Factors and a model to predict three-month mortality in patients with acute fatty liver of pregnancy from two medical centers.

BACKGROUND: Acute fatty liver of pregnancy (AFLP) is an uncommon but potentially life-threatening complication. Lacking of prognostic factors and models renders prediction of outcomes difficult. This study aims to explore factors and develop a prognostic model to predict three-month mortality of AFLP. METHODS: This retrospective study included 78 consecutive patients fulfilling both clinical and laboratory criteria and Swansea criteria for diagnosis of AFLP. Univariate and multivariate cox regression analyses were used to identify predictive factors of mortality. Predictive efficacy of prognostic index for AFLP (PI-AFLP) was compared with the other four liver disease models using receiver operating characteristic (ROC) curve. RESULTS: AFLP-related three-month mortality of two medical centers was 14.10% (11/78). International normalised ratio (INR, hazard ratio [HR] = 3.446; 95% confidence interval [CI], 1.324-8.970), total bilirubin (TBIL, HR = 1.005; 95% CI, 1.000-1.010), creatine (Scr, HR = 1.007; 95% CI, 1.001-1.013), low platelet (PLT, HR = 0.964; 95% CI, 0.931-0.997) at 72 h postpartum were confirmed as significant predictors of mortality. Artificial liver support (ALS, HR = 0.123; 95% CI, 0.012-1.254) was confirmed as an effective measure to improve severe patients' prognosis. Predictive accuracy of PI-AFLP was 0.874. Area under the receiver operating characteristic curves (AUCs) of liver disease models for end-stage liver disease (MELD), MELD-Na, integrated MELD (iMELD) and pregnancy-specific liver disease (PSLD) were 0.781, 0.774, 0.744 and 0.643, respectively. CONCLUSION: TBIL, INR, Scr and PLT at 72 h postpartum are significant predictors of three-month mortality in AFLP patients. ALS is an effective measure to improve severe patients' prognosis. PI-AFLP calculated by TBIL, INR, Scr, PLT and ALS was a sensitive and specific model to predict mortality of AFLP.

Dual-physical layer high-security encryption scheme for seven-core fiber FPS-OFDM-PON.

This paper proposes an encryption scheme for floating probabilistic shaping orthogonal frequency division multiplexing passive optical networks (FPS-OFDM-PON). Four chaotic sequences are generated by the 4D hyperchaotic model for floating probabilistic shaping (FPS) and bubble sort encryption scheme. An experiment is conducted to demonstrate the transmission of a 70Gb/s (7×10Gb/s) FPS-OFDM-PON signal across a 2km weakly coupled 7-core fiber. The keyspace of the 4D hyperchaotic model reaches 10120. The results show that a 1.82 dB gain in receiver sensitivity compared with the conventional uniform 16QAM-OFDM due to the introduction of FPS. When the system is assaulted by an unlawful receiver, the bit error rate (BER) can still remain at 0.49, successfully assuring the system's security. Due to its good transmission and security performance, the scheme has important application prospects in the future optical access network.

Fe2O3nanoparticles anchored on thermally oxidized MWCNTs as anode material for lithium-ion battery.

Thermally oxidized MWCNTs (OMWCNTs) are fabricated by a thermal treatment of MWCNTs at 500 °C for 3 h in an oxygen-containing atmosphere. The oxygen content of OMWCNTs increases from 1.9 wt% for MWCNTs to 8.3 wt%. And the BET specific surface area of OMWCNTs enhances from 254.2 m2g-1for MWCNTs to 496.1 m2g-1. The Fe2O3/OMWCNTs nanocomposite is prepared by a hydrothermal method. Electrochemical measurements show that Fe2O3/OMWCNTs still keeps a highly reversible specific capacity of 653.6 mA h g-1after 200 cycles at 0.5 A g-1, which shows an obviously higher capacity than the sum of that of single Fe2O3and OMWCNTs. The OMWCNTs not only buffer the volume changes of Fe2O3nanoparticles but also provide high-speed electronic transmission channels in the charge-discharge process. The thermal oxidation method of OMWCNTs avoids using strong corrosive acids such as nitric acid and sulfuric acid, which has the advantages of safety, environmental protection, macroscopic preparation, etc.

