Ethnobotanical investigation of medicinal plants used in Lingchuan county, Shanxi, China.

Medicinal plants are the primary sources of healthcare among the people of developing countries in villages and local towns. Documenting and reporting the traditional knowledge of medicinal plants may contribute to pharmaceutical research development. For this reason, we present our findings on ethnomedicinal plants from Lingchuan County, Shanxi, China, an unexplored area rich in medicinal plant resources. Information of ethnomedicinal plants were collected through questionnaire/semi-structured interviews from 180 informants, including traditional healers. Field surveys were conducted in 53 villages of Lingchuan County from 2017 to 2018. Informed consent was obtained from each participant before conducting the interview process. Quantitative analysis was performed for each recorded species, such as Relative Frequency Citation (RFC), Use Value (UV), and Factor of Informant Consensus (FIC). Diseases were categorized into twelve groups. A total 138 species of medicinal plants were recorded, belonging to 123 genera of 58 families. Asteraceae was the dominant plant family with 19 species, followed by Rosaceae and Fabaceae. Herbs were dominant among plant life-forms with 96 species, followed by shrubs and trees (15 species each). Roots were the most commonly used plant parts with 58 species, followed by whole plants and fruits (28 species each). Most plant species were reported non-toxic (84, 60%), followed by unknown toxicity (35, 25%), poisonous, and less toxic (19, 14%). Quantitative analysis revealed that Forsythia suspensa was with higher (0.33) RFC value, and Scutellaria baicalensis was recorded with a higher (0.91) UV. Treated diseases were categorized in 12 groups and evaluated by their FIC value, in which gynecological diseases have higher (0.93) FIC value followed by urinary system diseases. Most medicinal plants are used to clear away heat and relieve the surface. The present study revealed that local people of Lingchuan County confidently use ethnomedicinal plants for their healthcare needs. The higher indices value of a plant species resulted from quantitative analysis warrants further investigation, which may possess valuable phytochemical compounds that may result in new drugs for treating various human disorders.

Ethnobotanical investigation of medicinal plants used in Lingchuan county, Shanxi, China / Investigação etnobotânica de plantas medicinais usadas no condado de Lingchuan, Shanxi, China

Medicinal plants are the primary sources of healthcare among the people of developing countries in villages and local towns. Documenting and reporting the traditional knowledge of medicinal plants may contribute to pharmaceutical research development. For this reason, we present our findings on ethnomedicinal plants from Lingchuan County, Shanxi, China, an unexplored area rich in medicinal plant resources. Information of ethnomedicinal plants were collected through questionnaire/semi-structured interviews from 180 informants, including traditional healers. Field surveys were conducted in 53 villages of Lingchuan County from 2017 to 2018. Informed consent was obtained from each participant before conducting the interview process. Quantitative analysis was performed for each recorded species, such as Relative Frequency Citation (RFC), Use Value (UV), and Factor of Informant Consensus (FIC). Diseases were categorized into twelve groups. A total 138 species of medicinal plants were recorded, belonging to 123 genera of 58 families. Asteraceae was the dominant plant family with 19 species, followed by Rosaceae and Fabaceae. Herbs were dominant among plant life-forms with 96 species, followed by shrubs and trees (15 species each). Roots were the most commonly used plant parts with 58 species, followed by whole plants and fruits (28 species each). Most plant species were reported non-toxic (84, 60%), followed by unknown toxicity (35, 25%), poisonous, and less toxic (19, 14%). Quantitative analysis revealed that Forsythia suspensa was with higher (0.33) RFC value, and Scutellaria baicalensis was recorded with a higher (0.91) UV. Treated diseases were categorized in 12 groups and evaluated by their FIC value, in which gynecological diseases have higher (0.93) FIC value followed by urinary system diseases. Most medicinal plants are used to clear away heat and relieve the surface. The present study revealed that local people of Lingchuan County confidently use ethnomedicinal plants for their healthcare needs. The higher indices value of a plant species resulted from quantitative analysis warrants further investigation, which may possess valuable phytochemical compounds that may result in new drugs for treating various human disorders.

