Whole genome sequencing analysis of seven unknown resistance mechanisms of carbapenem-resistant Klebsiella pneumoniae strains resistance to ceftazidime-avibactam.

AIMS: To investigate alternative resistance mechanisms among seven ceftazidime-avibactam (CZA)-resistant carbapenem-resistant Klebsiella pneumoniae (CRKP) strains lacking common antimicrobial resistance genes (ARGs) using whole genome sequencing. METHODS AND RESULTS: ARG and virulence factors (VFs) were screened using the ARG database CARD and the VF database, respectively, and identified using genomic annotation data with BLAST+. Six strains were ST11 sequence types (STs), and one was ST2123. ST11 strains harbored more ARGs than the ST2123 strains. All seven strains carried multiple ARGs with efflux-mediated antibiotic resistance, including oqxA, oqxB, tet (A), qacEdltal, CRP, H-NS, Kpn-E, F, G, H, acrA, LptD, acrB, acrD, cpxA, mdtB, and mdtC. These efflux-mediated ARGs were identified in most strains and even all strains. Whole genome sequencing revealed that the ST11 strain carried multiple potential prophages, genomic islands, and integrative and conjugative elements, while the ST2123 strain carried an independent potential prophages and a genomic island. CONCLUSIONS: Whole genome sequencing analysis revealed that these seven CZA-resistant CRKP strains lacking common ARGs exhibited efflux-mediated antibiotic resistance-associated ARGs. The main mechanism by which CRKP resists CZA is antibiotic inactivation. Except for tet (A), no ARGs and validation experiments related to efflux were found. This study's results provide a new possibility for the resistance mechanism of CRKP to CZA, and we will verify this conclusion through experiments in the future.

One-year mortality risk in older individuals with femoral intertrochanteric fracture: a tertiary center in China.

BACKGROUND: The accelerated growth of older individuals worldwide has increased the number of patients presenting with fragility hip fractures. Having a hip fracture can cause excess mortality, and patients with hip fracture have a higher risk of death than those without hip fracture. Most studies have treated hip fracture as a single, homogeneous condition, but hip fracture includes two major anatomic types: intertrochanteric fracture and femoral neck fracture. Few studies have specifically evaluated 1-year mortality risk in older individuals with femoral intertrochanteric fracture. The aim of this study was to evaluate 1-year mortality and factors associated with mortality in older individuals with femoral intertrochanteric fracture. METHODS: A retrospective review was conducted of 563 patients ≥ 65 years old who underwent surgery for femoral intertrochanteric fractures at our institution between January 2010 and August 2018. Patient demographics, comorbidities, and treatment were collected by retrospective chart review. Age, sex, Body Mass Index (BMI), American Society of Anesthesiologists (ASA) classification, Charlson comorbidity index (CCI), Arbeitsgemeinschaft Für Osteosynthesefragen (AO) fracture classification, haemoglobin value at admission, time to surgery, operation time, and intraoperative blood loss were risk factors to be tested. Multivariable logistic regression was used to evaluate associations between variables and death. RESULTS: Among the 563 patients, 49 died within 1 year after surgery, and the 1-year mortality rate was 8.7%. Multivariate analysis identified age > 80 years (OR = 4.038, P = 0.011), haemoglobin < 100 g/l (OR = 2.732, P = 0.002), ASA score ≥ 3 (OR = 2.551, P = 0.005), CCI ≥ 3 (OR = 18.412, P = 0.018) and time to surgery > 14 d (OR = 3.907, P = 0.030) as independent risk factors for 1-year mortality. Comorbidities such as myocardial infarction and chronic pulmonary disease were associated with 1-year mortality after adjusting for age > 80 years and time to surgery > 14 days. CONCLUSIONS: Patients over 80 years old with haemoglobin < 100 g/l, ASA score ≥ 3, CCI ≥ 3, and multiple comorbidities, especially myocardial infarction and chronic pulmonary disease before surgery, are at a higher risk of 1-year mortality. Doctors should pay more attention to these vulnerable patients, and a surgical delay greater than 14 days should be avoided.

Wa-VP4* as a candidate rotavirus vaccine induced homologous and heterologous virus neutralizing antibody responses in mice, pigs, and cynomolgus monkeys.