A Biallelic Frameshift Mutation in Nephronectin Causes Bilateral Renal Agenesis in Humans.

BACKGROUND: Bilateral renal agenesis (BRA) is a lethal con genital anomaly caused by the failure of normal development of both kidneys early in embryonic development. Oligohydramnios on fetal ultrasonography reveals BRA. Although the exact causes are not clear, BRA is associated with mutations in many renal development genes. However, molecular diagnostics do not pick up many clinical patients. Nephronectin (NPNT) may be a candidate protein for widening diagnosis. It is essential in kidney development, and knockout of Npnt in mice frequently leads to kidney agenesis or hypoplasia. METHODS: A consanguineous Han family experienced three cases of induced abortion in the second trimester of pregnancy, due to suspected BRA. Whole-exome sequencing (WES)-based homozygosity mapping detected underlying genetic factors, and a knock-in mouse model confirmed the renal agenesis phenotype. RESULTS: WES and evaluation of homozygous regions in II:3 and II:4 revealed a pathologic homozygous frameshift variant in NPNT (NM_001184690:exon8:c.777dup/p.Lys260*), which leads to a premature stop in the next codon. The truncated NPNT protein exhibited decreased expression, as confirmed in vivo by the overexpression of WT and mutated NPNT. A knock-in mouse model homozygous for the detected Npnt mutation replicated the BRA phenotype. CONCLUSIONS: A biallelic loss-of-function NPNT mutation causing an autosomal recessive form of BRA in humans was confirmed by the corresponding phenotype of knock-in mice. Our results identify a novel genetic cause of BRA, revealing a new target for genetic diagnosis, prenatal diagnosis, and preimplantation diagnosis for families with BRA.

Wearable Mixed-Reality Holographic Navigation Guiding the Management of Penetrating Intracranial Injury Caused by a Nail.

Penetrating brain injury caused by a nail is an extremely rare neurosurgical emergency that poses a challenge for neurosurgeons. Nail entering the brain from the orbit and lodging within the cranial cavity is even more unusual. A 53-year-old male was found unconscious at a construction site, and brain CT revealed not only the presence of a nail beneath the inner table of the parietal bone, but also traumatic intracerebral hematoma. Consequently, accurate localization of the nail and hematoma was mandatory for surgical plan. During surgical planning, computational model reconstruction and trajectory calculation were completed using preoperative CT in 3D Slicer. Under the guidance of a head-mounted mixed-reality holographic computer, the neurosurgeon was able to visualize and interact with the hologram of the surgical plan, and intraoperative findings demonstrated that our low-cost portable wearable mixed-reality holographic navigation assisted precise localization of the nail and intracerebral hematoma, assuring less injury to the already compromised brain. After the surgery, the patient could obey commands, and postoperative imaging ruled out the possibility of brain abscess during follow-up. To the best of our knowledge, this is the first report on using a low-cost wearable mixed-reality holographic navigation to guide the management of penetrating intracranial injury caused by a nail.

Clinical classification and treatment of cesarean scar pregnancy.

AIM: Embryo implantation in a cesarean scar resulting in a cesarean scar pregnancy (CSP) is a special form of ectopic pregnancy. The aim of this article is to present our clinical classification and therapeutic strategy for CSP and to assess the efficacy, safety, and social benefits. METHODS: We categorized CSP as either risky or stable. Risky CSP have a high risk of severe hemorrhage and should be treated immediately, while stable CSP patients have neither obvious vaginal bleeding nor significantly elevated serum ß-human chorionic gonadotrophin (ß-hCG). According to the thickness of the myometrial wall between the sac and the bladder and the location of the gestational sac, risky CSP were classified into three types and the thinner myometrial wall type (type I) was divided into three subtypes. Four treatment categories were applied to the corresponding types and subtypes of CSP. A total of 331 patients with CSP in our hospital were studied. The study group (n = 81) was treated based on our classification and optimized treatment system, while the control group (n = 250) underwent the conventional methods. We assessed the efficacy, safety, and social benefits of our classification and optimized treatment system. RESULTS: The values of intraoperative blood loss, operative time, hospital stay, and hospital cost in the study group were significantly lower than those in the control group (P < 0.05). Suction curettage was more frequently used in the study group (P < 0.005). CONCLUSION: Our clinical classification system and therapeutic strategy provide an effective and safe way to treat CSP patients resulting in reduced intraoperative bleeding, operative time, hospital days, and hospital cost.