As plantas medicinais são as principais fontes de cuidados de saúde entre as pessoas dos países em desenvolvimento, nas aldeias e cidades locais. É importante documentar e relatar o conhecimento tradicional de plantas medicinais, dado que pode contribuir para o desenvolvimento da pesquisa farmacêutica. Por esta razão, apresentamos neste estudo nossas descobertas sobre plantas etnomedicinais do condado de Lingchuan, Shanxi, China, uma área inexplorada e rica em recursos de plantas medicinais. As informações sobre as plantas etnomedicinais foram coletadas por meio de questionário/entrevista semiestruturada com 180 participantes, incluindo curandeiros. As pesquisas de campo foram realizadas em 53 aldeias do condado de Lingchuan, entre 2017 e 2018. O consentimento informado foi obtido de cada participante antes de conduzir o processo de entrevista. Foi realizada uma análise quantitativa de cada espécie registrada, através da Frequência Relativa de Citação (RFC), Valor de Uso (UV) e Fator de Consenso dos Informantes (FCI). As doenças foram categorizadas em doze grupos. Foram registradas 138 espécies de plantas medicinais, pertencentes a 123 gêneros de 58 famílias. Asteraceae foi a família de plantas dominante, totalizando 19 espécies, seguida pelas famílias Rosaceae e Fabaceae. As ervas foram consideradas como as principais formas de vida vegetal usadas, com 96 espécies, seguidas por arbustos e árvores (15 espécies cada). As raízes foram as partes de plantas mais utilizadas com 58 espécies, seguidas de plantas inteiras e frutos (28 espécies cada). A maioria das espécies relatadas foram estabelecidas como não tóxicas (84, 60%), seguida de plantas com toxicidade desconhecida (35, 25%), venenosas e menos tóxicas (19, 14%). A análise quantitativa revelou que a espécie Forsythia suspensa alcançou o maior (0,33) valor de RFC, e a Scutellaria baicalensis obteve o maior (0,91) valor de UV registrado. As doenças tratadas foram categorizadas em 12 grupos e avaliadas pelos seus respectivos valores de FCI, onde as doenças ginecológicas apresentaram maior (0,93) valor de FCI, seguido pelas doenças do sistema urinário. Foi concluído que a maioria das plantas medicinais são usadas para amenizar calores e alívio tópico. O presente estudo revelou que a população local do condado de Lingchuan confia no uso de plantas etnomedicinais para lidar com seus problemas de saúde. Seria válido aprofundar as investigações relativas aos índices mais altos obtidos nas análises quantitativas das espécies analisadas, visto que podem possuir compostos fitoquímicos valiosos que podem resultar em novos medicamentos para o tratamento de diversas doenças humanas.

Propofol inhibited gastric cancer proliferation via the hsa-miR-328-3p/STAT3 pathway.

PURPOSE: The aim of the present study was to elucidate the functional role of hsa-miR-328-3p/STAT3 pathway in the effects of propofol on gastric cancer proliferation. METHODS: Bioinformatics was used to analyze the molecular expression differences of hsa-miR-328-3p/STAT3 axis in stomach adenocarcinoma (n = 435) and normal samples (n = 41) from TCGA database. The expression of the above molecules in gastric cancer cells SGC-7901 and normal gastric mucosal cells GES-1 was verified via qPCR. The dual-luciferase assay was carried out to confirm the interaction between hsa-miR-328-3p and STAT3. Subsequently, the cell proliferation and the expression of the above molecules in SGC-7901 and GES-1 cells were evaluated after 10 µM propofol treatment. Finally, we analyzed whether propofol still inhibited the proliferation of gastric cancer by suppressing STAT3 pathway after hsa-miR-328-3p down-regulation. RESULTS: Compared with normal samples, the expression of hsa-miR-328-3p was significantly down-regulated in stomach adenocarcinoma samples, while the expression of STAT3 and downstream target genes (MMP2, CCND1 and COX2) was up-regulated. The results were consistent with those in GES-1 and SGC-7901 cell lines. Meanwhile, we found that hsa-miR-328-3p can bind to the 3'-UTR of the potential target gene STAT3. Furthermore, propofol significantly inhibited the proliferation of gastric cancer cell line SGC-7901, where hsa-miR-328-3p was up-regulated and the expression of STAT3 and downstream proliferation-related target genes were down-regulated. However, the growth inhibition of propofol on SGC-7901 cell was significantly reversed after the inhibition of hsa-miR-328-3p. CONCLUSIONS: To sum up, propofol suppressed the STAT3 pathway via up-regulating hsa-miR-328-3p to inhibit gastric cancer proliferation.

