Prevalence and impact of frailty in patients undergoing colorectal cancer surgery: A systematic review and meta-analysis based on modified frailty index.

Frailty has been linked to unfavorable postoperative outcomes in patients with colorectal cancer (CRC). However, the prevalence of frailty among CRC surgery patients and its association with mortality and postoperative complications, as evaluated by the modified frailty index (mFI), have not been thoroughly investigated and necessitate clarification. PubMed, Web of Science, Embase, and CBM databases were systematically searched for relevant studies (up to January 2024), and the pooled prevalence and odds ratio (OR) estimate were calculated. A total of 16 studies containing 245 747 patients undergoing CRC surgery were included. The prevalence of frailty among CRC surgery patients was 31% (95% confidence interval [CI] = 20%-42%; I2 = 100%, p < 0.001). In patients undergoing CRC surgery, frailty was associated with a higher incidence of postoperative complications (OR = 1.94; 95% CI = 1.47-2.56; I2 = 91.9%, p < 0.001), but it did not exhibit any significant correlation with the 30-day mortality (OR = 5.17; 95% CI = 0.39-68.64; I2 = 94.4%, p < 0.001). Frailty is common in CRC surgery and exerts a significant negative impact on the postoperative outcomes. Future research could explore the potential of the mFI to facilitate a more streamlined and precise quantification of frailty, thereby establishing a refined understanding of its correlation with surgery prognosis.

A prospective, randomized clinical trial of emergency treatment of chemotherapy-induced neutropenia and febrile neutropenia by pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF).

AIMS: As one of the mainstays of breast cancer therapy, chemotherapy inevitably induces neutropenia. In this study, we explored the role of PEG-rhG-CSF (pegylated recombinant human granulocyte colony-stimulating factor) in the emergency treatment of chemotherapy-induced grades 3-4 neutropenia. METHODS: A total of 100 patients with breast cancer were randomized (1:1) into the study. Fifty patients randomized to the experimental group were treated with PEG-rhG-CSF after grades 3-4 neutropenia following the first cycle of chemotherapy, while 50 patients randomized to the control group received a daily injection of rhG-CSF (recombinant human granulocyte colony-stimulating factor). The primary endpoint was the recovery time of grades 3-4 neutropenia. RESULTS: Compared with patients in the control group, the mean ± SD recovery time of grades 3-4 neutropenia and febrile neutropenia (FN) was significantly shorter for patients in the experimental group (grades 3-4, P = .000; grade 4, P = .000; FN, P = .038). There is no significant difference in the incidence of FN for the two groups. In the experimental group, the duration of grades 3-4 neutropenia in patients aged <60 years and ≥60 years was 2.15 and 3.20 days, respectively (P = .037). Adverse events (AEs) of any grade were reported in 37 (75.5%) and 28 (59.6%) patients from the two groups, respectively. No grade ≥3 AEs were reported. CONCLUSION: This study supported that the PEG-rhG-CSF was more effective and convenient than rhG-CSF for treating grades 3-4 neutropenia and FN in patients with breast cancer and had manageable toxicity.

Comparison of clinical effects between microscopic surgery and conventional surgery in children with penile hypospadias and difference analysis of postoperative urodynamics.

Objective: To compare and analyze the clinical effects of microscopic surgery and conventional surgery in children with penile hypospadias and the differences in postoperative urodynamic indexes. Methods: It was a clinical comparative study. A total of 80 children with penile hypospadias admitted to Beijing Children's Hospital Affiliated to Capital Medical University Baoding Hospital from July 2018 to September 2022 were selected and randomly divided into two group. The experimental group were treated with microscopic urethroplasty, while the control group were treated with traditional urethroplasty. The operative effect, operation time, total intraoperative blood loss, postoperative hospital stay and incidence of surgical complications were compared and analyzed between the two groups. All the children were followed up for two years, and the changes in urodynamic parameters including maximum urine flow rate (Qmax), average urine flow rate (Qavc), urine flow time (FT), peak time (TQmax) and residual urine (PVR) were compared before, two weeks after, six months after and two years after surgery. Results: The efficacy of the experimental group was significantly higher than that of the control group (p=0.013). The intraoperative blood loss and postoperative hospital stay in the experimental group were significantly better than those in the control group (p=0.000). The incidences of urinary leakage and urethral stricture in the experimental group were lower than those in the control group (p<0.05). The Qmax level in the experimental group was higher than that in the control group at six months and two years after surgery, while the FT level was lower than that of the control group (p<0.05). Conclusion: Microscopic surgery is a method with significant clinical value in the treatment of penile hypospadias.

