Effect of acute alcohol consumption on blunt bowel mesenteric injury: a retrospective analysis.

BACKGROUND: The effect of alcohol consumption on trauma remains controversial. The effects of alcohol on hemorrhage and peritonitis after blunt abdominal trauma have rarely been discussed. This study aimed to explore the effects of acute alcohol intoxication on the clinical characteristics, injury patterns, and outcomes in a surgical blunt bowel mesenteric injury (BBMI) cohort. METHODS: A retrospective data analysis was performed using trauma cases of patients who had been tested for alcohol and had surgically proven BBMI from a Trauma Registry System from 2009 to 2021. Patients were grouped according to their positive blood alcohol concentration (BAC; >0.5% vs. no BAC; less than 0.5% no BAC) upon arrival at the emergency department (ED). The injury characteristics, physiological parameters, and outcomes with respect to post-injury complications and mortality were assessed. RESULTS: In total, 142 patients with surgical BBMI were included. Of these, 116 and 26 patients were assigned to the BAC-negative and BAC-positive groups, respectively. The overall injury severity, injury pattern, and age were comparable between the groups. The patients in the BAC-positive group had a significantly lower systolic blood pressure (99 mmHg vs. 119 mmHg; p = 0.046), worse shock index (0.96 vs. 0.82; p = 0.048), and lower percentage and number of packed red blood cells transfused (34.6% vs. 57.8%; p = 0.032 and 0 U vs. 2 U; p = 0.031) than those in the BAC-negative group. Additionally, although not statistically significant, patients in the BAC-positive group had lower leukocyte counts (9,700 cells/mm3 vs. 11,600 cells/mm3; p = 0.165 ) at the ED. However, significantly reduced percentages of leukocytes ≥ 12,000 cells/mm3 (26.9% vs. 48.3%; p = 0.048) and ≥ 12,000 or ≤ 4,000 cells/mm3 (26.9% vs. 50.9%; p = 0.027) were observed in the BAC-positive group at the ED. Furthermore, the 30-day mortality rate did not show statistically significant differences, and there was a higher incidence of bowel-related mortality in the BAC-positive group (11.5% vs. 1.7%, p = 0.043). CONCLUSIONS: For patients with BBMI arriving alive to the hospital, acute alcohol consumption was associated with significantly worse hemodynamic parameters, interfered inflammation status, and higher bowel related mortality rate.

Cathelicidin Antimicrobial Peptide Acts as a Tumor Suppressor in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is associated with high rates of metastasis and recurrence, and is one of the most common causes of cancer-associated death worldwide. This study examined the protein changes within circulating exosomes in patients with HCC against those in healthy people using isobaric tags for a relative or absolute quantitation (iTRAQ)-based quantitative proteomics analysis. The protein levels of von Willebrand factor (VWF), cathelicidin antimicrobial peptide (CAMP), and proteasome subunit beta type-2 (PSMB2) were altered in HCC. The increased levels of VWF and PSMB2 but decreased CAMP levels in the serum of patients with HCC were validated by enzyme-linked immunosorbent assays. The level of CAMP (the only cathelicidin found in humans) also decreased in the circulating exosomes and buffy coat of the HCC patients. The serum with reduced levels of CAMP protein in the HCC patients increased the cell proliferation of Huh-7 cells; this effect was reduced following the addition of CAMP protein. The depletion of CAMP proteins in the serum of healthy people enhances the cell proliferation of Huh-7 cells. In addition, supplementation with synthetic CAMP reduces cell proliferation in a dose-dependent manner and significantly delays G1-S transition in Huh-7 cells. This implies that CAMP may act as a tumor suppressor in HCC.

Improved miscibility and toughness of biological poly(3-hydroxybutyrate-co-4-hydroxybutyrate)/poly(lactic acid) blends via melt-blending-induced thermal degradation.

