1.Distribution characteristics of basic syndromes of chronic functional constipation and its related factors analysis.
Lei ZHAO ; Xiu-jun LIAO ; Guan-gen YANG ; Wei-ming MAO ; Xiu-feng ZHANG ; Qun DENG ; Wen-jing WU
Chinese Journal of Integrated Traditional and Western Medicine 2014;34(10):1173-1177
OBJECTIVETo explore the distribution characteristics of basic syndromes and its related factors in patients with chronic functional constipation (CFC).
METHODSThe complete data of 538 patients with CFC were collected and initial database was established with Epidata 3. 0. TCM syndrome typing was performed. The distribution characteristics of basic syndromes were analyzed using SPSS 17. 0 Software. The univariate and multivariate Logistic regression analyses were performed with SPSS 17. 0 Software to determine basic syndrome related factors such as age, engaged professionals, sleep quality, depression, mental stress, interpersonal relations, work fatigue, stimulating beverage, exercise conditions, Western medicine type of constipation, and so on.
RESULTSThe TCM syndrome frequency of CFC patients was sequenced from high to low as qi deficiency syndrome (380 cases, 70.6%), qi stagnation syndrome (337 cases, 62.6%), blood deficiency syndrome (234 cases, 43.5%), yin deficiency syndrome (220 cases, 40.9%), yang deficiency syndrome (197 cases, 36.6%), and others(58 cases, 10. 8%) . Most patients were complicated with complex syndromes, and the most common complex syndromes were qi deficiency complicated qi stagnation syndrome (275 cases, 51.1%) and qi deficiency complicated blood deficiency syndrome (222 cases, 41.3%). Aging, work fatigue, and exercise conditions were main related factors for qi deficiency syndrome (P <0. 01, P <0. 05). Poor emotional (depression and anxiety tendencies), mental stress, interpersonal relations, defecation barriers constipation were main related factors for qi stagnation syndrome (P <0.01). Sleep quality and poor emotional (depression and anxiety tendencies) were main related factors for blood deficiency syndrome (P <0. 01, P < 0.05). Stimulating beverages were main related factor for yin deficiency syndrome (P <0.05). Engaged in mental work and slow transit constipation were main related factors for yang deficiency syndrome (P < 0. 01, P <0. 05).
CONCLUSIONSCFC is featured as complex syndromes. The most common complex syndromes were qi deficiency complicated qi stagnation syndrome and qi deficiency complicated blood deficiency syndrome. Basic syndrome related factors such as age, engaged professionals, sleep quality, poor emotional (depression and anxiety tendencies), mental stress, interpersonal relations, work fatigue, stimulating beverage, exercise conditions, Western medicine type of constipation were associated with the distribution of CFC syndromes.
Anxiety ; complications ; Constipation ; complications ; diagnosis ; psychology ; therapy ; Depression ; complications ; Diagnosis, Differential ; Factor Analysis, Statistical ; Fatigue ; Humans ; Medicine, Chinese Traditional ; Qi ; Stress, Psychological ; complications ; Syndrome ; Yang Deficiency ; diagnosis ; Yin Deficiency ; diagnosis
2.Involvement of LMO4 in tumorigenesis associated epithelial-mesenchymal transition.
Jing-yi LI ; Xiu-jin SHEN ; Hong DENG
Journal of Zhejiang University. Medical sciences 2011;40(1):107-111
LMO4 is a novel member of the LIM-only (LMO) subfamily of LIM domain-containing transcription factors, so named because they are composed almost entirely of two tandem LIM domains. This subgroup of LIM proteins has 4 members: LMO-1, LMO-2, LMO-3 and LMO-4. They all play important roles in the normal mammalian development, functioning as an important regulator of cell proliferation. LMO4 is highly expressed in the epithelial compartments at locations of active epithelial-mesenchymal interactions, and can interact with some signaling pathways involved in epithelial-mesenchymal signaling. Thus the disregulation of LMO4 expression may be involved in tumorigenesis. In this paper, we will at first expound LMO4 in detail, based on which the possible mechanisms for its interaction with TGF-β signaling and the roles of this cross-talk between them in the vital process of cell will be introduced. All of those will add to our understanding of tumorigenesis and contribute to the search of new targets for the treatment of cancer.