The optimal immune checkpoint inhibitors combined with chemotherapy for advanced non-small-cell lung cancer: a systematic review and meta-analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) plus chemotherapy (CT) have strikingly expanded the therapeutic landscape for advanced non-small cell lung cancer (NSCLC), but little is known about which is superior. We performed a meta-analysis that compared the efficacy and safety of PD-1 inhibitor + CT with PD-L1 inhibitor + CT. METHODS: PubMed, Embase, Web of Science, Cochrane Library, and major international scientific meetings were searched for relevant randomized controlled trials (RCTs), and the indirect analysis was performed for PD-1 + CT vs PD-L1 + CT. The outcomes included progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and treatment-related adverse events (TRAEs). RESULTS: 8 phase III RCTs with 4253 patients comparing PD-1/PD-L1 + CT in NSCLC were included. The PD-1 + CT led to notably longer OS most in low/negative expression of PD-L1 for NSCLC patients compared with PD-L1 + CT. In terms of Grade 3-5 TRAEs, the results showed that PD-1 + CT and PD-L1 + CT exclusively increased the risk of adverse incidence than CT alone, especially for PD-L1 + CT (p < 0.00001). For subgroups including female, young patients, patients with nonsmoker, and EGFR/ALK wild-type, PD-1 + CT was associated with prolonged OS (p < 0.05). Meanwhile, for no liver metastasis of NSCLC patients, we found obviously OS advantage for patients treated with PD-1 + CT compared to PD-L1 + CT. CONCLUSIONS: ICIs + CT seemed to be more effective first-line regimen and PD-1 + CT could be recommended as the first-rank therapy for advanced NSCLC patients with low/negative expression of PD-L1. However, we should be particularly vigilant about the occurrence of the Grade 3-5 TRAEs.

Association Analysis Between Polymorphism of Gonadotrophin Releasing Hormone Genes and Growth Traits of Quail (Coturnix Coturnix)

This study investigated SNP mutation sites of Gonadotrophin releasing hormone (GnRH) gene in China yellow quail, Beijing white quail and Korean quail through PCR amplification and DNA sequencing technologies. Moreover, polymorphism of GnRH gene and its association with growth traits of quail were analyzed, aiming to get molecular markers associated to growth traits of quail, which could provide references for breeding of new quail species. According to research results, a total of 14 SNP mutation sites of GnRH were detected in China yellow quail, Beijing white quail and Korean quail, which were C71T, C108T, C168T, C178T, A184G, C206T, A209C, C215T, A252G, A279T, C281T, C293G, C339T and C458T. Except that only 2 genotypes were detected for A209C and C281T in China yellow quail and Beijing white quail, 3 genotypes were detected for all of the remaining 12 SNP mutation sites in three quail species. Of the 14 SNP sites, C71T, A209C, C215T, C281T, C293G, C339T and C458T were significantly associated with body weight (p 0.05), C71T, C108T, C168T, C178T, A184G, C206T, C215T, A252G, C293G, C339T and C458T were significantly associated with shank length (p 0.05), C71T, C215T, C293G and C458T were significantly associated with breastbone length (p 0.05), A209C and C281T were significantly associated with shank circumference (p 0.05).

Association Analysis Between Polymorphism of Gonadotrophin Releasing Hormone Genes and Growth Traits of Quail (Coturnix Coturnix)

This study investigated SNP mutation sites of Gonadotrophin releasing hormone (GnRH) gene in China yellow quail, Beijing white quail and Korean quail through PCR amplification and DNA sequencing technologies. Moreover, polymorphism of GnRH gene and its association with growth traits of quail were analyzed, aiming to get molecular markers associated to growth traits of quail, which could provide references for breeding of new quail species. According to research results, a total of 14 SNP mutation sites of GnRH were detected in China yellow quail, Beijing white quail and Korean quail, which were C71T, C108T, C168T, C178T, A184G, C206T, A209C, C215T, A252G, A279T, C281T, C293G, C339T and C458T. Except that only 2 genotypes were detected for A209C and C281T in China yellow quail and Beijing white quail, 3 genotypes were detected for all of the remaining 12 SNP mutation sites in three quail species. Of the 14 SNP sites, C71T, A209C, C215T, C281T, C293G, C339T and C458T were significantly associated with body weight (p 0.05), C71T, C108T, C168T, C178T, A184G, C206T, C215T, A252G, C293G, C339T and C458T were significantly associated with shank length (p 0.05), C71T, C215T, C293G and C458T were significantly associated with breastbone length (p 0.05), A209C and C281T were significantly associated with shank circumference (p 0.05).(AU)

Public Health Significance of Toxoplasma gondii Infections in Cattle: 2009-2020.

