[Application effect of a dual release system of androgen and its antagonist in the repair of full-thickness burn wounds in mice].

Objective: To explore the optimal ratio of dihydrotestosterone and hydroxyflutamide (hereinafter referred to as DH), construct a dual release system of androgen and its antagonist, and analyze the application effect of this system in the repair of full-thickness burn wounds in mice. Methods: This study was an experimental study. The HaCaT cells were divided into blank group (without drug culture), low baseline group, medium baseline group, and high baseline group according to the random number table (the same grouping method below), and the last three groups of cells were cultured by adding three different ratios of DH. Under a medium ratio, the mass of dihydrotestosterone in the three baseline groups from low to high was 1.4, 2.8, and 4.0 µg, respectively, and the mass of hydroxyflutamide was 1.2, 1.6, and 2.0 µg, respectively. On this basis, under a small ratio, the mass of dihydrotestosterone was reduced by half and the mass of hydroxyflutamide was increased by half; under a large ratio, the mass of dihydrotestosterone was increased by half and the mass of hydroxyflutamide was reduced by half. After culture of 2 days, the cell proliferation level was detected by cell counting kit 8 (n=4). Sixteen 6-8-week-old male BALB/c mice were used to establish a full-thickness burn wound on the back and divided into blank group, small ratio group, medium ratio group, and large ratio group, with 4 mice in each group. On post injury day (PID) 7, normal saline containing different ratios of DH was locally dropped to the wounds of mice in the last three groups of mice (the total mass of DH in the three ratio groups from small to large was 127.5, 165.0, and 202.5 µg, respectively, and the mass ratios of dihydrotestosterone to hydroxyflutamide (hereinafter referred to as drug mass ratio) were 8∶9, 8∶3, and 8∶1, respectively), afterwards, the administration was repeated every 48 hours until PID 27; normal saline was dropped to the wound of mice in blank group at the aforementioned time points. The wound healing status on PID 0 (immediately), 7, 14, 21, and 28 was observed, and the wound healing rates on PID 7, 14, 21, and 28 were calculated (n=4). On PID 28, the wound tissue was taken, which was stained with hematoxylin and eosin for observing re-epithelialization and with Masson for observing collagen fibers, and the proportion of collagen fibers was analyzed (n=3). Twenty 6-8-week-old male BALB/c mice were used to establish a full-thickness burn wound on the back and divided into ordinary scaffold group, small proportion scaffold group, medium proportion scaffold group, and large proportion scaffold group (with 5 mice in each group). On PID 7, the wound was continuously dressed with a polycaprolactone scaffold without drug and a polycaprolactone scaffold containing DH with a drug mass ratio of 1∶3, 1∶1, or 3∶1 (i.e. the dual release system of androgen and its antagonist, with total mass of DH being about 1.7 mg) prepared by using electrospinning technology until the end of the experiment. Histopathological analyses of tissue (n=3) at the same time points as those in the previous animal experiment were performed. On PID 7 and 14, the wound exudates were collected and the relative abundance of bacterial communities was analyzed using 16S ribosomal RNA high-throughput sequencing (n=3). Results: After culture of 2 days, under a small ratio, the proliferation levels of HaCaT cells in low baseline group and high baseline group were significantly higher than the level in blank group (P<0.05). As the time after injury prolonged, the wounds of all four groups of mice continued to shrink. On PID 14, the wound healing rate of mice in large ratio group was 72.5% (61.7%, 75.1%), which was close to 53.3% (49.5%, 64.4%) in blank group (P>0.05); the wound healing rates of mice in small and medium ratio groups were 74.2% (71.0%, 84.2%) and 70.4% (65.1%, 74.4%), respectively, which were significantly higher than the rate in blank group (with both Z values being -2.31, P<0.05). On PID 21, the wound healing rate of mice in small ratio group was significantly higher than that in blank group (Z=-2.31, P<0.05). On PID 28, the wounds of mice in the three ratio groups were completely re-epithelialized and the epidermis was thicker than that in blank group; compared with that in blank group, the collagen fiber content in the wound tissue of mice in the three ratio groups was higher and arranged more orderly, and the proportions of collagen fibers in the wound tissue of mice in small and large ratio groups were significantly increased (P<0.05). On PID 28, the wounds of mice in ordinary scaffold group were partially epithelialized, while the wounds of mice in the three proportion scaffold groups were almost completely epithelialized. Among them, the wounds of mice in small proportion scaffold group had the thickest epidermis. The proportion of collagen fibers in the wound tissue of mice in small proportion scaffold group was significantly increased compared with that in ordinary scaffold group (P<0.05). On PID 7, the bacterial communities with high relative abundance in the wound exudation of mice in the four groups included bacteria of Corynebacterium, Staphylococcus, and Rhodococcus. On PID 14, the bacterial communities with high relative abundance in the wound exudation of mice in the four groups included bacteria of Stenotrophomonas, Rhodococcus, and Staphylococcus, and the number of bacterial species in the wound exudation of mice in the three proportion scaffold groups was more than that in ordinary scaffold group. Conclusions: When the drug mass ratio is relatively small, DH has the effect of promoting the proliferation of HaCaT cells. The ratio of 8∶9 is the optimal mass ratio of dihydrotestosterone to hydroxyflutamide, and DH with this mass ratio can promote re-epithelialization and collagen deposition of full-thickness burn wounds in mice, and promote wound healing. The constructed dual release system of androgen and its antagonist with DH in a 1∶3 drug mass ratio contributes to the re-epithelialization and collagen deposition of the full-thickness burn wounds in mice, and can improve the diversity of wound microbiota.