Group A rotavirus (RVA) is the primary etiological agent of acute gastroenteritis (AGE) in children under 5 years of age. Despite the global implementation of vaccines, rotavirus infections continue to cause over 120,000 deaths annually, with a majority occurring in developing nations. Among infants, the P[8] rotavirus strain is the most prevalent and can be categorized into four distinct lineages. In this investigation, we expressed five VP4(aa26-476) proteins from different P[8] lineages of human rotavirus in E. coli and assessed their immunogenicity in rabbits. Among the different P[8] strains, the Wa-VP4 protein, derived from the MT025868.1 strain of the P[8]-1 lineage, exhibited successful purification in a highly homogeneous form and significantly elicited higher levels of neutralizing antibodies (nAbs) against both homologous and heterologous rotaviruses compared to other VP4 proteins derived from different P[8] lineages in rabbits. Furthermore, we assessed the immunogenicity of the Wa-VP4 protein in mice, pigs, and cynomolgus monkeys, observing that it induced robust production of nAbs in all animals. Interestingly, there was no significant difference between in nAb titers against homologous and heterologous rotaviruses in pigs and mankeys. Collectively, these findings suggest that the Wa-VP4* protein may serve as a potential candidate for a rotavirus vaccine.

Identification of a novel macrophage-related prognostic signature in colorectal cancer.

Colorectal cancer (CRC) is one of the most prevalent and deadliest illnesses all around the world. Growing proofs demonstrate that tumor-associated macrophages (TAMs) are of critical importance in CRC pathogenesis, but their mechanisms remain yet unknown. The current research was designed to recognize underlying biomarkers associated with TAMs in CRC. We screened macrophage-related gene modules through WGCNA, selected hub genes utilizing the LASSO algorithm and COX regression, and established a model. External validation was performed by expression analysis using datasets GSE14333, GSE74602, and GSE87211. After validating the bioinformatics results using real-time quantitative reverse transcription PCR, we identified SPP1, C5AR1, MMP3, TIMP1, ADAM8 as potential biomarkers associated with macrophages in CRC.

Global burden, risk factors, clinicopathological characteristics, molecular biomarkers and outcomes of microsatellite instability-high gastric cancer.

Microsatellite instability-high (MSI-H) has gained considerable interests since it was approved as a tumor-agnostic biomarker in immunotherapy. However, the reported characteristics of MSI-H gastric cancer (GC) are inconsistent due to the biological complexity. Here, we aim to clarify the prevalence, risk factors, clinicopathological/molecular features and outcomes of MSI-H GC though a comprehensive review on 43246 patients from 134 cohorts. Overall, the proportion of MSI-H GC was 14.5% (95% CI, 13.3%-15.8%). Patients with MSI-H GC were less likely to have Epstein-Barr virus infection. High incidences of MSI-H GC were associated with female, older age, lower gastric body, Lauren intestinal histology, WHO tubular and mucinous subtypes, and early disease stage. Additionally, patients with MSI-H GC harbored more KRAS mutation, PD-L1 positivity, CD8 overexpression, and higher TMB, but less HER2 positivity and TP53 mutation. When treated with conventional strategy, the 5-year survival rates in MSI-H patients (70.3%) and MSI-L/MSS patients (43.7%) were significantly different (p<0.001). Patients with MSI-H GC derived larger benefit from immunotherapy in term of overall survival (pInteraction<0.001) and objective response (pInteraction=0.02). Since the prevalence of MSI-H GC is relatively high and associated with distinct clinicopathological and molecular characteristics, MSI testing should be conducted during standard diagnostical activity. Moreover, giving MSI-H tumors are often diagnosed at early stage and have favorable outcomes, less aggressive treatment strategies may be considered in clinical practice. In summary, this panoramic review may assist in design and/or interpretation of clinical trials, provide references in drug development, and constitute complementary information in drafting the clinical practice guideline.

Intermediate endpoints as surrogates for outcomes in cancer immunotherapy: a systematic review and meta-analysis of phase 3 trials.

Background: Cancer immunotherapy shows unique efficacy kinetics that differs from conventional treatment. These characteristics may lead to the prolongation of trial duration, hence reliable surrogate endpoints are urgently needed. We aimed to systematically evaluate the study-level performance of commonly reported intermediate clinical endpoints for surrogacy in cancer immunotherapy. Methods: We searched the Embase, PubMed, and Cochrane databases, between database inception and October 18, 2022, for phase 3 randomised trials investigating the efficacy of immunotherapy in patients with advanced solid tumours. An updated search was done on July, 15, 2023. No language restrictions were used. Eligible trials had to set overall survival (OS) as the primary or co-primary endpoint and report at least one intermediate clinical endpoint including objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and 1-year overall survival. Other key inclusion and exclusion criteria included: (1) adult patients (>18 years old) with advanced solid tumour; (2) no immunotherapy conducted in the control arms; (3) follow-up is long enough to achieve OS; (4) data should be public available. A two-stage meta-analytic approach was conducted to evaluate the magnitude of the association between these intermediate endpoints and OS. A surrogate was identified if the coefficient of determination (R2) was 0.7 or greater. Leave-one-out cross-validation and pre-defined subgroup analysis were conducted to examine the heterogeneity. Potential publication bias was evaluated using the Egger's and Begg's tests. This trial was registered with PROSPERO, number CRD42022381648. Findings: 52,342 patients with 15 types of tumours from 77 phase 3 studies were included. ORR (R2 = 0.11; 95% CI, 0.00-0.24), DCR (R2 = 0.01; 95% CI, 0.00-0.01), and PFS (R2 = 0.40; 95% CI, 0.23-0.56) showed weak associations with OS. However, a strong correlation was observed between 1-year survival and clinical outcome (R2 = 0.74; 95% CI, 0.64-0.83). These associations remained relatively consistent across pre-defined subgroups stratified based on tumour types, masking methods, line of treatments, drug targets, treatment strategies, and follow-up durations. No significant heterogeneities or publication bias were identified. Interpretation: 1-year milestone survival was the only identified surrogacy endpoint for outcomes in cancer immunotherapy. Ongoing investigations and development of new endpoints and incorporation of biomarkers are needed to identify potential surrogate markers that can be more robust than 1-year survival. This work may provide important references in assisting the design and interpretation of future clinical trials, and constitute complementary information in drafting clinical practice guidelines. Funding: None.

