OBJECTIVE: Exposure to polycyclic aromatic hydrocarbons (PAHs) or metal(loid)s individually has been associated with neural tube defects (NTDs). However, the impacts of PAH and metal(loid) co-exposure and potential interaction effects on NTD risk remain unclear. We conducted a case-control study in China among population with a high prevalence of NTDs to investigate the combined effects of PAH and metal(loid) exposures on the risk of NTD. METHODS: Cases included 80 women who gave birth to offspring with NTDs, whereas controls were 50 women who delivered infants with no congenital malformations. We analyzed the levels of placental PAHs using gas chromatography and mass spectrometry, PAH-DNA adducts with ³²P-post-labeling method, and metal(loid)s with an inductively coupled plasma mass spectrometer. Unconditional logistic regression was employed to estimate the associations between individual exposures and NTDs. Least absolute shrinkage and selection operator (LASSO) penalized regression models were used to select a subset of exposures, while additive interaction models were used to identify interaction effects. RESULTS: In the single-exposure models, we found that eight PAHs, PAH-DNA adducts, and 28 metal(loid)s were associated with NTDs. Pyrene, selenium, molybdenum, cadmium, uranium, and rubidium were selected through LASSO regression and were statistically associated with NTDs in the multiple-exposure models. Women with high levels of pyrene and molybdenum or pyrene and selenium exhibited significantly increased risk of having offspring with NTDs, indicating that these combinations may have synergistic effects on the risk of NTDs. CONCLUSION Our findings suggest that individual PAHs and metal(loid)s, as well as their interactions, may be associated with the risk of NTDs, which warrants further investigation.
Humans ; Neural Tube Defects/chemically induced* ; Polycyclic Aromatic Hydrocarbons/adverse effects* ; Female ; Case-Control Studies ; China/epidemiology* ; Adult ; Pregnancy ; Environmental Pollutants ; Maternal Exposure/adverse effects* ; Metals/toxicity* ; Young Adult ; Risk Factors

