on Consciousness, Immune Function, and Prognosis in Patients with Myasthenia Gravis Crisis: A Prospective Randomized Test.

Background: Myasthenia gravis (MG) is an acquired autoimmune disease. The main clinical features of MG are skeletal muscle fatigue and pathological fatigue, which worsen at night or after fatigue, such as dyspnea, dysphagia, and systemic weakness. Plasma exchange (PE) is often used in patients with acute exacerbation of MG. Intravenous immunoglobulin (IVIG) is a collection of immunoglobulins from thousands of donors. IVIG can replace a variety of immunosuppressants or PE. However, the effect of PE or IVIG on patients' consciousness, immune function, and prognosis is not clear. Objective: A prospective randomized test of the effects of PE combined with immunoglobulin on consciousness, immune function, and prognosis in patients with myasthenia gravis crisis (MGC). Methods: Sixty patients with MGC treated from February 2019 to April 2021 were enrolled in our hospital. The cases who received PE were set as the PE group, and those who received PE combined with immunoglobulin were set as the PE+immunoglobulin group. The efficacy, clinical score, state of consciousness, immune function, acetylcholine receptor antibody (AChR-Ab), lymphocyte (LYM), albumin (ALB) levels, and the incidence of adverse reactions were compared. Results: The improvement rate was 100.005% in the treatment group and 83.33% in the PE group. After treatment, the clinical score of the PE+immunoglobulin group was lower than that of the PE group, and the clinical relative score of the PE+immunoglobulin group was higher than that of the PE group (P < 0.05). The number of conscious people in the PE+immunoglobulin group was more than that in the PE group (P < 0.05). Immunoglobulin A, immunoglobulin M, immunoglobulin G, and immunoglobulin G in the PE+immunoglobulin group were higher than those in the PE group (P < 0.05). The levels of AChR-Ab and ALB in the PE+immunoglobulin group were higher than those in the PE group, while the level of LYM in the PE+immunoglobulin group was lower than that in the PE group. The incidence of skin system, gastrointestinal system, nervous system, and systemic damage in the PE+immunoglobulin group was lower than that in the PE group (P < 0.05). Conclusion: The treatment of MGC with PE combined with immunoglobulin can not only effectively enhance the consciousness and immune function of patients but also effectively promote the prognosis, and the safety of treatment can be guaranteed.

Development and Validation of a Diagnostic Nomogram to Predict the Anthracycline-Induced Early Cardiotoxicity in Children with Hematological Tumors.

This study aimed to establish and validate an effective nomogram to predict the risk of cardiotoxicity in children after each anthracycline treatment. According to the inclusion and exclusion criteria, the eligible children were randomly divided into the training cohort (75%) and the validation cohort (25%). Least absolute shrinkage and selection operator (LASSO) regression was used to select the predictors and a nomogram was developed. Then, concordance index (C-index), the area under the curve (AUC), Hosmer-Lemeshow (H-L) test, and decision curve analysis (DCA) were employed to evaluate the performance and clinical utility of nomogram. Internal validation was processed to inspect the stability of the model. A total of 796 eligible children were included in this study and divided into a training set (n = 597) and a validation set (n = 199). LASSO regression analysis revealed that cumulative anthracycline dose, ejection fractions, NT-proBNP, and diastolic dysfunction were effective predictors of cardiotoxicity. The nomogram was established based on these variables. The C-index and the AUC of the predicting nomogram were 0.818 in the training cohort and 0.773 in the validation cohort, suggesting that the nomogram had good discrimination. The calibration curve of the nomogram presented no significant deviation from the reference line, and the P-value of the H-L test was 0.283, implying a preferable degree of calibration. The threshold of DCA also reflects that the nomogram is clinically useful. A nomogram was developed to predict anthracycline chemotherapy-induced cardiotoxicity in children with hematological tumors. The nomogram has a good prediction effect and can provide a reference for clinicians' diagnosis and treatment.

ER stress-related protein, CHOP, may serve as a biomarker of mechanical asphyxia: a primary study.