[Study on static parameters of internal nasal valve in 3-dimensional model of nasal cavity space].

Objective: To identify the internal nasal valve (INV) and to evaluate its key parameters in the established 3D models of nasal cavity space via Mimics from CT images, in order to provide evidence for quantitative diagnosis of nasal valve compromise. Methods: A total of 32 Han adults without nasal diseases who underwent maxillofacial CT test in Shanghai Ninth People's Hospital from January 2015 to December 2018 were retrospectively recruited, including 16 males and 16 females, with the age ranged from 20 to 80 years (50% age<50 years old). Maxillofacial CT images were used to create 3D model of nasal cavity space. The INV was identified and the following parameters were measured: the angle between the INV and the nasal bone (θINV-B), unilateral cross-sectional area of the INV (AINV-R, AINV-L), total cross-sectional area of the INV (AINV), unilateral height of the INV (HINV-R, HINV-L), unilateral nasal valve angle (αINV-R, αINV-L), and the sum of nasal valve angle (αINV). The AINV in our study was compared with the results of the previously adopted planes (PlaneC, perpendicular to the hard palate and PlaneB, plane perpendicular to the nasal bone). The parameters above were compared among genders, age and race groups. SPSS 26 and GraphPad Prism 9 software were used for statistical analysis and mapping of data. Results: The AINV in our study was (214.87±52.94) mm², which was significantly less than that of PlaneC (254.97±47.80) mm² and PlaneB (226.07±57.36) mm². The measured parameters were as follows: θINV-B was (82.07±7.06)°; AINV-R was (112.66±31.39) mm²; AINV-L was (102.21±27.14) mm²; AINV was (214.87±52.94) mm²; HINV-R was (24.87±4.62) mm; HINV-L was (24.35±4.86) mm; αINV-R was (20.48±2.99)°; αINV-L was (19.65±3.82)°; αINV was (40.13±6.24)°. The AINV-R was larger than AINV-L (t=2.33, P<0.05); The HINV, AINV-R, AINV-L and AINV of males were more than those of females (t value was 5.77, 3.21, 2.91 and 3.52, respectively, all P<0.01). The AINV of the young group (<50 years) was larger than that of the old group (t=2.83, P<0.01); The θINV-B was different between the Han people and the Caucasian (t=2.92,P<0.01). The αINV of the Han people was larger than that of Caucasians (Z=-6.92, P<0.01), but the HINV was smaller (Z=-3.89, P<0.01). Conclusion: The AINV carried out in 3D models of nasal cavity space is significantly smaller than that obtained by the previous methods of CT evaluation. INV static parameters differ among genders, age and race groups.

[Study on HBV-related acute-on-chronic liver failure risk factors and novel predictive survival model].

