Serum lncRNA THRIL predicts benign and malignant pulmonary nodules and promotes the progression of pulmonary malignancies.

BACKGROUND: This project aimed to research the significance of THRIL in the diagnosis of benign and malignant solitary pulmonary nodules (SPNs) and to investigate the role of THRIL/miR-99a in malignant SPNs. METHODS: The study groups consisted of 169 patients with SPN and 74 healthy subjects. The differences in THRIL levels were compared between the two groups and the healthy group. The receiver operating characteristic curve (ROC) was utilized to analyze the THRIL's significance in detecting benign and malignant SPN. Pearson correlation and binary regression coefficients represented the association between THRIL and SPN. CCK-8 assay, Transwell assay, and flow cytometry were utilized to detect the regulatory effect of THRIL silencing. The interaction between THRIL, miR-99a, and IGF1R was confirmed by the double luciferase reporter gene. RESULTS: There were differences in THRIL expression in the healthy group, benign SPN group, and malignant SPN group. High accuracy of THRIL in the diagnosis of benign SPN and malignant SPN was observed. THRIL was associated with the development of SPN. The expression of THRIL was upregulated and miR-99a was downregulated in lung cancer cells. The double luciferase report experiment confirmed the connections between THRIL/miR-99a/IGF1R. Silencing THRIL could suppress cell proliferation, migration, and invasion and promote cell apoptosis by binding miR-99a. CONCLUSION: The detection of THRIL in serum is useful for the assessment of malignant SPN. THRIL can regulate the expression of IGF1R through miR-99a, thereby promoting the growth of lung cancer cells and inhibiting apoptosis.

Can family doctor contracted services facilitate orderly visits in the referral system? A frontier policy study from Shanghai, China.

BACKGROUND: China committed to establishing a family doctor (FD)-based referral system following the medical reform in 2009. This paper explored the effect of FD on establishing the anticipated system. METHODS: Two waves of survey were conducted in Shanghai, China. 2754 and 1995 individuals were sampled in 2013 and 2016 respectively. We compared orderly visiting behaviour between contracted and non-contracted residents. Logistic regression models were performed to further test the effect of FD on orderly visits. RESULTS: More contracted residents first-contacted community health service centres (CHSCs; 45.48%) than non-contracted residents (28.93%). Contracted residents were also more likely to refer to specialists via CHSCs than the non-contracted (9.84% vs. 2.60%). The odds ratio (OR) for first-contact at CHSCs by contract status was 1.569 in 2013, but increased to 1.675 in 2016. Being contracted with a FD was associated with referral behaviour, but the OR declined from 2.692 to 2.487 over years. CONCLUSION: The survey from Shanghai showed that FD had a significant effect on attracting first-contact at CHSCs and referral via CHSCs; however, the effect on the latter decreased. The effectiveness of the FD role on referral behaviour requires a well-established referral system, which has not yet been completely achieved in China.

The developing family doctor system: evidence from the progress of the family doctor signing service from a longitudinal survey (2013-2016) in Pudong New Area, Shanghai.