Toxoplasma gondii infections are common in humans and animals worldwide. The ingestion of food or water contaminated with oocysts excreted by infected cats or ingesting uncooked or undercooked meat containing tissue cysts of T. gondii are the 2 major modes of transmission of T. gondii. Viable T. gondii is more prevalent in pork and lamb than in beef. In the past decade, there have been many articles on the high seroprevalence in cattle, particularly from China. There is a report of an outbreak of acute toxoplasmosis in humans suspected to be linked to the ingestion of Artisan fresh cheese from cow's milk. There are conflicting reports concerning the rate of congenital transmission of T. gondii in cattle, especially from Brazil. In a report from Brazil, viable T. gondii was isolated from the blood of 1 of 60 pregnant cows slaughtered at an abattoir and from 1 fetus. The role of beef in the epidemiology of T. gondii infections is still not clear. Here, we review prevalence, persistence of infection, clinical disease, epidemiology, and public health risks of T. gondii infections in cattle from beef and cow's milk worldwide for the past decade.

Epidemiologic significance of Toxoplasma gondii infections in chickens (Gallus domesticus): the past decade.

Toxoplasma gondii infections are common in humans and animals worldwide. Domestic free-range chickens (Gallus domesticus) are excellent sentinels of environmental contamination with T. gondii oocysts because they feed on the ground. Chickens can be easily infected with T. gondii; however, clinical toxoplasmosis is rare in these hosts. Chickens are comparatively inexpensive and thus are good sentinel animals for T. gondii infections on the farms. Here, the authors reviewed prevalence, the persistence of infection, clinical disease, epidemiology and genetic diversity of T. gondii strains isolated from chickens worldwide for the past decade. Data on phenotypic and molecular characteristics of 794 viable T. gondii strains from chickens are discussed, including new data on T. gondii isolates from chickens in Brazil. This paper will be of interest to biologists, epidemiologists, veterinarians and parasitologists.

Differential molecular markers of primary lung tumors and metastatic sites indicate different possible treatment selections in patients with metastatic lung adenocarcinoma.

PURPOSE: Detecting different molecular markers in primary tumors and metastases may provide therapeutic information. Here we investigated differences between primary tumors and four metastatic sites of lung adenocarcinoma in the biomarkers' features and discussed potential therapeutic implications. METHODS: A total of 228 patients with metastatic lung adenocarcinoma were analyzed for EGFR, KRAS, BRAF and PIK3CA mutations detected by xTAG liquidchip technology (xTAG-LCT), as well as ERCC1, TYMS, RRM1, TUBB3, STMN1, TOP2A and VEGFR1-3 mRNA expression detected by branched DNA-liquidchip technology (bDNA-LCT). RESULTS: Higher rates of low ERCC1 (35.6 vs. 20.3%, P = 0.0105), RRM1 (23.3 vs. 13.0%, P = 0.0437), STMN1 (72.2 vs. 42.8%, P = 0.0000) and high VEGFR2 (34.4 vs. 18.8%, P = 0.0078) mRNA expression were found in EGFR-mutated tumors, suggesting possible benefit from platinum, gemcitabine, taxanes or VEGFR2 inhibitors. Primary lesions showed low ERCC1 (31.6 vs. 18.5%, P = 0.0271), TYMS (17.6 vs. 7.6%, P = 0.0300), TUBB3 (16.9 vs. 7.6%, P = 0.0415), STMN1 (62.1 vs. 42.9%, P = 0.0065) and high TOP2A (48.7 vs. 33.1%, P = 0.0262) mRNA expression and higher KRAS mutations (25.7 vs. 14.1%, P = 0.0350), suggesting platinum, taxanes, pemetrexed, anti-TOP2A agents and resistant to anti-EGFR therapies. Liver metastases showed absence of low TYMS expression, indicating insensitivity to pemetrexed-based regimen. Pleura metastases harbored higher rates of high VEGFR2 expression (50.0 vs. 19.1%, P = 0.0127). Lymph node metastases presented higher rates of high VEGFR2 expression (37.5 vs. 19.1%, P = 0.0253) and EGFR mutations (59.4 vs. 34.4%, P = 0.0011), suggesting use of anti-VEGFR2 and anti-EGFR therapies. CONCLUSION: Molecular profiling of 228 lung adenocarcinomas determined a significant difference between biomarkers such as EGFR and KRAS subtypes at primary and metastatic sites. Our results serve as a reference for individual treatment based on different potential targets in metastatic lung adenocarcinoma directed by molecular profiling.

