Hong-Xiang Lu

Background: Current lines of evidence indicate that cysteine-rich secretory protein 3 (CRISP3) is an immunoregulatory factor. Nevertheless, no study has explored the relationships between the values of CRISP3 and sepsis.Methods: We conducted a comprehensive literature search and meta-analysis from the Gene Expression Omnibus (GEO) and ArrayExpress to determine the expression of CRISP3 in sepsis patients. Then, we explored whether plasma CRISP3 could serve as a potential biomarker to predict the risk of sepsis via two retrospective trauma cohorts. We evaluated the prediction power using the area under the curve (AUC).Results: A total of 23 datasets were recruited for the comprehensive meta-analysis, and the combined standardized mean difference (SMD) of CRISP3 was 0.90 (0.50–1.30) (p < 0.001), suggesting that CRISP3 was overexpressed in sepsis patients. Meanwhile, sepsis patients had higher CRISP3 concentrations than non-sepsis patients in 54 trauma patients (p < 0.001). Plasma CRISP3 on admission was significantly associated with the incidence of sepsis [OR = 1.004 (1.002–1.006), p < 0.001]. As a predictive biomarker, CRISP3 obtained a better AUC [0.811 (0.681–0.905)] than C-reactive protein (CRP) [0.605 (0.463–0.735)], procalcitonin (PCT) [0.554 (0.412–0.689)], and Sequential Organ Failure Assessment (SOFA) [0.754 (0.618–0.861)]. Additionally, the clinical relationships between plasma CRISP3 and sepsis were verified in another trauma cohort with 166 patients [OR = 1.002 (1.001–1.003), p < 0.001]. The AUC of CRISP3 was 0.772 (0.701–0.834), which was better than that of CRP [0.521 (0.442–0.599)] and PCT [0.531 (0.452–0.609)], but not SOFA [0.791 (0.717–0.853)].Conclusion: Our study indicated and validated that CRISP3 was highly expressed in sepsis. More importantly, CRISP3 may serve as a latent biomarker to predict the risk of sepsis.

Background: A novel coronavirus pneumonia outbreak began in Wuhan, Hubei Province, in December 2019; the outbreak was caused by a novel coronavirus previously never observed in humans. China has imposed the strictest quarantine and closed management measures in history to control the spread of the disease. However, a high level of evidence to support the surgical management of potential trauma patients during the novel coronavirus outbreak is still lacking. To regulate the emergency treatment of trauma patients during the outbreak, we drafted this paper from a trauma surgeon perspective according to practical experience in Wuhan. Main body: The article illustrates the general principles for the triage and evaluation of trauma patients during the outbreak of COVID-19, indications for emergency surgery, and infection prevention and control for medical personnel, providing a practical algorithm for trauma care providers during the outbreak period. Conclusions: The measures of emergency trauma care that we have provided can protect the medical personnel involved in emergency care and ensure the timeliness of effective interventions during the outbreak of COVID-19.

Background: Peroxisome proliferator-activated receptor gamma (PPARγ) is a major regulator in sepsis. Our previous study identified the enhancer polymorphism rs10865710C/G to be associated with susceptibility to sepsis in trauma patients. We performed two-stage cohort studies integrating biological experiments of potential functional variants that modify susceptibility to traumatic sepsis. Methods: Improved multiplex ligation detection reaction (iMLDR) was used to genotype rs10865710 in 797 Han Chinese trauma patients in Chongqing. Clinical relevance was validated in 334 patients in Guizhou. The potential function of rs10865710 in transcriptional regulation was explored through a dual luciferase reporter assay and electrophoretic mobility shift assay (EMSA). Expression of PPARγ was assessed by expression quantitative trait locus (e-QTL) and western blot analyses. Results: The association results confirmed rs10865710 to be significantly strongly associated with sepsis risk in trauma patients of the Chongqing and Guizhou cohorts (OR = 1.41 (1.11–1.79), P = 0.004 and OR = 1.45 (1.01–2.09), P = 0.046, both for allele-dose effect, respectively). A meta-analysis of both cohorts and a previous study indicated strong evidence for this association (OR = 1.41 (1.17–1.71), P = 0.0004 for the dominant model, OR = 1.78 (1.34–2.36), P < 0.0001 for the recessive model and OR = 1.38 (1.20–1.58), P < 0.0001 for the allelic model). Functional experiments verified that rs10865710 was a causative variant influencing enhancer activity (G vs. C, 0.068 ± 0.004 vs. 0.096 ± 0.002, P = 0.0005) and CREB2 binding. Expression analysis also indicatevd rs10865710 genotypes to be associated with levels of PPARγ expression (P = 9.2 × 10⁻⁵ for dominant effect and P = 0.005 for recessive effect). Conclusions: Our study provides evidence that the enhancer-region polymorphism rs10865710 might influence transcription factor binding and regulate PPARγ expression, thus conferring susceptibility to traumatic sepsis. Trial registration: ClinicalTrials.gov, NCT01713205. Registered 18 October 2012, retrospectively registered.