BACKGROUND: The family doctor system is a vital part of China's national medical and health system reform. Evidence of the degree of implementation of the family doctor system is required to assist managers and policy makers in Pudong with resource allocation planning. This study analyzed changes in indicators (family doctor team construction, contracted medical services, health management services and so on) over time to evaluate the progress of the family doctor system in Pudong. METHODS: We used a cross-sectional design with an online questionnaire survey to collect 3-year (2013-2016) consecutive data. The online questionnaires were completed by the doctors responsible for information reporting in each community health service center of Pudong. The data were sorted, and the indices calculated and analyzed using descriptive statistics and statistical tests. RESULTS: The proportion of registered general practitioners increased each year, from 50.8% in 2013 to 66.5% in 2016; this difference was statistically significant (P = 0.000). The number of family doctors per 10,000 permanent residents rose each year, from 1.7 in 2013 to 2.1 in 2016. The rate of contracted household residents was 55.7% in 2013 and increased to 71.7% in 2016, with the difference being significant in different years (P = 0.012). Analysis of referral services showed the people times of contracted residents transferring to higher-level hospitals from family doctors increased each year, from 172,734 in 2013 to 341,615 in 2016; differences among different regions were statistically significant for 2013-2016. The rate of health screening for contracted residents also increased each year, with statistically significant differences in different years (P = 0.000). The rate of health assessment interventions for contracted residents rose each year, with statistically significant differences in different years (P = 0.003). CONCLUSIONS: The family doctor signing service in Pudong made headway in general practitioner availability, contract service rate of household residents, and providing health management services. However, problems included family doctor shortages and limited supporting policies, especially in rural and suburban areas compared with urban divisions. Increasing the enrollment rate of family doctors and speeding up the implementation of "contract service fees" are key tasks for the sustainable development of the family doctor system in Pudong.

Yeast Synthetic Biology for the Production of Lycium barbarum Polysaccharides.

The fruit of Lycium barbarum L. (goji berry) is used as traditional Chinese medicine, and has the functions of immune regulation, anti-tumor, neuroprotection, anti-diabetes, and anti-fatigue. One of the main bioactive components is L. barbarum polysaccharide (LBP). Nowadays, LBP is widely used in the health market, and it is extracted from the fruit of L. barbarum. The planting of L. barbarum needs large amounts of fields, and it takes one year to harvest the goji berry. The efficiency of natural LBP production is low, and the LBP quality is not the same at different places. Goji berry-derived LBP cannot satisfy the growing market demands. Engineered Saccharomyces cerevisiae has been used for the biosynthesis of some plant natural products. Recovery of LBP biosynthetic pathway in L. barbarum and expression of them in engineered S. cerevisiae might lead to the yeast LBP production. However, information on LBP biosynthetic pathways and the related key enzymes of L. barbarum is still limited. In this review, we summarized current studies about LBP biosynthetic pathway and proposed the strategies to recover key enzymes for LBP biosynthesis. Moreover, the potential application of synthetic biology strategies to produce LBP using engineered S. cerevisiae was discussed.

Factors affecting the work competency and stability of family doctors in Shanghai: a tracking study.

BACKGROUND: Family doctors can fulfill the gatekeeper duty to protect the residents' health, which depends on their work competency and stability. The study aimed to identify factors influencing work competency and stability among Shanghai family doctors. METHODS: This study was a 2-year follow-up survey (2013/2016). A representative sample of 146 family doctors in Shanghai community health service centers was interviewed in 2013. The tracked sample (n = 142) was resurveyed in 2016. A 50-item questionnaire organized into four parts, i.e., general demographic characteristics, working conditions, cognition about family doctor services, and job satisfaction was issued to all family doctors. Models for factors influencing family doctors' work competency and stability were then established. The collected data were analyzed using ordinal regression methods and descriptive, factor, and multiple-factor analyses. RESULTS: The family doctors' work competency model showed demographic characteristics (education level and job title), family doctors' team, family doctors' training, grasp of specific content regarding the family doctor system, and whether the family doctors' ability was played and demonstrated were statistically significant at different levels (P < 0.05). The analysis of family doctors' work stability showed that work competency (whether it was possible to provide residents with all contents specified in the contract service package, employment form, and support satisfaction) and work cognition (whether the daily work was meaningful and had value) had a significant impact on work stability (P < 0.05). CONCLUSION: Family doctors' job satisfaction is a key factor affecting their work stability. Family doctors' competency can also affect their job stability, and their work cognition may play a role in work competency and stability. This study provides evidence for strengthening the stability of the family doctor teams in Shanghai.

A preliminary effect analysis of family doctor and medical insurance payment coordination reform in Changning District of Shanghai, China.