RETINOBLASTOMA-RELATED Genes Specifically Control Inner Floral Organ Morphogenesis and Pollen Development in Rice.

RETINOBLASTOMA-RELATED (RBR) is an essential gene in plants, but its molecular function outside of its role in cell cycle entry remains poorly understood. We characterized the functions of OsRBR1 and OsRBR2 in plant growth and development in rice using both forward- and reverse-genetics methods. The two genes were coexpressed and performed redundant roles in vegetative organs but exhibited separate functions in flowers. OsRBR1 was highly expressed in the floral meristem and regulated the expression of floral homeotic genes to ensure floral organ formation. Mutation of OsRBR1 caused loss of floral meristem identity, resulting in the replacement of lodicules, stamens, and the pistil with either a panicle-like structure or whorls of lemma-like organs. OsRBR2 was preferentially expressed in stamens and promoted pollen formation. Mutation of OsRBR2 led to deformed anthers without pollen. Similar to the protein interaction between AtRBR and AtMSI1 that is essential for floral development in Arabidopsis, OsMSI1 was identified as an interaction partner of OsRBR1 and OsRBR2. OsMSI1 was ubiquitously expressed and appears to be essential for development in rice (Oryza sativa), as the mutation of OsMSI1 was lethal. These results suggest that OsRBR1 and OsRBR2 function with OsMSI1 in reproductive development in rice. This work characterizes further functions of RBRs and improves current understanding of specific regulatory pathways of floral specification and pollen formation in rice.

Pulmonary hypertension in late-onset Methylmalonic Aciduria and Homocystinemia: a case report.

BACKGROUND: Methylmalonic Aciduria and Homocystinemia, cobalamin C (cblC) is an inherited disease of vitamin B12 metabolism with a wide spectrum of clinical manifestations. cblC presenting with pulmonary hypertension (PH) as leading sympotom is rare and easily misdiagnosed because of limited awareness. Timely diagnosis is crucial by the relentless progression without appropriate treatment. CASE PRESENTATION: We reported a 12-year-old girl with a 3-year history of progressively reduced activity tolerance and a 3-month history of orthopnea. Metabolic testing revealed increased levels of plasma homocysteine and urine methylmalonic acid. cblC deficiency was subsequently confirmed by genetic testing. The patient was treated with hydroxocobalamin, betaine, folinic acid and levocarnitine for cblC disease. Sildenafil, bosentan, spironolactone and hydrochlorothiazide was administrated for PH and right heart failure. At 3-month follow-up, she had an apparent resolution of dyspnea and cyanosis. Metabolic abnormalities resolved the decrease of plasma homocysteine and urine methylmalonic acid. A right heart catheterization showed a reduced pulmonary pressure. CONCLUSIONS: This case emphasizes the importance of an early diagnosis and initiation of treatment for cblC deficiency. Unexplained PH in children and young adults should prompt metabolic screening for the differential diagnosis.

Efficient production of antifungal proteins in plants using a new transient expression vector derived from tobacco mosaic virus.

Fungi that infect plants, animals or humans pose a serious threat to human health and food security. Antifungal proteins (AFPs) secreted by filamentous fungi are promising biomolecules that could be used to develop new antifungal therapies in medicine and agriculture. They are small highly stable proteins with specific potent activity against fungal pathogens. However, their exploitation requires efficient, sustainable and safe production systems. Here, we report the development of an easy-to-use, open access viral vector based on Tobacco mosaic virus (TMV). This new system allows the fast and efficient assembly of the open reading frames of interest in small intermediate entry plasmids using the Gibson reaction. The manipulated TMV fragments are then transferred to the infectious clone by a second Gibson assembly reaction. Recombinant proteins are produced by agroinoculating plant leaves with the resulting infectious clones. Using this simple viral vector, we have efficiently produced two different AFPs in Nicotiana benthamiana leaves, namely the Aspergillus giganteus AFP and the Penicillium digitatum AfpB. We obtained high protein yields by targeting these bioactive small proteins to the apoplastic space of plant cells. However, when AFPs were targeted to intracellular compartments, we observed toxic effects in the host plants and undetectable levels of protein. We also demonstrate that this production system renders AFPs fully active against target pathogens, and that crude plant extracellular fluids containing the AfpB can protect tomato plants from Botrytis cinerea infection, thus supporting the idea that plants are suitable biofactories to bring these antifungal proteins to the market.