DNA genetic markers have always played important roles in individual identification, kinship analysis, ancestry inference and phenotype characterization in the field of forensic medicine. DNA methylation has unique advantages in biological age inference, body fluid identification and prediction of phenotypes. The majority of current studies independently examine DNA and DNA methylation markers using various workflows, and they use various analytical procedures to interpret the biological information these two markers present. Integrated methods detect DNA and DNA methylation markers simultaneously through a single experimental workflow using the same preparation of sample. Therefore, they can effectively reduce consumption of time and cost, streamline experimental procedures, and preserve valuable DNA samples taken from crime scenes. In this paper, the integrated detection approaches of DNA and DNA methylation markers on different detection platforms were reviewed. In order to convert methylation modifications to detectable forms, several options were available for pretreatment of genomic DNA, including digestion with methylation-sensitive restriction enzyme, affinity enrichment of methylated fragments, conversion of methylated or unmethylated cytosine. Multiplexed primers can be designed for DNA markers and converted DNA methylation markers for co-amplification. The schemes of using capillary electrophoresis platform for integrated detection add the pretreatment of genomic DNA on the basis of detecting DNA genetic markers. DNA and DNA methylation markers are then integrated by co-amplification. But the limited number of fluorescent options available and the length of amplicons restrict the type and quantity of markers that can be integrated into a panel. Pyrophosphate sequencing also supports integrated detection of DNA and DNA methylation markers. On this platform, due to the conversion of unmethylated cytosine to thymine after treatment with bisulfite, the methylation level of CpG site can be directly calculated using the peak height ratio of cytosine bases and thymine bases. Therefore, the methylation levels and SNP typing can be simultaneously obtained. However, due to the limited read length of sequencing, the detection of markers with longer amplicons is restricted. It is not conducive to fully interpret the complete information of the target sequence. Next-generation sequencing also supports integrated detection of DNA and DNA methylation markers. A preliminary experimental process including DNA extraction, pretreatment of genomic DNA, co-preparation of DNA and DNA methylation library and co-sequencing, has been formed based on the next-generation sequencing platform. It confirmed the feasibility of next-generation sequencing technology for integrated detection of DNA and DNA methylation markers. In field of biomedicine, various integrated detection schemes and corresponding data analysis approaches of DNA and DNA genetic markers developed based on the above detection process.Co-analysis can simultaneously obtain the genomic genetic and epigenetic information through a single analytic process. These schemes suggest that next-generation sequencing may be an effective method for achieving more accurate and highly integrated detection, helping to explore the potential for application in forensic biological samples. We finally explore the impact of interactions between sites and different pretreatment methods on the integrated detection of DNA and DNA methylation markers, and also propose the challenge of applying third-generation sequencing for integrated detection in forensic samples.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Itch is an unpleasant sensation that provokes the desire to scratch. While acute itch serves as a protective system to warn the body of external irritating agents, chronic itch is a debilitating but poorly-treated clinical disease leading to repetitive scratching and skin lesions. However, the neural mechanisms underlying the pathophysiology of chronic itch remain mysterious. Here, we identified a cell type-dependent role of the anterior cingulate cortex (ACC) in controlling chronic itch-related excessive scratching behaviors in mice. Moreover, we delineated a neural circuit originating from excitatory neurons of the ACC to the ventral tegmental area (VTA) that was critically involved in chronic itch. Furthermore, we demonstrate that the ACC→VTA circuit also selectively modulated histaminergic acute itch. Finally, the ACC neurons were shown to predominantly innervate the non-dopaminergic neurons of the VTA. Taken together, our findings uncover a cortex-midbrain circuit for chronic itch-evoked scratching behaviors and shed novel insights on therapeutic intervention.
Mice ; Animals ; Gyrus Cinguli/physiology* ; Pruritus/pathology* ; Mesencephalon ; Cerebral Cortex/pathology* ; Neurons/pathology*

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology* ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Pregnancy ; Respiratory Distress Syndrome, Newborn/epidemiology* ; Retrospective Studies ; Treatment Outcome

OBJECTIVES: To study the characteristics of amino acid metabolism in preterm infants in Guangxi, China. METHODS: A retrospective analysis was performed on the medical data of 30 757 neonates who underwent the screening for inherited metabolic diseases and had negative results in Guangxi Neonatal Disease Screening Center from 2018 to 2020. Among these neonates, there were 28 611 normal full-term infants (control group) and 2 146 preterm infants (preterm birth group). According to gestational age, the preterm infants were further divided into four groups: very preterm (n=209), moderately preterm (n=307), and late preterm group (n=1 630). According to birth weight, they were divided into three groups: very low birth weight group (n=161), low birth weight group (n=1 085), and normal birth weight group (n=900). According to blood collection time, they were divided into three groups: 3-7 days group (n=1 664), 8-14 days group (n=314) and 15-28 days group (n=168). Tandem mass spectrometry was performed to measure the levels of 11 amino acids in dried blood spots, which were then compared between groups. RESULTS: After adjustment for confounding factors, there were significant differences in the levels of 11 amino acids among different gestational age groups (P<0.05), and significant differences were observed in the levels of the 11 amino acids between the control group and the various preterm groups (except for citrulline and methionine in the late preterm group). There were significant differences in the levels of 11 amino acids among different birth weight groups (P<0.05). Except for ornithine, there were significant differences in the levels of other amino acids among the different blood collection time groups (P<0.05). CONCLUSIONS Gestational age, birth weight and blood collection time all affect amino acid metabolism in preterm infants in Guangxi, China. This provides a basis for the laboratory to establish the reference standard and clinical interpretation of blood amino acid levels in preterm infants, and to improve the nutritional metabolism of preterm infants.
Amino Acids ; China ; Gestational Age ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Premature Birth ; Retrospective Studies