Polymer blending has been a facile method to resolve the brittle issue of poly(lactic acid) (PLA). Yet, miscibility becomes the primary concern that would affect the synergy effect of polymer blending. This study aimed to improve the miscibility of poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P34HB) and PLA by lowering their molecular weights via a melt-blending-induced thermal degradation during mechanical mixing to form m-P34HB/PLA blends. The molecular weight of the P34HB was significantly reduced after blending, thereby improving the miscibility of the blends, as evidenced by the shift of glass transition temperatures. Also, simulation based on Flory-Huggins theory demonstrated increased miscibility with decreasing molecular weight of the polymers. Moreover, the thermal gravimetric analysis revealed that the PLA provided a higher shielding effect to the P34HB in the blends prepared by melt-blending than those by solution-blending, that the addition of PLA could retard the chain scission of P34HB and delay its degradation. The addition of m-P34HB at 20 wt% in the blend contributed to a 60-fold enhancement in the elongation at break and an increment of 4.6 folds in the Izod impact strength. The enzymatic degradation using proteinase K revealed the preferential to degrade the PLA in the blends and followed the surface erosion mechanism.

Exploring the Regulatory Role of XIST-microRNAs/mRNA Network in Circulating CD4+ T Cells of Hepatocellular Carcinoma Patients.

Hepatocellular carcinoma (HCC) is one of the most common cancers and the main cause of cancer-related death globally. Immune dysregulation of CD4+ T cells has been identified to play a role in the development of HCC. Nevertheless, the underlying molecular pathways of CD4+ T cells in HCC are not completely known. Thus, a better understanding of the dysregulation of the lncRNA-miRNA/mRNA network may yield novel insights into the etiology or progression of HCC. In this study, circulating CD4+ T cells were isolated from the whole blood of 10 healthy controls and 10 HCC patients for the next-generation sequencing of the expression of lncRNAs, miRNAs, and mRNAs. Our data showed that there were different expressions of 34 transcripts (2 lncRNAs, XISTs, and MIR222HGs; 29 mRNAs; and 3 other types of RNA) and 13 miRNAs in the circulating CD4+ T cells of HCC patients. The expression of lncRNA-XIST-related miRNAs and their target mRNAs was confirmed using real-time quantitative polymerase chain reaction (qPCR) on samples from 100 healthy controls and 60 HCC patients. The lncRNA-miRNA/mRNA regulation network was created using interaction data generated from ENCORI and revealed there are positive correlations in the infiltration of total CD4+ T cells, particularly resting memory CD4+ T cells, and negative correlations in the infiltration of Th1 CD4+ T cells.

Association between Air Pollution and Short-Term Outcome of ST-Segment Elevation Myocardial Infarction in a Tropical City, Kaohsiung, Taiwan.

ST-segment elevation myocardial infarction (STEMI), one of the primary factors leading to global mortality, has been shown through epidemiological studies to have a relationship with short-term exposure to air pollutants; however, the association between air pollutants and the outcome of STEMI has not been well studied. The aim of this study was to estimate the impact of air pollutants on the outcomes of STEMI. Data on particulate matter <2.5 µm (PM2.5), <10 µm (PM10), nitrogen dioxide (NO2), and ozone (O3) at each of the 11 air monitoring stations in Kaohsiung City were collected between 1 January 2012 and 31 December 2017. Medical records of non-trauma patients aged > 20 years who had presented to the Emergency Department (ED) with a principal diagnosis of STEMI were extracted. The primary outcome measure was in-hospital mortality. After adjusting for potential confounders and meteorological variables, we found that an increase in the interquartile range (IQR) in NO2 was associated with an elevated risk of in-hospital mortality in patients with STEMI. Moreover, there was an observed higher risk of in-hospital mortality associated with an increase in the IQR of NO2 during the warm season, specifically in lag 3 (3 days prior to the onset, OR = 3.266; 95%CI: 1.203-8.864, p = 0.02). Conversely, an IQR increase in PM10 was associated with an increased risk of in-hospital mortality in patients with STEMI in lag 3 (OR = 2.792; 95%CI: 1.115-6.993, p = 0.028) during the cold season. Our study suggests that exposure to NO2 (during the warm season) and PM10 (during the cold season) may contribute to a higher risk of poor prognosis in patients with STEMI.

A High De Ritis Ratio is Associated with Mortality in Adult Trauma Patients.