Clinical and molecular spectrum of CHOPS syndrome.

CHOPS syndrome is a multisystem disorder caused by missense mutations in AFF4. Previously, we reported three individuals whose primary phenotype included cognitive impairment and coarse facies, heart defects, obesity, pulmonary involvement, and short stature. This syndrome overlaps phenotypically with Cornelia de Lange syndrome, but presents distinct differences including facial features, pulmonary involvement, and obesity. Here, we provide clinical descriptions of an additional eight individuals with CHOPS syndrome, as well as neurocognitive analysis of three individuals. All 11 individuals presented with features reminiscent of Cornelia de Lange syndrome such as synophrys, upturned nasal tip, arched eyebrows, and long eyelashes. All 11 individuals had short stature and obesity. Congenital heart disease and pulmonary involvement were common, and those were seen in about 70% of individuals with CHOPS syndrome. Skeletal abnormalities are also common, and those include abnormal shape of vertebral bodies, hypoplastic long bones, and low bone mineral density. Our observation indicates that obesity, pulmonary involvement, skeletal findings are the most notable features distinguishing CHOPS syndrome from Cornelia de Lange syndrome. In fact, two out of eight of our newly identified patients were found to have AFF4 mutations by targeted AFF4 mutational analysis rather than exome sequencing. These phenotypic findings establish CHOPS syndrome as a distinct, clinically recognizable disorder. Additionally, we report three novel missense mutations causative for CHOPS syndrome that lie within the highly conserved, 14 amino acid sequence of the ALF homology domain of the AFF4 gene, emphasizing the critical functional role of this region in human development.

NOTCH4 is a possible novel susceptibility gene for dilated cardiomyopathy in the Chinese population: A case-control study.

BACKGROUND: The incidence of dilated cardiomyopathy (DCM) has increased in recent years, and many studies have sought to further improve the general understanding of this condition. Previous studies have demonstrated that some single nucleotide polymorphisms (SNPs) associated with systemic lupus erythematosus also affect susceptibility to DCM, suggesting that immune-related diseases may share similar genetic susceptibility. Recent large-scale and genome-wide association studies have identified NCR3, NOTCH4, CYP1A2, ITGA1, OPRM1, ST8SIA2, and LINC00704 as genetic risk factors associated with cardiac manifestations of neonatal lupus. Here, we aimed to determine whether these SNPs conferred susceptibility to DCM in the Chinese Han population. METHODS: We investigated the relationship between these polymorphisms and DCM risk in 273 patients with DCM and 548 healthy controls. Genotyping was performed using MassArray iPLEX system. RESULTS: Logistic regression analysis indicated that the T allele of rs3134942 in NOTCH4 gene increased the risk of DCM by 61% compared with the G allele (Pa  = 6.57 × 10-3 ). The SNP rs3134942 was also significantly associated with increased DCM risk in the additive (Pa  = 6.57 × 10-3 ) and dominant models (Pa  = 1.01 × 10-2 ). Additionally, rs2472299 in CYP1A2 gene showed suggestive association with reduced risk of DCM in the dominant model (Pa  = 4.24 × 10-2 ) and was correlated with smoking status in patients with DCM (Pa  = 1.56 × 10-2 ). CONCLUSIONS: Our findings suggested that rs3134942 in NOTCH4 may be involved in DCM risk. Further, studies in larger and ethnically diverse populations are required to confirm the results reported in this study.

A Resonant Pressure Microsensor Based on Double-Ended Tuning Fork and Electrostatic Excitation/Piezoresistive Detection.