Objective: To identify the predisposing factors, clinical characteristics, and risk factors of disease progression to establish a novel predictive survival model and evaluate its application value for hepatitis B virus-related acute-on-chronic liver failure. Methods: 153 cases of HBV-ACLF were selected according to the guidelines for the diagnosis and treatment of liver failure (2018 edition) of the Chinese Medical Association Hepatology Branch. Predisposing factors, the basic liver disease stage, therapeutic drugs, clinical characteristics, and factors affecting survival status were analyzed. Cox proportional hazards regression analysis was used to screen prognostic factors and establish a novel predictive survival model. The receiver operating characteristic curve (ROC) was used to evaluate predictive value with the Model for End-Stage Liver Disease (MELD) and the Chronic Liver Failure Consortium Acute-on-Chronic Liver Failure score (CLIF-C ACLF). Results: 80.39% (123/153) based on hepatitis B cirrhosis had developed ACLF. HBV-ACLF's main inducing factors were the discontinuation of nucleos(t)ide analogues (NAs) and the application of hepatotoxic drugs, including Chinese patent medicine/Chinese herbal medicine, non-steroidal anti-inflammatory drugs, anti-tuberculosis drugs, central nervous system drugs, anti-tumor drugs, etc. 34.64% of cases had an unknown inducement. The most common clinical symptoms at onset were progressive jaundice, poor appetite, and fatigue. The short-term mortality rate was significantly higher in patients complicated with hepatic encephalopathy, upper gastrointestinal hemorrhage, hepatorenal syndrome, and infection (P < 0.05). Lactate dehydrogenase, albumin, the international normalized ratio, the neutrophil-to-lymphocyte ratio, hepatic encephalopathy, and upper gastrointestinal bleeding were the independent predictors for the survival status of patients. The LAINeu model was established. The area under the curve for evaluating the survival of HBV-ACLF was 0.886, which was significantly higher than the MELD and CLIF-C ACLF scores (P < 0.05), and the prognosis was worse when the LAINeu score ≥ -3.75. Conclusion: Discontinuation of NAs and the application of hepatotoxic drugs are common predisposing factors for HBV-ACLF. Hepatic decompensation-related complications and infection accelerate the disease's progression. The LAINeu model can predict patient survival conditions more accurately.

[SENP1 induced protein deSUMO modification increased the chemotherapy sensitivity of endometrial cancer side population cells].

Objective: To inhibit the stemness maintenance potential of endometrial cancer and increase the sensitivity of endometrial cancer side population cells to chemotherapy drugs by inducing extensive deSUMOylation modification of proteins. Methods: Flow cytometry was used to sort and culture CD133(+) CD44(+) KLE endometrial cancer cell clone spheres. Protein expression level of small ubiquitin-related modifier 1 (SUMO1) and two stemness maintenance genes of tumor side population cells, octamer binding transcription factor-4 (Oct4) and sex determining region Y-box2 (Sox2), were detected by western blotting method. Lentivirus-mediated Sentrin/SUMO-specific proteases 1 (SENP1) gene was stably transfected into KLE side population cells. Western blotting was used to detect the protein expressions of SENP1, SUMO1, Oct4 and Sox2. The clone formation rate was compared between KLE side population cells with or without SENP1 overexpression. Flow cytometry was applied to detect cell cycle changes. 3-(4, 5-Dimethylthiazole-2)-2, 5-diphenyl-tetrazolium bromide (MTT) experiment and flow cytometry apoptosis method were used to detect the chemosensitivity of the side population of endometrial cancer cells to cisplatin. Tumor-bearing mouse models of endometrial cancer were established to detect the effect of SENP1 overexpression on the chemotherapy sensitivity of cisplatin. Results: Compared with CD133(-)CD44(-) KLE cells, CD133(+) CD44(+) KLE side population cells could form clonal spheres and express higher levels of SUMO1, Oct4 and Sox2 proteins (P<0.05). Compared with KLE side population cells that were not transfected with SENP1 gene, the expression level of SENP1 protein in KLE side population cells overexpressing SUMO1、Oct4 and Sox2 were lower. The clonal sphere formation rate was reduced from (25.67±5.44)% to (7.46±1.42)%, and cell cycle shifted from G(0)/G(1) phase to G(2) phase. IC(50) of cisplatin decreased from (55.46±6.14) µg/ml to (11.55±3.12) µg/ml, and cell apoptosis rate increased from (9.76±2.09)% to (16.79±3.44)%. Overexpression of SENP1 could reduce the tumorigenesis rate of KLE side population cells in vivo and increase their chemotherapy sensitivity to cisplatin (P<0.05). Conclusion: Overexpression of SENP1 can induce protein deSUMOylation modification, inhibit the stemness maintenance potential of endometrial cancer side population cells, and enhance their chemotherapy sensitivity, which provides a new reference for gene therapy of endometrial cancer.

