The inhibition of VDAC1 oligomerization promotes pigmentation through the CaMK-CRTCs/CREB-MITF pathway.

The voltage-dependent anion channel 1 (VDAC1) forms an oligomeric structure on the mitochondrial outer membrane, which plays critical roles in many physiological processes. Research studies have demonstrated that the knockout of VDAC1 increases pigment content and up-regulates the expression of melanogenic genes. Due to its involvement in various physiological processes, the depletion of VDAC1 has significant detrimental effects on cellular functions and the inhibition of VDAC1 oligomerization has recently emerged as a promising strategy for the treatment of several diseases. In this study, we found that VDAC1 oligomerization inhibitors, VBIT-12 and NSC-15364, promote melanogenesis, dendrite formation and melanosome transport in human epidermal melanocytes (HEMCs). Mechanistically, treatment of HEMCs with an oligomerization inhibitor increased the level of cytoplasmic calcium ions, which activated calcium-calmodulin dependent protein kinase (CaMK) and led to the phosphorylation of CREB and the nuclear translocation of CREB-regulated transcription coactivators (CRTCs). Subsequently, CRTCs, p-CREB and CREB-binding protein (CBP) in the nucleus cooperatively recruit the transcription machinery to initiate the transcription of MITF thus promoting pigmentation. Importantly, our study also demonstrates that VDAC1 oligomerization inhibitors increase pigmentation in zebrafish and in human skin explants, highlighting their potential as a therapeutic strategy for skin pigmentation disorders.

Cholesterol-induced HRD1 reduction accelerates vascular smooth muscle cell senescence via stimulation of endoplasmic reticulum stress-induced reactive oxygen species.

Senescence of vascular smooth muscle cells (VSMCs) is a key contributor to plaque vulnerability in atherosclerosis (AS), which is affected by endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) production. However, the crosstalk between ER stress and ROS production in the pathogenesis of VSMC senescence remains to be elucidated. ER-associated degradation (ERAD) is a complex process that clears unfolded or misfolded proteins to maintain ER homeostasis. HRD1 is the major E3 ligase in mammalian ERAD machineries that catalyzes ubiquitin conjugation to the unfolded or misfolded proteins for degradation. Our results showed that HRD1 protein levels were reduced in human AS plaques and aortic roots from ApoE-/- mice fed with high-fat diet (HFD), along with the increased ER stress response. Exposure to cholesterol in VSMCs activated inflammatory signaling and induced senescence, while reduced HRD1 protein expression. CRISPR Cas9-mediated HRD1 knockout (KO) exacerbated cholesterol- and thapsigargin-induced cell senescence. Inhibiting ER stress with 4-PBA (4-Phenylbutyric acid) partially reversed the ROS production and cell senescence induced by HRD1 deficiency in VSMCs, suggesting that ER stress alone could be sufficient to induce ROS production and senescence in VSMCs. Besides, HRD1 deficiency led to mitochondrial dysfunction, and reducing ROS production from impaired mitochondria partly reversed HRD1 deficiency-induced cell senescence. Finally, we showed that the overexpression of HDR1 reversed cholesterol-induced ER stress, ROS production, and cellular senescence in VSMCs. Our findings indicate that HRD1 protects against senescence by maintaining ER homeostasis and mitochondrial functionality. Thus, targeting HRD1 function may help to mitigate VSMC senescence and prevent vascular aging related diseases. TRIAL REGISTRATION: A real-world study based on the discussion of primary and secondary prevention strategies for coronary heart disease, URL:https://www.clinicaltrials.gov, the trial registration number is [2022]-02-121-01.

Real-world data of immunotherapy from China in recurrent or metastatic head and neck squamous cell carcinoma.