CircHIPK3/miR-124 affects angiogenesis in early-onset preeclampsia via CPT1A-mediated fatty acid oxidation.

Multiple theories have been proposed to explain the pathogenesis of early-onset preeclampsia (EOPE), and angiogenic dysfunction is an important part of this pathogenesis. Carnitine palmitoyltransferase (CPT1A) is a key rate-limiting enzyme in the metabolic process of fatty acid oxidation (FAO). FAO regulates endothelial cell (EC) proliferation during vascular germination and is also essential for ab initio deoxyribonucleotide synthesis, but its role in EOPE needs to be further elucidated. In the present study, we investigated its functional role in EOPE by targeting the circHIPK3/miR-124-3p/CPT1A axis. In our study, reduced expression of circHIPK3 and CPT1A and increased expression of miR-124-3p in placental tissues from patients with EOPE were associated with EC dysfunction. Here, we confirmed that CPT1A regulates fatty acid oxidative activity, cell proliferation, and tube formation in ECs by regulating FAO. Functionally, knockdown of circHIPK3 suppressed EC angiogenesis by inhibiting CPT1A-mediated fatty acid oxidative activity, which was ameliorated by CPT1A overexpression. In addition, circHIPK3 regulates CPT1A expression by sponging miR-124-3p. Hence, circHIPK3 knockdown reduced fatty acid oxidation in ECs by sponging miR-124-3p in a CPT1A-dependent manner and inhibited EC proliferation and tube formation, which may have led to aberrant angiogenesis in EOPE. Thus, strategies targeting CPT1A-driven FAO may be promising approaches for the treatment of EOPE. KEY MESSAGES: Decreased Carnitine palmitoyltransferase (CPT1A) expression in preeclampsia(PE). CPT1A overexpression promotes FAO activity and tube formation in ECs. CircHIPK3 can affect CPT1A expression and impaire angiogenesis of EOPE. CircHIPK3 regulates CPT1A expression by acting as a ceRNA of miR-124-3p in HUVECs. Confirming the effect of circHIPK3/miR-124-3p/CPT1A axis on EOPE.

Quality evaluation of clinical practice guidelines for placenta accreta spectrum disorders.

Introduction: We evaluated the quality of the published clinical practice guidelines on placenta accreta spectrum (PAS) disorders to provide reference for the development of high-quality PAS guidelines. Methods: China National Knowledge Infrastructure (CNKI), Wan Fang, PubMed, Embase, Web of Science, and Cochrane Library were systematically searched. Quality assessments were conducted using the appraisal of guidelines for research and evaluation (AGREE) II framework and Reporting Items for practice Guidelines in Healthcare (RIGHT) checklist. Intraclass correlation coefficients (ICCs) were used to measure the agreement among reviewers. Results: In total, 13 guidelines from different countries, published between 2015 and 2021 were included. There included 9 official guidelines, 3 consensuses, and 1 standard reference and covered subjects including epidemiology, diagnosis and treatment. The mean standardized scores across 6 domains (scope and purpose, stakeholder involvement, rigor of development, clarity of presentation, applicability, and editorial independence) were 53.63%, 27.35%, 33.57%, 72.01%, 19.39% and 41.02%, respectively. Of the 13 guidelines, 11 were classified as grade B, whereas 2 as grade C. According to the RIGHT checklist, the overall reporting rate of the 13 guidelines ranged from 28.57% to 54.29%. Conclusion: The current guidelines for PAS demonstrate commendable methodological and reporting qualities. However, the methodological and reporting quality of PAS CPGs still need to be further improved, particularly in stakeholder involvement, the rigor of development, applicability, and editorial independence domains.