ObjectiveThis study investigated the mechanism of Wenjingtang in the prevention and treatment of endometriosis （EMT） from the perspective of regulating hypoxia stress and mitochondrial function. MethodPrimary human endometrial stromal cells （ESCs） form ectopic endometrial tissues were isolated and cultured， the cells were divided into control group （Control）， 5% control serum group （5% KBXQ）， 10% control serum group （10% KBXQ）， 5% Wenjingtang serum group （5% WJTXQ） and 10% Wenjingtang serum group （10% WJTXQ）. ESCs in different groups were detected for proliferation by methyl thiazolyl tetrazolium （MTT） assay， mRNA and protein expression of hypoxia inducible factor-1α （HIF-1α） by real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） and Western blot analysis， mitochondrial ultrastructure by transmission electron microscope， mitochondrial function ［mitochondrial membrane potential， mitochondrial membrane potential（MMP） and cytochrome C（Cyt C） content］ and apoptosis （cell membrane permeability， nuclear fluorescence intensity， nuclear size and cell counts） by high content screening （HCS） assay， apoptosis rate by flow cytometry， and proteins of B-cell lymphoma-2 （Bcl-2） associated X （Bax）， Bcl-2 and cleaved cysteinyl aspartate specific proteinase-3 （cleaved Caspase-3） by Western blot. ResultCompared with Control group， the 5% KBXQ and 10% KBXQ groups showed increased cell viability （P<0.01）， there was no significant change in HIF-1α mRNA and protein expression， transmission electron microscopy showed that the mitochondrial cristae were obvious and the inner and outer membranes of mitochondria were clear， HCS multichannel fluorescence staining showed that there were no significant changes in the expression of MMP， Cyt C and cell membrane permeability， and the nuclei showed uniform light staining， there were no significant changes in apoptosis rate， cleaved Caspase-3 protein expression and Bax/Bcl-2 ratio. Compared with Control group and corresponding concentration KBXQ group， the 5% WJTXQ and 10% WJTXQ group showed decreased cell viability （P<0.01） and HIF-1α mRNA and protein levels （P<0.05，P<0.01）， the ultrastructure of mitochondria was destroyed， some mitochondria were swollen and the cristae were blurred， moreover， decreased MMP and up-regulated Cyt C release （P<0.05，P<0.01）， increased cell membrane permeability （P<0.01）， and apoptosis characteristics included nuclear pyknosis， DNA agglutination in nucleus and decrease of cell numbers were observed （P<0.05，P<0.01）， increased apoptosis rate （P<0.01）， which was consistent with the results of HCS analysis， and up-regulated expression levels of cleaved Caspase-3 protein and Bax/Bcl-2 ratio （P<0.05，P<0.01）. ConclusionIn conclusion， the results suggest that Wenjingtang can improve hypoxia stress via down-regulating HIF-1α expression in ectopic ESCs， and inhibit cell proliferation， reduce mitochondrial biological activity and induce apoptosis， which might be the internal mechanism of Wenjingtang in preventing and treating EMT.