Linkage Disequilibrium between LDLR rs688 and AvaII Genes and its Significant Association with Ischemic Stroke.

BACKGROUND: To analyze the polymorphism distribution of low density lipoprotein receptor rs688, AvaII, NcoI gene in ischemic stroke, and explore the linkage disequilibrium among them. The correlation between the linkage disequilibrium and ischemic stroke was further analyzed. METHODS: The levels of serum lipid (triglyceride, cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, apolipoprotein A1, apolipoprotein B) and rs688, AvaII, NcoI polymorphism of low density lipoprotein receptor gene were tested in patients with ischemic stroke (n = 140), healthy control (n = 129) and patients with other cerebrovascular diseases (n = 122). Chi-square test was used to compare the gene frequency and allele frequency of each group. Both the linkage disequilibrium of the three genes and the alleles correlated with ischemic stroke were analyzed. The correlation of linkage disequilibrium gene and ischemic stroke was analyzed with logistic binary regression. RESULTS: In the ischemic stroke group, significant difference was observed in frequencies and allelic frequencies of low density lipoprotein receptor (LDLR) rs688 and AvaII. No difference of NcoI was found. Linkage disequilibrium was found for rs688 and AvaII (D' = 0.927, R2 = 0.509). Allelic genes correlate with ischemic stroke included T of rs688 (X2 = 46.105, p < 0.001) and C of AvaII (X2 = 20.436, p < 0.001). CONCLUSIONS: Linkage disequilibrium existed between LDLR rs688 and AvaII genes. With the wild type gene (WT) (rs688/AvaII: CC/TT) as reference, rs688/AvaII: CT/TC, CT/CC and TT/CC increased the risk of ischemic stroke, which might be a genetic marker used for the screen of high-risk population contributing to the prevention of the disease.

Incidence and cost of vertebral fracture in urban China: a 5-year population-based cohort study.

BACKGROUND: Osteoporotic vertebral fractures cause pain and disability, which result in a heavy socioeconomic burden. However, the incidence and cost of vertebral fractures in China are unknown. We aimed to assess the incidence and cost of clinically recognized vertebral fractures among people aged 50 years and older in China from 2013 to 2017. MATERIALS AND METHODS: This population-based cohort study was conducted by using Urban Employee Basic Medical Insurance (UEBMI) and Urban Resident Basic Medical Insurance (URBMI) data in China from 2013 to 2017, which covered more than 95% of the Chinese population in urban areas. Vertebral fractures were identified by the primary diagnosis (i.e. International Classification of Diseases code or text of diagnosis) in UEBMI and URBMI. The incidence and medical cost of these clinically recognized vertebral fractures in urban China were calculated. RESULTS: A total of 271 981 vertebral fractures (186 428, 68.5% females and 85 553, 31.5% males) were identified, with a mean age of 70.26 years. The incidence of vertebral fractures among patients aged 50 years and over in China increased ~1.79-fold during the 5 years, from 85.21 per 100 000 person-years in 2013 to 152.13 per 100 000 person-years in 2017. Medical costs for vertebral fractures increased from US$92.74 million in 2013 to US$505.3 million in 2017. Annual costs per vertebral fracture case increased from US$3.54 thousand in 2013 to US$5.35 thousand in 2017. CONCLUSION: The dramatic increase in the incidence and cost of clinically recognized vertebral fractures among patients aged 50 and over in urban China implies that more attention should be given to the management of osteoporosis to prevent osteoporotic fractures.

A Novel Classification of Cervical Spine Trauma in Ankylosing Spondylitis and Corresponding Surgical Outcomes.