Bibliometric study and visualization of cellular senescence associated with osteoarthritis from 2009 to 2023.

BACKGROUND: Osteoarthritis is a common degenerative joint disease that is highly prevalent in the elderly population. Along with the occurrence of sports injuries, osteoarthritis is gradually showing a younger trend. Osteoarthritis has many causative factors, and its pathogenesis is currently unknown. Cellular senescence is a stable form of cell cycle arrest exhibited by cells in response to external stimuli and plays a role in a variety of diseases. And it is only in the last decade or so that cellular senescence has gradually become cross-linked with osteoarthritis. However, there is no comprehensive bibliometric analysis in this field. The aim of this study is to present the current status and research hotspots of cellular senescence in the field of osteoarthritis, and to predict the future trends of cellular senescence in osteoarthritis research from a bibliometric perspective. METHODS: This study included 298 records of cellular senescence associated with osteoarthritis from 2009 to 2023, with data from the Web of Science Core Collection database. CiteSpace, Scimago Graphica software, VOSviewer, and the R package "bibliometrix" software were used to analyze regions, institutions, journals, authors, and keywords to predict recent trends in cellular senescence related to osteoarthritis research. RESULTS: The number of publications related to cellular senescence associated with osteoarthritis is increasing year by year. China and the United States contribute more than 70% of the publications and are the mainstay of research in this field. Central South University is the most active institution with the largest number of publications. International Journal of Molecular Sciences is the most popular journal in the field with the largest number of publications, while Osteoarthritis and Cartilage is the most cited journal. Loeser, Richard F. is not only the most prolific author, but also the most frequently cited author, contributing greatly to the field. CONCLUSION: In the last decade or so, this is the first bibliometric study that systematically describes the current status and development trend of research on cellular senescence associated with osteoarthritis. The study comprehensively and systematically summarizes and concludes the research hotspots and development trends, providing valuable references for researchers in this field.

Evaluation of Guidelines and Consensus on Ectopic Pregnancy Based by AGREE II Method.

Introduction: To evaluate the methodological quality of diagnosis and treatment guidelines/consensus related to ectopic pregnancy. Materials and methods: Use the "Appraisal of Guidelines and Research and Evaluation" (AGREE II) method to evaluate the differences among the guideline/consensus. Results: We appraised 9 clinical practice guidelines for ectopic pregnancy (9 clinical practice guidelines from 5 countries) including the United States, United Kingdom, Ireland, Canada, and China. The guidelines received the highest scores for clarity of presentation (82.72%) and lowest scores for editorial independence (30.56%). The comprehensive recommendations of the 7 guidelines were Grade B, the other 2 guidelines were Grade C. Conclusion: The overall quality of the ectopic pregnancy guidelines had room for improvement. It is recommended to supplement and improve the four fields of "independence", "rigor", "participants" and "application", especially the "independence" and "application" fields.

Termination of a second-trimester pregnancy with placenta accreta spectrum disorder.