ObjectiveTo investigate the effects and mechanism of baicalin （BA） on lipopolysaccharide （LPS）-induced acute lung injury in rats. MethodEighty healthy male SD rats were randomly divided into the control group， model group， low-dose BA （BA-L） group， medium-dose BA （BA-M） group， high-dose BA （BA-H） group， dexamethasone （DEX） group， SB203580 group， and BA + SB203580 group， with 10 rats in each group. The rats in the BA-L， BA-M， and BA-H groups were injected intraperitoneally with different doses （10， 50， 100 mg·kg^-1） of BA solution， the ones in the DEX group with 5 mg·kg^-1 DEX solution， the ones in the SB203580 group with 0.5 mg·kg^-1 SB203580 solution， the ones in the BA + SB203580 group with 100 mg·kg^-1 BA solution and 0.5 mg·kg^-1 SB203580， and those in both the control group and model group with the same volume of normal saline， once per day， for seven successive days. One hour after the last administration， rats in all groups except for the control group were given 5 mg·kg^-1 LPS via intratracheal instillation for inducing the acute lung injury， whereas those in the control group received the same volume of normal saline solution. Twelve hours later， the lung tissues were sampled and stained with htoxylin-eosin （HE） for observing the pathological changes， followed by the counting of the total number of cells and neutrophils in bronchoalveolar lavage fluid （BALF）. The wet/dry weight ratio of the lung tissue and the contents of serum superoxide dismutase （SOD） and malondialdehyde （MDA） were measured. The activity of reactive oxygen species （ROS） in the lung tissue was detected by immunofluorescence and the levels of interleukin-1β （IL-1β）， interleukin-18 （IL-18）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in BALF by enzyme-linked immunosorbent assay （ELISA）. Immunohistochemistry （IHC） was conducted to determine the relative expression of p-p38 mitogen-activated protein kinase （MAPK） and Western blotting was carried out to detect the protein expression levels of p-p38 MAPK， thioredoxin interacting protein （TXNIP）， NOD-like receptor protein 3 （NLRP3）， and cysteinyl aspartate specific protease-1 （Caspase-1） in the lung tissue. ResultCompared with the control group， the model group displayed inflammatory pathological changes in lung tissue， elevated wet/dry weight ratio， total number of cells and neutrophils in BALF， and ROS and MDA levels （P<0.01）， decreased SOD activity （P<0.01）， and up-regulated IL-1， IL-18， IL-6， TNF-α， p-p38 MAPK， NLRP3， and Caspase-1 expression （P<0.01）. Compared with the model group， BA at different doses， SB203580， and BA + SB203580 all effectively alleviated the pathological changes in lung tissue induced by LPS， reduce the lung wet/dry weight ratio， the total number of cells and neutrophils in BALF， and ROS and MDA levels （P<0.05，P<0.01）， enhanced the activity of SOD （P<0.05，P<0.01）， and down-regulated the expression of IL-1β， IL-18， IL-6，TNF-α， p-p38 MAPK， NLRP3， and Caspase-1 in lung tissue （P<0.05，P<0.01）. ConclusionBA has a protective effect against LPS-induced acute lung injury， which may be related to its inhibition of p38MAPK/NLRP3 signaling pathway and the improvement of inflammatory response.

OBJECTIVES: To study the safety and efficacy of dexmedetomidine hydrochloride combined with midazolam in fiberoptic bronchoscopy in children. METHODS: A total of 118 children who planned to undergo fiberoptic bronchoscopy from September 2018 to February 2021 were enrolled. They were divided into a control group ( RESULTS: Compared with the control group, the observation group had significantly decreased MAP at T CONCLUSIONS Dexmedetomidine hydrochloride combined with midazolam is a safe and effective way to administer general anesthesia for fiberoptic bronchoscopy in children, which can ensure stable vital signs during examination, reduce intraoperative adverse reactions and postoperative agitation, shorten examination time, and increase amnesic effect.
Bronchi ; Bronchoscopy ; Child ; Dexmedetomidine/adverse effects* ; Humans ; Hypnotics and Sedatives/adverse effects* ; Midazolam ; Prospective Studies

Cerebral ischemia can induce weak endogenous neurogenesis, which is not enough to repair neural injury after cerebral ischemia.In the treatment of cerebral ischemic diseases with Chinese medicine, different treatment methods based on syndrome differentiation are adopted according to the pathological mechanism of the diseases, and the advantages of neural repair after cerebral ischemia are well shown through comprehen-sive regulation.And in this paper, the effects of inflammation, neurovascular units, exogenous stem cell transplantation, exo- somes and other factors on neurogenesis and repair after cerebral ischemia and the intervention of Chinese medicine are described.