PURPOSE: Immune checkpoint inhibitors (ICIs) have become a standard therapy for recurrent or metastatic head and neck squamous cell carcinoma (R/MHNSCC), however, there are still unanswered questions about immunotherapy. Furthermore, immunotherapy for R/MHNSCC of the mainland Chinese population are lacking. The aim of this study is to evaluate the efficacy and safety of ICIs in real-world settings in China. MATERIALS AND METHODS: We retrospectively reviewed 59 patients with R/MHNSCC who received immunotherapy between May 2019 and December 2021. We assessed demographics, efficacy, survival and safety. RESULTS: Fifty-nine patients were included in the study, all of whom had R/MHNSCC affecting the oral cavity, oropharynx, hypopharynx, larynx, nasal cavity, paranasal sinuses and metastatic cancer in the neck with an unknown primary. The objective response rate (ORR) for all patients was found to be 40.6 %. Out of these patients, 11 patients achieved a complete response and 13 achieved a partial response. The median progression-free survival (PFS) was calculated to be 10.64 months (range: 1.15-29.24 months), while the median overall survival (OS) was 21.75 months (range 2.0-37.55 months). The addition of local radiotherapy resulted in higher ORR and PFS compared to previous reports. Notably, patients with R/MHNSCC in the paranasal sinuses and nasal cavity also showed benefits from immunotherapy. Additionally, patients who achieved stable disease (SD) had similar survival rates to those who achieved partial response (PR), indicating that SD is also an indicator of clinical benefit from immunotherapy. The overall incidence of immune-related adverse reactions in this study was low, with fatigue and rash being the most common side effects. CONCLUSION: These findings highlight the effectiveness and safety of immunotherapy for R/MHNSCC in a real-world setting in China. Further investigation is warranted to explore the potential benefits of incorporating local radiotherapy into the treatment of R/MHNSCC.

[Research progress in chemical constituents and pigment extraction process of Carthami Flos].

Carthami Flos(flowers of Carthamus tinctorius) with the effects of activating blood, dredging meridians, dissipating stasis, and relieving pain is one of the commonly used traditional Chinese medicines for promoting blood circulation and resolving stasis in clinical practice. So far, more than 210 compounds in Carthami Flos have been isolated and reported, including quinochalcones(safflower yellow pigments and red pigments), flavonoids, spermidines, alkaloids, polyacetylenes, and organic acids. Safflower yellow pigments, as the main water-soluble active components of Carthami Flos, is commonly obtained by the water extraction method, while red pigments are commonly obtained by the alkali extraction and acid precipitation method. In recent years, natural deep eutectic solvents as green solvents have demonstrated promising application prospects in the extraction and separation of pigments from Carthami Flos. This review systematically summarizes the chemical constituents of Carthami Flos and analyzes the extraction process of pigment components from Carthami Flos, aiming to provide a reference for further utilization of Carthami Flos resources.

The two sides of resistance-resilience relationship in both aboveground and belowground communities in the Eurasian steppe.

The ongoing nitrogen (N) deposition has led to profound changes in aboveground and belowground ecosystems. However, the stability of plant and soil microbial community toward N addition in terms of resistance and resilience is less understood. We established a long-running field trial (2008-2018) in a series of N applications in combination with a mowing and fencing (unmown) treatment in a semiarid steppe. We assessed the resistance via ongoing N treatment of one subplot and the resilience via discontinuing N treatment in another to promote natural recovery since 2014. Plant resistance was negatively correlated with N application rate, while microbial resistance was independent of N rate. Mowing significantly reduced plant resistance and resilience, reduced soil microbial resistance but improved its resilience. Generally, plants are more resilient but less resistant to N than soil microbes. The two sides of resistance-resilience relationship were revealed: trade-offs exist between resistance and resilience for both plants and microbes at the community level; and trade-offs between resistance and resilience cannot be scaled down to species/group level. This study provided an important theoretical basis for the recovery and conservation of semiarid steppe and new insight into resistance-resilience relationship.

Evidence of cure for extranodal nasal-type natural killer/T-cell lymphoma with current treatment: an analysis of the CLCG database.

Survival from extranodal nasal-type NK/T-cell lymphoma (ENKTCL) has substantially improved over the last decade. However, there is little consensus as to whether a population of patients with ENKTCL can be considered "cured" of the disease. We aimed to evaluate the statistical "cure" of ENKTCL in the modern treatment era. This retrospective multicentric study reviewed the clinical data of 1,955 patients with ENKTCL treated with non-anthracycline-based chemotherapy and/or radiotherapy in the China Lymphoma Collaborative Group multicenter database between 2008 and 2016. A non-mixture cure model with incorporation of background mortality was fitted to estimate cure fractions, median survival times and cure time points. The relative survival curves attained plateau for the entire cohort and most subsets, indicating that the notion of cure was robust. The overall cure fraction was 71.9%. The median survival was 1.1 years in uncured patients. The cure time was 4.5 years, indicating that beyond this time, mortality in ENKTCL patients was statistically equivalent to that in the general population. Cure probability was associated with B symptoms, stage, performance status, lactate dehydrogenase, primary tumor invasion, and primary upper aerodigestive tract site. Elderly patients (>60 years) had a similar cure fraction to that of younger patients. The 5-year overall survival rate correlated well with the cure fraction across risk-stratified groups. Thus, statistical cure is possible in ENKTCL patients receiving current treatment strategies. Overall probability of cure is favorable, though it is affected by the presence of risk factors. These findings have a high potential impact on clinical practice and patients' perspective.