Adaptor Proteins, Signal Transducing
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Epithelial-Mesenchymal Transition
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Homeodomain Proteins
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metabolism
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physiology
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Humans
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LIM Domain Proteins
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Neoplasms
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metabolism
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pathology
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Signal Transduction
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Transcription Factors
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metabolism
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physiology
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Transforming Growth Factor beta
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metabolism
3.Clinical analysis about 5 cases of actinomycete keratitis
Xiao-Tang YIN ; Shi-Yun LUO ; Ran LI ; Shi-Jing DENG ; Zhi-Qun WANG ; Xiu-Ying JIN ; Xu-Guang SUN ;
Ophthalmology in China 1993;0(03):-
Objective To analyze clinical diagnosis and management of 5 patients with actinomycete keratitis.Design Retro- spective case series.Participants 5 patients (5 eyes) with actinomycete keratitis.Methods The clinical features and microbiologic da- ta of 5 culture-proven cases of actinomycete keratitis recorded between October 2004 to March 2006 were analyzed.Main Outcome Measures clinical characteristics,isolations identification,drug susceptibility test and treatments.Results All patients were males and farmers.Of the 5 cases presented in this study,4 cases were followed by minor trauma as a predominant risk factor,and were pre- sented by a chronic progressive corneal ulcer with a wreath pattern of infiltrate.The diagnosis of all cases was based on laboratory in- vestigations,by which 4 cases of nocardia and one case of streptomyce were identified.A variable drug sensitivities were presented in nocardia isolates,which including TMP-SMZ,amicasin,gentamicin and fluorine-quinolones.Conclusions Nocardia keratitis is mainly followed by a minor trauma.It is identified predominantly by laboratory investigations.Tropical and systemically sensitive biotic are the initial choice,while debridement and amnionic transplantation could be an effective alternative.
4.Clinical analysis of outpatients with ametropia in Hebeisheng Eye Hospital
Chen XIAO ; Zhang JIAN ; Zhang LI-KE ; Wang XIAO-BING ; Deng XIU-JING
International Eye Science 2017;17(11):2177-2179
AIM:To perform a clinical analysis of 1 500 cases of outpatients with ametropia in Hebeisheng Eye Hospital,to provide a theoretical basis for diagnosis,treatment,and prevention of patients with ametropia.METHODS:Totally 1500 cases (2840 eyes) of outpatient with ametropia were chosen as the research objects in Hebeisheng Eye Hospital from June 2013 to July 2014.All cases were treated with TOPCON RM-8800 computer optometry instrument for objective optometry,and used TOPCON phoropter for subjective optometry.The combination of the two instruments was taken to determine the diopter later.Diopter and axial distribution of the myopic astigmatism and hyperopic astigmatism were observed,age of astigmatic patient,distribution of astigmatism axis were observed as well.Meanwhile,a total of 150 cases were chosen randomly to measure their corneal curvature,anterior chamber depth,axial length and other static refractive index.All indexes were compared with those of the normal people subsequently,such as amplitude of accommodation,negative relative accommodation,positive relative accommodation,sensitivity of accommodation and other dynamic refractive index.RESULTS:Ametropia types of all patients were mainly simple myopia,simple myopia astigmatism,compound myopic astigmatism,simple hypermetropia,simple hyperopia astigmatism,compound hyperopic astigmatism and mixed astigmatism,the proportion were 38.99%,3.27%,23.94%,4.68%,1.34%,13.52%,15.25% respectively.There were 773 eyes with myopia astigmatism.The proportion of people with a myopia astigmatism diopter of above-0.25 to-0.50,-0.75 to -1.00,-1.25 to-1.50,above-1.75 were 31.05%,38.55%,16.56%,13.84%.There were 421 eyes with hyperopia astigmatism,the proportion of people with hyperopia astigmatism diopter of 0.25-0.50,0.75-1.00,1.25-1.50,>1.75 were 26.60%,24.94%,16.63%,31.83%.Static refractive index of 