OBJECTIVE: Currently, there are no reports on the specific classification of cervical spine trauma (CST) in ankylosing spondylitis (AS) based on the trauma mechanism. In this study, we aimed to describe a novel classification of CST in AS with more details, and put forward the corresponding surgical outcomes related to different types, hoping to provide a practical reference for clinical decision-making and academic communication. METHODS: From January 2008 to December 2021, AS patients who experienced CST were retrospectively reviewed and included. Clinical data including gender, age, reason of trauma, time interval between AS diagnosis and trauma were collected. The American Spinal Injury Association (ASIA) grade system was used to describe patients' neurological status. Based on the combination of surgical experience and follow-up observation, the lower cervical spine trauma in AS patients was divided into three main types, namely single level fracture-dislocation (type 1), spinal cord injury without fracture-dislocation (type 2), and Andersson lesion (type 3). Furthermore, we performed detailed subtypes according to whether cervical spine was completely fused and the location of injury. Meanwhile, according to different approaches, surgical methods mainly included Anterior Cervical Discectomy and Fusion (ACDF), Anterior Cervical Corpectomy and Fusion (ACCF), Posterior Expansive Open-door Cervical Laminoplasty (PEOLP), Posterior Cervical Laminectomy Decompression and Fusion (PCLDF), and their combination. Postoperative general and surgery-related complications were also recorded. RESULTS: A total of 102 patients were enrolled, including 91 males and 11 females, with an average age of 51.9 years. Their average interval time between AS diagnosis and injury was 27.8 years. Patients with high-energy and low-energy trauma were 54 and 48 respectively. There were 79 patients suffering spinal cord nerve impairment after trauma. With regard to the distribution of different types, the number of patients in type 1, type 2, and type 3 were 86, 14, and two, respectively. For different types, PCLDF was the most commonly used surgical method, accounting for 55.9%, while ACCF was only applied for one time. In type 1, the frequencies of ACDF, ACCF, PCLDF, and ACDF+PCLDF were 10.5%, 1.2%, 55.8%, and 32.5%. In type 2, the frequencies of ACDF, PCLDF, ACDF+PCLDF, and PEOLP were 7.1%, 50.0%, 7.1%, 35.8%. Postoperatively, 21 patients achieved neurological function improvement. The incidences of general and surgery-related complications were 19.6% and 5.9%, respectively. All patients achieved bone fusion and durable decompression at the last follow-up. CONCLUSIONS: Our novel classification could enrich the scope of CST in AS patients and provide valuable references to the corresponding clinical management. Besides, there are strict indications of different surgical methods, factors like patient's physical condition, trauma type, surgical purpose, and expected efficacy were all required to consider before making a clinical decision.

Positive correlation between the proximal femur Hounsfield units from routine CT and DXA results.

To determinate the correlation between the proximal femur Hounsfield unit (HU) value and dual-energy X-ray absorptiometry (DXA) results, and to identify its feasibility for opportunistic screening osteoporosis. A total of 680 patients underwent computed tomography (CT) containing proximal femur and DXA test within 6 months between 2010 and 2020 in our hospital. The CT HU value of four axial slices of the proximal femur were measured. The measurements were compared with the DXA results by Pearson correlation coefficient. Receiver operator characteristic curve were generated to identify the best cutoff for diagnosing osteoporosis. These 680 consecutive patients included 165 male and 515 female; the average age was 63.66 ± 11.36 years old, the mean interval time between two examinations was 45.43 days. The most representative CT HU value measurement was the 5-mm slice measurement. The average CT HU value was 59.3 ± 36.5 HU, and the differences among the three DXA defined bone mineral density (BMD) categories were significant (all p < 0.001). The Pearson correlation analysis showed that the proximal femur CT values had strong positive correlation with femoral neck T-score, femoral neck BMD and total hip BMD (r = 0.777, r = 0.748, r = 0.746, respectively; all p < 0.001). The area under the curve for CT value for diagnosing osteoporosis was 0.893 (p < 0.001), the best cutoff was 67 HU with 84% sensitivity, 80% specificity, 92% positive predictive value and 65% negative predictive value. Proximal femur CT values had good positive correlation with DXA results, which could be used to opportunistic screening for potential osteoporosis patient.

Combination of UC-3500 and UF-5000 as a quick and effective method to exclude bacterial urinary tract infection.