Introduction: The De Ritis ratio, which is the ratio of aspartate aminotransferase (AST) to alanine aminotransferase (ALT), has been suggested as a potential prognostic marker for various diseases. This study aimed to investigate the association between the De Ritis ratio and in-hospital mortality in adult trauma patients. Methods: A total of 17,472 adult trauma patients hospitalized between January 1, 2009, and December 31, 2020, were allocated into groups according to the De Ritis ratio. The normal range of the De Ritis ratio was calculated from 3320 individuals in the National Taiwan Biobank. Statistical analyses were performed using SPSS software. Results: Patients with a De Ritis ratio >1.6 had a significantly higher in-hospital mortality rate (7.3% vs 1.5%, odds ratio 5.29; Q1-Q3 2.72-10.30; p < 0.001) and a 2.71-fold higher in-hospital mortality rate (Q1-Q3 1.24-5.92; p = 0.012), after adjusting for sex, age, comorbidities, consciousness level, and injury severity, than those with a De Ritis ratio within the reference values. Discussion: This study revealed that a De Ritis ratio >1.6 may serve as an early prognostic tool to identify adult trauma patients at high risk of in-hospital mortality.

Nerve growth factor-basic fibroblast growth factor poly-lactide co-glycolid sustained-release microspheres and the small gap sleeve bridging technique to repair peripheral nerve injury.

We previously prepared nerve growth factor poly-lactide co-glycolid sustained-release microspheres to treat rat sciatic nerve injury using the small gap sleeve technique. Multiple growth factors play a synergistic role in promoting the repair of peripheral nerve injury; as a result, in this study, we added basic fibroblast growth factors to the microspheres to further promote nerve regeneration. First, in an in vitro biomimetic microenvironment, we developed and used a drug screening biomimetic microfluidic chip to screen the optimal combination of nerve growth factor/basic fibroblast growth factor to promote the regeneration of Schwann cells. We found that 22.56 ng/mL nerve growth factor combined with 4.29 ng/mL basic fibroblast growth factor exhibited optimal effects on the proliferation of primary rat Schwann cells. The successfully prepared nerve growth factor-basic fibroblast growth factor-poly-lactide-co-glycolid sustained-release microspheres were used to treat rat sciatic nerve transection injury using the small gap sleeve bridge technique. Compared with epithelium sutures and small gap sleeve bridging alone, the small gap sleeve bridging technique combined with drug-free sustained-release microspheres has a stronger effect on rat sciatic nerve transfection injury repair at the structural and functional level.

Study on construction of c-Met specific CAR-T cells and its killing effect on non-small cell lung carcinoma / 中华肿瘤杂志

Objective: To produce chimeric antigen receptor T cells (CAR-T) targeting human hepatocyte growth factor/c-Met (HGF/c-Met) protein and detect its cytotoxicity against non-small cell lung cancer (NSCLC) cells H1975 in vitro. Methods: The whole gene sequence of c-Met CAR containing c-Met single-chain fragment variable was synthesized and linked to lentiviral vector plasmid, plasmid electrophoresis was used to detect the correctness of target gene. HEK293 cells were transfected with plasmid and the concentrated solution of the virus particles was collected. c-Met CAR lentivirus was transfected into T cells to obtain second-generation c-Met CAR-T and the expression of CAR sequences was verified by reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) and western blot, and the positive rate and cell subtypes of c-Met CAR-T cells were detected by flow cytometry. The positive expression of c-Met protein in NSCLC cell line H1975 was verified by flow cytometry, and the negative expression of c-Met protein in ovarian cancer cell line A2780 was selected as the control. The cytotoxicity of c-Met CAR-T to H1975 was detected by lactate dehydrogenase (LDH) cytotoxicity assay at 1∶1, 5∶1, 10∶1 and 20∶1 of effector: target cell ratio (E∶T). Enzyme-linked immunosorbent assay (ELISA) was used to detect the release of cytokines such as TNF-α, IL-2 and IFN-γ from c-Met CAR-T co-cultured with H1975. Results: The size of band was consistent with that of designed c-Met CAR, suggesting that the c-Met CAR plasmid was successfully constructed. The results of gene sequencing were consistent with the original design sequence and lentivirus was successfully constructed. CAR molecules expression in T cells infected with lentivirus was detected by western blot and RT-qPCR, which showed c-Met CAR-T were successfully constructed. Flow cytometry results showed that the infection efficiency of c-Met CAR in T cells was over 38.4%, and the proportion of CD8(+) T cells was increased after lentivirus infection. The NSCLC cell line H1975 highly expressed c-Met while ovarian cancer cell line A2780 negatively expressed c-Met. LDH cytotoxicity assay indicated that the killing efficiency was positively correlated with the E∶T, and higher than that of control group, and the killing rate reached 51.12% when the E∶T was 20∶1. ELISA results showed that c-Met CAR-T cells released more IL-2, TNF-α and IFN-γ in target cell stimulation, but there was no statistical difference between c-Met CAR-T and T cells in the non-target group. Conclusions: Human NSCLC cell H1975 expresses high level of c-Met which can be used as a target for immunotherapy. CAR-T cells targeting c-Met have been successfully produced and have high killing effect on c-Met positive NSCLC cells in vitro.