150 patients (300 eyes) showed that corneal curvature was (41.23 ± 2.43) φ/D,anterior chamber depth was 3.71 ± 0.43mm,axial length 23.45 ± 1.43mm.Dynamic refractive index showed that the amplitude of accommodation 10.56±2.32D,negative relative accommodation 2.31 ±0.47D,positive relative accommodation-1.82-± 0.67D,sensitivity of accommodation 11.34±2.21D.All kinds of static and dynamic refractive indexes,the length of ocular axis were statistically different from those of the normal population (P < 0.05).Regular astigmatism number rate in 1 194 cases of astigmatism eyes of 3-7 years old,8-18 years old,19-45 years old,46-60 years old were 35.85%,11.98%,45.64%,6.53%.Among 150 cases of patients (300 eyes),there were 152 eyes of equivalent sphere mirror <-0.5D,48 eyes of equivalent sphere mirror ≥ 0.5D,100 eyes of equivalent sphere mirror between-0.5D to 0.5D.And there were 150 eyes of equivalent sphere mirror <-0.5D,50 eyes of equivalent sphere mirror ≥0.5D,100 eyes of equivalent sphere mirror between-0.5D to 0.5D in a total of 300 eyes of 150 normal people.CONCLUSION:The 1500 cases of patients with ametropia (2 840 eyes) contains mainly simple myopia and compound myopic astigmatism,diopter range in myopia astigmatism were chiefly-0.25 to-0.50,-0.75 to-1.00,hyperopia diopter range consists of > 1.75 mostly,among the patients with astigmatism,the older the age,the bigger the number of people with irregular astigmatism,static and dynamic refractive index of patients with ametropic eye shows apparent difference with that of the normal population.
5.Association of RAS mutations in circulating cell-free DNA in the plasma with clinicopathological features of colorectal cancer.
Jing WU ; Li-Rong ZHAO ; Xiu-Qiang LIN ; Fen FENG ; Yong-Chang CHEN ; Wei-Ying DENG ; Yan-Ming DENG ; Wei WANG
Journal of Southern Medical University 2017;37(7):962-966
OBJECTIVETo detect RAS mutations in the circulating cell-free DNA (cfDNA) in the plasma and explore the their correlation with the clinicopathological features in patients with colorectal cancer.
METHODSReal-time PCR was used to detect RAS mutations in plasma cfDNA and matched tumor tissue DNA samples from 71 colorectal cancer patients. The correlation of RAS mutations with the clinicopathological features of the patients were analyzed.
RESULTSOf the 71 patients with colorectal cancer, 23 (32.39%) showed RAS mutations in the cfDNA and 36 (50.7%) showed RAS mutations in tumor tissue DNA, with a concordance rate of 76.06% in the results between the two samples (Kappa=0.523). RAS mutations in the cfDNA were not related to the patients' age (P=0.072), gender (P=0.320), tumor stage (IVa and IVb, P=0.450), primary tumor position (P=0.324), lung metastasis (P=0.237), CEA level (P=0.284) or CA199 level (P=0.427). The positivity rate of RAS mutations in plasma cfDNA was significantly higher in patients with liver metastasis than those without liver metastasis (P=0.045).
CONCLUSIONPlasma cfDNA can be a reliable source of diagnostic DNA to replace the tumor tissue DNA for diagnosis of RAS mutations. RAS mutations in plasma cfDNA occur more frequently in colorectal cancer patients with liver metastasis.
6.Effects of different ways in repairing scrotum of pigs with full-thickness burn on apoptosis and bcl-2 protein expression of spermatogenic cells.
Xiu-jun TANG ; Zai-rong WEI ; Guang-feng SUN ; Zhao-hui HUANG ; Jing-jing ZHU ; Cheng-liang DENG ; Da-li WANG
Chinese Journal of Burns 2012;28(2):138-141
OBJECTIVETo observe the effects of different ways in repairing scrotum of pigs with full-thickness burn on spermatogenesis of testis.
METHODSTwenty male Guizhou miniature pigs were divided into normal control (NC), natural-healing (NH), flap-repairing (FR), and skin-grafting (SG) groups according to the random number table, with 5 pigs in each group. Pigs in NC group were not subjected to any injury. Scrotum of pigs in the latter three groups were inflicted with full-thickness burn. Wounds in NH group healed naturally. Wounds in FR group were repaired with inguinal region flap, and those in SG group with full-thickness skin from lower abdomen. Appearance of scrotum in the latter three groups was observed right after injury, and three months post injury or surgery (PIM or PSM). Specimens of testes of pigs in the latter three groups were obtained in PIM or PSM 3 to detect apoptosis of spermatogenic cells with TUNEL, and bcl-2 protein expression with immunohistochemistry. The same indexes were observed and determined in pigs of NC group. Data were processed with one-way analysis of variance and LSD test.