This paper presents a resonant pressure microsensor relying on electrostatic excitation and piezoresistive detection where two double-ended tuning forks were used as resonators, enabling differential outputs. Pressure under measurement caused the deformation of the pressure sensitive membrane, leading to stress buildup of the resonator under electrostatic excitation with a corresponding shift of the resonant frequency detected piezoresistively. The proposed microsensor was fabricated by simplified SOI-MEMS technologies and characterized by both open-loop and closed-loop circuits, producing a quality factor higher than 10,000, a sensitivity of 79.44 Hz/kPa and an accuracy rate of over 0.01% F.S. In comparison to the previously reported resonant piezoresistive sensors, the proposed device used single-crystal silicon as piezoresistors, which was featured with low DC biased voltages, simple sensing structures and fabrication steps. In addition, the two double-ended tuning forks were used as resonators, producing high quality factors and differential outputs, which further improved the sensor performances.

Delineation of contaminant plume for an inorganic contaminated site using electrical resistivity tomography: comparison with direct-push technique.

Precise delineation of contaminant plume distribution is essential for effective remediation of contaminated sites. Traditional in situ investigation methods like direct-push (DP) sampling are accurate, but are usually intrusive and costly. Electrical resistivity tomography (ERT) method, as a non-invasive geophysical technique to map spatiotemporal changes in resistivity of the subsurface, is becoming increasingly popular in environmental science. However, the resolution of ERT for delineation of contaminant plumes still remains controversial. In this study, ERT and DP technique were both conducted at a real inorganic contaminated site. The reliability of the ERT method was validated by the direct comparisons of their investigation results that the resistivity acquired by ERT method is in accordance with the total dissolved solid concentration in groundwater and the overall variation of the total iron content in soil obtained by DP technique. After testifying the applicability of ERT method for contaminant identification, the extension of contaminant plume at the study site was revealed by supplementary ERT surveys conducted subsequently in the surrounding area of the contaminant source zone.

Association of XRCC1 Arg399Gln and Arg194Trp polymorphisms with susceptibility to multiple autoimmune diseases: a meta-analysis.

The role of the X-ray repair cross-complementing gene 1(XRCC1) Arg399Gln and Arg194Trp polymorphisms has been involved in the investigations of susceptibility to multiple autoimmune diseases, but the results were inconsistent. Here, we have performed a meta-analysis to clarify the relationship between them. All appropriate case-control studies were searched in the PubMed, EMBASE and Chinese National Knowledge Infrastructure (CNKI) database. A meta-analysis was conducted on the association between the XRCC1 two polymorphisms (Arg399Gln, Arg194Trp) and risk of autoimmune diseases. Pooled odds ratios (OR) with 95% confidence intervals (CI) were conducted to assess the association. Fourteen relevant studies with a total of 2886 cases and 3257 controls were analyzed in our research. Analysis for the XRCC1 Arg399Gln polymorphism under recessive model (OR 1.53, 95% CI 1.07-2.18, P = 0.019), dominant model (OR 1.36, 95% CI 1.04-1.77, P = 0.026) and homozygous model (OR 1.67, 95% CI 1.07-2.62, P = 0.024) indicated an association in the overall population, as well as in Caucasian populations under the recessive model (OR 1.73, 95% CI 1.03-2.91, P = 0.039) and Asian populations under dominant model (OR 1.31, 95% CI 1.02-1.70, P = 0.037). Stratification by disease indicated significant association between XRCC1 Arg399Gln and rheumatoid arthritis (RA) in all genetic models (P < 0.05). However, there was no significant association between XRCC1 Arg194Trp polymorphism and autoimmune diseases in different genetic models. The current meta-analysis demonstrates that the XRCC1 Arg399Gln polymorphism confers susceptibility to autoimmune diseases in Asians and Caucasians and, in particular, shows that XRCC1 Arg399Gln polymorphism is associated with RA.

Retention and Release of Graphene Oxide in Structured Heterogeneous Porous Media under Saturated and Unsaturated Conditions.