Background: The termination of pregnancy in patients with placenta accreta spectrum disorder (PASD) during the second trimester remains uncertain. In addition, interventional radiology techniques, such as arterial embolization and balloon placement, are potential options. We evaluated the outcomes of pregnancy termination in patients with PASD during the second trimester and the effectiveness of preoperative interventional radiology techniques.Methods: This retrospective study analyzed 48 PASD patients who underwent pregnancy termination during the second trimester between January 2016 and May 2021.Results: Of the 48 patients, 20 (41.67%) underwent transvaginal termination, whereas 28 (58.33%) underwent cesarean section. Notably, no significant differences were observed in success rates between the transvaginal termination and cesarean section groups (80.00% vs. 92.86%, P = 0.38). Furthermore, no statistically significant differences were observed in the success rates (94.12% vs 90.32%, P = 1.00) and blood loss (512.35 ± 727.00 ml vs 804.00 ± 838.98 ml, P = 0.23) between the artery embolization and non-embolization groups. In the vaginal termination group, statistically significant differences were observed in gestational weeks (16.70 ± 3.12 vs 22.67 ± 3.63, P < 0.01) and blood loss (165.00 ± 274.43 ml vs 483.64 ± 333.53 ml, P = 0.04) between the (artery embolization and non-embolization) subgroups. Conversely, in the cesarean section group, no significant differences were observed in gestational weeks (23.59 ± 3.14 vs 23.20 ± 4.37, P = 0.79) and blood loss (811.11 ± 879.55 ml vs 989.47 ± 986.52 ml, P = 0.76) between the subgroups.Conclusions: Further studies are needed to evaluate the efficacy of vaginal termination in PASD patients during the second trimester. Regarding cesarean termination, arterial embolization did not demonstrate increased effectiveness.

Comparison of risk assessments for venous thromboembolism during the puerperium.

Objective: To compare the predictive value of different risk assessment methods for puerperium venous thromboembolism (VTE). Methods: This study included 55 women with and 165 women without puerperal VTE. Using the cases, 11 assessment methods were compared. Results: The area under the curve (AUC) value of the 11 assessments was highest for the modified Caprini risk assessment model for pregnancy (a modified risk scoring method from Caprini, AUC = 0.805). Pairwise comparison of the AUC values of the 11 assessment methods indicated no significant difference among the five methods with AUC values > 0.7. Among them, the modified Caprini, the risk scoring method recommended by the Swedish Guidelines (Swedish method), and the risk scoring method recommended by the Shanghai consensus (Shanghai method) performed better than the other six methods with AUC values < 0.7 (P < 0.05). The sensitivities of the five methods for predicting a high risk of VTE were 69.09-94.55% and the specificities were 25.45-77.58%. The sensitivity of the modified Caprini was higher than those of the risk management method from the Chinese consensus (Chinese consensus method), Royal College of Obstetricians and Gynaecologists risk assessment scale (RCOG), and Swedish method (P < 0.05), but the specificity was only 25.45%. No significant difference in sensitivity was detected among the Swedish, Shanghai, RCOG, and Chinese consensus methods, whereas the specificity of the Swedish method was higher than that of the Shanghai, RCOG, and Chinese consensus methods. Conclusion: The predictive value of different risk assessment methods for puerperium VTE varies greatly. Considering the sensitivity and specificity, the Swedish method may have better clinical application value among the 11 methods.

Structures of human prostaglandin F2α receptor reveal the mechanism of ligand and G protein selectivity.

Prostaglandins and their receptors regulate various physiological processes. Carboprost, an analog of prostaglandin F2α and an agonist for the prostaglandin F2-alpha receptor (FP receptor), is clinically used to treat postpartum hemorrhage (PPH). However, off-target activation of closely related receptors such as the prostaglandin E receptor subtype EP3 (EP3 receptor) by carboprost results in side effects and limits the clinical application. Meanwhile, the FP receptor selective agonist latanoprost is not suitable to treat PPH due to its poor solubility and fast clearance. Here, we present two cryo-EM structures of the FP receptor bound to carboprost and latanoprost-FA (the free acid form of latanoprost) at 2.7 Å and 3.2 Å resolution, respectively. The structures reveal the molecular mechanism of FP receptor selectivity for both endogenous prostaglandins and clinical drugs, as well as the molecular mechanism of G protein coupling preference by the prostaglandin receptors. The structural information may guide the development of better prostaglandin drugs.

The preventive effects of aspirin on preeclampsia based on network pharmacology and bioinformatics.