BACKGROUND: Changning District of Shanghai pioneered in implementing Family Doctor and Medical Insurance Payment Coordination Reform. The survey aimed to assess the effect of the reform to provide a decision-making basis for ensuring the "gatekeeper" role of the family doctor. METHODS: A cross-sectional survey was conducted using a self-designed questionnaire in Changning District of Shanghai during January and February in 2014. Multi-stage random cluster was applied and 3040 residents were selected. Comparisons were made with statistically test between the contracted and non-contracted residents in four policy targeted dimensions, doctor-visiting behavior, health management and status, medical cost control and satisfaction. RESULTS: Compared with the non-contracted residents, the contracted residents (72.9%) presented a higher prevalence rate of chronic diseases (32.6%), a higher proportion (51.9%) in first-contact in the community health service center and a higher proportion to refer to specialists as well (P < 0.001).The result showed that the average annual medical expense were significantly higher than non-contracted residents (P < 0.001), however, the difference disappeared after age, medical insurance and other socio-demographic variables were controlled. In terms of self-management of non-communicable diseases and complication prevention, the blood pressure control rate and blood glucose control rate for the contracted group were also higher than the counterparts, reaching up to 85.6 and 72.7% respectively. CONCLUSION: The preliminary analysis indicated that the contracted residents performed better in orderly doctor visiting behavior, health management behavior, health status and satisfaction. Follow up survey is necessary to further analyze the policy effect.

The effect of family doctor-contracted services on noncommunicable disease self-management in Shanghai, China.

BACKGROUND: Noncommunicable diseases (NCDs) are a major threat to population health worldwide. In Shanghai, China, a new pattern of NCD management-self-management-has been developed in community health service centres (CHSCs). OBJECTIVE: To clarify how contracting with CHSC-based family doctors (FDs) influences the engagement in and effectiveness of self-management behaviour among NCD patients. METHOD: We conducted two waves of a questionnaire survey (in 2013 and 2016) to collect data on patients with NCDs. Separate logistic regression models and longitudinal analysis were performed to examine the effect of contracting with an FD on NCD self-management and the effectiveness of this self-management. RESULTS: Nearly all contracted patients (80.79%) had implemented NCD self-management, while only 55.57% of non-contracted patients did so. The self-management effectiveness rate was also higher among contracted patients than among non-contracted ones (86.66% vs. 54.79%). In the population-averaged models, contracted patients had 2.25 and 2.91 times greater odds of implementing self-management and reporting that the self-management was effective, respectively, after controlling for all related variables. Additionally, awareness of FD-contracted services, satisfaction with CHSCs, and experiencing first contact at CHSCs had positive impacts on the implementation and effectiveness of self-management. CONCLUSIONS: FDs were important for ensuring that NCD patients engaged in self-management behaviour, the most common form of which was focus group. Participation in NCD focus groups may be key for attaining the effects of self-management, including improved health knowledge, greater health awareness, more frequent engagement in health behaviour, and, most importantly, greater practice of self-monitoring. Self-management might help to achieve greater NCD control.

The complete genome sequence of a double-stranded RNA mycovirus from Fusarium graminearum strain HN1.

The complete nucleotide sequence of a double-stranded RNA (dsRNA) mycovirus, Fusarium graminearum dsRNA virus 5 (FgV5), was identified and characterized. The FgV5 genome comprises two dsRNA genome segments of 2030 bp and 1740 bp. FgV5 dsRNA1 contains a single open reading frame (ORF1), which is predicted to encode a protein of 613 amino acids (aa) with a molecular mass of 70.4 kDa and has a conserved RNA-dependent RNA polymerase (RdRp) motif. FgV5 dsRNA2 is predicted to contain two discontinuous ORFs (ORF2 and ORF3) that code for products of unknown function. Sequence comparisons showed that FgV5 has the highest aa sequence identities to Fusarium graminearum virus 4 (FgV4) (83.01% for ORF1, 78.70% for ORF2, and 76.27% for ORF3), suggesting that FgV5 and FgV4 should be regarded as members of different species. Phylogenetic analysis indicated that FgV5 belongs to a taxonomically unassigned dsRNA mycovirus group that is related to the families Amalgaviridae and Partitiviridae. Here, we propose that FgV5 and related viruses are members of a yet to be named and formally recognized new family.

