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Objective:To summarize clinical manifestations and histopathological features of granular parakeratosis (GP) after exposure to benzalkonium chloride.Methods:A retrospective analysis was performed on 7 GP cases with a history of benzalkonium chloride exposure in the Department of Dermatology at Wuhan No.1 Hospital from April to August 2022. Data were collected on the general condition, skin lesion manifestations, pathological examination, treatment, and follow-up of the patients, and retrospectively analyzed.Results:The 7 adult patients with GP typically presented with erythema and brown scales in the intertriginous area, exhibiting an annular distribution pattern. All the 7 patients reported recent exposure to disinfectants containing benzalkonium chloride. A total of 10 skin biopsies were taken from the 7 patients. Histopathological examination showed characteristic hyperkeratosis and fine blue-gray parakeratotic granules in the stratum corneum. All skin lesions improved 1 month after cessation of exposure to benzalkonium chloride.Conclusion:GP has a distinct clinical pattern and histopathological manifestations, and a history of exposure to benzalkonium chloride can be helpful for the diagnosis of GP.
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Objective:To preliminarily investigate dermoscopic characteristics of trichoblastoma, and to provide ideas for clinical diagnosis of trichoblastoma.Methods:Clinical data were collected from 5 patients with trichoblastoma who underwent both dermoscopic and histopathological examinations in Wuhan No.1 Hospital from November 2018 to July 2021, and dermoscopic features were analyzed retrospectively.Results:According to the presence or absence of pigments, trichoblastoma was divided into 2 subtypes: pigmented trichoblastoma (3 cases) and non-pigmented trichoblastoma (2 cases) . Dermoscopic examination of the 3 cases of pigmented trichoblastoma showed blue-gray ovoid nests (3 cases) , arborizing vessels (2 cases) , blue-gray globules (2 cases) , bright white structureless areas (2 cases) , concentric structures (1 case) and ulcers (1 case) ; no yellow-whitish homogenous structure was found. As for non-pigmented trichoblastoma, dermoscopic features included arborizing vessels (2 cases) , yellow-whitish homogenous structures (2 cases) , bright white structureless areas (2 cases) and blue-gray globules (1 case) ; no ulcers or blue-gray ovoid nests were observed in either case.Conclusion:Dermoscopic patterns differ between pigmented and non-pigmented trichoblastoma, so dermoscopy can provide preliminary diagnostic clues for trichoblastoma.
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The cerebellum is conceptualized as a processor of complex movements and is also endowed with roles in cognitive and emotional behaviors. Although the axons of deep cerebellar nuclei are known to project to primary thalamic nuclei, macroscopic investigation of the characteristics of these projections, such as the spatial distribution of recipient zones, is lacking. Here, we studied the output of the cerebellar interposed nucleus (IpN) to the ventrolateral (VL) and centrolateral (CL) thalamic nuclei using electrophysiological recording in vivo and trans-synaptic viral tracing. We found that IpN stimulation induced mono-synaptic evoked potentials (EPs) in the VL but not the CL region. Furthermore, both the EPs induced by the IpN and the innervation of IpN projections displayed substantial heterogeneity across the VL region in three-dimensional space. These findings indicate that the recipient zones of IpN inputs vary between and within thalamic nuclei and may differentially control thalamo-cortical networks.
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A 9-year-old boy presented with pruritic erythema and erosions of the scalp for 1 month, which spread all over the body for 1 week. Histopathological examination of the skin lesions showed blisters forming under the granular layer of the epidermis, a large number of acantholytic cells in the blisters, and perivascular infiltration of lymphocytes and eosinophils in the superficial dermis. Direct immunofluorescence study showed reticular deposition of IgG and complement C3 between epidermal cells, and negative staining for IgM and IgA. Enzyme-linked immunosorbent assay showed the presence of serum anti-Dsg1 antibody (157.00 U/ml) . The patient was diagnosed with pemphigus foliaceus. After admission, the patient showed poor response to the treatment with prednisone at a dose of 40 mg/d. After the treatment with low-dose rituximab (100 mg per week, 4 weeks) combined with prednisone (20 mg/d) , her condition was well controlled. The dosage of prednisone gradually decreased to 7.5 mg/d for maintenance treatment, and no recurrence was observed during 24-month follow-up.