[Study on heme oxygenase-1 and HAP model for the diagnosis of chronic hepatitis B-related liver fibrosis].

Objective: To determine the diagnostic value of plasma heme oxygenase 1 (HO-1) in the occurrence, development, and pathological stages of chronic hepatitis B-related liver fibrosis. Methods: 211 outpatients and inpatients with chronic hepatitis B (CHB) and 57 healthy controls who visited the Third Hospital of Hebei Medical University were selected. Simultaneously, clinical data, peripheral blood routine and serum biochemical test results of the research subjects were collected. Plasma HO-1 levels were detected by enzyme-linked immunosorbent assay (ELISA). Liver fibrosis (S1 ~ 4) was staged according to liver biopsy and liver stiffness measurement (LSM). Statistical analysis: binary logistic regression was used to analyze the independent risk factors of hepatitis B-related liver fibrosis to establish a diagnostic model, and the receiver operating characteristic curve (ROC) was used to compare and analyze the staging efficiency of HO-1, new model, FIB-4 and APRI for the diagnosis of liver fibrosis. Results: Plasma HO-1 levels were significantly higher in CHB patients than healthy controls [10.11 (7.08 ~ 13.12) ng/ml and 6.71 (5.56 ~ 8.45) ng/ml, (P < 0.001)]. There were 37, 38, 38, and 98 cases with liver fibrosis stages S1, S2, S3, and S4, respectively and plasma HO-1 level was (6.91 ± 2.80) ng/ml, (8.24 ± 2.44) ng/ml, (9.96 ± 3.46) ng/ml, (12.65 ± 3.70) ng/ml, P < 0.001. HO-1, albumin, and platelets (PLT) were independent risk factors for liver fibrosis. A HAP model was established. HAP, FIB-4 and APRI sensitivity and specificity for the diagnosis of liver fibrosis staging were as follows: ≥S2 were 84.62%, 72.35 %, 81.18% and 83.78%, 81.08%, 67.57%; ≥S3 were 80.15%, 82.09%, 85.82% and 88.64%, 76.19%, 60.32%; S4 were 90.82%, 82.29%, 86.46% and 74.37%, 65.77%, 48.65%, respectively. Conclusion: Plasma HO-1 level can reflect the severity of liver fibrosis. HAP diagnostic model can more accurately mirror the process of liver fibrosis than FIB-4 and APRI, and point clinical diagnosis and prognosis assessment.

[Study on plasma Golgi protein 73 and related models in the diagnosis of nonalcoholic fatty liver disease].

Objective: To investigate the relationship between plasma Golgi protein 73 (GP73) levels and the occurrence and development of non-alcoholic fatty liver disease (NAFLD), and to establish a diagnostic model based on this combination with lipid metabolism indicators to clarify its diagnostic efficacy and clinical application value for NAFLD. Methods: 225 cases with NAFLD [diagnosed by ultrasound, transient elastography (FibroScan502) and liver biopsy (some patients)] and 108 healthy controls were selected from the Department of Hepatology and Physical Examination Center of Integrated Traditional Chinese and Western Medicine, The Third Hospital of Hebei Medical University. Clinical data, routine peripheral blood and serum biochemical test results were collected. The plasma GP73 level was detected by enzyme-linked immunosorbent assay. SPSS 21.0 statistical software was used for statistical analysis. Binary logistic regression model was used to calculate the NAFLD diagnostic model. Receiver operating characteristic curve was used to evaluate the NAFLD constructed model diagnostic efficacy. Results: NAFLD incidence was significantly reduced in younger age group, mostly in young and middle-aged male. However, the NAFLD incidence was increased with increasing age in female. The analysis of age ratio composition showed that the average age for NAFLD onset was 20 ~ 50 years old, and the incidence rate was as high as 47% in among 30 ~ 39 years old, but the incidence rate was significantly decreased in over 60 years old (4.00%). GP73 was an independent risk factor for the occurrence and development of NAFLD. The diagnostic models of GBT, GB and GT were established by GP73 (G) combined with body mass index (BMI, B) and serum triglyceride (TG, T), and the results showed that the areas under the curves of GBT, GB and GT models were 0.969, 0.937 and 0.909, respectively. The sensitivity and the specificity were 84.90%, 77.80% and 84.00%, and 95.40%, 95.40% and 82.40%, respectively, P < 0.05. The GBT model had efficacy of best diagnostic performance. Conclusion: NAFLD is more common in young and middle-aged male, but with advanced age, the incidence of female patients gradually increases. Plasma GP73 levels are related to the occurrence and development of NAFLD. The GBT model can be used as a new model for non-invasive diagnosis and one of the indicators for clinical evaluation of diagnostic efficacy of NAFLD.