Outcome and risk prediction of early progression in patients with extranodal natural killer/T cell lymphoma from the CLCG study.

Recently, progression-free survival at 24 months (PFS24) was defined as clinically relevant for patients with extranodal NK/T cell lymphoma. Herein, the clinical data from two independent random cohorts (696 patients each in the primary and validation datasets) were used to develop and validate a risk index for PFS24 (PFS24-RI), and evaluate its ability to predict early progression. Patients achieving PFS24 had a 5-year overall survival (OS) of 95.8%, whereas OS was only 21.2% in those failing PFS24 (P<0.001). PFS24 was an important predictor of subsequent OS, independent of risk stratification. The proportion of patients achieving PFS24 and 5-year OS rates correlated linearly among risk-stratified groups. Based on multivariate analysis of the primary dataset, the PFS24-RI included five risk factors: stage II or III/IV, elevated lactate dehydrogenase, Eastern Cooperative Oncology Group score ≥2, primary tumor invasion, and extra-upper aerodigestive tract. PFS24-RI stratified the patients into low-risk (0), intermediate-risk (1-2), high-risk (≥3) groups with different prognoses. Harrell's C-index of PFS24-RI for PFS24 prediction was 0.667 in the validation dataset, indicating a good discriminative ability. PFS24-RI calibration indicated that the actual observed and predicted probability of failing PFS24 agreed well. PFS24-RI provided the probability of achieving PFS24 at an individual patient level.

HRD1 reduction promotes cholesterol-induced vascular smooth muscle cell phenotypic change via endoplasmic reticulum stress.

Phenotypic change of vascular smooth muscle cells (VSMCs) is the main contributor of vascular pathological remodeling in atherosclerosis. The endoplasmic reticulum (ER) is critical for maintaining VSMC function through elimination of misfolded proteins that impair VSMC cellular function. ER-associated degradation (ERAD) is an ER-mediated process that controls protein quality by clearing misfolded proteins. One of the critical regulators of ERAD is HRD1, which also plays a vital role in lipid metabolism. However, the function of HRD1 in VSMCs of atherosclerotic vessels remains poorly understood. The level of HRD1 expression was analyzed in aortic tissues of mice fed with a high-fat diet (HFD). The H&E and EVG (VERHOEFF'S VAN GIESON) staining were used to demonstrate pathological vascular changes. IF (immunofluorescence) and WB (western blot) were used to explore the signaling pathways in vivo and in vitro. The wound closure and transwell assays were also used to test the migration rate of VSMCs. CRISPR gene editing and transcriptomic analysis were applied in vitro to explore the cellular mechanism. Our data showed significant reduction of HRD1 in aortic tissues of mice under HFD feeding. VSMC phenotypic change and HRD1 downregulation were detected by cholesterol supplement. Transcriptomic and further analysis of HRD1-KO VSMCs showed that HRD1 deficiency induced the expression of genes related to ER stress response, proliferation and migration, but reduced the contractile-related genes in VSMCs. HRD1 deficiency also exacerbated the proliferation, migration and ROS production of VSMCs induced by cholesterol, which promoted the VSMC dedifferentiation. Our results showed that HRD1 played an essential role in the contractile homeostasis of VSMCs by negatively regulating ER stress response. Thus, HRD1 in VSMCs could serve as a potential therapeutic target in metabolic disorder-induced vascular remodeling.

Experience of patients with diabetic retinopathy: A qualitative study.