Silencing of astrocyte elevated gene-1 inhibits proliferation and migration of melanoma cells and induces apoptosis.

Melanoma is an aggressive skin malignancy with a high mortality. Astrocyte elevated gene-1 (AEG-1), a downstream target of Ras and c-Myc, has been implicated in the development of multiple tumours, but its role in melanoma remains unclear. In the present study, the role of AEG-1 in melanoma was explored through AEG-1 silencing. Our results showed that silencing AEG-1 inhibited the proliferation of melanoma cells, induced cell cycle arrest, and reduced levels of cyclin A, cyclin B, cyclin D1, cyclin E, and cyclin-dependent kinase 2. AEG-1silencing also induced apoptosis in melanoma cells and altered the levels of cleaved caspase-3, B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein. Moreover, silencing AEG-1 suppressed the migration and invasion of melanoma cells, reduced the expressions and activities of matrix metallopeptidase (MMP)-2 and MMP-9, and inhibited the activation of the Wnt/ß-catenin signalling pathway in melanoma cells. Furthermore, in vivo experiments revealed that AEG-1 silencing inhibited the growth of melanoma xenografts in nude mice. In summary, our study demonstrates an oncogenic role of AEG-1 in melanoma and suggests that AEG-1 may serve as a potential therapeutic target in the treatment of melanoma.

Two Novel Relative Double-Stranded RNA Mycoviruses Infecting Fusarium poae Strain SX63.

Two novel double-stranded RNA (dsRNA) mycoviruses, termed Fusarium poae dsRNA virus 2 (FpV2) and Fusarium poae dsRNA virus 3 (FpV3), were isolated from the plant pathogenic fungus, Fusarium poae strain SX63, and molecularly characterized. FpV2 and FpV3, with respective genome sequences of 9518 and 9419 base pairs (bps), are both predicted to contain two discontinuous open reading frames (ORFs), ORF1 and ORF2. A hypothetical polypeptide (P1) and a RNA-dependent RNA polymerase (RdRp) are encoded by ORF1 and ORF2, respectively. Phytoreo_S7 domain (pfam07236) homologs were detected downstream of the RdRp domain (RdRp_4; pfam02123) of the ORF2-coded proteins of both FpV2 and FpV3. The same shifty heptamers (GGAAAAC) were both found immediately before the stop codon UAG of ORF1 in FpV2 and FpV3, which could mediate programmed -1 ribosomal frameshifting (-1 PRF). Phylogenetic analysis based on RdRp sequences clearly place FpV2 and FpV3 in a taxonomically unassigned dsRNA mycovirus group. Together, with a comparison of genome organization, a new taxonomic family termed Fusagraviridae is proposed to be created to include FpV2- and FpV3-related dsRNA mycoviruses, within which FpV2 and FpV3 would represent two distinct virus species.

Effects of autologous adipose-derived stem cell infusion on type 2 diabetic rats.

The effects and possible mechanisms of adipose-derived stem cells (ASC) infusion on type 2 diabetic rats were investigated in this study. Twenty normal male Sprague-Dawley rats were included in normal control group, and 40 male diabetic rats were randomly divided into diabetic control group and ASC group (which received ASC infusion). After therapy, levels of fasting plasma glucose (FPG), HbA1c, serum insulin and C-peptide, recovery of islet cells, inflammatory cytokines, and insulin sensitivity were analyzed. After ASC infusion, compared with diabetic control group, hyperglycemia in ASC group was ameliorated in 2 weeks and maintained for about 6 weeks, and plasma concentrations of insulin and C-peptide were significantly improved (P<0.01). Number of islet ß cells and concentration of vWF in islets in ASC group increased, while activity of caspase-3 in islets was reduced. Moreover, concentrations of TNF-α, IL-6 and IL-1ß in ASC group obviously decreased (P<0.05). The expression of GLUT4, INSR, and phosphorylation of insulin signaling molecules in insulin target tissues were effectively improved. ASC infusion could aid in T2DM through recovery of islet ß cells and improvement of insulin sensitivity. Autologous ASC infusion might be an effective method for T2DM.