[Investigation of contact dermatitis caused by hard metal dust].

Objective: To investigate the incidence of contact dermatitis among workers in cemented carbide production enterprises. Methods: From October 1997 to October 2017, an occupational epidemiological survey was conducted on a large-scale cemented carbide production enterprise, and occupational health examinations were conducted for employees. 152 people were exposed to hard metal dust (hard metal raw material dust and alloy dust) . The employees in the work group were contact groups, and 142 employees in the non-dusting operation of the company were in the control group. A detailed retrospective survey of hard metal production workers with contact dermatitis history in the two groups was conducted to analyze the risk factors of contact dermatitis exposure to hard metal dust. Results: The incidence of allergic diseases in the exposed group was significantly higher than that in the control group. The difference was statistically significant (χ(2)=23.793, P<0.05) . The incidence of contact dermatitis in the exposed group was significantly higher than that in the control group. The difference was statistically significant (χ(2)=24.659, P<0.05) ; the changes of contact dermatitis in the contact group were mainly allergic contact dermatitis, and some showed irritative contact dermatitis; the operator had respiratory symptoms (including work-related nasal congestion, cough, wheezing) , difficulty breathing may be the influencing factors of contact dermatitis (RR=2.60, 95%CI: 1.10-6.20, P<0.05) . Conclusion: Hard metal alloy enterprises are exposed to hard metal dust. The incidence of contact dermatitis is high in workers, and the occurrence of contact dermatitis may be associated with those with respiratory symptoms.

[A case report on multiple organ dysfunction syndrome caused by acute carbon tetrachloride poisoning].

Occupational acute carbon tetrachloride poisoning occurs when a worker is exposed to highly condensed carbon tetrachloride in a short time and suffers from diseases damaging mainly his neutral system and (or) liver and kidney. This article reports a case of what clinical symptoms MODS patients show and how to diagnose, differential diagnosis and therapy process.

[Delphy expert survey on diagnosis of chronic obstructive pulmonary disease caused by occupational irritant chemicals].

Objective: o explore the problems encountered in the application of GBZ/T 237-2011 edition of "Diagnosis of Chronic Obstructive Pulmonary Disease Caused by Occupational Stimulating Chemicals" , and to provide reference for the revision of the new standard. Methods: Delphi expert survey method was used to consult experts on the reasonableness of six primary indicators (scope of application, diagnostic principles, diagnostic indicators, treatment principles, diagnostic grading, appendix A) and their corresponding secondary indicators in the Diagnosis of Chronic Obstructive Pulmonary Disease (COPD) caused by Occupational Stimulant Chemicals. Results: The results of the first round of Delphi method showed that the reasonable mean of the diagnostic criteria about long-term occupational history, smoking history and clinical diagnostic criteria was less than 7, and the coefficient of variation was greater than 0.25, indicating that the experts disagreed with the scope of application of the original criteria; the average of smoking history and 3-year working age were 1.78 and 3.43 (less than 7) respectively, which indicated that the experts agreed that the two diagnostic indexes were not conducive to the practical work of occupational disease clinicians; among the diagnostic indicators, smoking history and smoking volume were taken into account in a comprehensive way, and the average values were 7.61 and 7.61 (greater than 7) , respectively. the coefficient of variation was less than 0.25, indicating that the experts had concentrated their opinions and agreed that such indicators could be considered into the diagnostic index system. Conclusion: "Diagnosis of Chronic Obstructive Pulmonary Disease Caused by Occupational Stimulating Chemicals" should be improved by expanding the scope of occupational irritant gases. Smoking problems can be considered in combination with clinical practice, and occupational exposure history can be considered to reduce appropriately.

Variability of cadmium, lead, and zinc tolerance and accumulation among and between germplasms of the fiber crop Boehmeria nivea with different root-types.