Patients suffering from major trauma often experience complications such as sepsis. The early recognition of patients at high risk of sepsis after trauma is critical for precision therapy. We aimed to derive and validate a novel predictive score for sepsis risk using electronic medical record (EMR) data following trauma. Clinical and laboratory variables of 684 trauma patients within 24 h after admission were collected, including 411 patients in the training cohort and 273 in the validation cohort. The least absolute shrinkage and selection operator (LASSO) technique was adopted to identify variables contributing to the early prediction of traumatic sepsis. Then, we constructed a traumatic sepsis score (TSS) using a logistic regression model based on the variables selected in the LASSO analysis. Moreover, we evaluated the discrimination and calibration of the TSS using the area under the curve (AUC) and the Hosmer-Lemeshow (H-L) goodness-of-fit test. Based on the LASSO, seven variables (injury severity score, Glasgow Coma Scale, temperature, heart rate, albumin, international normalized ratio, and C-reaction protein) were selected for construction of the TSS. Our results indicated that the incidence of sepsis after trauma increased with an increasing TSS (Ptrend = 7.44 × 10−21 for the training cohort and Ptrend = 1.16 × 10−13 for the validation cohort). The areas under the receiver operating characteristic (ROC) curve of TSS were 0.799 (0.757–0.837) and 0.790 (0.736–0.836) for the training and validation datasets, respectively. The discriminatory power of our model was superior to that of a single variable and the sequential organ failure assessment (SOFA) score (P < 0.001). Moreover, the TSS was well calibrated (P > 0.05). We developed and validated a novel TSS with good discriminatory power and calibration for the prediction of sepsis risk in trauma patients based on the EMR data.

Published data revealed that host genetic variants have a substantial influence on sepsis susceptibility. However, the results have been inconsistent. We aimed to systematically review the published studies and quantitatively evaluate the effects of these variants on the risk of sepsis. We searched the PubMed, EMBASE, Medline, Web of Knowledge, and HuGE databases to identify studies that investigated the associations between genetic variants and sepsis risk. Then, we conducted meta-analyses of the associations for genetic variants with at least three study populations and applied the Venice criteria to assess the association result credibility. A literature search identified 349 eligible articles that investigated 405 variants of 172 distinct genes. We performed 204 primary and 185 subgroup meta-analyses for 76 variants of 44 genes. The results showed that 29 variants of 23 genes were significantly associated with the risk of sepsis, including 8 variants of pattern recognition receptors (PRRs), 14 variants of cytokines, one variant of an immune-related gene and 6 variants of other genes. Furthermore, the cumulative epidemiological evidence of a significant association between each variant and the risk of sepsis was classified as strong or moderate for 18 variants. For the 329 variants with fewer than three study populations, 63 variants of 48 genes have been reported to be significantly associated with the risk of sepsis in a systematic review. We identified several genetic variants that could influence the susceptibility to sepsis by systematic review and meta-analysis. This study provides a comprehensive overview of the genetic architecture of variants involved in sepsis susceptibility and novel insight that may affect personalized targeted treatment in the future clinical management of sepsis.

Previous study revealed that rs2232618 polymorphism (Phe436Leu) within LBP gene is a functional variant and associated with susceptibility of sepsis in traumatic patients. Our aim was to confirm the reported association by enlarging the population sample size and perform a meta-analysis to find additional evidence. Traumatic patients from Southwest (n = 1296) and Southeast (n = 445) of China were enrolled in our study. After genotyping, the relationship between rs2232618 and the risk of sepsis was analyzed. Furthermore, we proceeded with a comprehensive literature search and meta-analysis to determine whether the rs2232618 polymorphism conferred susceptibility to sepsis. Significance correlation was observed between rs2232618 and risk of sepsis in Southwest patients (P = 0.002 for the dominant model, P = 0.006 for the recessive model). The association was confirmed in Southeast cohort (P = 0.005 for the dominant model) and overall combined cohorts (P = 4.5 × 10−4, P = 0.041 for the dominant and recessive model). Multiple logistical regression analyses suggested that rs2232618 polymorphism was related to higher risk of sepsis (OR = 1.77, 95% CI = 1.26–2.48, P = 0.001 in Southwest patients; OR = 2.11, 95% CI = 1.24–3.58, P = 0.006 in Southeast cohort; OR = 1.54, 95% CI = 1.34–2.08, P = 0.006 in overall cohort). Furthermore, meta-analysis of four studies (including the present study) confirmed that rs2232618 within LBP increased the risk of sepsis (OR = 1.75, P < 0.001 for the dominant model; OR = 6.08, P = 0.003 for the recessive model; OR = 2.72, P < 0.001 for the allelic model). The results from our replication study and meta-analysis provided firm evidence that rs2232618T allele significantly increased the risk of sepsis.