Deciphering the Divergent Gene Expression Landscapes of m6A/m5C/m1A Methylation Regulators in Hepatocellular Carcinoma Through Single-Cell and Bulk RNA Transcriptomic Analysis.

Introduction: RNA modifications mediated by the m6A, m1A, and m5C regulatory genes are crucial for the progression of malignancy. This study aimed to explore the expression of regulator genes for m6A/m5C/m1A methylation at the single-cell level and to validate their expression in cancerous and adjacent para-cancerous liver tissues of adult patients with HCC who underwent tumor resection. Methods: The bulk sequencing from The Cancer Genome Atlas (TCGA) database and the single-cell RNA sequencing (scRNA-seq) data obtained from the Gene Expression Omnibus (GEO) database were used to identify the dysregulated m6A/m5C/m1A genes for hepatocellular carcinoma (HCC). A real-time polymerase chain reaction (real-time PCR) was used to measure the expression of dysregulated m6A/m5C/m1A genes in collected human HCC tissues and compared with adjacent para-cancerous liver tissues. Immune cell infiltration with these significantly expressed methylation-related genes was evaluated using Timer2.0. Results: A discrepancy in m6A/m5C/m1A gene expression was observed between bulk sequencing and scRNA-seq. The clustered heatmap of the scRNA-seq-identified dysregulated m6A/m5C/m1A genes in TCGA cohort revealed heterogeneous expression of these methylation regulators within the cancer, whereas their expression in the adjacent liver tissues was more homogeneous. The real-time PCR validated the significant overexpression of DNMT1, NSUN5, TRMT6, IGF2BP1, and IGFBP3, which were identified using scRNA-seq, and IGFBP2, which was identified using bulk sequencing. These dysregulated methylation genes are mainly correlated with the infiltration of natural killer cells. Discussion: This study suggests that cellular diversity inside tumors contributes to the discrepancy in the expression of methylation regulator genes between traditional bulk sequencing and scRNA-seq. This study identified five regulatory genes that will be the focus of further studies regarding the function of m6A/m5C/m1A in HCC.

Impact of Pelvic Fracture on Patients with Blunt Bowel Mesenteric Injury: Is Immediate Laparotomy Warranted?

The management of blunt abdominopelvic trauma with combined hemoperitoneum and pelvic fractures is challenging for trauma surgeons. Although angioembolization can achieve hemostasis in most visceral organ injuries and pelvic fractures after blunt abdominal trauma, it cannot effectively control hemorrhage in patients with blunt bowel mesenteric injury (BBMI). This study aimed to determine the risk factors associated with hemodynamically unstable patients with BBMI and to test the hypothesis that pelvic fracture is an independent risk factor for patients with unstable BBMI and concomitant pelvic fracture to guide the therapeutic sequence for difficult-to-manage patients. This retrospective study reviewed the data of hospitalized patients with trauma between 2009 and 2021 and included 158 adult patients with surgically proven BBMI. The patients were divided on the basis of the presence of a shock episode before emergency laparotomy. The shock group included 44.3% of all patients in the study (n = 70). Clinical injury severity and prognosis for patients in the shock group were poorer than those for patients in the non-shock group, and more invasive treatments and transfusions were performed for patients in the shock group than for those in the non-shock group. Pelvic fractures were more frequently associated with the shock group than with the non-shock group (21.4% vs. 5.7%; p = 0.003). In multivariate analysis, the presence of intracerebral hemorrhage (odds ratio [OR] = 10.87, 95% confidence intervals [CIs]: 1.70-69.75) and rib fracture (OR = 5.94, 95% CIs = 1.06-33.45) was identified as an independent predictor of shock, whereas the effect of pelvic fracture did not achieve statistical significance (OR = 2.94, 95% CIs = 0.66-13.13) after adjusting for confounding factors. For patients with BBMI, outcomes need to be improved during early diagnosis, and treatments should be expeditiously performed on the basis of the rapid identification of unstable hemodynamic status. Our results support the recommendation of emergency laparotomy in unstable patients with concomitant pelvic fractures, followed by damage control TAE if needed.