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The cerebellum is conceptualized as a processor of complex movements and is also endowed with roles in cognitive and emotional behaviors. Although the axons of deep cerebellar nuclei are known to project to primary thalamic nuclei, macroscopic investigation of the characteristics of these projections, such as the spatial distribution of recipient zones, is lacking. Here, we studied the output of the cerebellar interposed nucleus (IpN) to the ventrolateral (VL) and centrolateral (CL) thalamic nuclei using electrophysiological recording in vivo and trans-synaptic viral tracing. We found that IpN stimulation induced mono-synaptic evoked potentials (EPs) in the VL but not the CL region. Furthermore, both the EPs induced by the IpN and the innervation of IpN projections displayed substantial heterogeneity across the VL region in three-dimensional space. These findings indicate that the recipient zones of IpN inputs vary between and within thalamic nuclei and may differentially control thalamo-cortical networks.
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Axons , Cerebellar Nuclei , Cerebellum , Thalamic NucleiABSTRACT
ObjectiveTo analyze the epidemic situation and epidemiological characteristics of malaria in Lishui City from 2013 to 2018, so as to provide the evidence for formulating the malaria control strategy. MethodsThe data pertaining malaria cases in Lishui City from 2013 to 2018 were captured from National Notifiable Communicable Disease Reporting System and the Information System for Parasitic Diseases Control and Prevention, and the epidemiological features of malaria cases were analyzed. Results A total of 119 malaria cases were reported in Lishui City from 2013 to 2018, including 101 cases with falciparum malaria (84.87%), 6 cases with vivax malaria (5.04%), 8 cases with ovale malaria (6.72%), and 4 cases with mixed infection (3.36%). Among the 119 cases, there were one local case with blood transfusion-induced malaria and 118 cases with over- seas imported malaria. There were 98.32% of the imported malaria cases acquiring infection in African countries, and most cases were reported in Qingtian County (60.50%) and Liandu District (22.69%). In addition, 86.55% of the malaria cases were detected in individuals at ages of 20 to 50 years, and most cases were found in oversea workers (52.94%) and businessmen (38.65%). Conclusions Most of the malaria cases in Lishui City are imported from Africa, and the monitoring and health education pertaining to malaria control knowledge requires to be intensified among high-risk populations.
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Objective: To compare the differences of Gardeniae Fructus and its stir-baked preparation and screen out the differential markers, and provide reference for the establishment of quality standard. Methods: The whole and partial fingerprints of Gardeniae Fructus and its stir-baked prepared slices were established by HPLC-UV analysis. And the fingerprints were statistically analyzed using hierarchical clustering analysis (HCA), principle component analysis (PCA), and orthogonal partial least squares-discriminant analysis (OPLS-DA), then the characteristic markers were screened out. And then content of 6-α-hydroxygeniposide, gentioside, geniposide, crocin I, and crocin II was determined. Results: A total of 15 peaks were acquired for Gardeniae Fructus and stir-baked Gardeniae Fructus respectively, 12 peaks of which were the common peaks. The similarity of whole and partial reference fingerprints of Gardeniae Fructus and its stir-baked prepared slices was 0.991 and 0.880, respectively, and partial fingerprint can successfully distinguished Gardeniae Fructus from its stir-baked prepared slices. HCA and OPLS-DA results showed that significant differences were observed between Gardeniae Fructus and stir-baked Gardeniae Fructus with peak 3, peak 5, peak 9 (geniposide), and peak 11 (crocin I), which being identified as the main differential markers. Contents of geniposide, crocin I and crocin II in Gardeniae Fructus were higher than those in stir-baked Gardeniae Fructus, while 6-α-hydroxygeniposide was lower. Conclusion: The composition was significantly different before and after stir-baked. The established partial fingerprints combined with multi-component determination method can effectively distinguish them. And the differential markers obtained by multivariate statistical analysis can provide reference for the selection of quality markers.