AIMS: To understand the status quo and needs of self-management of patients with diabetic retinopathy (DR) and to provide a reference for formulating management programs that meet the needs of these patients. DESIGN: A qualitative interview study. METHODS: Semi-structured, in-depth interviews were conducted between November and December 2021. A purposive sample of 15 patients with DR who were hospitalized in the Retinal Department of Eye Hospital was recruited. Colaizzi's analysis was used to organize and analyse the interview data. This study followed the Consolidated Criteria for Reporting Qualitative Research (COREQ) checklist. RESULTS: The experience of patients with DR can be summarized into four themes: (1) lack of DR knowledge, (2) low quality of life, (3) poor self-management behaviour and (4) seek for support from many aspects. CONCLUSION: Patients with DR lack disease knowledge and have poor self-management abilities and adherence. Medical staff should provide personalized care according to the patient's self-management status and needs, promote the establishment of self-management behaviours and prevent and delay disease progression. IMPACT: This study helps assist medical staff in the early management of patients with DR and provides a reference for the construction of prevention programs for patients.

C-Reactive Protein in Bipolar Disorder and Unipolar Depression.

ABSTRACT: This study aimed to explore the role of C-reactive protein (CRP) in the pathological mechanism and differential diagnoses of bipolar disorder (BD) and unipolar depression (UD). We tested serum CRP levels of 176 BD and 86 UD patients, and 82 healthy controls (HCs), at acute and remission phases. In the acute phase, CRP levels were higher in BD than in UD patients and HC, and lower in UD patients than in HC. The CRP levels of BD patients in a manic episode were higher than those of HC; in a depressive or mixed episode, they were comparable to those of HC. The CRP levels of BD and UD patients during an acute depressive episode yielded an area under the curve of 0.676. CRP may be a state marker of acute manic episodes in BD and acute depressive episodes in UD, and a biomarker for distinguishing BD and UD.

Comparative study of Curcumin and Lucentis on retinal neovascularization.

Introduction To investigate the effect of Curcumin on retinal neovascularization in mice with oxygen-induced lesions. Methods 7-day-old (P7) C57/BL6J mice were randomly divided into control group, OIR group, DMSO group, 100 mg/kg, 50 mg/kg and 25 mg/kg curcumin group and Lucentis group (15 mice per group). Mice in the experimental group were fed for 5 days in high oxygen partial pressure environment, and then in normal oxygen air environment for another 5 days. Corresponding interventions were given at 12-16 days of age (P12-16). At 17 days of age (P17), the eyeball was removed and the retina was paved with Isolectin GS-IB4 fluorescence staining. Real-time PCR was used to detect VEGF mRNA levels in tissues and cells. The protein expression level of VEGF was detected by Western blot. Results Immunofluorescence showed that curcumin injection could significantly reduce the formation of retinal neovascularization and astrocyte injury in OIR, and 100 mg/kg curcumin group had the best effect. Compared with the control group, mRNA and protein expression of VEGF in retina of mice in OIR and DMSO groups were significantly up-regulated (P<0.05); Compared with OIR group, curcumin group and Lucentis group were down-regulated (P<0.05). The protein expression and mRNA level of VEGF in HRCECs of curcumin group decreased with the increase of curcumin concentration, and the effect of curcumin group at 80µmol/L was similar to that of Lucentis group. In the HRCECs cultured with the same concentration of curcumin, the protein expression and mRNA level of VEGF decreased with the prolongation of drug intervention time. Conclusion Curcumin can down-regulate the expression of VEGF in retinal tissues and cells, thereby inhibiting retinal neovascularization and HRCECs cell proliferation.

Hypoxic drive caused type 3 neovascularization in a preclinical model of exudative age-related macular degeneration.

Hypoxia associated with the high metabolic demand of rods has been implicated in the pathology of age-related macular degeneration (AMD), the most common cause of adult blindness in the developed world. The majority of AMD-associated severe vision loss cases are due to exudative AMD, characterized by neovascularization. To further investigate the causes and histopathology of exudative AMD, we conditionally induced hypoxia in a novel preclinical AMD model (Pde6gcreERT2/+;Vhl-/-) by targeting Vhl and used multimodal imaging and immunohistochemistry to track the development of hypoxia-induced neovascularization. In addition to developing a preclinical model that phenocopies exudative AMD, our studies revealed that the photoreceptor hypoxic response initiates and drives type 3 neovascularization, mainly in the outer retina. Activation of the VHL-HIF1a-VEGF-EPO pathway in the adult retina led to long-term neovascularization, retinal hemorrhages and compromised retinal layers. Our novel preclinical model would accelerate the testing of therapies that use metabolomic approaches to ameliorate AMD.