The Network of miRNA-mRNA Interactions in Circulating T Cells of Patients Following Major Trauma - A Pilot Study.

Purpose: Following major trauma, genes involved in adaptive immunity are downregulated, which accompanies the upregulation of genes involved in systemic inflammatory responses. This study investigated microRNA (miRNA)-mRNA interactome dysregulation in circulating T cells of patients with major trauma. Patients and Methods: This study included adult trauma patients who had an injury severity score ≥16 and required ventilator support for more than 48 h in the intensive care unit. Next-generation sequencing was used to profile the miRNAs and mRNAs expressed in CD3+ T cells isolated from patient blood samples collected during the injury and recovery stages. Results: In the 26 studied patients, 9 miRNAs (hsa-miR-16-2-3p, hsa-miR-16-5p, hsa-miR-185-5p, hsa-miR-192-5p, hsa-miR-197-3p, hsa-miR-23a-3p, hsa-miR-26b-5p, hsa-miR-223-3p, and hsa-miR-485-5p) were significantly upregulated, while 58 mRNAs were significantly downregulated in T cells following major trauma. A network consisting of 8 miRNAs and 22 mRNAs interactions was revealed by miRWalk, with three miRNAs (hsa-miR-185-5p, hsa-miR-197-3p, and hsa-miR-485-5p) acting as hub genes that regulate the network. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis suggested that "chemokine signaling pathway" was the predominant pathway. Conclusion: The study revealed a miRNA-mRNA interactome consisting of 8 miRNAs and 22 mRNAs that are predominantly involved in chemokine signaling in circulating T cells of patients following major trauma.

Protective Role of Obesity on Trauma Impact: A Retrospective Analysis of Patients with Surgical Blunt Bowel Mesenteric Injury Due to Road Traffic Accidents.

Background: The "cushion effect" theory proposes that increased body mass index (BMI) is associated with less severe abdomen injury following blunt abdomen trauma, while the "obesity paradox" describes the protective effect of obesity against mortality. However, most previous studies used the abdominal abbreviated injury scale as the outcomes seemed to be inadequate owing to the injuries to the abdominal organs, such as the spleen and liver, which may be attributable to the force that caused the chest trauma. This study aimed to use adult trauma patients with surgical blunt bowel mesenteric injuries (BBMIs) to investigate the influence of obesity on the clinical outcomes and overall morbidities. Methods: This retrospective study reviewed the data of all hospitalized trauma patients between 2009 and 2019 and included all patients with surgically proven small bowel, colon, or mesenteric injuries due to a road traffic accident. Comparison of the outcomes was performed among 123 patients with surgically proven BBMI, who were categorized by BMI into the normal-weight (n = 73, BMI<25 kg/m2), overweight (n = 37, 25≤BMI≤30 kg/m2), and obese groups (n = 13, BMI>30 kg/m2). Results: The obese group had a significantly lower incidence of isolated bowel injury (0%) compared with the normal-weight (35.6%) and overweight (16.2%) groups (p=0.005), but with higher incidence of isolated mesenteric injury or combined injury, although this was not significant. The obese group (92.3%) had a significantly higher percentage of overall morbidity than the normal-weight (61.6%) and overweight (70.3%) groups (p = 0.047). No significant difference was observed in the in-hospital mortality and 24-hour mortality among the three study groups. Conclusion: The study findings do not support the existence of a cushion effect and obesity paradox of obesity in blunt abdominal trauma.

A Retrospective Cohort Study on the Clinical Characteristics of Patients with Surgical Blunt Bowel and/or Mesenteric Injuries among Motorcyclists and Car Occupants.