The precise authentication of death from mechanical asphyxia (DMA) has been a complex problem in forensic medicine. Besides the traditional methods that concern the superficial characterization of the body, researchers are now paying more attention to the biomarkers that may help the identification of DMA. It has been reported that the extremely hypoxic environment created by DMA can cause the specific expression of mitochondria-related protein, which may sever as the biomarkers of DMA authentication. Since endoplasmic reticulum stress (ER stress) has been found to be related to the dysfunction of mitochondria, it is promising to look for the biomarkers of DMA among ER stress-related proteins. In this article, animal and cell experiments were conducted to examine how ER-mitochondria interaction may be influenced in the hypoxic condition caused by DMA primarily. Human samples were then used to verify the possible biomarkers of DMA. We found that ER stress-related protein CHOP was significantly up-regulated within a short-term postmortem interval (PMI) in brain tissue of DMA samples, which may interact with a series of ER stress- and mitochondria-related protein, leading to the apoptosis of the cells. It was also verified in human samples that the expression level of CHOP can sever as a potential biomarker of DMA within a specific PMI.

Endoplasmic reticulum stress-related secretory proteins as biomarkers of early myocardial ischemia-induced sudden cardiac deaths.

Early myocardial ischemia-induced sudden cardiac deaths (EMI-SCD) remain a great diagnostic challenge for forensic pathologists due to no gross or non-specific histological pathology. The goal of this study was to assess whether three secretory proteins, related with cellular endoplasmic reticulum stress, can be applied in forensic diagnosis of EMI-SCD. These markers included LMAN2, CAPN-1, and VCP and were compared with two clinically used markers (CK-MB and cTnI). A total of 21 EMI-SCD cases with a mean age of 53.0 (± 10.5) years and a mean ischemia interval of < 2.77 (± 2.56) hours were collected. Another 23 cases (mean 44.6 ± 15.0 year old) that died from non-cardiac causes served as control. Enzyme-linked immunosorbent assay (ELISA) was performed to detect target proteins' serum concentrations in the EMI-SCD and control groups. We found that LMAN2, CAPN-1, and VCP were all significantly increased in the EMI-SCD group as compared with control serum, with the fold changes ranging from 1.48 (p = 0.0022, LMAN2), 1.33 (p = 0.041, CAPN-1), to 1.26 (p = 0.021, VCP), respectively. The concentrations of these proteins remained highly stable within 6 h and were not affected by death time, postmortem interval (< 4 h), age, and month at death. Receiver operating characteristic (ROC) curves showed that the areas under the curve (AUC) were 0.8178 (LMAN2), 0.6988 (CAPN-1), and 0.7267 (VCP), all of which were higher than CK-MB (AUC 0.5590) and cTn-I (AUC 0.5911). The diagnostic specificity (all above 60%) was obviously higher than CK-MB (43.48%) and cTnI (34.78%). In conclusion, LMAN-2, CAPN-1, and VCP could be stable serological biomarkers for diagnosis of EMI-SCD cases.

Acute carbon monoxide poisoning with low saturation of carboxyhaemoglobin: a forensic retrospective study in Shanghai, China.

Carbon monoxide (CO) poisoning is a common cause of death, leading to morbidity and mortality worldwide. Features of the CO poisoning with low carboxyhemoglobin (COHb) levels remain to be characterized. This study collected a total of 307 CO poisoning cases from Shanghai Public Security Bureau, an official organization that handles the most complicated and life-threatening cases across Shanghai municipality in China, and regrouped these cases into three categories: group 1, 10% < COHb% < 30% (n = 58); group 2, 30% ≤ COHb% < 50% (n = 79); group 3, COHb% ≥ 50% (n = 170). Epidemiological, demographic, and forensic aspects of the CO poisoning cases, particularly those with low COHb levels, were analyzed. Our results showed that group 2 and 3 were mostly observed in younger victims (≤ 30 years), while group 1 equally distributed to all age groups (p = 0.03). All the CO poisoning from group 2 and 3 occurred in enclosed spaces, whereas cases from group 1 died additionally in outdoor spaces (p = 0.01). 81.03% of group 1 cases died in fire circumstances, while only 45.57% from group 2 and 30.59% from group 3 were fire-related (p = 0.00). Accordingly, group 1 was mostly related with fire burns, while group 2 or 3 were largely associated with gas leakage (p = 0.00). A combination with alcohol, but not other psychotropic drugs, associated with significant higher levels of blood COHb% in fire-unrelated (p = 0.021) but not fire-related cases (p = 0.23). Five extremely low COHb% (< 30%)-related poisoning deaths were negative of any cardiopulmonary pathology and psychoactive substances. In conclusion, CO poisoning with low COHb% significantly associates with fire circumstances and outdoor spaces and has no age preference. Further diagnostic markers mandates to be identified in order to avoid disputes in cases of extremely low COHb%-related poisoning.

