ObjectiveTo clearly identify the difference between rescue injuries and agonal injuries and to avoid duplicate identifications and misidentifications. MethodsBased on the forensic pathological data of 5 923 cases of death cause identification from 2013 to 2022 in Sun Yat-sen University Forensic Identification Center and Guangzhou Tianhe District Branch of Guangzhou Public Security Bureau， this study retrospectively studied the characteristics of rescue injuries and agonal injuries seen in cause of death identification and their influence on cause of death identification. ResultsAmong all the 5 923 cases， 640 cases were found to have rescue injuries or agonal injuries， and 624 cases received treatment， of which 609 cases were found to have rescue injuries （97.60%）， 44 cases were found to have agonal injuries， and 13 cases were found to have both types of injuries. Among the 640 cases， 441 were male and 199 were female. The age of death was discontinuously distributed from 0 to 95 years old. The leading cause of death was disease， followed by mechanical injury and asphyxia. The main manifestations of rescue injuries were rib and sternum fractures， soft tissue injuries in the prechest area or face， and pericardial rupture. The most common injuries in agonal stage were falling after unconsciousness， inhalation of foreign body in respiratory tract or multiple violent injuries. Among the 640 cases， 19 cases were repeatedly identified， including 15 cases of rescue injuries， 6 cases of agonal injuries， and 2 cases of both types of injuries. Compared with the cases where neither type of injuries was detected， the repeated identification rate of treatment injuries and agonal injuries was significantly increased （χ²=4.04， P=0.044； χ²=43.49， P<0.001）. Among the 640 cases， 11 cases （1.72%） were misidentified as the initial injuries in the first identification， and 13 cases had combined rescue injuries or agonal injuries that were involved in death. ConclusionsBy elucidating the epidemiological characteristics of the two types of injuries， this study proved that the two types of injuries were associated with higher rates of repeated identification and misidentification， which provided a reference for reducing repeated identification and misidentification and improving the accuracy of cause of death identification.

OBJECTIVES: To investigate the therapeutic mechanism of Huoxue Shufeng Granules (HXSFG) for alleviating central sensitization in a mouse model of chronic migraine (CM). METHODS: We analyzed the main chemical components of HXSFG through literature review and explored their pharmacological mechanisms by bioinformatics analyses. In a male C57BL/6J mouse model of CM established by intraperitoneal injections of nitroglycerin (10 mg/kg) every other day (5 injections), the effects of gavage with low, and high doses of HXSFG or intraperitoneal injections of topiramate for ameliorating central sensitization were evaluated using Von Frey test and a hot plate apparatus; the changes in expressions of inflammatory factors, the proteins in the TLR4/NF‑κB signaling pathway, and activation of c-Fos and CGRP were detected using RT-qPCR, Western blotting and immunofluorescence staining. RESULTS: Network pharmacology analysis suggested that the main active components in HXSFG for alleviating CM included formononetin, paeoniflorin, quercetin, and tanshinone. Gene Ontology (GO) enrichment analysis identified 492 GO entries, comprising 366 biological processes, 46 cellular components, and 80 molecular functions. KEGG pathway enrichment analysis indicated that the Toll-like receptor and NF‑κB signaling pathways were crucial in mediating the therapeutic effects of HXSFG on CM. In the mouse models of CM, both topiramate and HXSFG treatments alleviated the symptoms of central sensitization, evidenced by improved mechanical and thermal pain thresholds in the mice. HXSFG significantly reduced the expression of c-Fos and CGRP, improved inflammatory markers, and downregulated the expressions of TLR4, p-NF‑κB, IL-1β, and TNF‑α proteins in the mouse models. CONCLUSIONS HXSFG effectively alleviates central sensitization in CM mice by modulating the inflammatory pathways and inhibiting the TLR4/ NF-κB signaling pathway, suggesting its potential as a therapeutic option for CM.
Animals ; Toll-Like Receptor 4/metabolism* ; NF-kappa B/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Mice ; Male ; Mice, Inbred C57BL ; Signal Transduction/drug effects* ; Migraine Disorders/metabolism* ; Disease Models, Animal ; Inflammation