(1) Background: Surgical blunt bowel and/or mesenteric injuries (BBMIs) are rare but challenging for trauma surgeons. Surgical BBMI is associated with specific injury mechanisms, such as direct compression by the handlebar in motorcycle accidents or rapid acceleration and deceleration of the impact forces associated with seatbelt injuries in motor vehicle collisions. However, the discussions on the implications of BBMI and the mechanisms of road traffic accidents remain scarce. This retrospective study assessed the clinical and injury characteristics of surgically proven BBMI among motorcyclists and car occupants based on trauma-registered data obtained from a level I trauma center in Taiwan. (2) Methods: Medical data of 72 motorcyclists and 38 car occupants who had surgical BBMI between January 2009 and December 2020 were reviewed. Patient characteristics, injuries, and outcomes in both groups were compared and analyzed. (3) Results: Motorcyclists with surgical BBMI had a significantly higher Injury Severity Score (median [Q1-Q3], 18 (9-27) vs. 16 (9-18), p = 0.044) and lower Glasgow Coma Scale score (15 (11-15) vs. 15 (15-15), p = 0.034]) than car occupants. Motorcyclists with surgical BBMI had a higher incidence of pelvic fractures (18.1% vs. 2.6%, p = 0.032) and upper limb fractures (23.6% vs. 7.9%, p = 0.042) and a significantly higher rate of chest tube insertion than car occupants (29.2% vs. 10.5%, p = 0.027). However, there were no significant differences in the outcomes of morbidity and mortality between motorcyclists and car occupants with surgical BBMI. (4) Conclusions: This study demonstrated there were no significant differences in outcomes between motorcyclists and car occupants with surgical BBMI. However, motorcyclists with surgical BBMI were injured more severely, along with injuries to the head/neck and extremities, than car occupants.

Acupuncture Analgesia in Patients With Traumatic Rib Fractures: A Randomized-Controlled Trial.

Pain management for traumatic rib fracture is important to prevent complications and reduce associated comorbidities. This trial investigated the analgesic efficacy of acupuncture on traumatic rib fracture. Patients with traumatic rib fracture were randomly assigned to traditional acupuncture (TA), laser acupuncture (LA) or sham laser acupuncture (SLA) groups in a 1:1:1 ratio. The intervention was performed on days 1 to 3 after treatment allocation. The acupoints included bilateral LI4 (Hegu), SJ6 (Zhigou), ST36 (Zusanli) and GB34 (Yanglingquan). The primary outcome was Numeric Rating Scale (NRS) scores for pain after the intervention. Secondary outcomes included sustained maximal inspiration (SMI) lung volume, stress responses, the use of analgesics, and associated complications. Data were analyzed via one-way analysis of variance (ANOVA) with Scheffé's post hoc testing or chi-squared testing. Of the 120 study participants, 109 completed all interventions and measurements. The primary outcomes, which indicated average pain intensity levels and pain while deep breathing, were both significantly lower in the TA and LA groups than in the SLA group after 2 treatments. No between-group differences were observed in SMI lung volume, stress response, analgesics use or associated complications. These findings suggest that TA and LA are safe and effective analgesic modalities for pain management for traumatic rib fracture. Clinical Trial Registration: [ClinicalTrials.gov], identifier [NCT03822273].

The Association between Skull Bone Fractures and the Mortality Outcomes of Patients with Traumatic Brain Injury.

Introduction: Skull fractures are often found in patients with traumatic brain injury (TBI). Although skull fractures may indicate greater force impact and are associated with local or diffuse brain injuries, the prognostic value of skull fractures remains unclear. This retrospective study aimed to assess the association between skull fractures and mortality in patients with TBI. Methods: This study included 5,430 TBI patients registered in the trauma registry system from January 2009 to December 2018. Clinical and demographic data including age, sex, trauma mechanisms, comorbidities, Glasgow Coma Scale (GCS) score, abbreviated injury score (AIS)-head, injury severity score (ISS), and in-hospital mortality were acquired. Multiple logistic regression and propensity score matching were used to elucidate the effect of skull fractures on mortality outcomes of TBI patients. Results: Compared to TBI patients without skull fracture, patients with skull fractures were predominantly male, younger, had lower GCS upon arrival at the emergency room, and had higher AIS-head, ISS, and in-hospital mortality. The patients with skull fracture had 1.7-fold adjusted odds of mortality (95% confidence interval (CI): 1.27-2.25; p < 0.001) than those without skull fracture, controlling for age, sex, comorbidities, and AIS-head. Additionally, the propensity score-matched analysis of 1,023 selected paired patients revealed that skull fracture was significantly associated with increased 1.4-fold odds of risk for mortality (95% CI: 1.02-1.88; p=0.036). Conclusions: Using a propensity score-matched cohort to attenuate the confounding effect of age, comorbidities, and injury severity, skull fracture was identified as a significant independent risk factor for mortality in patients with TBI.