Model for the prediction of mechanical asphyxia as the cause of death based on four biological indexes in human cardiac tissue.

Determination of mechanical asphyxia as the cause of death has always been difficult for forensic pathologists, particularly when signs of asphyxia are not obvious on the body. Currently, depending on only physical examination of corpses, pathologists must be cautious when making cause-of-death appraisals. In a previous study, four biomarkers-dual-specificity phosphatase 1 (DUSP1), potassium voltage-gated channel subfamily J member 2 (KCNJ2), miR-122, and miR-3185-were screened in human cardiac tissue from cadavers that died from mechanical asphyxia compared with those that died from craniocerebral injury, hemorrhagic shock, or other causes. Expression of the markers correlated with death from mechanical asphyxia regardless of age, environmental temperature, and postmortem interval. However, a single biological index is not an accurate basis for the identification of the cause of death. In this study, receiver operating characteristic curves of the ΔCq values of the four indexes were generated. The diagnostic accuracy of the indexes was judged according to their area under the curve (DUSP1: 0.773, KCNJ2: 0.775, miR-122: 0.667, and miR-3185: 0.801). Finally, a nomogram was generated, and single blind experiment was conducted to verify the cause of death of mechanical asphyxia.

Synthesis of New Piperazine Substituted Chalcone Sulphonamides as Antibacterial Agents.

BACKGROUND: Infection is a global threat to human health, and there is an urgent need to develop new effective antibacterial drugs to treat bacterial infections. OBJECTIVE: To study the antibacterial activity of piperazine substituted chalcone sulphonamides. MATERIALS AND METHODS: A series of novel piperazine substituted chalcone sulphonamides have been prepared, and in vitro antibacterial activity against Staphylococcus aureus, Bacillus subtilis and Escherichia coli strains were evaluated. RESULTS: The results showed that derivatives 6a, 6c and 6h displayed good antibacterial activity against Bacillus subtilis with MIC values of 4.0-8.0 mg/mL. CONCLUSION: Piperazine substituted chalcone sulphonamides may be used as potential antibacterial agents.

Identification of the miRNA-3185/CYP4A11 axis in cardiac tissue as a biomarker for mechanical asphyxia.

Death by mechanical asphyxia is one of the most difficult conclusions to make in forensic science, especially in corpses displaying slight or no trauma to the surface of the body. Therefore, death by mechanical asphyxia is difficult to prove in medico-legal practice. MicroRNAs (miRNAs) are a class of small, non-coding RNAs involved in the regulation of numerous physiological and pathological cellular processes. In the present study, we demonstrate that significantly increased expression of miR-3185 in cardiac tissues was detected among cases of mechanical asphyxia compared to case of craniocerebral injury, hemorrhagic shock, sudden cardiac death and poisoning. We observed no correlation between the expression of miR-3185 and postmortem interval, age or temperature. Further work indicated that CYP4A11 is a putative target gene of miR-3185 and expressed at a relatively low level in cardiac tissue specimens from cases of mechanical asphyxia compared with specimens from cases of craniocerebral injury, hemorrhagic shock, sudden cardiac death and poisoning. Our results suggest that the miRNA-3185/CYP4A11 axis is associated with mechanical asphyxia-induced death and may provide new insight into asphyxial death investigations.

Antimicrobial photodynamic therapy in skin wound healing: A systematic review of animal studies.

Bacterial infection is a common wound complication that can significantly delay healing. Classical local therapies for infected wounds are expensive and are frequently ineffective. One alternative therapy is photodynamic therapy (PDT). We conducted a systematic review to clarify whether PDT is useful for bacteria-infected wounds in animal models. PubMed and Medline were searched for articles on PDT in infected skin wounds in animals. The language was limited to English. Nineteen articles met the inclusion criteria. The overall study methodological quality was moderate, with a low-moderate risk of bias. The animal models were mice and rats. The wounds were excisional, burn, and abrasion wounds. Wound size ranged from 6 mm in diameter to 1.5 × 1.5 cm2 . Most studies inoculated the wounds with Pseudomonas aeruginosa or methicillin-resistant Staphylococcus aureus. Eleven and 17 studies showed that the PDT of infected wounds significantly decreased wound size and bacterial counts, respectively. Six, four, and two studies examined the effect of PDT on infected wound-cytokine levels, wound-healing time, and body weight, respectively. Most indicated that PDT had beneficial effects on these variables. PDT accelerated bacteria-infected wound healing in animals by promoting wound closure and killing bacteria.