This study aimed to reveal the key targets and molecular mechanisms of aspirin in preventing preeclampsia. We used bioinformatics databases to collect the candidate targets for aspirin and preeclampsia. The biological functions and signaling pathways of the intersecting targets were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Then, the hub targets were identified by cytoscape plugin cytoHubba from the protein-protein interaction network. We collected 90 targets for aspirin in preventing preeclampsia. The biological processes of the intersecting targets are mainly involved in xenobiotic metabolic process, inflammatory response, negative regulation of apoptotic process, and protein phosphorylation. The highly enriched pathways were FoxO signaling pathway, circadian rhythm, insulin resistance, arachidonic acid metabolism, and drug metabolism-cytochrome P450. The hub targets for aspirin in preventing preeclampsia were tumor protein p53 (TP53), C-X-C motif chemokine ligand 8 (CXCL8), mitogen-activated protein kinase 3 (MAPK3), mitogen-activated protein kinase 1 (MAPK1), mitogen-activated protein kinase 14 (MAPK14), epidermal growth factor receptor (EGFR), estrogen receptor (ESR1), and prostaglandin-endoperoxide synthase 2 (PTGS2). Molecular docking results showed good bindings between the proteins and aspirin. In conclusion, these findings highlight the key targets and molecular mechanisms of aspirin in preventing preeclampsia.

Intrauterine infusion of clinically graded human umbilical cord-derived mesenchymal stem cells for the treatment of poor healing after uterine injury: a phase I clinical trial.

BACKGROUND: Intrauterine adhesion and cesarean scar diverticulum are the main complications of poor healing after uterine injury. Human umbilical cord MSCs transplantation has been regarded as the most potential treatment in the clinic, the safety and efficacy of which in the clinic, however, remains unclear. METHODS: In this study, ten patients were enrolled: six with intrauterine adhesion and four with cesarean scar diverticulum. All the patients were injected with human umbilical cord MSCs twice into the uterus. Beside the chest X-ray, ECG and abdominal ultrasound, many laboratory tests including blood routine, liver and renal function, ovarian function, tumor biomarkers, and immune function were used to estimate the safe after stem cell transplanted. In addition, the efficacy of stem cell transplanted was shown by the endometrial thickness, the volume of the uterus, and cesarean scar diverticulum based on 3D ultrasound imaging. RESULTS: We found that all results of these laboratory tests were normal in these enrolled patients before and after cell injection. Meanwhile, the results of the chest X-ray and ECG were also normal in the treatment process. The abdominal ultrasound showed that the size of the left and right kidneys was inconsistent in one patient after cell therapy, while those of other patients were normal. In addition, endometrial thickness, the volume of the uterus, and cesarean scar diverticulum showed an improving tendency, but no significant difference was noted. CONCLUSION: In summary, intrauterine injection of clinically graded human umbilical cord MSCs was safe for poor healing after uterus injury. Trial registration NCT03386708. Registered 27 December 2017, https://clinicaltrials.gov/ct2/show/NCT03386708?cond=CSD&cntry=CN&draw=2&rank=2.

Phosphoglycerate mutase 5 promotes necroptosis in trophoblast cells through activation of dynamin-related protein 1 in early-onset preeclampsia.

OBJECTIVES: Placentae from patients with preeclampsia have increased susceptibility to necroptosis and phosphoglycerate mutase 5 (PGAM5) plays a role in many necrosis pathways. We determined whether PGAM5 promotes necroptosis of trophoblast cells and the underlying mechanisms in this study. METHODS: The injury model was established by treating JEG3 cells with hypoxia for 24 h. The functional measurements were assessed by the cell counting kit-8, propidium iodide (PI)/Annexin V staining, JC-1 staining and firefly luciferase ATP assay. The expression of proteins in human placentae and JEG3 cells was measured Western blot. PGAM5 was knocked down to study its role in hypoxia-induced necroptosis. RESULTS: The placentae from patients with preeclampsia showed up-regulation of PGAM5 and decreased levels of p-Drp1-S637, accompanied by increased necroptosis-relevant proteins expression. The expression of PGAM5 in JEG3 cells was up-regulated under hypoxia, which promoted dephosphorylation of Drp1 at Serine 637 residue, mitochondrial dysfunction (elevated ROS level and reduced mitochondrial membrane potential and ATP content) and cellular necroptosis (increased PI+ /Annexin V+ cells and decreased cell viability), accompanied by increased expression of necroptosis-relevant proteins; knockdown of PGAM5 attenuated these phenomena. CONCLUSIONS: Our results indicate that PGAM5 can promote necroptosis in trophoblast cells through, at least in part, activation of Drp1. It may be used as a new therapeutic target to prevent trophoblast dysfunction in preeclampsia.