Application of vermicompost and biochar suppresses Fusarium root rot of replanted American ginseng.

Soil sterilization integrated with agronomic measures is an effective method to reduce soilborne replant diseases. However, the effect of vermicompost or biochar application after soil sterilization on soilborne diseases is poorly understood. A pot experiment was conducted in American ginseng to investigate the effects of vermicompost (VF), biochar (BF), and a combination of vermicompost and biochar (VBF) applied after soil sterilization on the incidence of Fusarium root rot using natural recovery (F) as control. After one growing season, the disease index of root rot, the phenolic acids, and the microbial communities of American ginseng rhizosphere soil were analyzed. The disease index of VF, BF, and VBF decreased by 33.32%, 19.03%, and 80.96%, respectively, compared with F. The highest bacterial richness and diversity were observed in the rhizosphere soil of VBF. Besides, VF and VBF significantly increased the relative abundance of beneficial bacteria (Pseudomonas, Lysobacter, and Chryseolinea) in the rhizosphere soil. Higher concentrations of vanillin, one of the phenolic acids in the roots exudates, were recorded in the rhizosphere soils of BF and VBF. The vanillin concentration showed a significant negative correlation with the disease index. To conclude, vermicompost improved the beneficial bacteria of the rhizosphere soil, while biochar regulated the allelopathic effect of the phenolic acids. The study proposes a combined application of biochar and vermicompost to the rhizosphere soil to control Fusarium root rot of replanted American ginseng effectively. KEY POINTS: Vermicompost improves the relative abundance of rhizosphere beneficial bacteria. Biochar inhibits the degradation of phenolic acids by adsorption. The combination of vermicompost and biochar enhances the disease control effect.

Salvianolic acid B improved insulin resistance through suppression of hepatic ER stress in ob/ob mice.

Impaired insulin sensitivity of insulin-sensitive tissues plays a major role in the pathogenesis of type 2 diabetes, salvianolic acid B (SalB), a natural antioxidant usually treated various cardiovascular diseases was also reported potential utility on diabetes and dyslipidemia. Based on these, we aimed to explored whether the antioxidant effect of SalB play a pivotal role in the molecular mechanisms leading to insulin resistance. We found that SalB improved glucose tolerance and insulin sensitivity, decreased serum ALT, AST and ALP levels of ob/ob mice. Also, transcription of Bip and CHOP, phosphorylation of PERK and IRE1 for endoplasmic reticulum stress (ER) and phosphorylation of IRS-1 for insulin sensitivity in the liver of ob/ob mice were relieved by SalB. Further, SalB decreased phosphorylation of PERK, IRE1 and IRS1 and transcription of Bip and CHOP stimulated by palmitate of hepatic cells HL7702, but did not reversed phosphorylation of JNK and IRS1 and transcription of Bip and CHOP when ER stress was stimulated by tunicamycin. These data shows that SalB improved insulin resistance of ob/ob mice through suppression of hepatic ER stress.

The progress and prospect of regulatory T cells in autoimmune diseases.

Regulatory T cells (Treg) are an important immune cell population, playing a crucial role in regulating immune tolerance and preventing autoimmune diseases. These cells consist of various cell sub-populations and generally have an immunoregulatory or suppressive role against immune responses. They also have a different cell heterogeneity and each populations has own biological characteristics. Treg deficiency, reduction, instability, reduced vitality and dysfunction all account for multiple autoimmune diseases. In this review, we have systemically reviewed Treg classification, phenotypic features, regulation of Foxp3 expression, plasticity and stability of Treg as well as their relationship with several important autoimmune diseases. We particularly focus on why and how inflammatory and diet environments affect the functional capacity and underlying mechanisms of Treg cell populations. We also summarize new advances in technologies which help to analyze and dissect these cells in molecular levels in-depth. We also clarify the possible clinical relevance on application of these cells in patients with autoimmune diseases. The advantages and weaknesses have been carefully discussed as well. We also propose the possible approaches to overcome these weaknesses of Treg cells in complicate environments. Thus, we have displayed the updated knowledge of Treg cells, which provides an overall insight into the role and mechanisms of Treg cells in autoimmune diseases.

Clinical analysis and predictive factors associated with improved visual acuity of infectious endophthalmitis.