The anatomical, electrophysiological and histological observations of muscle contraction units in rabbits: a new perspective on nerve injury and regeneration.

In the conventional view a muscle is composed of intermediate structures before its further division into microscopic muscle fibers. Our experiments in mice have confirmed this intermediate structure is composed of the lamella cluster formed by motor endplates, the innervating nerve branches and the corresponding muscle fibers, which can be viewed as an independent structural and functional unit. In this study, we verified the presence of these muscle construction units in rabbits. The results showed that the muscular branch of the femoral nerve sent out 4-6 nerve branches into the quadriceps and the tibial nerve sent out 4-7 nerve branches into the gastrocnemius. When each nerve branch of the femoral nerve was stimulated from the most lateral to the medial, the contraction of the lateral muscle, intermediate muscle and medial muscle of the quadriceps could be induced by electrically stimulating at least one nerve branch. When stimulating each nerve branch of the tibial nerve from the lateral to the medial, the muscle contraction of the lateral muscle 1, lateral muscle 2, lateral muscle 3 and medial muscle of the gastrocnemius could be induced by electrically stimulating at least one nerve branch. Electrical stimulation of each nerve branch resulted in different electromyographical waves recorded in different muscle subgroups. Hematoxylin-eosin staining showed most of the nerve branches around the neuromuscular junctions consisted of one individual neural tract, a few consisted of two or more neural tracts. The muscles of the lower limb in the rabbit can be subdivided into different muscle subgroups, each innervated by different nerve branches, thereby allowing much more complex muscle activities than traditionally stated. Together, the nerve branches and the innervated muscle subgroups can be viewed as an independent structural and functional unit. This study was approved by the Animal Ethics Committee of Peking University People's Hospital (approval No. 2019PHE027) on October 20, 2019.

The effects of electroacupuncture and laser acupuncture therapy for patients with major trauma: A study protocol.

BACKGROUND: Major trauma is the leading cause of death in the young population. The inflammatory and anti-inflammatory responses are associated with posttraumatic morbidity and mortality; however, it is not fully clear how to reestablish the homeostasis in patients with major trauma. METHODS: This study will be a prospective, randomized, placebo-controlled, partially double-blinded, three-armed trial. One hundred eighty participants diagnosed with major trauma will be randomly assigned to an electroacupuncture (EA), a laser acupuncture (LA), or a sham laser acupuncture group in a 1:1:1 ratio. All participants will undergo EA, LA, or sham laser acupuncture intervention once a day on 5 acupoints (LI4, PC6, ST36, SP6, and EX-HN1) for 14 consecutive days after enrollment. The primary outcome measure will be the length of hospital stay. Secondary outcomes will be inflammatory mediators, including serum C-reactive protein, interleukin (IL)-6, tumor necrosis factor-α, IL-1ß, and IL-10. Clinical outcomes will be numeric rating scale scores for pain, sequential organ failure assessment, ICU length of stay, 30-day mortality, and WHO Disability Assessment Schedule. Data will be analyzed by chi-square test or t test for pairwise comparisons, as well as one-way ANOVA followed by post hoc Tukey method between groups. OBJECTIVES: The aim of this protocol is to investigate the clinical effects of EA and LA on major trauma. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04970433. Registered on July 21, 2021.

Profiling the Expression of Circulating Acute-Phase Proteins, Cytokines, and Checkpoint Proteins in Patients with Severe Trauma: A Pilot Study.