BACKGROUND: Our study aims to evaluate the performance of the combination of Sysmex urine dry chemistry analyzer UC-3500 and urine particle analyzer UF-5000 in screening bacterial urinary tract infection (UTI). METHODS: We analyzed 2000 urine specimens from patients with suspected UTI by using a urine dry chemistry analyzer (UC-3500) and a fully automated sediment analyzer (UF-5000). After being tested by the instrument, all specimens were sent to our clinical microbiology laboratory for culture. In addition, 600 urine specimens were selected to evaluate the accuracy of the six screening strategies established in this study. RESULTS: The consistency of UF-5000 bacterial classification and bacterial culture was fair (Kappa = 0.339). The counts of WBC and BACT elevated with sequential group designs (P < 0.001). The cut-off value of WBC was 32.20/µL for males (AUC, 0.942, 95%CI, 0.930-0.955) and 39.15/µL for females (AUC, 0.931, 95%CI, 0.914-0.948). The sensitivity and specificity of WBC were relatively higher than those of BACT. Strategy④ and Strategy⑥ in all six strategies had a good negative predictive value (NPV) which was 98.73%. CONCLUSION: UF-5000 bacterial classification cannot be used as a practical reference. 32.20/µL (male) and 39.15/µL (female) for WBC as well as 22.35/µL (male) and 127.25/µL (female) for BACT were used as cut-off values to effectively determine whether UTI occurs. WBC, BACT and LEU joint screening programs were suitable to rapidly and effectively exclude bacterial UTI.

Trochanteric and subtrochanteric fractures irreducible by closed reduction: a retrospective study.

AIM: To explore the preoperative radiographic features and reduction methods of irreducible trochanteric and subtrochanteric fractures of the femur and to compare the perioperative characteristics and prognoses of irreducible and reducible fractures. METHODS: The data of 1235 patients with femoral trochanteric fractures surgically treated in our hospital between January 2010 and January 2021 were retrospectively analyzed. According to the inclusion criteria and exclusion criteria, 1163 cases of femoral trochanteric and subtrochanteric fractures were included in this study. Fractures in which good or acceptable reduction could not be reached by closed manipulation were defined as irreducible fractures. The preoperative radiographic features, fracture displacement patterns after closed manipulation and intraoperative reduction methods used to treat irreducible fractures were analyzed, and the perioperative characteristics and prognoses of irreducible fractures and reducible fractures were compared. RESULTS: There were 224 patients in the irreducible group and 939 patients in the reducible group. According to the radiographic features of fractures, irreducible fractures could be divided into four types: those with interlocking of the fracture, sagging of the femoral shaft, splitting of the lateral wall or medial wall, and comminution of the subtrochanteric area. Various kinds of reduction techniques were needed for different types. CONCLUSIONS: The incidence of irreducible trochanteric fractures was 15.4%, while the incidence of irreducible subtrochanteric fractures was 84.6%. According to the radiographic features of fractures, they can be divided into four types. It is important to identify irreducible fractures preoperatively and make comprehensive plans to the greatest extent possible to shorten the operation time, reduce intraoperative blood loss, and reduce the incidence of complications.

Association between P2Y1 and P2Y12 polymorphisms and acute myocardial infarction and ADP-induced platelet aggregation.

BACKGROUND: The objective of this study was to investigate the relationship between P2Y1 and P2Y12 genotypes and the risk of acute myocardial infarction (AMI) in the Quanzhou population and to determine associations between P2Y1 and P2Y12 genotypes and ADP-induced platelet aggregation in this population. METHODS: All subjects were screened for P2Y1 (c.1622A > G) and P2Y12 (H1/H2, c.34C > T) polymorphisms by direct DNA sequencing. The maximal platelet aggregation rate (MAR) in AMI patients (n = 61) and healthy control subjects (n = 50) was measured by a PL-12 platelet function analyzer, and adenosine diphosphate (ADP) (5 µmol/L) was used as an agonist. RESULTS: The haploid H2 allele in the P2Y12 gene was more frequent in patients with AMI than in control subjects (OR 1.887, P = 0.005). The P2Y12 H2 haplotype was significantly associated with AMI in the codominant (P = 0.008), dominant (OR 2.103, P = 0.003), and overdominant models (OR 2.133, P = 0.003). After adjusting for potential confounders, H2 haplotype carriers had a 2.132-fold increased risk for AMI (OR 2.132, P = 0.012) compared with noncarriers. Moreover, we observed that the ADP-induced MAR in the carriers of the H2 haplotype from the control group was somewhat higher than that in noncarriers of this group (P = 0.020). However, we failed to demonstrate that the P2Y1 H1/H2 polymorphism affected ADP-induced MAR in AMI patients. Additionally, P2Y1 c.1622A > and P2Y12 c.34C > T polymorphisms were not associated with the risk of AMI or ADP-induced MAR in either group. CONCLUSIONS: Therefore, our results suggest that the P2Y12 H2 haplotype was associated with a higher risk of AMI, while its effect on increased ADP-induced platelet aggregation remains to be investigated. Thus, the P2Y12 H2 haplotype may be a potential marker for AMI.

Comparison of femoral neck system to multiple cancellous screws and dynamic hip screws in the treatment of femoral neck fractures.