Analysis of Clinical Characteristics and Prognosis of Traumatic Brain Injury in Papua New Guinea.

OBJECTIVE: To evaluate the clinical characteristics and prognosis of TBI patients from 2016 to 2019 admitted to Port Moresby General Hospital (PMGH) of Papua New Guinea (PNG) and compare the results with previous researches to analyze current clinical characteristics and prognosis. METHODS: A retrospective study was performed on 389 TBI patients in Port Moresby General Hospital (PMGH) over a 48-month period (from January 2016 to December 2019). The clinical and radiographic data were collected. Patients were followed up for at least 3 months, and outcomes were assessed using the Glasgow Outcome Scale (GOS). Univariate and multivariate logistic regressions were performed to analyze the prognosis and intracranial infection of patients, as well as the effect of surgery on the prognosis of TBI patients. RESULTS: The average age of the 389 TBI patients was 24.9 years old, and the most common age was 18-40 years old, accounting for 55.5%. The proportion of male patients was 79.4%, and the proportion of juvenile patients (≤18 years) was 30.8%. The most primary cause of injury was fighting and brawling (38.0%). At admission, patients had an average GCS score of 9.1, and patients with severe TBI accounted for 46.8%. Overall, 32.1% of the patients had a good prognosis, with a mortality rate of 13.9% (54 cases). Analyzing the relationship between surgical treatment and prognosis in 303 patients with moderate or severe TBI, there was no statistical significance. Univariate and logistic regression analyses for poor prognosis included gender, GCS, multiple injuries, Rotterdam CT scores, and intracranial infection. Univariate and logistic regression analyses for intracranial infection included GCS, open brain trauma, and postoperative drainage time. CONCLUSION: Despite there has been a secular trend towards reduced incidence of TBI, the prognosis of moderate or severe TBI patients who received surgery showed no significant improvement, indicating that PNG, as a backward developing country, faced a huge problem in TBI prevention and control.

Loss-of-Function Plays a Major Role in Early Neurogenesis of Tubulin α-1 A (TUBA1A) Mutation-Related Brain Malformations.

Tubulin α-1 A (TUBA1A) mutations cause a wide spectrum of brain abnormalities. Although many mutations have been identified and functionally verified, there are clearly many more, and the relationship between TUBA1A mutations and brain malformations remains unclear. The aim of this study was to identify a TUBA1A mutation in a fetus with severe brain abnormalities, verify it functionally, and determine the mechanism of the mutation-related pathogenesis. A de novo missense mutation of the TUBA1A gene, c.167C>G p.T56R/P.THR56Arg, was identified by exon sequencing. Computer simulations showed that the mutation results in a disruption of lateral interactions between the microtubules. Transfection of 293T cells with TUBA1A p.T56R showed that the mutated protein is only partially incorporated into the microtubule network, resulting in a decrease in the rate of microtubule re-integration in comparison with the wild-type protein. The mechanism of pathological changes induced by the mutant gene was determined by knockdown and overexpression. It was found that knockdown of TUBA1A reduced the generation of neural progenitor cells, while overexpression of wild-type or mutant TUBA1A promoted neurogenesis. Our identification and functional verification of the novel TUBA1A mutation extends the TUBA1A gene-phenotype database. Loss-of-function of TUBA1A was shown to play an important role in early neurogenesis of TUBA1A mutation-related brain malformations.