In this work, saturated and unsaturated structured heterogeneous sand columns were used to examine the fate of graphene oxide (GO) nanoparticles in heterogeneous porous media under various conditions. A two-domain model considering mass exchange between zones was applied to describe GO retention and transport in structured, heterogeneous porous media, which matched the transport experimental breakthroughs well. Experimental and model results showed that GO retention and transport in all the heterogeneous columns were dominated by the preferential flow phenomena. Under saturated conditions, the coarse sand with higher hydraulic conductivity was the fast-flow domain (FFD), and the fine sand was the slow-flow domain (SFD), and both FFD and SFD affected GO particles fate in structured heterogeneous media. When the heterogeneous columns were drained, the fine sand with higher moisture content became the FFD, and the coarse sand was the SFD, however, preferential flows in the FFD dominated GO retention and transport processes. For all the columns, the mobility of GO decreased with the increasing ionic strength (IS), and the previous retained particles were released by reducing solution IS, indicating part of the retained particles were trapped in the secondary minimum energy well.

[Diagnostic Value of Cystain C in Contrast Associated Acute Kidney Injury after Transcatheter Closure for Children with Congenital Heart Disease].

OBJECTIVES: To investigate the diagnostic value of cystain C (SCys-C) in contrast associated acute kidney injury (AKI) after transcatheter closure for children with congenital heart disease. METHODS: There were 128 children with congenital heart disease (interventricular septal defect or patent ductus arteriosus) underwent transcatheter closure in West China Second University Hospital during 2013. Blood urea nitrogen (BUN), serum creatinine (SCr) and SCys-C were examined before surgery and at 24 and 48 h after surgery. The incidence of AKI was calculated. The children were divided into two groups according to glomerular filtration rate: AKI group (renal function stage 1, renal function stage 2 subgroups) and non-AKI group. Differences in renal function indexes and SCys-C were compared between AKI group ( n=16) and non-AKI group ( n=112), renal function stage 1 and stage 2 subgroups. ROC curve analysis was used to calculate the cut-off value of SCys-C in the diagnosis of AKI . RESULTS: The levels of SCr and SCys-C in AKI group were significantly higher than those in non-AKI group ( P<0.05). However, there was no significant difference in BUN between the two groups ( P>0.05). Only SCys-C had a significant difference between renal function stage 1 and stage 2 subgroups ( P<0.05). The cut-off value of 24 h SCys-C in the diagnosis of AKI was 1.055 mg/L according to area under curve (AUC). AUC indicated that AKI could be diagnosed earlier with SCys-C than SCr ( P<0.05). CONCLUSIONS: The contrast agent could increase the risk of child AKI after transcatheter closure for congenital disease children.SCys-C is an important index for this risk with its cut-off value of 1.055 mg/L at 24 h post-surgery.

Do specialized flowers promote reproductive isolation? Realized pollination accuracy of three sympatric Pedicularis species.

BACKGROUND AND AIMS: Interest in pollinator-mediated evolutionary divergence of flower phenotype and speciation in plants has been at the core of plant evolutionary studies since Darwin. Specialized pollination is predicted to lead to reproductive isolation and promote speciation among sympatric species by promoting partitioning of (1) the species of pollinators used, (2) when pollinators are used, or (3) the sites of pollen placement. Here this last mechanism is investigated by observing the pollination accuracy of sympatric Pedicularis species (Orobanchacae). METHODS: Pollinator behaviour was observed on three species of Pedicularis (P. densispica, P. tricolor and P. dichotoma) in the Hengduan Mountains, south-west China. Using fluorescent powder and dyed pollen, the accuracy was assessed of stigma contact with, and pollen deposition on, pollinating bumble-bees, respectively. KEY RESULTS: All three species of Pedicularis were pollinated by bumble-bees. It was found that the adaptive accuracy of female function was much higher than that of male function in all three flower species. Although peak pollen deposition corresponded to the optimal location on the pollinator (i.e. the site of stigma contact) for each species, substantial amounts of pollen were scattered over much of the bees' bodies. CONCLUSIONS: The Pedicularis species studied in the eastern Himalayan region did not conform with Grant's 'Pedicularis Model' of mechanical reproductive isolation. The specialized flowers of this diverse group of plants seem unlikely to have increased the potential for reproductive isolation or influenced rates of speciation. It is suggested instead that the extreme species richness of the Pedicularis clade was generated in other ways and that specialized flowers and substantial pollination accuracy evolved as a response to selection generated by the diversity of co-occurring congeners.