OBJECTIVE: To compare the short-term outcomes of the femoral neck system (FNS) with multiple cancellous screws (MCS) and dynamic hip screws (DHS) in the treatment of femoral neck fractures. METHODS: A retrospective analysis was performed on 157 patients with fresh femoral neck fractures treated with FNS (from September 2019 to October 2020), MCS, and DHS (from January 2018 to October 2020). According to internal fixation methods, all patients were divided into the FNS group (54 cases), MCS group (51 cases), and DHS group (52 cases). Demographic data were also collected, recorded, and compared, including the follow-up time, days of hospitalization, operation time, blood loss, intraoperative fluoroscopy times (IFT), weight-bearing time (WBT), length of femoral neck shortening (LFNS), Harris hip score, and complications (such as internal fixation failure, bone nonunion, and avascular necrosis of the femoral head) between the three groups. RESULTS: Overall, 157 patients with a mean age of 61.8 (range, 18-89) years were analyzed. In the FNS group, IFT (median 10.5) was significantly lower than that in the MCS group (median 21) and DHS group (median 20.5) (P<0.05), and WBT was significantly earlier than that of the MCS group (P<0.05). In the FNS group, the median hospitalization time, operation time, and blood loss were 2 (2, 4) days, 45 (40-59) min, and 30 (20, 50) ml, respectively. They were all significantly less than 3.5 (3, 6) days, 72 (55-88.75) min, and 50 (30, 50) ml in the DHS group, respectively (P < 0.05). There was no statistical difference in LFNS, quality of reduction, internal fixation failure rate, and Harris hip score at the latest follow-up (P>0.05). No surgical complications such as incision infection, deep infection, pulmonary embolism, or femoral head necrosis were found in any of the three groups. CONCLUSION: FNS, MCS, and DHS are all effective for femoral neck fractures. However, a lower IFT of FNS shortens the operation time. Compared to MCS, FNS has the advantages of being a simple operation, with early WBT; compared to DHS, a minimally invasive operation is the main advantage of FNS.

Hydraulic trade-off and coordination strategies mediated by leaf functional traits of desert shrubs.

Desert shrubs play important roles in desertification control and vegetation restoration, which are particularly affected by droughts caused by climate change. However, the hydraulic strategies associated with hydraulic functional traits of desert shrubs remain unclear. Here, eight desert shrub species with different life forms and morphologies were selected for a common garden experiment at the southeast edge of the Tengger Desert in northern China to study the hydraulic strategies mediated by leaf hydraulic functional traits. Diurnal leaf water potential change, leaf hydraulic efficiency and safety, hydraulic safety margin, hydraulic capacitance, and water potential and relative water content at the turgor loss point were observed to significantly differ among species, suggesting that leaf hydraulic functional traits were strongly associated with species even when living in the same environment. Additionally, shrubs with greater leaf hydraulic efficiency had lower midday leaf water potential and leaf hydraulic safety, suggesting that leaf hydraulic efficiency had a strong trade-off with hydraulic safety and minimum leaf water potential, whereas there was also a coordination between leaf hydraulic safety and the leaf minimal water potential. Moreover, shrubs with higher leaf hydraulic capacitance had greater hydraulic safety margins, indicating coordination between leaf hydraulic capacitance and hydraulic safety margin. Overall, this study indicated that minimal daily leaf water potential, as an easily measured parameter, may be used preliminarily to predict leaf hydraulic conductivity and the resistance to embolism of desert shrubs, providing critical insights into hydraulic trade-off and coordination strategies for native shrubs as priority species in desert vegetation restoration and reconstruction.

Elevated sdLDL level and LDLR rs688 C>T mutation are independent risk factors for ischemic stroke

Purpose: To investigate the level of sdLDL and the frequency of LDLR rs688 polymorphisms, as well as the correspondence between them, and to analyze the risk factors for stroke.MethodsBetween March 2019 and November 2019, 232 patients diagnosed with stroke and 96 health volunteers were enrolled in Quanzhou First Hospital. Subjects were divided into control group, ischemic stroke group (n=120) and hemorrhagic stroke group (n=112). The level of sdLDL and the genotypes and allele frequencies of LDLR rs688 were compared between groups, the correspondence was analyzed with Spearman method. Risk factors were analyzed with Binary logistic regression.ResultsThe level of sdLDL was highest in ischemic group, followed by hemorrhagic stroke group and lowest control group. The differences of genotypes and allele frequencies of LDLR rs688 were significant in ischemic stroke group (p=0.0000 and 0.0000 respectively), while were not significant in hemorrhagic group (p=0.184 and .0137). There was no obvious correlation between the level of sdLDL and LDLR rs688 genotype by Spearman analysis (p=0.116).ConclusionElevated sdLDL level and the C>T mutation of LDLR rs688 are independent risk factors for ischemic stroke, while they are not correlative to hemorrhagic stroke. The surveillance and regulatory of sdLDL level, the detection of LDLR rs688 gene polymorphisms may contribute to the prevention of ischemic stroke. (AU)