RESULTS(1) Scrotum of pigs in NC group had skin folds with contraction function. Scrotum of pigs became hard with a leathery appearance right after burn in the other three groups. In PIM or PSM 3, wounds of pigs in NH group healed with scar, and the testes were squeezed into inguinal region. Scrotal skin of pigs in FR group was thick with testes in the scrotum, and that of pigs in SG group was thin with testes in the scrotum. (2) Spermatogenic cells in each level in NC group were arranged regularly, with few apoptotic spermatocytes and spermatoblasts. In NH, FR, and SG groups, seminiferous epithelium was thinner with most of the spermatogenic cells showing apoptosis, and they were mainly spermatogonia and spermatocytes. Apoptotic index of spermatogenic cells in NH, FR, SG, and NC groups was respectively (46.3 ± 3.3)%, (40.9 ± 3.5)%, (20.6 ± 2.3)%, (7.5 ± 1.9)%, and the difference among them was statistically significant (F = 405.65, P < 0.01). There were significant statistical differences among the former three groups (with P values below 0.01). (3) bcl-2 protein expression in NH, FR, SG, and NC groups was respectively (52 ± 5)%, (53 ± 4)%, (64 ± 5)%, (75 ± 5)%, and the difference among them was statistically significant (F = 56.63, P < 0.01). There was no significant statistical difference in bcl-2 expression between NH group and FR group (P = 0.66), and it was lower in both groups as compared with SG group (with P values below 0.01).
CONCLUSIONSEither scar healing, flap transplantation, or SG in repairing scrotum with full-thickness burn in pigs inhibits spermatogenesis, but repair with SG produces less deleterious effect on the testis.
Animals ; Apoptosis ; Burns ; metabolism ; pathology ; surgery ; Male ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Reconstructive Surgical Procedures ; methods ; Scrotum ; injuries ; metabolism ; Skin Transplantation ; Spermatogenesis ; Swine
7.Impact of the reconstruction of the scrotum with third-degree burns on spermatogenic function: experimental study of three different methods.
Xiu-Jun TANG ; Zai-Rong WEI ; Guang-Feng SUN ; Bin ZHANG ; Jing-Jing ZHU ; Cheng-Liang DENG ; Da-Li WANG
National Journal of Andrology 2012;18(4):318-322
OBJECTIVETo explore the effects of different methods of scrotal reconstruction on the apoptosis of spermatogenic cells and expression of the bcl-2 protein in patients with third-degree scrotal burns.
METHODSForty male and 24 female 2-month-old Guizhou mini-pigs were used in this study, the former equally randomized to groups I (normal control), II (natural healing), III (skin grafting) and IV (skin flap grafting). Ten months after the establishment of the model of third-degree burns, 6 male pigs from each group were paired with the female pigs and fed for 3 weeks. Then the female pigs were fed for another 4 months, followed by observation of their reproductivity. At 12 months, the bilateral testes were taken from the male pigs for detection of the apoptosis index of spermatogenic cells by TUNEL and determination of the expression of the bcl-2 protein by immunohistochemistry. The data obtained were subjected to single factor analysis of variance.
RESULTSThe apoptosis indexes of spermatogenic cells were (7.07 +/- 3.5), (40.34 +/- 4.85), (15.14 +/- 1.36) and (39.29 +/- 5.73)% in groups I , II, III and IV, respectively, significantly higher in groups II , III and IV than in I (P<0.05), with statistically significant differences between group III and groups II and IV (P<0.05) but not between II and IV (P>0.05). The expression rates of the bcl-2 protein were (75.07 +/- 3.74), (54.93 +/- 4.03), (66.85 +/- 3.06) and (53.33 +/- 5.22)% in groups I, II, III, and IV, respectively, remarkably higher in I than in the other three (P<0.05), with significant differences between group III and groups II and IV (P<0.05) but not between II and IV (P>0.05). Pregnancies were found in all the female pigs of group I with 10.0 +/- 1.18 newborns and in 4 of group III with 9.92 +/- 1.31 newborns, but in none of groups II and IV, with significant differences between group I and the other three (P<0.05) as well as between group III and groups II and IV (P<0.05), but not between II and IV (P>0.05).