Anti-tumor effect of endostatin in a sleep-apnea mouse model with tumor.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with cancer incidence and mortality. The underlying mechanism is unclear. This study aims to evaluate the influence of intermittent hypoxia (IH), a novel hallmark of OSA, on tumor and to access the anti-tumor effect of endostatin on a mouse model with OSA. METHODS: The C57BL/6 J mice were randomly classified into four groups: control (normoxia) (CTL), control plus endostatin (CTL + ED), IH, and IH plus endostatin (IH + ED). Mice in IH and IH + ED groups were subjected to IH 8 h per day in 5 weeks. Lewis lung cancer cells were injected into the flank of each mouse after 1 week of IH exposure. Endostatin was also intraperitoneally injected after tumor volume reached about 200 mm3. The maximum standard uptake values (SUVmax) were detected by micro-positron emission tomography-computed tomography (micro-PET-CT) imaging prior and post-endostatin administration. Microvessel density (MVD) and vascular endothelial growth factor (VEGF) were determined for evaluating the anti-tumor effect of endostatin among the normoxia and IH conditions. RESULTS: Mice had higher SUVmax in the IH group than the CTL group (p < 0.01). When compared with mice in the CTL group, those in the IH group had significantly greater MVD values (p < 0.001). The SUVmax can be attenuated by endostatin both in the CTL (p < 0.01) and IH conditions (p < 0.001). When compared with CTL group, mice in the IH group had increased MVD values (p < 0.001) and VEGF expression both at mRNA (p < 0.05) and protein levels (p < 0.001 in western blotting results). Treatment with endostatin attenuated serum and tissue VEGF levels, lowering the MVD values. As compared to normoxia condition, the endostatin-therapeutic effects were more significant under the IH condition (p < 0.05 in western blotting results). CONCLUSIONS: Micro-PET-CT imaging is a promising non-invasive technique to evaluate the tumor metabolic characteristics under IH condition in vivo. The anti-tumor effect of endostatin under IH condition is superior to that of the normoxia condition.

Effect of oxidized soybean oils on oxidative status and intestinal barrier function in broiler chickens

The objective of this study was to evaluate the effect of oxidized soybean oils on the growth performance, metabolic oxidative status and intestinal barrier function of broiler chickens. A total of 240 one-day-old female broiler chickens were assigned to four dietary treatments with six replicates (cages) of 10 birds each. The dietary treatments comprised of a basal diet supplemented with 4% of: non-oxidized (fresh) soybean oil (control treatment, SNX); lowly-oxidized soybean oil (SLX) (oil heated for 10h at 200°C); moderately-oxidized soybean oil (SMX) (oil heated for 18h at 200°C); or highly-oxidized soybean oil (SHX) (oil heated for 30h at 200°C). Diets and water were offered ad libitum. The experiment was lasted 21d.The growth performance of broilers, determined from 1 to 14 d and from 1 to 21 d of age, was not affected by the dietary treatments (p>0.05). Broilers fed oxidized soybean oils presented higher corticosterone serum levels compared with those fed non-oxidized oil (p<0.05). Higher malondialdehyde (MDA) levels onday14 and 21 (p<0.05), and lower total antioxidant capacity (T-AOC) and totalsuperoxide dismutase (T-SOD) values on day 21were obtained in the liver of broiler fed oxidized oils relative to those fed the non-oxidized oil (p<0.05). Broilers fed the highly-oxidized soybean oil had higher (p<0.05) MDA levels in the jejunum on day 21 compared with those fed non-oxidized soybean oil. Chickens fed moderately- and highly-oxidized soybean oil presented lower (p<0.05) T-SOD activity inileal mucosa compared with those fed non-oxidized soybean oil. Ileal mRNA expression of claudin-1 tended to be down regulated by the dietary addition of oxidized oils (p=0.056). The mRNA expression of interleukin-22 (IL-22) of broilers fed moderately-oxidized and highly-oxidized soybean oil was higher (p<0.05), and the mRNA expression of occludin and catalase was lower (p<0.05) than those fed non-oxidized soybean oil. However, the morphology of the jejunal and ileal...(AU)