Strong association of high urinary iodine with thyroid nodule and papillary thyroid cancer.

This study demonstrates a strong association of high urinary iodine with thyroid nodules and papillary thyroid cancer as well as aggressive cancer features, suggesting that high urinary iodine is a risk factor for thyroid cancer. The risk of high iodine intake for thyroid cancer has been suggested but not established. The objective of the study was to evaluate the relationship between urine iodine levels and thyroid nodule and thyroid cancer. We preoperatively tested fasting urine iodine in 154 thyroid nodule patients and correlated the results with pathological diagnoses and compared with 306 subjects as normal control. The median urine iodine (MUI) was 331.33 µg/L in patients with benign thyroid nodules versus 466.23 µg/L in patients with papillary thyroid cancer (PTC) (P=0.003), both of which were in the excessive iodine state and higher than the MUI of 174.30 µg/L in the control group (P < 0.001), which was in the sufficient iodine state. Excessive iodine state (MUI>300 µg/L) was seen in 62.75% of patients with benign thyroid nodules and 66.99% of patients with PTC, both of which were significantly higher than the iodine excessive rate of 19.93% in the control group (P<0.001). Moreover, MUI in patients with PTC with lymph node metastasis was significantly higher than that of PTC patients without lymph node metastasis (P<0.001). Urine iodine of thyroid cancer patients with stage III and IV disease was significantly higher than that of patients with stage I and II diseases (P<0.001). Multivariable analyses showed that, like sand calcification of thyroid nodule and TSH, urine iodine was an independent risk factor for PTC. These data demonstrate a significant association between high urinary iodine and benign and malignant thyroid nodules and PTC aggressiveness, supporting high urinary iodine as a risk factor for thyroid malignancy. Further studies are warranted to confirm these findings.

Chuanhu anti-gout mixture versus colchicine for acute gouty arthritis: a randomized, double-blind, double-dummy, non-inferiority trial.

BACKGROUND: The Chuanhu anti-gout mixture has been used for many years in the treatment of gout in Chinese Traditional Medicine, and current methods for treatments for acute gouty arthritis have been either less effective or have had serious side effects. METHODS: In this 12-week, double-blind, double-dummy, non-inferiority study, outpatient individuals with newly diagnosed acute gouty arthritis were randomly assigned to receive Chuanhu anti-gout mixture or colchicine. Both the study investigators and the participants were masked to the treatment assignments. The primary outcome was the recurrence rate of acute gouty arthritis, and the secondary outcomes were changes in white blood cells (WHC) and C-reactive protein (CRP). This trial is registered at ISRCTN.org as trial ISRCTN65219941. RESULTS: A total of 176 patients were randomly assigned to receive either the Chuanhu anti-gout mixture or Colchicine. The overall recurrence rates in the Chuanhu anti-gout mixture group (CH group) and the Colchicine group (Col group) were 12.50% vs 14.77% (difference -2.22%, 95% confidence interval (95% CI): -10.78%~6.23%), meeting the predefined non-inferiority criterion of 15%, as did the data for WHC and CRP. The incidence of adverse events (mainly diarrhea) was less in the Col group than in the CH group (2.27% vs 28.41%, 95% CI 0.01~0.26). In addition, changes in blood uric acid, alanine aminotransferase, aspartate aminotransferase and creatinine in the CH group were significantly larger compared to those in the Col group (P<0.05). CONCLUSIONS: The Chuanhu anti-gout mixture was non-inferior to colchicine for the treatment of acute gouty arthritis. The study suggested that the Chuanhu anti-gout mixture can be considered an alternative choice for the treatment of acute gouty arthritis because of its lower incidence of adverse events and its protection of kidney and renal function.