Objetivo: Investigar el nivel de sdLDL y la frecuencia de los polimorfismos LDLR rs688, así como la correspondencia entre ellos, y analizar los factores de riesgo de accidente cerebrovascular isquémico.MétodosEntre marzo de 2019 y noviembre de 2019, 232 pacientes diagnosticados de accidente cerebrovascular y 96 voluntarios de salud se inscribieron en el Primer Hospital de Quanzhou. Los sujetos se dividieron en grupo de control, grupo de accidente cerebrovascular isquémico (n=120) y grupo de accidente cerebrovascular hemorrágico (n=112). El nivel de sdLDL y los genotipos y las frecuencias alélicas de LDLR rs688 se compararon entre grupos, y la correspondencia se analizó con el método de Spearman. Los factores de riesgo se analizaron con regresión logística-binaria.ResultadosEl nivel de sdLDL fue más alto en el grupo isquémico, seguido por el grupo de accidente cerebrovascular hemorrágico y el grupo de control más bajo. Las diferencias de genotipos y las frecuencias alélicas de LDLR rs688 fueron significativas en el grupo de ictus isquémico (p=0,0000 y p=0,0000, respectivamente), mientras que no lo fueron en el grupo de hemorragia (p=0,184 y p=0,0137). No hubo una correlación obvia entre el nivel de sdLDL y el genotipo rs688 de LDLR según el análisis de Spearman (p=0,116).ConclusiónEl nivel elevado de sdLDL y la mutación C>T de LDLR rs688 son factores de riesgo independientes para el accidente cerebrovascular isquémico, mientras que no son correlativos para el accidente cerebrovascular hemorrágico. La vigilancia y la regulación del nivel de sdLDL, así como la detección de polimorfismos del gen LDLR rs688, pueden contribuir a la prevención del accidente cerebrovascular isquémico. (AU)

Sysmex UN2000 detection of protein/creatinine ratio and of renal tubular epithelial cells can be used for screening lupus nephritis.

OBJECTIVES: This study is aimed to evaluate if automated urine sediment analysis UN2000 can be used to screen lupus nephritis. METHODS: UN2000 was used to examine 160 urine samples from patients with systemic lupus erythematosus and 124 urine samples from Lupus nephritis. The result of protein/creatinine ratio(P/C) and renal tubular epithelial cells (RTEC) were evaluated. With biochemical analysis and microscopic examination as the gold standard, the Kappa consistency test was used to analyze the accuracy of P/C and RTEC. Analysis was to evaluate the accuracy of P/C single item or RTEC single item and both screening lupusnephritis. RESULTS: The consistency of P/C and the gold standard, and that of RTEC and the gold standard are respectively strong and good (0.858 vs. 0.673). The specificity, positive predictive value, and coincidence were the highest when P/C ≥ 2 + was set as the only screening standard for lupus nephritis. When the standard was selected between P/C ≥ 2 + or RTEC > 2.8 cells/µl, the sensitivity and negative predictive value were the highest. CONCLUSION: UN 2000 can be used to screen lupus nephritis by detecting P/C and RTEC.

Cervical Spine Fracture Prediction by Simple Plain X-Ray in Ankylosing Spondylitis Patients after Low-Energy Trauma.

OBJECTIVE: Timely diagnosis is essential in the management of cervical spine fracture (CSF) in ankylosing spondylitis (AS) patients. However, the value of simple plain X-ray in the early management of ASCSF has not been well-studied. This study aimed to explore the prediction ability of simple plain X-ray for CSF in AS patients who suffer from low-energy trauma (LET). METHODS: From January 2010 to December 2020, AS patients who experienced LET were retrospectively reviewed. Clinical data including gender, age, body mass index, time interval between AS diagnosis and trauma, smoking or not, and a presence of continuous bony bridge between anterior margin of C1 and C2 body or not were collected. Morphological features including atlanto-occipital gap, Pavlov ratio of C2-7, Angle A-D, Borden's index, and Harrison's value were measured by the lateral cervical X-ray. All data was compared between patients who had CSF and those who did not. Binary logistic regression analysis and receiver operator characteristic (ROC) curves were applied to discriminate and assess the predictive parameters. RESULTS: A total of 129 AS patients were divided into Fracture group (41 cases) and Non-fracture group (88 cases) based on whether CSF existed. Twelve parameters showed significant differences between two groups (p < 0.05). According to the binary logistic regression model, four of the 12 parameters showed a further correlation with the occurrence of CSF, namely, mean Pavlov ratio (p < 0.001, OR = 0.067, 95% CI: 0.023 to 0.194), Angle D (p = 0.031, OR = 1.057, 95% CI: 1.005 to 1.112), Borden's index (p = 0.042, OR = 1.131, 95% CI: 0.994 to 1.287), the time interval between the AS diagnosis and the trauma (p < 0.020, OR = 0.935, 95% CI: 0.883 to 0.990). The ROC curve further revealed the mean Pavlov ratio had the largest AUC (0.793) with the cut-off of 0.72. While the optimal cut-off value was 45.65° for Angle D (sensitivity = 61.0%, specificity = 78.4%), 9.79 for Borden's index (sensitivity = 87.8%, specificity = 37.5%), 15.50 years for the time interval between AS diagnosis and trauma (sensitivity = 70.7%, specificity = 56.8%). CONCLUSIONS: The time interval between the AS diagnosis and the trauma, mean Pavlov ratio, Angle D, and Borden's index showed predictive ability for the occurrence of CSF in AS patients who encounter LET. Surgeons should consider measuring these parameters in the management of AS patient.