Effect of oxidized soybean oils on oxidative status and intestinal barrier function in broiler chickens

The objective of this study was to evaluate the effect of oxidized soybean oils on the growth performance, metabolic oxidative status and intestinal barrier function of broiler chickens. A total of 240 one-day-old female broiler chickens were assigned to four dietary treatments with six replicates (cages) of 10 birds each. The dietary treatments comprised of a basal diet supplemented with 4% of: non-oxidized (fresh) soybean oil (control treatment, SNX); lowly-oxidized soybean oil (SLX) (oil heated for 10h at 200°C); moderately-oxidized soybean oil (SMX) (oil heated for 18h at 200°C); or highly-oxidized soybean oil (SHX) (oil heated for 30h at 200°C). Diets and water were offered ad libitum. The experiment was lasted 21d.The growth performance of broilers, determined from 1 to 14 d and from 1 to 21 d of age, was not affected by the dietary treatments (p>0.05). Broilers fed oxidized soybean oils presented higher corticosterone serum levels compared with those fed non-oxidized oil (p<0.05). Higher malondialdehyde (MDA) levels onday14 and 21 (p<0.05), and lower total antioxidant capacity (T-AOC) and totalsuperoxide dismutase (T-SOD) values on day 21were obtained in the liver of broiler fed oxidized oils relative to those fed the non-oxidized oil (p<0.05). Broilers fed the highly-oxidized soybean oil had higher (p<0.05) MDA levels in the jejunum on day 21 compared with those fed non-oxidized soybean oil. Chickens fed moderately- and highly-oxidized soybean oil presented lower (p<0.05) T-SOD activity inileal mucosa compared with those fed non-oxidized soybean oil. Ileal mRNA expression of claudin-1 tended to be down regulated by the dietary addition of oxidized oils (p=0.056). The mRNA expression of interleukin-22 (IL-22) of broilers fed moderately-oxidized and highly-oxidized soybean oil was higher (p<0.05), and the mRNA expression of occludin and catalase was lower (p<0.05) than those fed non-oxidized soybean oil. However, the morphology of the jejunal and ileal...

Stromal expression of JNK1 and VDR is associated with the prognosis of esophageal squamous cell carcinoma.

PURPOSE: Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers worldwide, and its outcome is poor. The purpose of this study was to determine the association between JNK1 and vitamin D receptor (VDR) expression and the prognosis of ESCC. METHODS: Immunohistochemical staining was conducted on ESCC tissue microarrays (362 pairs of ESCC and normal esophagus tissues). The epithelial and stromal expression levels of c-jun NH2-terminal kinase 1 (JNK1) and VDR were scored and correlated with the ESCC characteristics. Laser-capture-based quantitative RT-PCR was performed on ESCC tissues. The effects of JNK1 and VDR on ESCC cell proliferation and migration were analyzed in vitro by transient transfection, and protein changes were evaluated by immunoblotting. RESULTS: Both JNK1 and VDR were reduced in ESCC epithelial cells in comparison with the normal esophagus, but the expression of JNK1 and VDR in ESCC stromal tissues, not epithelial cells, was strongly associated with the survival time of ESCC patients. Functional studies showed that increased JNK1 suppressed cancer cell proliferation, mobility, and migration, which were linked to the alterations of VDR and metastasis-associated proteins. CONCLUSION: JNK1 and VDR act as tumor suppressors, and their stromal expression levels are associated with prognosis in esophageal squamous cell carcinoma.

Analysis of serum microRNA expression in male workers with occupational noise-induced hearing loss.