Visualizing ClO- fluctuations in drug-induced liver injury and bacterium via a robust ratiometric fluorescent probe.

As a type of reactive oxygen species, hypochlorous acid (ClO-) plays an important role in sterilization, disinfection and protection in organisms. However, excessive production of ClO- is closely related to various diseases. In this work, we have designed a robust ratiometric fluorescent probe, RDB-ClO, using the excited-state intramolecular proton transfer (ESIPT) strategy. RDB-ClO was achieved by modifying 2-(2-(benzo[d]thiazol-2-yl)-6-(diethylamino)-3-oxo-3H-xanthen-9-yl) benzoic acid (RDB-OH) with a 1-naphthoyl chloride group, specifically for the sensitive detection of ClO-. In the presence of ClO-, RDB-ClO demonstrated relatively good performance, showing swift response time (35 s), low detection limit of 5.1 nM and high selectivity towards ClO-. Notably, the convenience and accessibility detection of ClO- has been implemented using test strip and agarose probe. RDB-ClO effectively tracked both endogenous and exogenous ClO- in HeLa cells, HepG2 cells and zebrafish. Additionally, it is successfully applied to detect changes of exogenous ClO- content in E. coli. and acetaminophen (APAP)-induced liver injury in mice. The development of RDB-ClO represents a promising molecular tool for studying the pathogenesis of DILI and biotransformation of ClO- in bacteria.

Dual-channel versatile molecular sensing platform for individual and successive HClO and H2S detection: Applicable in toxic alerts of environmental samples and living organisms.

In this study, we have successfully developed a novel dual-response fluorescent probe, NACou, designed for the visual and quantitative detection of HClO/H2S in real water samples and liquid beverages by a thin-film sensing platform. Additionally, NACou demonstrated efficacy for sensing HClO/H2S in HeLa cells, plants and zebrafish through distinct fluorescent channels, yielding satisfactory results. NACou exhibited a multi-modal fluorescence response mechanism for detecting HClO and H2S with remarkable low detection limits of 27.8 nM and 34.4 nM, accompanied by outstanding fluorescent enhancement (209-fold and 148-fold, respectively). These advantages position NACou as a potent molecular tool for HClO and H2S sensing. The specific recognition performance of NACou towards HClO/H2S were confirmed through fluorescence spectroscopy, mass analysis and UV-vis spectroscopy. Importantly, the thin-film sensing platform with the visible fluorescence change can enable rapid assays for water quality and food safety monitoring, showcasing significant practical application value. Impressively, NACou has been employed in warning against liver injury induced by multiple drugs, allowing for the exploration of the pathogenesis and degree of drug-induced injury.

Rapid-response near-infrared fluorescence probe for colorimetric detection of HClO and its applications in environmental monitoring and biological imaging.

As a crucial endogenous reactive oxygen species, hypochlorous acid (HClO) plays an indispensable role in numerous physiological and pathological processes. Additionally, it serves as a biomarker closely associated with inflammation and liver injury. The utilization of near-infrared fluorescence probes has surged in recent years for live biological imaging, owing to their minimal tissue damage and potent tissue penetration capabilities. In this work, a novel near-infrared fluorescence probe MB-HPD was synthesized to sensitively detect HClO. Probe MB-HPD exhibits remarkable selectivity, high sensitivity (14.3 nM), and rapid response towards HClO (20 s). Probe MB-HPD has demonstrated successful application in the imaging of HClO within cells and zebrafish. Remarkably, it has proven to be effective for detecting HClO within environmental samples, as well as imaging HClO in mice models of arthritis and APAP-induced liver injury. These findings indicate the broad applicability of probe MB-HPD, offering a promising avenue for designing highly selective near-infrared fluorescence probes suitable for real-time HClO monitoring.