CONCLUSIONAll the three methods of reconstruction for the scrotum with third-degree burns can suppress spermatogenic function, increase the apoptosis of spermatogenic cells and decrease the expression of the bcl-2 protein, among which, skin grafting least affects spermatogenic function.
Animals ; Apoptosis ; Burns ; surgery ; Disease Models, Animal ; Female ; Male ; Reconstructive Surgical Procedures ; methods ; Scrotum ; injuries ; metabolism ; surgery ; Seminiferous Epithelium ; cytology ; metabolism ; Skin Transplantation ; methods ; Spermatogenesis ; Swine ; Swine, Miniature
8.Pollutions of indoor fine particles in four types of public places and the influencing factors.
Bo LIU ; Fu-rong DENG ; Xin-biao GUO ; Dong-mei YANG ; Xiu-quan TENG ; Xu ZHENG ; Jing GAO ; Jing DONG ; Shao-wei WU
Chinese Journal of Preventive Medicine 2009;43(8):664-668
OBJECTIVETo study the levels of pollutions caused by fine particulate matter (PM(2.5)) in the public places and investigate the possible influencing factors.
METHODSA total of 20 public places in four types such as rest room in bath center, restaurant, karaoke bars and cyber cafe in Tongzhou district in Beijing were chosen in this study; indoor and outdoor PM(2.5) was monitored by TSI sidepak AM510. Data under varying conditions were collected and analyzed, such as doors or windows or mechanical ventilation devices being opened, rooms cramped with people and smoking.
RESULTSThe average concentration of indoor PM(2.5) in 20 public places was (334.6 +/- 386.3) microg/m(3), ranging from 6 microg/m(3) to 1956 microg/m(3); while in bath center, restaurant, karaoke bars and cyber cafe were (116.9 +/- 100.1)microg/m(3), (317.9 +/- 235.3) microg/m(3), (750.6 +/- 521.6)microg/m(3) and (157.5 +/- 98.5) microg/m(3) respectively. The concentrations of PM(2.5) in restaurant (compared with bath center: Z = -10.785, P < 0.01; compared with karaoke bars: Z = -10.488, P < 0.01; compared with cyber cafe: Z = -7.547, P < 0.01) and karaoke bars (compared with bath center: Z = -16.670, P < 0.01; compared with cyber cafe: Z = -15.682, P < 0.01) were much higher than those in other two places. Single-factor analysis revealed that the average concentration of indoor PM(2.5) in 20 public places was associated with the number of smokers per cube meters(9.13 x 10(-3); r = 0.772, F = 26.579, P < 0.01) and ventilation score [(2.5 +/- 1.5) points; r = 0.667, F = 14.442, P < 0.01], and there were significant correlation between the average indoor and outdoor levels in restaurant [(317.9 +/- 235.3) microg/m(3), (67.8 +/- 78.9) microg/m(3); r = 0.918, F = 16.013, P = 0.028] and cyber cafe [(157.5 +/- 98.5) microg/m(3), (67.7 +/- 43.7) microg/m(3); r = 0.955, F = 30.785, P = 0.012]. Furthermore, significant correlation was observed between the average concentration of indoor PM(2.5) [(157.5 +/- 98.5) microg/m(3)]and the number of people per cube meters (288.7 x 10(-3)) in cyber cafe (r = 0.891, F = 11.615, P = 0.042). Multiple regression analysis showed that smoking (b' = 0.581, t = 3.542, P = 0.003) and ventilation (b' = -0.348, t = -2.122, P = 0.049) were the major factors that may influence the concentration of indoor PM(2.5) in four public places. With cluster analysis, the results showed that the major factors that influence the concentration of indoor PM(2.5) was the outdoor PM(2.5) levels [(49.6 +/- 39.5) microg/m(3); b = 1.556, t = 3.760, P = 0.007] when ventilation (score > 2) was relatively good. The number of smokers per cube meters (14.7 x 10(-3)) became the major influence factor when the ventilation score = 2 (b = 140.957, t = 3.108, P = 0.013) and 51.8% increases of indoor PM(2.5) was attributed to smoking.