Congenital orofacial cleft, the most common birth defect in the maxillofacial region, exhibits a wide range of prognosis depending on the severity of deformity and underlying etiology. Non-syndromic congenital orofacial clefts typically present with milder deformities and more favorable treatment outcomes, whereas syndromic congenital orofacial clefts often manifest with concomitant organ abnormalities, which pose greater challenges for treatment and result in poorer prognosis. This consensus provides an elaborate classification system for varying degrees of orofacial clefts along with corresponding diagnostic and therapeutic guidelines. Results serve as a crucial resource for families to navigate prenatal screening results or make informed decisions regarding treatment options while also contributing significantly to preventing serious birth defects within the development of population.
Humans ; Cleft Lip/diagnosis* ; Cleft Palate/diagnosis* ; Consensus ; Prenatal Diagnosis ; Female

Objective: To investigate the causal association between amino acids and the primary malignant bone tumor and its underlying mechanism. Methods: Genome-wide association study (GWAS) data of glycine, serine, arginine, glutamine, methionine, and leucine was sourced from the IEU OpenGWAS database and the GWAS Catalog. GWAS data of primary malignant bone tumor were obtained from the FinnGen database. Using each of the six amino acids as the exposure and primary malignant bone tumor as the outcome, two-sample Mendelian randomization (MR) analysis was performed with the inverse-variance weighted method as the primary approach. Multivariable MR analysis was employed to control for collinearity among amino acids. Sensitivity analyses were conducted using Cochran's Q test, MR-Egger regression and the MR Steiger test. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and protein-protein interaction network analysis were explored to explore potential mechanisms and identify key genes. Results: MR analysis results indicated a statistically significant causal association between glycine and primary malignant bone tumor (OR=1.719, 95%CI: 1.083-2.728). No significant causal associations were found for the other five amino acids (all P>0.05). Multivariable MR analysis revealed that, after adjusting for the other five amino acids, confirmed a positive causal association between glycine and primary malignant bone tumor (OR=1.512, 95%CI: 1.125-2.031). Sensitivity analyses revealed no significant heterogeneity, horizontal pleiotropy, or reverse causality (all P>0.05). Genes associated with both glycine metabolism and primary malignant bone tumor were enriched in the JAK-STAT signaling pathway, with serine hydroxymethyltransferase 2 (SHMT2) identified as a key gene. Conclusion Higher glycine levels may increase the risk of primary malignant bone tumor via the SHMT2-JAK-STAT pathway.

Epilepsy is often comorbid with other neuropsychiatric conditions,which are known as epilepsy comor-bidities.Among these conditions,the comorbidity of epilepsy and migraine is very common.Although they are two differ-ent diseases,they overlap in terms of pathophysiological features and clinical symptoms,and several anti-seizure medica-tions(ASMs)have been proved to be effective in migraine.However,there are still controversies over the concept of epi-lepsy comorbid with migraine,and there is often a lack of effective treatment for migraine due to missed diagnosis or misdi-agnosis.In order to improve the ability for identification and precise treatment of epilepsy comorbid with migraine among clinicians,this article elaborates on the possible mechanism of epilepsy comorbid with migraine and discusses the con-cept,identification,and diagnosis and treatment regimens for epilepsy comorbid with migraine by considering the tempo-ral association between headache symptoms and epileptic seizures,with reference to the classification of epilepsy comorbid with migraine and related diagnostic criteria in Chinese expert consensus(2019)and the ICHD-3-2018 guidelines issued by the International Headache Society.