Cytoplasmic upregulation of Cyto c and AIF serve as biomarkers of mechanical asphyxia death.

The certification of death due to mechanical asphyxia has been a complex problem in some cases. The use of protein expression to identify mechanical asphyxia death has recently attracted attention. Asphyxia creates an extremely hypoxic environment for cells, which should reactivate the mitochondria in the cells. Cyto c and AIF, located in the mitochondria, are transferred to the cytoplasm under hypoxia to trigger the apoptotic process. Based this phenomenon, we designed the animal asphyxia model and cell hypoxia model to examine whether Cyto c and AIF are expressed in the cytoplasm, and we used human samples to verify the results. We found that the two proteins were detectably expressed in the cytoplasm of mechanical asphyxia groups and were hardly detected in the cytoplasm of other groups. This is a promising finding that may shed light on the precise mechanisms associated with mechanical asphyxia.

Forensic age estimation based on the pigmentation in the costal cartilage from human mortal remains.

Age estimation is considered a crucial and challenging issue in forensic casework. Costal cartilage appears a potential mortal remain in age-at-death estimation attributable to its correlative alteration in color based on pigment accumulation with the advancing age. In this study, samples from the second costal cartilage were collected in a Chinese Han population, and the cross sections were subsequently scanned and digitalized in a standard way. Color change was quantified using mean gray value (MGV), which was measured by Photoshop CS5. After the exclusion of samples with factors which could impair the quality of images and the accuracy of values, a high correlation was demonstrated between age and MGV in samples. A linear regression model (AGE = 173.425-0.755*aveMGV) was established for age prediction, with its performance evaluated using both samples from the training set and the blind test set, in which a mean absolute deviation of 4.42 years and 3.57 years was obtained, respectively. Altogether, MGV could be reckoned as a precise quantification of pigmentation in costal cartilage and an excellent indicator of age prediction in the age interval from 20 to 60 years. Moreover, our strategy appears more user-friendly and accurate, thus exceedingly practical for age estimation in forensic anthropology.

Early postmortem interval (EPMI) estimation using differentially expressed gene transcripts.

Genes differentially expressed after death were selected to construct a mathematical model for early postmortem interval estimation. Sprague Dawley rats were sacrificed and placed at temperatures of 4 °C, 15 °C, 25 °C, and 35 °C. Brain tissues were collected at 0, 6, 12, 18, and 24 h after death and total RNA was extracted. Changes in gene transcript levels after death were detected using microarray expression profiling and differentially expressed genes was screened. Expanded experiments were performed to validate gene transcript levels at different temperatures using the reverse transcription real-time quantitative polymerase chain reaction. Six genes with high coefficients of determination were chosen for construction of mathematical models. Optimal ternary cubic equations were built using R software with temperature, postmortem interval and ΔCq defined as the independent variable x, y and z, respectively. Equations were converted into a three-dimensional visual statistical model using MATLAB. Animal samples were used to validate the mathematical models. Results showed that the 5srRNA showed best stability at four temperatures. The genes Ninj2, Grifin, Arpp19, and Hopx showed high coefficients of determination (>80%) and low error (<3h) in verification experiments which indicate that they are potential markers for early postmortem interval estimation.

Performance of cement-stabilized macadam roads based on aggregate gradation interpolation tests.

This study adopted the uniform interpolation method to obtain five gradation types (labeled A, B, C, D, and E, from "coarse-grained" to "fine-grained" types) based on the skeleton dense structure and cement-stabilized macadam (CSM) aggregate gradation range recommended by current specifications. The optimum water content of the CSM exhibited a linear increase with gradation, whereas the maximum dry density exhibited a variation that can be described by a quadratic curve, for which the peak maximum dry density was near the maximum dry density of the Type B gradation. In the CSM structure, the skeleton void effect of the coarse-grained aggregate, the filling effect of the fine-grained aggregate, and the cementation effect of the cement and aggregate exhibited corresponding fluctuations. The ability to resist temperature shrinkage deformation was reduced. Additionally, the optimum values of the compressive strength and compression rebound modulus of the CSM plotted near the curve of the Type D gradation.