Occupational noise-induced hearing loss (ONIHL) is a prevalent occupational disorder that impairs auditory function in workers exposed to prolonged noise. However, serum microRNA expression in ONIHL subjects has not yet been studied. We aimed to compare the serum microRNA expression profiles in male workers of ONIHL subjects and controls. MicroRNA microarray analysis revealed that four serum microRNAs were differentially expressed between controls (n=3) and ONIHL subjects (n=3). Among these microRNAs, three were upregulated (hsa-miR-3162-5p, hsa-miR-4484, hsa-miR-1229-5p) and one was downregulated (hsa-miR-4652-3p) in the ONIHL group (fold change >1.5 and Pbon value <0.05). Real time quantitative PCR was conducted for validation of the microRNA expression. Significantly increased serum levels of miR-1229-5p were found in ONIHL subjects compared to controls (n=10 for each group; P<0.05). A total of 659 (27.0%) genes were predicted as the target genes of miR-1229-5p. These genes were involved in various pathways, such as mitogen-activated protein kinase (MAPK) signaling pathway. Overexpression of miR-1229-5p dramatically inhibited the luciferase activity of 3' UTR segment of MAPK1 (P<0.01). Compared to the negative control, HEK293T cells expressing miR-1229-5p mimics showed a significant decline in mRNA levels of MAPK1 (P<0.05). This preliminary study indicated that serum miR-1229-5p was significantly elevated in ONIHL subjects. Increased miR-1229-5p may participate in the pathogenesis of ONIHL through repressing MAPK1 signaling.

MRI-guided radiotherapy for head and neck cancer: initial clinical experience.

PURPOSE: To report a single-institutional experience with the use of magnetic resonance imaging (MRI)-guided radiotherapy for cancers of the head and neck. MATERIALS AND METHODS: Between October 2014 and October 2016, 18 patients with newly diagnosed cancers of the head and neck were prospectively enrolled on an institutional registry trial investigating the feasibility and efficacy of external-beam radiotherapy delivered using on-board MRI. All patients had biopsy-proven evidence of malignancy, measurable disease, and the ability to provide consent. None had previously received any treatment. Median dose was 70 Gy (range 54-70 Gy). MRI scans were obtained as part of an image-guided registration protocol for alignment prior to and during each treatment. Concurrent chemotherapy was administered to 14 patients (78%). Patient-reported outcomes were assessed using the University of Washington quality of life instrument. RESULTS: Seventeen of 18 patients completed the planned intensity-modulated radiotherapy (IMRT) treatment of which 15 (83%) had a complete response and 2 (11%) had a partial response based on initial post-therapy positron emission tomography (PET) at 3 months. The 1-year estimates of progression-free survival, overall survival, and local-regional control were 95, 96, and 95%, respectively. There were no treatment-related fatalities. The incidence of grade 3+ acute toxicity was 44%. The proportion of patients rating their health-related quality of life as "very good" or "outstanding" at 6 months and 1 year after completion of radiation therapy was 60 and 70%, respectively. CONCLUSIONS: MRI-guided radiotherapy achieves clinical outcomes comparable to contemporary series reporting on IMRT for head and neck cancer.

Sustained Posttransplantation Diabetes Is Associated With Long-Term Major Cardiovascular Events Following Liver Transplantation.

Cardiovascular disease is a leading cause of death among liver transplant (LT) recipients. With a rising burden of posttransplantation metabolic disease, increases in cardiovascular-related morbidity and mortality may reduce life expectancy after LT. It is unknown if the risk of long-term major cardiovascular events (MCEs) differs among LT recipients with varying diabetic states. We performed a retrospective cohort study of LT recipients from 2003 through 2013 to compare the incidence of MCEs among patients (1) without diabetes, (2) with pretransplantation diabetes, (3) with de novo transient posttransplantation diabetes, and (4) with de novo sustained posttransplantation diabetes. We analyzed 994 eligible patients (39% without diabetes, 24% with pretransplantation diabetes, 16% with transient posttransplantation diabetes, and 20% with sustained posttransplantation diabetes). Median follow-up was 54.7 months. Overall, 12% of patients experienced a MCE. After adjustment for demographic and clinical variables, sustained posttransplantation diabetes was the only state associated with a significantly increased risk of MCEs (subdistribution hazard ratio 1.95, 95% confidence interval 1.20-3.18). Patients with sustained posttransplantation diabetes mellitus had a 13% and 27% cumulative incidence of MCEs at 5 and 10 years, respectively. While pretransplantation diabetes has traditionally been associated with cardiovascular disease, the long-term risk of MCEs is greatest in LT recipients with sustained posttransplantation diabetes mellitus.

Clinicopathologic parameters associated with postoperative complications and risk factors for tumor recurrence and mortality after tumor resection of patients with colorectal cancer.