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Objective To investigate dermoscopic,reflectance confocal microscopic (RCM) and histopathological features of trichoepithelioma.Methods A total of 23 outpatients with histopathologically confirmed trichoepithelioma were enrolled from Department of Dermatology,Wuhan No.1 Hospital between January 2017 and December 2018.Dermoscopic and RCM images were collected,and the consistency was analyzed between dermoscopic or RCM features and histopathological features.Results Among the 23 patients,5 were male,and 18 were female.Their age was 39.5 ± 22.1 years.Histopathological examination showed that the tumor was well-circumscribed and surrounded by abundant fiber matrices,consisted of many basaloid cells forming clusters or interlacing cords with surrounding cells arranged in a fence-like pattern.Tumor cells differentiated into dermal papilla cells to different extents,and varying amounts of keratinous cysts were observed.RCM showed bud-like downward extension of cord-like cells at the dermoepidermal junction in 8 patients,which tended to be arranged in a fence-like pattern;seemingly lobulating nodular tumor masses were scattered in the dermis in 18 patients,which appeared as extended hypoechoic structures,with no constriction gap between tumor masses and surrounding tissues;tumor masses were surrounded by moderately to highly refractive amorphous substance in 16 patients;characteristic hair papilla structures suspected to be derived from primary differentiation were observed in 16 patients;keratinous cysts were clearly observed in 20 patients.Dermoscopy clearly showed that homogeneous pearlwhite structures in 20 patients,and linear telangiectasia in 10 patients.Conclusion RCM features of trichoepithelioma are highly consistent with its histopathological features,so reflectance confocal microscopy can serve as an efficient method for auxiliary and differential diagnosis.
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Objective: To evaluate the effect of irradiation of 60Co-γ on composition change of Curcuma Longa through HPLC fingerprint analysis and determination of curcumin content. Methods: An Agilent SB-C18 column (250 mm × 4.6 mm, 5 μm) was used as the column. Curcumin content was measured according to the method in 2015 edition of the “Pharmacopoeia of the People’s Republic of China”. Acetonitrile-0.1% phosphoric acid aqueous solution was used as the mobile phase of fingerprint analysis, and it was programmed in a gradient elution model and the detection wavelength was 240 nm. The effects of irradiation on content of curcumin and components change were analyzed by paired t-test and similarity evaluation. And then the comprehensive evaluation of constituent difference of C. Longa before and after irradiation was carried out by HCA and PCA analysis. Further more the stability of curcumin content and fingerprint similarity of three patches samples storage for 3 and 6 months was compared with that of 0 month. Results: There was no significant difference before and after irradiation for curcumin content (P > 0.05). The fingerprints of C. Longae were established and 16 peaks were identified as the common peaks. The similarity of each batch before and after irradiation was more than 0.998 and the same batch before and after irradiation have better clustering consistency. The changes of curcumin content for 3 and 6 months compared with 0 month was less than 5%, and the fingerprint similarity was all greater than 0.95. Conclusion: The established fingerprinting method is accurate and reliable. 60Co-γ irradiation has no significant effect on the curcumin content and chemical composition consistency of C. Longa, which did not affect its stability. It was a good way to evaluate the 60Co-γ irradiation effect on C. Longa by combining fingerprint analysis and the index components content determination. This method can provide reference for the utilization of irradiation on C. Longa.
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Objective To investigate dermoscopic and reflectance confocal microscopic (RCM)features of sebaceous nevus in patients of different ages.Methods A total of 83 patients histopathologically diagnosed with sebaceous nevus were enrolled from Department of Dermatology of Wuhan No.1 Hospital between January 2016 and December 2016,and divided into 4 age groups (＜ 10 years,10-20 years,21-59 years,≥ 60 years) according to the age.The dermoscopic and RCM features were collected and analyzed.Results Among the age group of ＜ 10 years (21 cases),dermoscopic images of skin lesions showed that uniform,globular or plaque-shaped yellowish-red structures arranged in a cobblestone-like pattern were independently distributed in an orange background,with vascular proliferation and dilatation,while RCM images showed sebaceous gland hypoplasia and juvenile hair follicles.Among the age group of 10-20 years (28 cases),dermoscopy showed aggregated,non-hair follicle,round or oval yellow structures of varying sizes with telangiectases,while RCM showed botryoidal sebaceous glands at the dermal-epidermal junction and superficial dermis,which were characterized by tube-like or handle-like structure in the center,aggregated fish roe-like or frogspawn-like sebaceous gland lobules in the surrounding area and verrucous or papillomatous hyperplasia in the epidermis.The age groups of 21-59 years (30 cases) and 10-20 years showed the similar imaging manifestations.The main imaging manifestation of the age group of ≥ 60 years (4cases) was papillomatous hyperplasia.Conclusions Sebaceous nevus is a dynamic developmental disease,and its imaging characteristics obviously differ among different age stages.Sebaceous nevus has characteristic structures under dermoscopy and RCM,which can serve as efficient noninvasive diagnostic methods for sebaceous nevus.