Arsenic affects on cerebellar development of mice.

To evaluate arsenic affects on the development of cerebellum, the mother mice received drinking water containing arsenic trioxide (As2O3) 4 ppm during gestation and lactation period. The cytogenesis was observed by immunohistochemical technique using 5'-bromo-2'-deoxyuridine (BrdU) antibody. To characterize the arsenic neurotoxicity, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), an oxidative DNA lesion marker, and 8-nitroguanine, a nitrative DNA lesion marker were used to verify DNA damage. Arsenic-exposed litters showed neuron necrosis. The mitosis of granule cells decreased dramatically in arsenic-exposed mice as compared with arsenic unexposed mice. 8-OxodG was formed in neurons of all the layers, especially in the granular layer in cerebellum of arsenic-exposed mice. There is no significant difference, however, in the expression of 8-nitroguanine between arsenic-exposed and -unexposed mice. These results indicate that arsenic can disturb the mitosis of granule cells and interfere with the normal development of mice cerebellum. Arsenic-induced pathological changes in vivo may be caused by oxidative DNA damage other than nitrative DNA damage.

Raf kinase inhibitor protein combined with phosphorylated extracellular signal-regulated kinase offers valuable prognosis in gastrointestinal stromal tumor.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Tyrosine kinase inhibitors, such as imatinib, have been used as first-line therapy for the treatment of GISTs. Although these drugs have achieved considerable efficacy in some patients, reports of resistance and recurrence have emerged. Extracellular signal-regulated kinase 1/2 (ERK1/2) protein, as a member of the mitogen-activated protein kinase (MAPK) family, is a core molecule of this signaling pathway. Nowadays, research reports on the important clinical and prognostic value of phosphorylated-ERK (P-ERK) and phosphorylated-MAPK/ERK kinase (P-MEK) proteins closely related to raf kinase inhibitor protein (RKIP) have gradually emerged in digestive tract tumors such as gastric cancer, colon cancer, and pancreatic cancer. However, literature on the expression of these downstream proteins combined with RKIP in GIST is scarce. This study will focus on this aspect and search for answers to the problem. AIM: To detect the expression of RKIP, P-ERK, and P-MEK protein in GIST and to analyze their relationship with clinicopathological characteristics and prognosis of this disease. Try to establish a new prognosis evaluation model using RKIP and P-ERK in combination with analysis and its prognosis evaluation efficacy. METHODS: The research object of our experiment was 66 pathologically diagnosed GIST patients with complete clinical and follow-up information. These patients received surgical treatment at China Medical University Affiliated Hospital from January 2015 to January 2020. Immunohistochemical method was used to detect the expression of RKIP, P-ERK, and P-MEK proteins in GIST tissue samples from these patients. Kaplan-Meier method was used to calculate the survival rate of 63 patients with complete follow-up data. A Nomogram was used to represent the new prognostic evaluation model. The Cox multivariate regression analysis was conducted separately for each set of risk evaluation factors, based on two risk classification systems [the new risk grade model vs the modified National Institutes of Health (NIH) 2008 risk classification system]. Receiver operating characteristic (ROC) curves were used for evaluating the accuracy and efficiency of the two prognostic evaluation systems. RESULTS: In GIST tissues, RKIP protein showed positive expression in the cytoplasm and cell membrane, appearing as brownish-yellow or brown granules. The expression of RKIP was related to GIST tumor size, NIH grade, and mucosal invasion. P-ERK protein exhibited heterogeneous distribution in GIST cells, mainly in the cytoplasm, with occasional presence in the nucleus, and appeared as brownish-yellow granules, and the expression of P-ERK protein was associated with GIST tumor size, mitotic count, mucosal invasion, and NIH grade. Meanwhile, RKIP protein expression was negatively correlated with P-ERK expression. The results in COX multivariate regression analysis showed that RKIP protein expression was not an independent risk factor for tumor prognosis. However, RKIP combined with P-ERK protein expression were identified as independent risk factors for prognosis with statistical significance. Furthermore, we establish a new prognosis evaluation model using RKIP and P-ERK in combination and obtained the nomogram of the new prognosis evaluation model. ROC curve analysis also showed that the new evaluation model had better prognostic performance than the modified NIH 2008 risk classification system. CONCLUSION: Our experimental results showed that the expression of RKIP and P-ERK proteins in GIST was associated with tumor size, NIH 2008 staging, and tumor invasion, and P-ERK expression was also related to mitotic count. The expression of the two proteins had a certain negative correlation. The combined expression of RKIP and P-ERK proteins can serve as an independent risk factor for predicting the prognosis of GIST patients. The new risk assessment model incorporating RKIP and P-ERK has superior evaluation efficacy and is worth further practical application to validate.