OBJECTIVE: To delineate the association of postoperative complications with clinicopathologic factors and to identify risk factors for tumor recurrence and mortality after tumor resection in patients with colorectal cancer (CRC). METHODS: The clinical data of 1144 patients with CRC who underwent surgical intervention between 2003 and 2013 were retrieved. Correlations of postoperative complications with clinicopathologic factors were examined using univariate analysis. Risk factors for tumor recurrence and mortality of the patients after tumor resection were identified using multivariate Cox proportional hazards models. Time to relapse and overall survival were analyzed using log-rank test of Kaplan-Meier analysis. RESULTS: Blood carcinoembryonic antigen (CEA) significantly correlated with early symptoms, preoperative manifestations, and tumor pathology. Low differentiation grade of tumor increased the risk of recurrence after surgery in all patients with CRC. In the same cohort of patients, elevated blood CEA, low differentiation grade of tumor, laparotomy, smoking history, and TNM stage IV and III increased the mortality risk after tumor resection. In patients with advanced colon cancer, risk for postoperative mortality was increased by blood CEA, advanced tumor stage, and low tumor differentiation grade; while in those with advanced rectal cancer, blood CEA, pathologic type other than mucinous/adenocarcinoma, and laparotomy were identified as significant risk factors. In both groups of patients, postoperative chemotherapy significantly reduced the risk of mortality. CONCLUSIONS: The present work has identified clinical factors increasing the risk of recurrence as well as mortality after surgery in more than 1,000 patients with CRC. Postoperative chemotherapy is associated with a significant reduction in the risk of mortality. All of these findings should provide insights into the better management of critically ill patients with CRC.

Analysis of serum microRNA expression in male workers with occupational noise-induced hearing loss

Occupational noise-induced hearing loss (ONIHL) is a prevalent occupational disorder that impairs auditory function in workers exposed to prolonged noise. However, serum microRNA expression in ONIHL subjects has not yet been studied. We aimed to compare the serum microRNA expression profiles in male workers of ONIHL subjects and controls. MicroRNA microarray analysis revealed that four serum microRNAs were differentially expressed between controls (n=3) and ONIHL subjects (n=3). Among these microRNAs, three were upregulated (hsa-miR-3162-5p, hsa-miR-4484, hsa-miR-1229-5p) and one was downregulated (hsa-miR-4652-3p) in the ONIHL group (fold change >1.5 and Pbon value <0.05). Real time quantitative PCR was conducted for validation of the microRNA expression. Significantly increased serum levels of miR-1229-5p were found in ONIHL subjects compared to controls (n=10 for each group; P<0.05). A total of 659 (27.0%) genes were predicted as the target genes of miR-1229-5p. These genes were involved in various pathways, such as mitogen-activated protein kinase (MAPK) signaling pathway. Overexpression of miR-1229-5p dramatically inhibited the luciferase activity of 3′ UTR segment of MAPK1 (P<0.01). Compared to the negative control, HEK293T cells expressing miR-1229-5p mimics showed a significant decline in mRNA levels of MAPK1 (P<0.05). This preliminary study indicated that serum miR-1229-5p was significantly elevated in ONIHL subjects. Increased miR-1229-5p may participate in the pathogenesis of ONIHL through repressing MAPK1 signaling.

Cerebrospinal fluid-contacting nucleus mediates nociception via release of fractalkine.

Increasing evidence suggests that the cerebrospinal fluid-contacting nucleus (CSF-contacting nucleus) mediates the transduction and regulation of pain signals. However, the precise molecular mechanisms remain unclear. Studies show that release of fractalkine (FKN) from neurons plays a critical role in nerve injury-related pain. We tested the hypothesis that release of FKN from the CSF-contacting nucleus regulates neuropathic pain, in a chronic constriction injury rat model. The results show that FKN is expressed by neurons, via expression of its only receptor CX3CR1 in the microglia. The levels of soluble FKN (sFKN) were markedly upregulated along with the increase in FKN mRNA level in rats subjected to chronic constriction injury. In addition, injection of FKN-neutralizing antibody into the lateral ventricle alleviated neuropathic pain-related behavior followed by reduction in microglial activation in the CSF-contacting nucleus. The results indicate that inhibition of FKN release by the CSF-contacting nucleus may ameliorate neuropathic pain clinically.