CONCLUSIONThis study indicated that smoking was the main source of indoor PM(2.5) in public places. Outdoor PM(2.5) should be correlated with indoor PM(2.5) concentration under drafty situation.
Air Pollution, Indoor ; analysis ; Environmental Monitoring ; methods ; Particulate Matter ; analysis ; Public Facilities ; Tobacco Smoke Pollution ; analysis
9.Single-nucleotide Polymorphism rs2275294 in ZNF512B is not Associated with Susceptibility to Amyotrophic Lateral Sclerosis in a Large Chinese Cohort.
Xiao-Dong JU ; Tao LIU ; Jing CHEN ; Xiao-Gang LI ; Xin-Xiu LIU ; Wen-Chao LIU ; Kai WANG ; Min DENG
Chinese Medical Journal 2015;128(24):3305-3309
BACKGROUNDAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that primarily affects motor neurons and has no effective treatment. Recently, Iida et al. identified a single-nucleotide polymorphism (SNP) rs2275294 in the ZNF512B gene that is significantly associated with susceptibility to ALS in the Japanese population. Here, we performed a case-control study examining the possible association of rs2275294 with risk of sporadic ALS (SALS) in a large Chinese cohort.
METHODSTo assess this association, we performed a replication study in 953 SALS patients and 1039 age- and gender-matched healthy control subjects, who were recruited from Peking University Third Hospital and the First Affiliated Hospital of Anhui Medical University from January 2004 to December 2013 throughout China. We genotyped the rs2275294 SNP using polymerase chain reaction and direct sequencing.
RESULTSThe allele frequency of rs2275294 in ZNF512B was different between Japanese and Chinese. The association in Chinese between ALS patients and controls did not reach statistical significance (P = 0.54; odds ratio = 0.94; 95% confidence interval = 0.76-1.15).
CONCLUSIONSThe SNP rs2275294 in ZNF512B is not considered to be associated with ALS susceptibility in the Chinese population. Our study highlights genetic heterogeneity in ALS susceptibility in different population. Given our negative results, further replication study involving larger and more homogeneous samples in different ethnicities should be performed in the future.
Adult ; Amyotrophic Lateral Sclerosis ; epidemiology ; genetics ; Asian Continental Ancestry Group ; genetics ; Carrier Proteins ; genetics ; Case-Control Studies ; China ; epidemiology ; Female ; Genetic Predisposition to Disease ; genetics ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; genetics
10.Catgut implantation at acupoints for allergic rhinitis: a systematic review.
Xin-rong LI ; Qin-xiu ZHANG ; Min LIU ; Qing CHEN ; Yang LIU ; Fu-bing ZHANG ; Jing DENG ; Zhen-dong ZHONG
Chinese journal of integrative medicine 2014;20(3):235-240
OBJECTIVETo assess the effectiveness and the possible adverse effects of catgut implantation at acupoints for allergic rhinitis (AR).
METHODSThis systematic review was carried out in accordance with the Cochrane Handbook version 5.1.0 and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Extensive literature searches were conducted in PubMed, Excerpta Medical Databases, the Cochrane Library, the China National Infrastructure, Wanfang Chinese Digital Periodical and Conference Database, and the Weipu Chinese Science and Technique Journals Database. The Chinese Clinical Trial Registry Center was also searched for ongoing trials up to September 2012. Randomized controlled trials (RCTs) or quasi-RCTs were included. Risk of bias assessment was performed using the Cochrane tool for assessing risk of bias.
RESULTSFive RCTs with 285 participants were found from 49 relevant studies, but there was just one RCT which met the inclusion criteria for this review. The study showed that treatment of catgut implantation at acupoints could lead to a better alleviation of the signs and symptoms of AR than the crude herb moxibustion. No adverse events were reported in this study.
CONCLUSIONSBecause of the methodological shortcoming and the risk of bias of the included trial, catgut implantation was proved with only limited evidence for the treatment of AR. Robust RCTs with high quality and larger sample size in this field are hoped to be carried out in the future.
Acupuncture Points ; Catgut ; adverse effects ; Clinical Trials as Topic ; Humans ; Publication Bias ; Rhinitis, Allergic ; Rhinitis, Allergic, Perennial ; therapy ; Risk Factors