BACKGROUND: To describe the clinical characteristics and analyze the predictive factors associated with improved visual acuity of 359 patients with infectious endophthalmitis. METHODS: This study retrospectively analyzed 359 eyes of 359 patients with infectious endophthalmitis from January 2014 to December 2018. The findings summarized some epidemiological characteristics of these patients, including age, sex, occupation, patient visit time, etiology, causative organisms, therapy, and best-corrected visual acuity. Multivariate logistic regression was performed to predict the relative factors of improved visual acuity (VA). RESULTS: Overall, 283 (78.83%) patients were male. The mean age was 48.0 ± 18.27 years. Ocular trauma, especially open globe injuries (246, 68.5%) was the most common etiology of infectious endophthalmitis in this study. The etiologies of infectious endophthalmitis were open globe injuries (68.5%), intraocular surgery (22.6%), and corneal ulcer-associated (6.7%) and endogenous causes (2.2%). In the etiology classification and visual acuity improvement group, had statistically significant differences in factors such as age, sex, patient visit time, pre-therapy visual acuity, etc. The average Logarithm of the Minimum Angle of Resolution (logMAR) best-corrected visual acuity on pre-therapy was 2.28 ± 0.60, and it had significantly improved to 1.67 ± 0.83 post-therapy (P < 0.05). Logistic regression analysis showed that visit time > 7 day (P = 0.034, OR = 0.522, 95% CI: 0.286-0.953), pre-therapy VA ≦logMAR 2.3 (P = 0.032, OR = 1.809, 95% CI: 1.052-3.110), post-surgical (vs. posttraumatic; P = 0.023, OR = 2.100, 95% CI: 1.109-3.974), and corneal ulcer-associated etiologies (vs. posttraumatic; P = 0.005, OR = 0.202, 95%CI: 0.066-0.621) were significantly associated with improved visual acuity after adjusting for possible confounding factors. CONCLUSIONS: Among the patients with infectious endophthalmitis, middle-aged male, especially farmers and workers, accounted for a large proportion. Open globe injuries were the main cause and the gram-positive bacteria were the major causative organisms. The final visual outcomes seemed to vary according to the type of endophthalmitis, but early treatment and good initial visual acuity were important factors for visual acuity improvement.

First report of root rot caused by Fusarium armeniacum on American ginseng in China.

American ginseng (Panax quinquefolius) is an important medicinal plant cultivated in China since the 1980s. Its dried roots are used for food, health care products, and medicine in China (Yuan et al. 2010). Root rot caused by Fusarium spp. was a major disease, with 33 to 41% incidence surveyed in main production areas of Wendeng County (121.80 °E, 37.09 °N) in Shandong Province, China in 2016 to 2019. Symptoms included soft, water-soaked, dark brown to black lesions on the roots. Lesions progressed and the inner parts gradually disintegrated. One-year-old diseased roots were collected in September 2016. Symptomatic tissues were surface-sterilized in 75% ethanol for 30 s and 0.8% NaOCl for 3 min, rinsed in sterile water, plated on potato dextrose agar (PDA), and incubated at 25°C in darkness. Single colonies were then obtained and transferred to carnation leaf agar (CLA) (Burgess et al. 1993) for growth at 25°C with a 12-h photoperiod. Colonies cultured on PDA for 7 days were white to light pink, turning to apricot pigmentation in color. After 30 days on CLA, the colonies produced elongate, falcate macroconidia having 3 to 5 septa, with a long, tapering and curved apical cell, and having the size ranging from 31.1 to 45.6 µm long x 4 to 4.6 µm wide. Microconidia were zero to 1septate, ellipsoid to ovoid and varied in size from 9.5 to 16.8 µm long x 3 to 3.2 µm wide. Chlamydospores formed abundantly, in chains or clusters. This fungus was identified as F. armeniacum (Burgess et al. 1993). Identification was confirmed by sequencing three DNA regions including the internal spacer ribosomal DNA (ITS), elongation factor 1α and ß-tubulin genes (Lu et al. 2019). The three DNA regions (MN417271, MG457199, and MN427653) had 100% homology to the sequences of F. armeniacum (KJ737378, HM744664 and HQ141640) (Wang et al. 2015, Yli-Mattila et al. 2011). Pathogenicity tests were conducted on 1- to 2-year-old bare roots and 2-year-old whole plants. For root inoculation, 14 healthy roots were inoculated with two mycelial PDA plugs/root. After 3 to 10 days at 25°C, all the inoculated roots showed water-soaked and root rot symptoms while no lesions were observed in the control roots. For plant inoculation, eight seedlings planted in pots filled with sterilized soil were inoculated by pouring a conidial suspension of 1×105 conidia/ml at 30 ml/pot. Eight seedlings inoculated with sterilized water served as the controls. After 90 days, only 37.5% of the roots survived with typical root rot symptoms whereas the control plants remained symptomless. F. armeniacum was re-isolated from symptomatic roots but not from the control roots. Besides F. armeniacum, F. solani and F. oxysporum that have been reported to be associated with American ginseng root rot in China and Canada (Reeleder et al. 2002; Punja et al. 2008) were also obtained from the diseased root samples in this study. However, the development of root rot caused by F. armeniacum was much more rapid and its symptoms were more severe. Moreover, F. armeniacum could directly infect American ginseng with no wound requirement. F. armeniacum was previously reported on Glycine max (Leguminosae) (Ellis et al. 2012), Platycodon grandiflorus (Campanulaceae) (Wang et al. 2015) and natural grasses (Poaceae) (Nichea et al. 2015). This is the first report of F. armeniacum causing root rot on American ginseng in China. As this species is more virulent to American ginseng, more research is needed to work on this disease.