PURPOSE: Severe trauma may lead to the systemic release of inflammatory mediators into the circulation with profound acute-phase responses; however, the understanding of the expression of these mediators remains limited. This study aimed to characterize the alterations in the expression of circulating acute-phase proteins, cytokines, and checkpoint proteins in patients with severe trauma injuries. PATIENTS AND METHODS: The study population included trauma patients in the intensive care unit (ICU) with an injury severity score equal to or greater than 16 and who had used a ventilator for 48 hours. A total of 12 female and 28 male patients were recruited for the study; six patients died and 34 survived. Blood samples collected at acute stages were compared with those drawn at the subacute stage, the time when the patients were discharged from the ICU, or before the discharge of the patients from the hospital. RESULTS: The study identified that the expression of acute-phase proteins, such as alpha-1-acid glycoprotein and C-reactive protein, and cytokines, including granulocyte colony-stimulating factor, interleukin-6, and interleukin-1 receptor antagonist, was elevated in the circulation after severe trauma. In contrast, the levels of acute-phase proteins, such as alpha-2-macroglobulin, serum amyloid P, and von Willebrand factor, and cytokines, including interleukin-4 and interferon gamma-induced protein 10, were reduced. However, there were no significant differences in the expression of checkpoint proteins in the circulation. CONCLUSION: The dysregulated proteins identified in this study may serve as potential therapeutic targets or biomarkers for treating patients with severe trauma. However, the related biological functions of these dysregulated factors require further investigation to validate their functions.

Disparity of Hepatocellular Carcinoma in Tumor Microenvironment-Related Genes and Infiltrating Immune Cells between Asian and Non-Asian Populations.

Hepatocellular carcinoma (HCC) is the most common cause of primary liver cancer deaths worldwide. The major risk factors for liver cancer development are cirrhosis, hepatitis B virus (HBV), hepatitis C virus (HCV) infection, and chronic alcohol abuse. HCC displays heterogeneity in terms of biology, etiology, and epidemiology. In Southeast Asia and Africa, chronic HBV infection is a major risk factor for HCC, whereas chronic HCV infection is a risk factor for HCC in western countries and Japan. Environmental and genetic conditions also play a role in the regional and temporal variations in the incidence of HCC. In this study, we used the ESTIMATE (ESTIMATE, Estimation of stromal and immune cells in malignant tumor tissues using expression data) algorithm and the CIBERSOFT tool to analyze gene expression profiles and infiltrating immune cells in HCC between Asian and non-Asian patients. The results showed that stromal and immune scores were dependent on overall survival (OS) in non-Asian patients but not in Asian patients. Kaplan-Meier survival analysis revealed four differentially expressed genes (DEGs) that were significantly associated with OS in non-Asian patients only. CIBERSORT (CIBERSORT, Cell type identification by estimating relative subsets of known RNA transcripts) analysis indicated that the composition of infiltrating immune cells was significantly different between Asian and non-Asian patients. By parsing the subclasses of HCC, the ability to predict prognosis and guide therapeutic targets for potentially actionable HCC may be improved.

Increased Angiogenesis by Exosomes Secreted by Adipose-Derived Stem Cells upon Lipopolysaccharide Stimulation.

Exosomes secreted by adipose-derived stem cells (ADSCs) enhance angiogenesis and wound healing. However, in clinical settings, wounds may be infected by various bacteria or pathogens. We investigated whether human ADSCs stimulated with lipopolysaccharide (LPS) secrete exosomes (ADSC-LPS-exo) that augment the angiogenesis of human umbilical vein endothelial cells (HUVECs). ExoQuick-TC exosome precipitation solution was used to purify exosomes from human ADSC culture media in the presence or absence of 1 µg/mL LPS treatment for 24 h. The uptake of ADSC-LPS-exo significantly induced the activation of cAMP response element binding protein (CREB), activating protein 1 (AP-1), and nuclear factor-κB (NF-κB) signaling pathways and increased the migration of and tube formation in HUVECs. RNA interference with CREB, AP-1, or NF-κB1 significantly reduced the migration of and tube formation in HUVECs treated with ADSC-LPS-exo. An experiment with an antibody array for 25 angiogenesis-related proteins revealed that only interleukin-8 expression was significantly upregulated in HUVECs treated with ADSC-LPS-exo. In addition, proteomic analysis revealed that eukaryotic translation initiation factor 4E, amyloid beta A4 protein, integrin beta-1, and ras-related C3 botulinum toxin substrate 1 may be potential candidates involved in ADSC-LPS-exo-mediated enhanced angiogenesis.