Crop germplasms substantially vary in their tolerance for and accumulation of heavy metals, and assessment of this variability plays a significant role in selecting species to use in phytoremediation projects. Here, we examined germplasm-variations in cadmium (Cd), lead (Pb), and zinc (Zn) tolerance and accumulation in ramie (Boehmeria nivea), a fiber crop native to China, which has received little attention. In an 8-week greenhouse test, fourteen germplasms of ramie, among and within deep, middle, and shallow rooted-types, were compared for growth and metal accumulation traits. Results showed that both tolerance and accumulation traits varied across germplasms and rooted-types. The deep rooted-type germplasms produced more biomass and had higher tolerance to metals than the two others. In addition, considerable variations in metal accumulation were observed among plant organs (root, stem, and leaf), rooted-types, germplasms, and metal supply. However, the observed variations in metal tolerance and accumulation among both germplasms and rooted-types were not significant in most cases. In addition to supporting the idea of a certain degree of constitutional metal tolerance for ramie, our results also contribute to deep-rooted germplasms of ramie as a good candidate, rather than middle-/shallow- ones as a least-bad option, for the remediation of multi metal-contaminated soils.

Lipoprotein lipase gene polymorphisms and risks of childhood obesity in Chinese preschool children.

Childhood obesity is increasingly prevalent in the community and is related to many adult diseases. Lipoprotein lipase (LPL) plays a central role in dyslipidemia, and polymorphisms of the LPL gene may result in the disturbance in the lipid's metabolism. The aim of this study is to test the hypothesis that genetic variants of LPL and serum lipid levels are associated with the risk of childhood obesity. We genotyped +495T > G and PvuII T > C in an LPL gene and measured the serum lipid levels in a case-control study of 124 obese children and 346 frequency-matched normal controls in preschool Chinese children. The variant genotypes of LPL + 495GG and PvuII CC were associated with a significantly increased risk of childhood obesity [adjusted odds ratio (OR) = 2.39, 95% CI = 1.09-5.23 for +495 GG; adjusted OR = 2.00, 95% CI = 1.04-3.83 for PvuII CC], compared with their wild-type genotypes, respectively. In addition, compared with the lower serum level cut off by the control median, the higher level of serum triglyceride (TG) (>0.59 mmol/L) was associated with a 1.32-fold increased risk of childhood obesity, and the higher level of high density lipoprotein cholesterol (HDLC) (>1.14 mmol/L) was associated with a 36% decrease in risk of childhood obesity. Furthermore, the median levels of TG were higher in obese children carrying LPL +495TT/TG and PvuII TT/CT genotypes than those in controls, the HDLC levels were lower in obese children carrying LPL +495TG and PvuII CT/CC genotypes than those in controls. In conclusion, the LPL gene +495T > G and PvuII T > C polymorphisms may modulate the magnitude of dyslipidemia in Chinese early-onset obesity.

Three-dimensional molecular packing of thin organic films of PTCDI-C8 determined by surface X-ray diffraction.

We have determined the full molecular 3D packing of thin organic films of the archetypical organic n-type semiconductor N, N'-dioctyl-3,4:9,10-perylene tetracarboxylic diimide (PTCDI-C 8) by surface X-ray crystallography. We show that PTCDI-C 8 forms smooth layered films on Al 2O 3 (11-20) with an outstanding degree of molecular order. The thin-film structure is found to consist of a triclinic unit cell with the plane of the aromatic core tilted by 67 +/- 2 degrees with respect to the surface plane, which differs significantly from the bulk structure. The 3D crystallites extend with vertical coherent order across the entire film thickness.

Activation of Stat1 by mutant fibroblast growth-factor receptor in thanatophoric dysplasia type II dwarfism.

The achondroplasia class of chondrodysplasias comprises the most common genetic forms of dwarfism in humans and includes achondroplasia, hypochondroplasia and thanatophoric dysplasia types I and II (TDI and TDII), which are caused by different mutations in a fibroblast growth-factor receptor FGFR3 (ref. 1). The molecular mechanism and the mediators of these FGFR3-related growth abnormalities are not known. Here we show that mutant TDII FGFR3 has a constitutive tyrosine kinase activity which can specifically activate the transcription factor Stat1 (for signal transducer and activator of transcription). Furthermore, expression of TDII FGFR3 induced nuclear translocation of Stat1, expression of the cell-cycle inhibitor p21(WAF1/CIP1), and growth arrest of the cell. Thus, TDII FGFR3 may use Stat1 as a mediator of growth retardation in bone development. Consistent with this, Stat1 activation and increased p21(WAF1/CIP1) expression was found in the cartilage cells from the TDII fetus, but not in those from the normal fetus. Thus, abnormal STAT activation and p21(WAF1/CIP1) expression by the TDII mutant receptor may be responsible for this FGFR3-related bone disease.