Breast cancer has been the second most common solid tumor that metastasizes to the central nervous system after lung cancer.Triple-negative breast cancer(TNBC)has an earlier occurrence and high incidence of brain metastasis with its associated poor prognosis and limited treatment options due to the presence of the blood-brain barrier and lack of targeted drugs.Local treatment,including surgery and radiation therapy,are still the main therapy for brain metastasis.Surgical resection can not only relieve neurologic impairment of brain metastasis patients,but also can clarify the pathological type.Moreover,surgical resection combined with radiotherapy can improve the prognosis of brain metastasis patients compared to surgery or radiotherapy alone.By now,whole-brain radiation therapy(WBRT)is still considered the gold standard for multiple brain metastases,and meningeal metastases,but it will lead to neurocognitive decline,so hippocampal avoidance is essential.For selected patients with oligometastases,stereotactic radiotherapy has replaced WBRT to reduce cognitive toxicity.However,local treatment of TNBC brain metastasis cannot control the progress of brain metastasis and has significant side effects,so systemic therapy is needed.Chemotherapy drugs such as capecitabine and cisplatin can penetrate the blood-brain barrier,but their efficacy is limited.Therefore,the research and development of new targeted drugs and the exploration of new targets are necessary for TNBC brain metastasis.Research has found that patients carrying germline BRCA1/2 mutations have a higher risk of brain metastasis.Currently,the poly adenosine diphosphate ribose polymerase(PARP)inhibitor demonstrated antitumor activity in patients with advanced breast cancer and a germline BRCA1/2 mutation,and it can penetrate the blood-brain barrier.The phase Ⅲ trial EMBRACA reported that the PARP inhibitor talazoparib can prolong the progression-free survival of TNBC patients with brain metastasis.In addition,antibody drug conjugates(ADCs)trastuzumab deruxtecan(T-DXd)can also penetrate the blood-brain barrier.Studies such as DEBBRAH have shown that T-DXd has significant therapeutic effects in HER2 positive brain metastasis patients,while research on HER2 low expression patients has not yet reached the endpoint,and its role in TNBC brain metastasis is worth looking forward to.Sacituzumab govitecan(SG)is also an ADC composed of an antibody targeting the human trophoblast cell-surface antigen 2.The phase Ⅲ ASCENT study showed that in the full population(including 61 patients with brain metastasis),SG could significantly prolong the progression-free survival of advanced TNBC patients compared to the patients who received chemotherapy.ANG1005,a novel taxane derivative,can cross the blood-brain barrier as well.A multicenter,open-label phase Ⅱ study revealed that ANG1005 could prolong overall survival of patients with brain metastasis.In addition,phosphoinositide3-kinase,(PI3K)/protein kinase(AKT)/mammalian target of rapamycin(mTOR)pathway inhibitors,fatty acid synthase inhibitors,and the drugs with new delivery systems have become potential treatment options for TNBC brain metastasis patients.Although the Impassion 130 reported that no benefit trend for immunotherapy in TNBC brain metastasis,basic research has shown that radiotherapy combined with immunotherapy has a synergistic effect.Currently,multiple clinical trials(NCT03483012,NCT03449238,etc.)are exploring the efficacy of radiotherapy combined with immunotherapy in brain metastasis,and the results are promising.This article reviewed the research progress of TNBC brain metastasis treatment.

Objective To analyze the correlation between the lung allocation score (LAS) and the risk of early death and complications in patients with idiopathic pulmonary fibrosis (IPF) after lung transplantation. Methods Clinical data of 275 patients with IPF were retrospectively analyzed. The correlation between LAS and the risk of early death in IPF patients after lung transplantation and the correlation between LAS and complications at postoperative 1 year was assessed by univariate and multivariate Cox regression analyses. Results Among 275 recipients, 62, 83, 95 and 108 cases died within postoperative 30, 90, 180 and 365 d, respectively. LAS was correlated with 30-, 90-, 180- and 365-d fatality of IPF patients (all P<0.05), whereas it was not correlated with the incidence of primary graft dysfunction (PGD) and acute kidney injury (AKI) at 365 d after lung transplantation (both P>0.05). Conclusions LAS is correlated with the risk of early death of IPF patients after lung transplantation. While, it is not correlated the incidence of PGD and AKI early after lung transplantation. Special attention should be paid to the effect of comprehensive factors upon PGD and AKI.

Objective To develop a highly sensitive and rapid nucleic acid detection method for the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2). Methods We designed,developed,and manufactured an integrated disposable device for SARS-CoV-2 nucleic acid extraction and detection.The precision of the liquid transfer and temperature control was tested.A comparison between our device and a commercial kit for SARS-Cov-2 nucleic acid extraction was performed using real-time fluorescence reverse transcription polymerase chain reaction(RT-PCR).The entire process,from SARS-CoV-2 nucleic acid extraction to amplification,was evaluated. Results The precision of the syringe transfer volume was 19.2±1.9 μL(set value was 20),32.2±1.6(set value was 30),and 57.2±3.5(set value was 60).Temperature control in the amplification tube was measured at 60.0±0.0 ℃(set value was 60)and 95.1±0.2 ℃(set value was 95)respectively.SARS-Cov-2 nucleic acid extraction yield through the device was 7.10×106 copies/mL,while a commercial kit yielded 2.98×106 copies/mL.The mean time to complete the entire assay,from SARS-CoV-2 nucleic acid extraction to amplification detection,was 36 min and 45 s.The detection limit for SARS-CoV-2 nucleic acid was 250 copies/mL. Conclusion The integrated disposable devices may be used for SARS-CoV-2 Point-of-Care test(POCT).

