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.

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.

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.

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.

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.

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.

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.

A case of severe hookworm infection. / 临床极重症钩虫感染1例.

With the improvement of sanitation, the infection rate of hookworm is greatly reduced and the severe infected case is rarely reported. Combined morphological and molecular biological examinations, a severe hookworm infection patient was diagnosed in Department of Laboratorial Examination, Quanzhou First Affiliated Hospital of Fujian Medical University. The morphological methods such as direct fecal smear microscopy, saturated brine flotation and hookworm larvae culture methods were used to identify the eggs and larvae from stool samples of the patient. There were a large number of hookworm eggs in patient's stool samples, and the average count was 60 840 per gram by modified Kato method, which belonged to severe hookworm infection. Meanwhile, to distinguish the hookworm species, the semi-nested RT-PCR assay was employed to detect hookworm internal transcribed spacer series from eggs in patient's stool samples, and the result showed that the hookworm species was confirmed to be Necator americanus.

Clinical predictors for deep vein thrombosis on admission in patients with intertrochanteric fractures: a retrospective study.

BACKGROUND: Limited studies were available to investigate the prevalence of deep vein thrombosis (DVT) on admission in elderly patients with intertrochanteric fractures. The aim of present study was to evaluate risk factors and the prevalence of pre-admission DVT in elderly patients with intertrochanteric fractures. METHODS: This retrospective study included 788 elderly patients with intertrochanteric fracture who were eligible for this study from January 1, 2010, to December 31, 2019. Color doppler ultrasonography was performed for DVT detection at admission. All patients' clinical data were collected. Univariate analysis and stepwise backward multivariate logistic regression were used to identify the risk factors contributing to the occurrence of DVT. RESULTS: The overall prevalence of pre-admission DVT in patients with intertrochanteric fractures was 20.81% (164 of 788 patients). The mean time from injury to admission was 2.1 days in the total population, 2.96 and 1.87 days in patients with and without DVT. Univariate analysis showed that significantly elevated risk of DVT were found in patients with longer time from injury to admission, high energy injury, lower Hb value, higher BMI, diabetes, chronic obstructive pulmonary disease (COPD), atrial fibrillation, dementia, varicose veins, higher age-adjusted CCI, higher ASA class and A3 type intertrochanteric fractures (P < 0.05). The adjusted multivariate logistic regression analysis demonstrated that longer time from injury to admission, high energy trauma, COPD, lower Hb, diabetes and A3 type intertrochanteric fractures were independent risk factors of pre-admission DVT. CONCLUSIONS: A high prevalence of pre-admission DVT was found in elderly Chinese patients with intertrochanteric fractures. Therefore, surgeons should be aware of the high prevalence of DVT for elderly patients with intertrochanteric fractures in order to prevent intraoperative and postoperative PE and other lethal complications.

Characteristics of vertebral CT Hounsfield units in elderly patients with acute vertebral fragility fractures.

OBJECTIVE: To explore the characteristics of vertebral CT Hounsfield units (HU) in elderly patients with acute vertebral fragility fractures. METHODS: A total of 299 patients aged ≥ 65 years with acute vertebral fragility fractures were retrospectively reviewed, and 77 patients of them were age- and sex-matched with 77 control patients without any fractures. The vertebral HU value of L1(L1-HU) was measured, and T12 and L2 were used as alternatives for L1 in the case of L1 fracture. RESULTS: There were 460 thoracic and lumbar vertebral fractures in the 299 elderly patients, including 349 acute vertebral fragility fractures and 111 chronic fractures. The average L1-HU value was 66.0 ± 30.6 HU and showed significant difference among patients having different numbers of vertebral fractures (one fracture: 73.3 ± 27.0 HU, two fractures: 58.7 ± 32.5 HU, three or more fractures: 40.7 ± 28.8 HU; P < 0.001). As for the 1:1 age- and sex-matched patients, the L1-HU of the 77 patients with fractures was lower than that of the control patients (70.6 ± 23.4 HU vs. 101.5 ± 36.2 HU, P < 0.001). The area under the receiver operating characteristic curve of using L1-HU to differentiate patients with fractures from controls was 0.77(95% CI 0.70-0.85, P < 0.001). The cutoff value had high specificity of 90% or high sensitivity of 90% to identify patients with fractures of 60 HU and 100 HU, respectively. CONCLUSIONS: The elderly patients with acute vertebral fragility fractures have much lower HU values than those without fractures. Moreover, the lower the vertebral HU value is, the more likely the patients have more than one vertebral fracture. These slides can be retrieved under Electronic Supplementary Material.

An innovative strategy to treat large metaphyseal segmental femoral bone defect using customized design and 3D printed micro-porous prosthesis: a prospective clinical study.