Construction of machine learning tools to predict threatened miscarriage in the first trimester based on AEA, progesterone and ß-hCG in China: a multicentre, observational, case-control study.

BACKGROUND: Endocannabinoid anandamide (AEA), progesterone (P4) and ß-human chorionic gonadotrophin (ß-hCG) are associated with the threatened miscarriage in the early stage. However, no study has investigated whether combing these three hormones could predict threatened miscarriage. Thus, we aim to establish machine learning models utilizing these three hormones to predict threatened miscarriage risk. METHODS: This is a multicentre, observational, case-control study involving 215 pregnant women. We recruited 119 normal pregnant women and 96 threatened miscarriage pregnant women including 58 women with ongoing pregnancy and 38 women with inevitable miscarriage. P4 and ß-hCG levels were detected by chemiluminescence immunoassay assay. The level of AEA was tested by ultra-high-performance liquid chromatography-tandem mass spectrometry. Six predictive machine learning models were established and evaluated by the confusion matrix, area under the receiver operating characteristic (ROC) curve (AUC), accuracy and precision. RESULTS: The median concentration of AEA was significantly lower in the healthy pregnant women group than that in the threatened miscarriage group, while the median concentration of P4 was significantly higher in the normal pregnancy group than that in the threatened miscarriage group. Only the median level of P4 was significantly lower in the inevitable miscarriage group than that in the ongoing pregnancy group. Moreover, AEA is strongly positively correlated with threatened miscarriage, while P4 is negatively correlated with both threatened miscarriage and inevitable miscarriage. Interestingly, AEA and P4 are negatively correlated with each other. Among six models, logistic regression (LR), support vector machine (SVM) and multilayer perceptron (MLP) models obtained the AUC values of 0.75, 0.70 and 0.70, respectively; and their accuracy and precision were all above 0.60. Among these three models, the LR model showed the highest accuracy (0.65) and precision (0.70) to predict threatened miscarriage. CONCLUSIONS: The LR model showed the highest overall predictive power, thus machine learning combined with the level of AEA, P4 and ß-hCG might be a new approach to predict the threatened miscarriage risk in the near feature.

Ion-selective electrode-based potentiometric immunoassays for the quantitative monitoring of alpha-fetoprotein by coupling rolling cycle amplification with silver nanoclusters.

Potentiometric immunoassays have been utilized for the quantitative detection of alpha-fetoprotein (AFP) in hepatocellular carcinoma, but most of them involve low sensitivity and enzyme labels, and thus are unfavorable for routine use. In this work, we report the proof-of-concept of a sensitive and powerful ion-selective potentiometric sensing method for AFP detection with an in situ amplified signal readout. This potentiometric immunoassay mainly contains a silver nanocluster-functionalized single-stranded DNA (AgNC-DNA), a short DNA primer and two antibodies. A sandwich-type immunoreaction is employed for AFP determination on an anti-AFP capture antibody-coated microplate using a biotinylated human AFP secondary antibody. Coupling with a typical biotin-avidin system, the biotinylated DNA initiator strands are conjugated on the microplate in the presence of AFP to induce the rolling cycle amplification (RCA) reaction, followed by AgNC-DNA hybridization. Upon addition of HNO3, the hybridized AgNCs are dissolved into numerous Ag(I) ions, which can be readily determined on a portable handheld silver-ion selective electrode (Ag-ISE). Under optimal conditions, the electrode potential increases with an increase in AFP concentration and exhibits a good linear range of 0.01-100 ng mL-1 at a detection limit of 7.9 pg mL-1. Moreover, the Ag-ISE-based potentiometric immune assay also shows good reproducibility, high specificity and long-term storage stability. Importantly, 18 human serum specimens containing the AFP analyte are screened using the potentiometric immunoassay, giving well-matched experimental results relative to the referenced enzyme-linked immunosorbent assay (ELISA) method.