Objective To analyze the interaction between voriconazole(VRC)and immunosuppressants such as tacrolimus and cyclosporine and the effect of CYP2C19 gene polymorphism on the interaction and adverse reactions(ADR)based on the results of CYP2C19 gene polymorphism and therapeutic drug monitoring,so as to provide a basis for the development of individualized VRC combined with immunosuppressants.Methods Two-dimensional liquid chromatography and pyrosequencing was used to detect the concentration of VRC and the CYP2C19 gene pol-ymorphism,respectively.And the concentration of immunosuppressants was detected at the same time.The rela-tionship among CYP2C19 gene polymorphism,the concentration of VRC and immunosuppressant and ADR was an-alyzed.Results A total of 61 patients were enrolled in this study,and the mutation rates of CYP2C19*2 and CYP2C19*3 were 54.1％(33/61)and 9.84％(6/61),respectively.The concentrations of VRC in patients with extensive metabolism(EMs),intermediate metabolism(IMs)and poor metabolism(PMs)were(4.44±3.46),(3.62±3.02)and(10.05±1.46)μg/ml(P＜0.05),respectively.The concentration of tacrolimus af-ter combined with VRC significantly increased compared to tacrolimus alone[(13.4±9.2)ng/ml vs(6.5±3.6)ng/ml;P=0.002],and the concentration of tacrolimus increased along with an increasing of VRC concentration.The concentration of VRC in patients combined with tacrolimus was lower than that in patients without immunosup-pressants[(3.81±3.48)μg/ml vs(5.84±3.71)μg/ml;P=0.032].The concentration of VRC inpatients with cyclosporine significantly decreased(P＜0.01),while tacrolimus and mycophenolate mofetil had no signifi-cant effect on the concentration of VRC.45.90％(28/61)of the patients had adverse reactions,the concentration of VRC in patients with ADR was significantly higher than that in patients without ADR[(7.07±3.43)μg/ml vs(3.06±2.90)μg/ml;P＜0.001].And the concentration of VRC in patients with ADR was higher than patients without ADR with based on CYP2C19 genotype.Conclusion CYP2C19 gene polymorphism can significantly affect the concentration and adverse reactions of VRC,and VRC has significant interaction with immunosuppressants such as tacrolimus.CYP2C19 gene polymorphism combined with therapeutic drug monitoring can improve the individual-ized treatment of tacrolimus and voriconazole,and is expected to minimize toxicity and improve treatment effects.

Objective:This study aimed to develop a rapid and accurate integrated nucleic acid detection method tailored for the influenza virus.Methods:We designed primers and probes targeting the predominant influenza virus strains circulating in China in recent years. These were integrated with extraction and amplification reagents and a point of care testing (POCT) system to facilitate a seamless and expedited process involving nucleic acid extraction, reaction system preparation, amplification, and result interpretation for the influenza virus. The specificity of the POCT system was evaluated using cultured influenza viruses, while its cross-reactivity was assessed against common respiratory pathogens, including adenovirus and respiratory syncytial virus.Results:Our study successfully developed duplex amplification primers and probes for both influenza A and B viruses, achieving a detection threshold as low as 500 copies/ml. Specificity tests confirmed that the detection reagents did not show cross-reactivity with other respiratory pathogens such as adenovirus and respiratory syncytial virus. The POCT-based rapid nucleic acid detection method for influenza virus was established, it is capable of completing the entire process from nucleic acid extraction to amplification and result interpretation within 50 minutes, while enabling real-time data upload.Conclusions:The POCT-based rapid influenza virus detection kit developed in this study offers a " sample in, results out" convenience, making it suitable for rapid influenza virus detection in primary care settings. This innovation has significant potential for clinical application.