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Objective To explore structural differences of intestinal flora in primary insomnia patients with different TCM syndromes through the high-throughput 16S rDNA sequencing analysis. Methods Totally 65 patients with primary insomnia were divided into 22 patients with syndrome of liver depression transforming into fire, 17 patients with deficiency of both heart and spleen syndrome, 26 patients with syndrome of hyperactivity of fire due to yin deficiency, with 47 cases of healthy people as the control group. The fecal flora structure of the subjects was analyzed by high-throughput 16S rDNA sequencing. QIIME software and R language stats package were used to analyze the diversity of flora. Results Totally 1226 different operational taxonomic units (OUTs) were obtained, and there were 180 significant differences among the 4 groups (P<0.05), indicating that the samples were rich in microbial colonies. The mapped reads in group of liver depression transforming into fire and hyperactivity of fire due to yin deficiency were more than the group of deficiency of both heart and spleen and the control group (P<0.05). Unweighted UniFrac analysis showed that the difference among groups was remarkably greater than the difference within group, and the grouping was statistically significant (R=0.103, P=0.002). It suggested that the diversity of intestinal flora was highly correlated with different TCM syndromes of insomnia. There were a total of 57 genera found significant differences among the different groups at the genus level (P<0.05), and 115 species at all species level. The dominant flora of the control group were prevotella, megamonas, clostridium Ⅺ (clostridium ⅩⅧ), weissella, and alloprevotella; The dominant flora of liver depression transforming into fire syndrome were phascolarctobacterium, flavonifractor, eggerthella, and bilophila; The dominant flora of deficiency of both heart and spleen syndrome were sphingomonas and methylobacterium; The dominant flora in hyperactivity of fire due to yin deficiency syndrome group were bacteroides, parabacteroides, parasutterella, butyricimonas, odoribacter. Conclusion The patients with primary insomnia have abundant intestinal flora diversity and diverse flora structure, which may affect the occurrence, development and outcome of different TCM syndromes.
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Diabetes mellitus (DM) is one of the most important chronic diseases currently threatening human health worldwide.However,Diabetic kidney disease (DKD) is one of the main microvascular complications of DM;Vitamin D is a steroid hormone that is expressed in bone,kidney,intestines and other tissues.Vitamin D not only plays an important role in regulating calcium and phosphorus metabolism,but also involves the multiple biological effects of immune regulation,inflammatory response,cell proliferation and differentiation.In this paper,the effects of vitamin D on DKD and its research progress are discussed.
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Objective To explore the relationship between selenium and diabetic nephropathy (DN)by determining the selenium content in the plasma and whole blood of DN patients and the changes of selenoprotein expressions in human mesangial cells stimulated by high glucose.Methods We collected the samples and clinical indicators of DN patients and healthy controls to determine selenium content by atomic absorption spectrometry method.The mRNA in human mesangial cells was isolated after stimulation with 30 mmol/L of glucose for 24 hours by Trizol method to detect the changes of selenoprotein expressions by Real-time PCR.We analyzed the differences between DN patients and healthy controls and the relationship between clinical indicators by unpaired t-test and Pearson correlation analysis,respectively.Results The selenium contents in the plasma (P＜0.0001)and whole blood (P＜0.001)were significantly lower in DN patients than in the healthy controls.In addition,plasma selenium contents had a significant negative correlation with renal function and a positive correlation with glycosylated hemoglobin in DN patients.Among the 2 1 human selenoproteins,the mRNAs of Gpx1 ,TrxR2 ,TrxR3 ,Dio2 , Dio3 ,SelK,SelN,SelP,SelR,SelT,SelW and SPS2 were significantly lower in the high-glucose group than in the normal-glucose group which produced by human mesangial cells after high glucose stimulation for 24 hours. Conclusion There was obvious selenium deficiency in DN patients.Human mesangial cells have a significantly low expression of some selenoproteins in the high glucose environment.These results provide clinical and experimental evidence for illuminating the role of low selenium-sensitive selenoproteins in the occurrence and development of DN.