[Effects of nutrients deficiency on growth and saponin accumulation of American ginseng].

Mineral nutrient elements are the key factors to maintain the growth and quality of American ginseng. In order to understand the comprehensive effect of different nutrient elements deficiency on American ginseng, 2-year-old American ginsengs were cultivated by Hoagland solution(CK) or 10 different nutrients deficiency solution in sand culture. During the cultivation, the deficient symptom was observed. The plant height, leaf area, biomass, photosynthetic index, root activity, ginsenoside content were measured. The results showed that N, K or Fe deficiency could lead to leaves of American ginseng yellowing. Deficiency N, K, Ca, Mg and B were the main factors that decrease plant height and leaf area. The biomass of plant decreased significantly in all the nutrient deficient treatments(P<0.05)compared with control group, and N, K, Ca or Fe deficiency groups descended over 50%. In the absence of N, K and Fe elements, the P_n, G_s, C_i, T_r and chlorophyll of leaves were decreased mostly. The first three factors decreasing root activity were N, K and Ca deficiency. The effects of nutrient deficiency on saponins of American ginseng were different.Generally, N, P, B, Zn and Cu deficiency resulted the synthesis of saponins decreased significantly(P<0.05). This study contributed to clarify the demand characteristics of American ginseng for different nutrient elements,which is of great significance for the diagnose of nutrient deficiency, the rational fertilizer and the improvement of yield and quality of American ginseng.

Determination of Risk Factors Related to Supraclavicular Recurrence for Limited-Stage Small Cell Lung Cancer (SCLC) Patients.

BACKGROUND This research aimed to determine high-risk factors of supraclavicular recurrence for limited-stage small cell lung cancer (LS-SCLC) patients to discover a potential subpopulation that can benefit from prophylactic supraclavicular irradiation (PSCI). MATERIAL AND METHODS Between July 2006 and July 2011, LS-SCLC patients without supraclavicular lymph node (SCLN) involvement consecutively treated with concurrent chemo-radiation but without PSCI in the Radiotherapy Department of the Cancer Institute and Hospital of Tianjin Medical University, were retrospectively analyzed. SCLN recurrence rate, overall survival (OS), and distant metastasis-free survival (DMFS) were assessed. Binary logistic regression analysis was conducted to discover the high-risk factors related to the SCLN recurrence. The receiver operating characteristic (ROC) curves were drawn to evaluate logistic regression model prediction performance. RESULTS Eighty-eight LS-SCLC patients were analyzed in this study. During 99 months (ranging from 72 months to 124 months) for survivors, 28 (31.8%) had SCLN recurrence. There were significant differences for median DMFS and OS between LS-SCLC patients with and without SCLN recurrence. The logistic regression model revealed that lymphadenopathy at mediastinal level 2 and level 3 prior to chemotherapy were significantly associated with SCLN recurrence, which was validated by ROC. CONCLUSIONS Lymphadenopathy at mediastinal level 2 and level 3 prior to chemotherapy were the high-risk factors associated with SCLN recurrence for patients with LS-SCLC. Further work is needed to determine whether patients with these factors can benefit from PSCI.