Risk factors and prognosis of atrioventricular block after atrial septum defect closure using the Amplatzer device.

Amplatzer septal occluder (ASO)-induced complications have been observed. However, little attention is paid to the atrioventricular block (AVB) induced by atrial septum defect (ASD) closure using the Amplatzer device. This study aimed to analyze the risk factors and prognosis of AVB after catheter closure and to reduce the incidence of adverse events. In this study, 706 ASD patients who received closure in our division were investigated retrospectively for the relationship between AVB and factors such as age, size of the ASD (D(d)), diameter of the occluder (D(o)), diameter of the septum (D(s)), D(o)/D(d) ratio, and D(o)/D(s) ratio. Data distribution was evaluated with the Kolmogorov-Smirnov normality test. The Wilcoxon rank sum test was used to compare non-normal distribution data. A p value lower than 0.05 was considered significant. Of the 706 patients, six had experienced the development of AVB, giving an incidence of 0.85%. The risk factors included younger age, larger size of the ASD, larger size of the device, and the D(o)/D(s) ratio (≥0.45). The milder AVB is, the better the prognosis. An AVB of III° and an unchanged electrocardiogram (ECG) within 3 days after the procedure are poor prognostic indicators. More attention should be paid to AVB induced by ASD closure. Younger age, size of the ASD, size of the device, and a D(o)/D(s) ratio of 0.45 or higher are the risk factors associated with AVB after closure. A timely retrieval of the device should be considered for a good prognosis.

[Detection of Bruton's tyrosine kinase gene mutations and clinical analysis of 6 patients with X-linked agammaglobulinemia].

OBJECTIVE: To explored the relationship between genotype of Bruton's tyrosine kinase (BTK) gene and X-linked agammaglobulinemia (XLA). METHODS: Six patients who were clinically suspected as XLA based on immunological results were studied. Peripheral blood samples were collected for DNA extraction. The 19 exons and exon-intron boundaries of the BTK gene were amplified by PCR, and the products were directly sequenced. RESULTS: All of the 6 patients were confirmed to have XLA due to the mutations in exons of the BTK gene. Among these, 3 mutations were located in the kinase domain (TK), 2 were located in pleckstrin homology (PH) domain, and 1 was located in Src homology (SH2) domain. The mutations have included 3 missense mutations, i.e., c.1105C to T (p.L369F), c.82C to T(p.R28C) and c.1754T to C (p.V585A), 2 nonsense mutations, i.e., c.1834C to T (p.Q612X) and c.37C to T (p.R13X). One patient was found to have complex (missense and nonsense) mutations, i.e., c.1802-1803TT to GC (p.F601C) and c.1803-1804insC (p.T602fsX603). There were 3 novel mutations (p.F601C, p.T602fsX603 and p.V585A). The mothers of 5 patients were also detected with BTK gene mutations, among whom 4 were demonstrated to be carriers and one was normal (her son had p.V585A mutation). Therefore, p.V585A was a de novo mutation. CONCLUSION: Detection of BTK gene mutation can confirm clinical diagnosis which is critical for patients to take regular immunoglobulin replacement therapy for life. Early genetic diagnosis can also identify carriers and make genetic counseling possible.

Optical Genome Mapping Identifies a Novel Unbalanced Translocation Between Chromosomes 4q and 6q Leading to Feeding Difficulties and Hypotonia in a Neonate: A Case Report.

Optical Genome Mapping (OGM) technology has garnered growing interest for the identification of chromosomal structural variations (SVs), particularly complex ones that are implicated in genetic diseases in humans. In this study, we performed genetic diagnostics on a neonatal patient who presented with feeding difficulties, hypotonia, and an atrial septal defect. We utilized a combination of trio-whole exome sequencing and OGM for our analysis. The results revealed an unbalanced translocation between maternal chromosomes 4 and 6 in the proband, ogm[GRch38]t(4:6)(q35.2;q25.3), resulting in a 2.8 Mb deletion at the 4q35 terminal and a 10.2 Mb duplication at the 6q25 terminal. In summary, this study highlights how OGM, in conjunction with other genetic approaches, can unveil the genetic etiology of complex clinical syndromes. Neonatal patients often exhibit low specific phenotypes, underlining the significance of SV detection.