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Objective To construct the recombinant plasmids of normal and truncated selenoprotein S genes so as to observe their biological function in vitro or in vivo.Methods We constructed the recombinant plasmids of normal and truncated selenoprotein genes by gene recombinant technology.The gene of truncated selenoprotein was coding domain sequence(CDS)fragment of mRNA;the gene of normal selenoprotein was CDS and 3'untranslated region(including Sec insertion sequence)fragment of mRNA.We confirmed the sequence of recombinant genes by sending them to a company for comparison.The recombinant plasmids of normal and truncated genes of SelS were transfected into cells by Lipofectamine 2000.After 24 hours,the expression of green fluorescent protein was observed and transfection efficiency was detected by FACS analysis.We collected the cells to isolate the total RNA by TRIzol method,and then cDNA was obtained by mRNA reverse transcription and amplified by PCR.Results The sequencing results showed that the recombinant genes were completely the same as the target genes,indicating that we constructed the plasmids successfully.The expression of green fluorescent protein could be observed and transfection efficiency was detected up to 40% by FACS analysis.PCR results showed that the target selenoprotein gene was highly expressed in the experimental group than in control group.Conclusion The truncated and normal selenoprotein S genes were successfully constructed and transfected into cells where they were highly expressed.It lays foundation for observing the biological effect of truncated and normal selenoprotein in cell line or animal body.
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AIM To establish HPLC fingerprints of Zhihuang Tongfeng Decoction (Phellodendri chinensis Cortex,Anemarrhenae Rhizoma,Plantaginis Semen,etc.) and to determine the contents of four constituents.METHODS The analysis of aqueous extract of this drug was performed on a 30 ℃ thermostatic Wondasil C18 column (4.6 mm ×250 mm,5 μm),with the mobile phase comprising of acetonitrile-0.5％ acetic acid in a gradient elution manner,and the detection wavelength was set at 245 nm.RESULTS There were sixteen common peaks in the HPLC fingerprints of ten batches of samples with the similarities of more than 0.9.Berberine hydrochloride,mangiferin,geniposidic acid and salvianolic acid B showed good linear relationships within the ranges of 0.636 2-3.575 μg (R2 =0.9999),0.338-1.425 μg (R2 =0.9990),0.6452-2.7188 μg (R2 =1) and0.938 8-5.275 μg (R2 =0.999 3),whose average recoveries were 100.56％,98.35％,100.25％ and 102.11％ with the RSDs of 2.41％,1.17％,1.24％ and 2.02％,respectively.CONCLUSION This accurate,reliable and specific method can be used for the quality control of Zhihuang Tongfeng Decoction.
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Objective To establish the reference intervals(RIs) for plasma presepsin in healthy population.Methods The document C28-A3 issued by CLSI was a guideline about how to define,establish,and verify reference intervals in the clinical laboratory.Plasma values were determined with CLEIA for 1 250 healthy adults(aged 20-90 years old),including 624 males and 626 females.The central 95 percentile of RIs were determined using nonparametric statistical methods.Results The presepsin values in elderly population showed a Gaussian distribution and age/sex related changes.The RIs for plasma presepsin in the reference population respective of age(ranged from 20-＜30,30-＜ 60,60-＜ 90 years) were 50-195,47-170,41-142 pg/mL for males and 43-173,44-162,38-137 pg/mL for females respectively.Conclusion The RIs for plasma presepsin were established according to the gender and age groups in the healthy adults,and could provide a reference for the clinical and laboratory.
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To analyze the epidemiology,genetic variation and genetic evolution of coxsackievirus A4 (CVA4) in patients with hand,foot and mouth disease in Fujian,the virus isolates were molecular typed and amplified the whole VP1 region by RT-PCR,then the genetic variation and evolution were studied.The results showed that 33 CVA4 cases (8.1％) were confirmed from the 407 non-EV71 non-CVA16 HFMD cases in Fujian Province during 2011 and 2014,accounting for 31 cases in 2012 and 2 cases in 2014.Compared with common characteristics of the HFMD epidemic,no specificity in the distribution of CVA4 cases was found between gender and age groups.Sequence analysis of VP1 nucleotide sequences of Fujian CVA4 isolates showed that the nucleotide and amino acid sequences similarity were 92.6 ％-100 ％ and 95.7 ％-100 ％ respectively,low similarity with the prototype (83.7％-85.4％,96.1％-99.0％) and abroad isolates (82.1％-89.1％,90.4％-99.6％) both in nucleotide and amino acid sequences,high similarity with domestic isolates both in nucleotide and amino acid sequences,with the similarity of 87.9％ 99.2 ％ and 96.1％-100 ％.The results from phylogenetic tree showed that the genetic distance between Fujian CVA4 isolates and the prototype and abroad strains was far,and the genetic distance was close to domestic isolates in China.The distribution of the phylogenetic trees of Fujian CVA4 strains showed multiple branches.Therefore,CVA4 is the major HFMD associated-pathogen other than EV71,CVA 16,CVA6,and CVA10 in Fujian Province from 2011 to 2014.CVA4 strains from Fujian Province is co-circulating and co-evolving with other domestic isolates.There is existence of multiple closely related CVA4 transmission chains in various regions of Fujian.