Five patients with segmental irregular-shaped bone defect of the femur were recruited in this study from 2017.12 to 2018.11. All patients were treated by customized design and 3D printed micro-porous prosthesis. And the procedure was divided into stages: radical debridement and temporary fixation (the first stage); the membrane formation and virtual surgery (intervening period for 6-8 weeks); definite reconstruction the defects (the second stage). Routine clinical follow-up and radiographic evaluation were done to assess bone incorporation and complications of internal fixation. The weight-bearing time and the joint function of the patients were recorded. The patients were followed up for an average of 16.4 months. The average length of bone defect and the distal residual bone was 12 cm and 6.5 cm. The average time of partial weight-bearing and full weight-bearing was 12.7 days and 2.6 months. X-ray demonstrated good osseous integration of the implant/bone interface. No complications occurred such as implant loosening, subsidence, loss of correction and infection. At the last follow-up, Harris score of hip joint was excellent in 2 cases, good in 2 cases, fair in 1 case; HSS score of knee joint was good in 4 cases, middle in 1 case. From our study, we concluded that meticulous customized design 3D printed micro-porous prosthesis combined with intramedullary nail may be a promising and an alternative strategy to treat metaphyseal segmental irregular-shaped femoral bone defect, especially for cases with massive juxta-articular bone loss.

Hydrological response of biological soil crusts to global warming: A ten-year simulative study.

Biological soil crusts across the desert regions play a key role in regional ecological security and ecological health. They are vital biotic components of desert ecosystems that maintain soil stability, fix carbon and nitrogen, influence the establishment of vascular plants, and serve as habitats for a large number of arthropods and microorganisms, as well as influencing soil hydrological processes. Changes in temperature and precipitation are expected to influence the functioning of desert ecosystems by altering biotic components such as the species composition of biological soil crusts. However, it remains unclear how these important components will respond to the prolonged warming and reduced precipitation that is predicted to occur with climate change. To evaluate how the hydrological properties of these biological soil crusts respond to these alterations, we used open-top chambers over a 10-year period to simulate warming and reduced precipitation. Infiltration, dew entrapment, and evaporation were measured as surrogates of the hydrological functioning of biological soil crusts. It was found that the ongoing warming coupled with reduced precipitation will more strongly affect moss in crustal communities than lichens and cyanobacteria, which will lead to a direct alteration of the hydrological performance of biological soil crusts. Reductions in moss abundance, surface cover, and biomass resulted in a change in structure and function of crustal communities, decreased dew entrapment, and increased infiltration and evaporation of biological soil crusts in desert ecosystems, which further impacted on the desert soil water balance.

[Phenotypic and mutational analysis of a pedigree affected with hereditary coagulation factor â ¤ deficiency].

OBJECTIVE: To explore the molecular pathogenesis for a pedigree affected with coagulation factor Ⅴ (FⅤ) deficiency. METHODS: Prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), coagulation factor Ⅱ activity (FⅡ: C), FⅤ activity (FⅤ: C), coagulation factor Ⅶ activity (FⅦ: C), and coagulation factor Ⅹ activity (FⅩ: C) were determined with a STAGO automatic coagulometer. FⅤ antigen (FⅤ: Ag) was detected with enzyme linked immunosorbent assay (ELISA). All exons and their flanking regions, and 5' and 3' untranslated regions of the F5 gene were analyzed by direct sequencing. Suspected mutation was verified by reverse sequencing as well as testing of family members. ClustalX software was used to analyze the conservative property of the mutation sites. PROVEAN and MutationTaster online software was used to predict the effect of the mutation on the protein function. Swiss-pdbViewer was used to analyze the protein model and interaction of amino acids. RESULTS: The PT and APTT of the proband were slightly prolonged to 15.2 s and 41.8 s, respectively. And the FⅤ: C and FⅤ: Ag measured 55% and 62%, respectively. The FⅤ: C and FⅤ: Ag of his father and son were decreased to various extent (60%, 65% and 31%, 40%, respectively). A c.911G>A heterozygous mutation (Gly276Glu) was detected in exon 6 of the proband, for which her father and son were heterozygotes. The same mutation was not found in her mother, brother and husband. Conservation analysis showed that the Gly276 is highly conserved across various species. By bioinformatic analysis, the PROVEAN (scored -6.214) indicated Gly276Glu was harmful, and MutationTaster (scored 0.976) suggested that it is pathogenic. Model analysis suggested there are two hydrogen bonds between Gly276 and Ile298 in the wild type protein. When Gly276 was replaced by Glu276, the original hydrogen bond did not change, but the side chain of Glu was extended, which added steric hindrance with the surrounding amino acids, which resulted in decreased protein stability. CONCLUSION: The heterozygous c.911G>A (Gly276Glu) mutation of the F5 gene probably underlies the decreased level of FⅤin the proband.

Incidence of human rabies and characterization of rabies virus nucleoprotein gene in dogs in Fujian Province, Southeast China, 2002-2012.