Real-time monitoring of in situ chemical oxidation (ISCO) of dissolved TCE by integrating electrical resistivity tomography and reactive transport modeling.

Successful in situ chemical oxidation (ISCO) applications require real-time monitoring to assess the oxidant delivery and treatment effectiveness, and to support rapid and cost-effective decision making. Existing monitoring methods often suffer from poor spatial coverage given a limited number of boreholes in most field conditions. The ionic nature of oxidants (e.g., permanganate) makes time-lapse electrical resistivity tomography (ERT) a potential monitoring tool for ISCO. However, time-lapse ERT is usually limited to qualitative analysis because it cannot distinguish between the electrical responses of the ionic oxidant and the ionic products from contaminant oxidation. This study proposed a real-time quantitative monitoring approach for ISCO by integrating time-lapse ERT and physics-based reactive transport models (RTM). Moving past common practice, where an electrical-conductivity anomaly in an ERT survey would be roughly linked to concentrations of anything ionic, we used PHT3D as our RTM to distinguish the contributions from the ionic oxidant and the ionic products and to quantify the spatio-temporal evolution of all chemical components. The proposed approach was evaluated through laboratory column experiments for trichloroethene (TCE) remediation. This ISCO experiment was monitored by both time-lapse ERT and downstream sampling. We found that changes in inverted bulk electrical conductivity, unsurprisingly, did not correlate well with the observed permanganate concentrations due to the ionic products. By integrating time-lapse ERT and RTM, the distribution of all chemical components was satisfactorily characterized and quantified. Measured concentration data from limited locations and the non-intrusive ERT data were found to be complementary for ISCO monitoring. The inverted bulk conductivity data were effective in capturing the spatial distribution of ionic species, while the concentration data provided information regarding dissolved TCE. Through incorporating multi-source data, the error of quantifying ISCO efficiency was kept at most 5 %, compared to errors that can reach up to 68 % when relying solely on concentration data.

NGF Signaling Exacerbates KOA Peripheral Hyperalgesia via the Increased TRPV1-Labeled Synovial Sensory Innervation in KOA Rats.

Objectives: Knee osteoarthritis (KOA) pain is caused by nociceptors, which are actually sensory nerve fiber endings that can detect stimuli to produce and transmit pain signals, and high levels of NGF in synovial tissue led to peripheral hyperalgesia in KOA. The purpose of this study is to investigate how sensory nerve fibers respond to the NGF/TrKA signal pathway and mediate the peripheral hyperalgesia in KOA rats. Methods: Forty SD male rats were randomly divided into 4 groups: normal, KOA, KOA + NGF, and KOA + siRNA TrKA. KOA model rats were induced by anterior cruciate ligament transection (ACLT). Mechanical and cold withdrawal thresholds (MWT and CWT) were measured 4 times in each group. The synovial tissues were harvested on day 28, and the expressions of NGF, TrKA, TRPV1, IL-1ß, and PGP9.5 were determined using western blot, qPCR, and immunofluorescence staining. The primary rat fibroblast-like synoviocytes (FLSs) and DRG cells were divided into 4 groups as in vivo. The expressions of NGF, TrKA, TRPV1, and CGRP in vitro were determined using western blot and qPCR. Results: KOA and intra-articular injection with NGF protein increased both mRNA and protein levels, not only TRPV1, PGP 9.5, and IL-1ß in the synovial tissue, but also TRPV1, PGP 9.5, and S100 in the DRG tissue, while above changes were partly reversed after siRNA TrKA intervention. Besides, siRNA TrKA could improve peripheral hyperalgesia and decreased the TRPV1 positive nerve fiber innervation in synovial tissue. The results in vitro were consistent with those in vivo. Conclusion: This study showed the activation of the NGF/TrKA signaling pathway in KOA promoted the release of pain mediators, increased the innervation of sensory nerve fibers in the synovium, and worsened peripheral hyperalgesia. It also showed increased TRPV1 positive sensory innervation in KOA was mediated by NGF/TrKA signaling and exacerbated peripheral hyperalgesia.