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AIM To establish HPLC fingerprints of Zhihuang Tongfeng Decoction (Phellodendri chinensis Cortex,Anemarrhenae Rhizoma,Plantaginis Semen,etc.) and to determine the contents of four constituents.METHODS The analysis of aqueous extract of this drug was performed on a 30 ℃ thermostatic Wondasil C18 column (4.6 mm ×250 mm,5 μm),with the mobile phase comprising of acetonitrile-0.5％ acetic acid in a gradient elution manner,and the detection wavelength was set at 245 nm.RESULTS There were sixteen common peaks in the HPLC fingerprints of ten batches of samples with the similarities of more than 0.9.Berberine hydrochloride,mangiferin,geniposidic acid and salvianolic acid B showed good linear relationships within the ranges of 0.636 2-3.575 μg (R2 =0.9999),0.338-1.425 μg (R2 =0.9990),0.6452-2.7188 μg (R2 =1) and0.938 8-5.275 μg (R2 =0.999 3),whose average recoveries were 100.56％,98.35％,100.25％ and 102.11％ with the RSDs of 2.41％,1.17％,1.24％ and 2.02％,respectively.CONCLUSION This accurate,reliable and specific method can be used for the quality control of Zhihuang Tongfeng Decoction.
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Objective To establish the reference intervals(RIs) for plasma presepsin in healthy population.Methods The document C28-A3 issued by CLSI was a guideline about how to define,establish,and verify reference intervals in the clinical laboratory.Plasma values were determined with CLEIA for 1 250 healthy adults(aged 20-90 years old),including 624 males and 626 females.The central 95 percentile of RIs were determined using nonparametric statistical methods.Results The presepsin values in elderly population showed a Gaussian distribution and age/sex related changes.The RIs for plasma presepsin in the reference population respective of age(ranged from 20-＜30,30-＜ 60,60-＜ 90 years) were 50-195,47-170,41-142 pg/mL for males and 43-173,44-162,38-137 pg/mL for females respectively.Conclusion The RIs for plasma presepsin were established according to the gender and age groups in the healthy adults,and could provide a reference for the clinical and laboratory.
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Objective To explore the clinical value of combined detection of SCC and CEA in the diagnosis of lung cancer.Methods 382 cases from January 2015 to April 2016 in the respiratory department of our hospital were selected in this survey.Among which 172 cases with lung cancer,110cases with benign lung diseases and 100 healthy person.The CEA and SCC content in serum of all these cases were determined by chemical chemiluminescence,and the diagnostic efficacy of lung cancer by CEA or SCC alone and CEA and SCC combined examination was compared.Results In lung cancer group,the serum levels of CEA and SCC content were significantly higher than those of the normal control group and lung benign disease group(P＜0.05),and benign lung disease group were significantly higher than that of the normal control group(P＜0.05).and compared with squamous cell carcinoma and small cell lung cancer,CEA has the highest content in adenocarcinoma(P＜0.05).Meanwhile,the content of SCC in squamous cell carcinoma was obviously higher than that of small cell lung cancer and adenocarcinoma(P＜0.05),The sensitivity of CEA was significantly higher than that of SCC(P＜0.05),and the sensitivity and negative predictive value in combined detection group was significantly higher than that of CEA or SCC(P＜0.05).Conclusion SCC and CEA could be used to identify different types of lung cancer,and the combination of the two methods could improve the positive diagnosis rate,facilitate the early detection of lung cancer,early treatment,has the promotion value.