Management of acute carbamazepine poisoning: A narrative review.

Standard management protocols are lacking and specific antidotes are unavailable for acute carbamazepine (CBZ) poisoning. The objective of this review is to provide currently available information on acute CBZ poisoning, including its management, by describing and summarizing various therapeutic methods for its treatment according to previously published studies. Several treatment methods for CBZ poisoning will be briefly introduced, their advantages and disadvantages will be analyzed and compared, and suggestions for the clinical treatment of CBZ poisoning will be provided. A literature search was performed in various English and Chinese databases. In addition, the reference lists of identified articles were screened for additional relevant studies, including non-indexed reports. Non-peer-reviewed sources were also included. In the present review, 154 articles met the inclusion criteria including case reports, case series, descriptive cohorts, pharmacokinetic studies, and in vitro studies. Data on 67 patients, including 4 fatalities, were reviewed. Based on the summary of cases reported in the included articles, the cure rate of CBZ poisoning after symptomatic treatment was 82% and the efficiency of hemoperfusion was 58.2%. Based on the literature review, CBZ is moderately dialyzable and the recommendation for CBZ poisoning is supportive management and gastric lavage. In severe cases, extracorporeal treatment is recommended, with hemodialysis as the first choice.

[The correlation between BRAF mutations, RET/PTC rearrangements and platelet-derived growth factor B expression in papillary thyroid carcinomas].

OBJECTIVE: To investigate the prevalence of BRAF T1799A mutation and RET/PTC rearrangement in Qingdao and detect the expression of platelet-derived growth factor B (PDGF-B) in order to investigate the correlation between gene mutation and PDGF-B. METHODS: Fresh tissue from 48 papillary thyroid carcinomas (PTC) patients was examined for BRAF mutation RET rearrangements (RET/PTC1 and RET/PTC3) by PCR, followed by direct-sequence analysis. The expression of PDGF was analyzed by immunohistochemistry. RESULTS: Among the 48 patients, 14 (29.2%) were micro PTC; 18 (37.5%) had BRAF T1799A mutations and 23(47.9%) had RET/PTC rearrangement. There were 17 (35.4%) cases of RET/PTC1 and 6 (12.5%) of RET/PTC3, with no multiple rearrangements. Both BRAF T1799A mutation and RET/PTC rearrangement were present in 6 (12.5%) cases of non-micro PTC. The level of PDGF-B expression in BRAF T1799A positive was higher than that in the negative, and the level of PDGF-B expression in RET/PTC3 was higher than that in RET/PTC1 (P < 0.05). The more advanced neoplasm stage was, the stranger PDGF-B expression was. CONCLUSIONS: The incidence of BRAF T1799A mutation and RET/PTC rearrangement is higher in Qingdao. BRAF T1799A mutation and RET/PTC3 rearrangement in patients suggests a poorer prognosis than the negative one. The BRAF T1799A mutation and RET/PTC3 rearrangement may strengthen the expression of PDGF-B. Both variations suggest a poor prognosis.