BACKGROUND: Rabies is a global fatal infectious viral disease that is characterized by a high mortality after onset of clinical symptoms. Recently, there has been an increase in the incidence of rabies in China. The aim of this study was to investigate the incidence of human rabies and characterize the rabies virus nucleoprotein gene in dogs sampled from Fujian Province, Southeast China from 2002 to 2012. METHODS: Data pertaining to human rabies cases in Fujian Province during the period from 2002 through 2012 were collected, and the epidemiological profiles were described. The saliva and brain specimens were collected from dogs in Quanzhou, Longyan and Sanming cities of the province, and the rabies virus antigen was determined in the canine saliva specimens using an ELISA assay. Rabies virus RNA was extracted from canine brain specimens, and rabies virus nucleoprotein gene was amplified using a nested RT-PCR assay, followed by sequencing and genotyping. RESULTS: A total of 226 human rabies cases were reported in Fujian Province from 2002 to 2012, in which 197 cases were detected in three cities of Quanzhou, Longyan and Sanming. ELISA assay revealed positive rabies virus antigen in six of eight rabid dogs and 165 of 3492 seemingly healthy dogs. The full-length gene fragment of the rabies virus nucleoprotein gene was amplified from the brain specimens of seven rabid dogs and 12 seemingly healthy dogs. Sequence alignment and phylogenetic analysis revealed that these 19 rabies virus nucleoprotein genes all belonged to genotype I, and were classified into three genetic groups. Sequencing analysis showed a 99.7% to 100% intra-group and an 86.4% to 89.3% inter-group homology. CONCLUSIONS: This study is the first description pertaining to the epidemiological characteristics of human rabies cases and characterization of the rabies virus nucleoprotein gene in dogs in Fujian Province, Southeast China. Our findings may provide valuable knowledge for the development of strategies targeting the prevention and control of rabies.

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.

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.

Molecular epidemiology of hepatitis C virus among different groups of people in the province of Fujian, China.

Genotyping of hepatitis C virus (HCV) can provide valuable information for prognosis and treatment duration prediction. To explore the genetic diversity of HCV in Fujian Province, China, 112, 104 and 48 anti-HCV-positive serum samples were collected from volunteer blood donors, IDUs and patients, respectively, from Jan 2008 to Dec 2008 and were genotyped through sequence analysis, followed by phylogenetic analysis in the C/E1 and NS5B regions. Genotypes could be determined for 85.61 and 84.85 % of samples in the C/E1 and NS5B region, respectively. 6a was the most prevalent subtype, which accounted for 42.04 and 43.75 % in the C/E1 and NS5B region, respectively. Mixed infection and potential recombination were detected in this study. Kappa tests indicated that similar results were obtained by two genotyping methods targeting the C/E1 and NS5B regions. The differences in the main prevalent subtype between the three target groups suggest diversity of HCV prevalence in different populations.

[Comparison of curative effects between minimally invasive locking plate internal fixation and open reduction with internal fixation for the treatment of proximal humerus fractures].

OBJECTIVE: To investigate the comparison of curative effects in treating proximal humerus fractures' patients between minimally invasive locking plate internal fixation and open reduction with internal fixation, and to provide guidance for the operation method of the proximal humerus fracture patients. METHODS: In the study, 157 patients of proximal humerus fractures from May 2006 to December 2012 in Peking University Third Hospital were analyzed retrospectively, of whom 78 were followed up, including 19 males and 59 females. They were from 15 to 90 years old, with the mean age of 60.5 years. According to Neer classification, there were 53 cases of two-part fractures, 19 cases of three-part fractures and 6 cases of four-part fractures. According to AO classification, there were 49 cases of type A,21 cases of type B and 8 cases of type C. There were 24 cases treated with minimally invasive locking plate internal fixation operation and 54 cases treated with open reduction with internal fixation operation. The patients were followed up with postoperative physical examinations and X ray examinations. Postoperative shoulder pain after 1 week and more than 6 months was assessed using the VAS score. Postoperative shoulder joint function with the use of Constant-Murley score and ASES score were evaluated after 3 months and more than 6 months. The results were analyzed by SPSS 18.0. RESULTS: The follow-up time was 6 to 85 months, with the mean time of 33.8 months. According to the rank sum test: there were significant differences in operation time (P=0.002), postoperative hospital day (P=0.001), the satisfaction of patients (P=0.029), postoperative shoulder pain after 1 week (P=0.024), postoperative Constant-Murley score after 3 months (P=0.012) and postoperative ASES score after 3 months (P=0.001) between minimally invasive group and non-minimally invasive group. There weren't significant differences in clinical union time of bone (P=0.446), postoperative shoulder pain after more than 6 months (P=0.894), postoperative Constant-Murley score after more than 6 months (P=0.122) and postoperative ASES score after more than 6 months (P=0.351) between minimally invasive group and non-minimally invasive group. There were no breakage of the internal fixation and humeral head osteonecrosis. Minimally invasive group had 2 cases with internal fixation loosening (8.3%) and 1 case with complete limitation of abduction (4.2%). Non-minimally invasive group had 1 case with tracture nonunion (1.9%), 1 case with internal fixation loosening (1.9%) and 1 case with complete limitation of abduction (1.9%). CONCLUSION: The operation method of proximal humerus fractures is an important factor affecting the recovery of shoulder joint function. Minimally invasive locking plate internal fixation operation in early stage (1 week) of pain control, early (3 months) functional recovery, operation time, postoperative hospital day and patient satisfaction are better than those of traditional operation.