Myeloid-derived suppressor cells and pulmonary hypertension.

Pulmonary hypertension (PH) is a chronic pulmonary vascular disorder characterized by an increase in pulmonary vascular resistance and pulmonary arterial pressure. The detailed molecular mechanisms remain unclear. In recent decades, increasing evidence shows that altered immune microenvironment, comprised of immune cells, mesenchymal cells, extra-cellular matrix and signaling molecules, might induce the development of PH. Myeloid-derived suppressor cells (MDSCs) have been proposed over 30 years, and the functional importance of MDSCs in the immune system is appreciated recently. MDSCs are a heterogeneous group of cells that expand during cancer, chronic inflammation and infection, which have a remarkable ability to suppress T-cell responses and may exacerbate the development of diseases. Thus, targeting MDSCs has become a novel strategy to overcome immune evasion, especially in tumor immunotherapy. Nowadays, severe PH is accepted as a cancer-like disease, and MDSCs are closely related to the development and prognosis of PH. Here, we review the relationship between MDSCs and PH with respect to immune cells, cytokines, chemokines and metabolism, hoping that the key therapeutic targets of MDSCs can be identified in the treatment of PH, especially in severe PH.

TP53-mediated miR-2861 promotes osteogenic differentiation of BMSCs by targeting Smad7.

Bone defect seriously affects the quality of life. Meanwhile, osteogenic differentiation in BMSCs could regulate the progression of bone defect. Transcription factors are known to regulate the osteogenic differentiation in BMSCs. The study aimed to investigate the detailed mechanism by which TP53 regulates the osteogenic differentiation. To study bone defect in vitro, BMSCs were isolated from spinal cord injury rats. CCK-8 assay was applied to test the cell viability. The mineralized nodules in BMSCs was tested by alizarin red staining. Meanwhile, TUNEL staining and flow cytometry were performed to test the cell apoptosis. mRNA expression was tested by qRT-PCR. Starbase and dual-luciferase reporter assay were used to predict the downstream mRNA of miR-2861. Moreover, western blot was applied to detect the protein expressions (TP53 and Smad7). BMSCs were successfully isolated from rats. The expressions of miR-2861 were significantly upregulated in osteogenic medium, compared with growth medium. MiR-2861 inhibitor significantly decreased the levels of OCN, ALP, BSP, and Runx2 in BMSCs. In addition, miR-2861 inhibitor notably inhibited the mineralized nodules, viability, and induced the apoptosis of BMSCs. Smad7 was identified to be the downstream target of miR-2861, and knockdown of Smad7 notably reversed miR-2861 inhibitor-induced inhibition of osteogenic differentiation and promotion of apoptosis in BMSCs. Moreover, miR-2861 was transcriptionally regulated by TP53 in BMSCs. TP53-meidiated miR-2861 promotes osteogenic differentiation of BMSCs by targeting Smad7. Thereby, our research might provide new methods for bone defect treatment.

Huayu Pill () Promotes Fluorescent Doxorubicin Delivery to Tumors in Mouse Model of Lung Cancer.

OBJECTIVE: To study the effect and mechanism of Huayu Wan (, HYW) in combination of chemotherapy of tumor treatment. METHODS: HYW serum was added in Lewis cells to assess its impact on fluorescent doxorubicin delivery in vitro. Then, Lewis tumor cells was implanted in C57BL/6 mice via xenograft transplantation. Tumor growth was measured and signal intensity corresponding to blood flow was assessed by laser doppler perfusion imaging (LDPI). Finally, the effect of HYW on the effificacy of doxorubicin was studied. RESULTS: HYW can improve the transfer of fluorescent doxorubicin into cells. The blood flow signal in the tumor tissues of the HYW group was higher than that of the control group (P<0.01). Furthermore, HYW improved drug delivery of doxorubicin to tumor tissues, and this activity was associated with HYW-induced microvascular proliferation (P<0.01). CONCLUSIONS: HYW can promote microangiogenesis and increase blood supply in tumor tissues, which in turn may increase the risk of metastasis. At the same time, HYW increases drug delivery and improves the effificacy of chemotherapy drugs through vascular proliferation. Therefore, rational judgment must be exercised when considering applying HYW to an antitumor regimen.

SANT, a novel Chinese herbal monomer combination, decreasing tumor growth and angiogenesis via modulating autophagy in heparanase overexpressed triple-negative breast cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: Astragalus mongholicus, Solanum nigrum Linn, Lotus plumule, Ligusticum are widely used traditional herbal medicines for cancer treatment in China. They were typical drugs selected from Gubenyiliu II and series of formula (GYII), which were developed on the foundation of YIQIHUOXUEJIEDU theory. In the present study, four active ingredients (Astragaloside IV, α-solanine, neferine, and 2,3,5,6-tetramethylpyrazine) derived from medicines above were applied in combination as SANT. AIM OF THE STUDY: Triple-negative breast cancer (TNBC) is a serious threat to women's health worldwide. Heparanase (HPSE) is often up-regulated in breast cancer with the properties of facilitating tumorigenesis and influencing the autophagy process in cancer cells. This study aimed at evaluating the anti-tumor potential of SANT in treating HPSE related TNBC both in-vitro and in-vivo. MATERIALS AND METHODS: In this study, we explored the correlation between HPSE expression and survival of breast cancer patients in databases. We performed MTS, trans-well and wound scratch assays to assess the impact of SANT on cell proliferation and migration. Confocal microscopy observation and western blots were applied to verify the autophagy flux induced by SANT. Mice models were employed to evaluate the efficacy and safety of SANT in-vivo by tumor weights and volumes or serum index, respectively. To analyze the underlying mechanisms of SANT, we conducted human autophagy PCR array and angiogenesis proteome profiler on tumor tissues. RESULTS: Patients with elevated HPSE expression were associated with a poor outcome in both RFS (P = 1.7e-12) and OS (P = 0.00016). SANT administration significantly inhibited cancer cells' proliferation and migration, enhanced autophagy flux, and slightly reduced the active form of HPSE in-vitro. SANT also suppressed tumor growth and angiogenesis in-vivo. Human autophagy PCR array results indicated that SANT increased the ATG16L1, ATG9B, ATG4D gene expressions while decreased TMEM74 and TNF gene expressions.Angiogenesis proteome profiler results showed SANT reduced protein level of HB-EGF, thrombospondin-2, amphiregulin, leptin, IGFBP-9, EGF, coagulation factor III, and MMP-9 (pro and active form) in tumor, raised the protein expression of serpin E1 and platelet factor 4. CONCLUSIONS: These findings indicated that herbal compounds SANT may be a promising candidate in anti-cancer drug discovery. It also provides novel strategies for using natural compounds to achieve optimized effect.

Efficacy of acupuncture in the prevention and treatment of chemotherapy-induced nausea and vomiting in patients with advanced cancer: a multi-center, single-blind, randomized, sham-controlled clinical research.

BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) is a common and distressing side effect. We conducted this clinical trial to compare the effectiveness of true acupuncture vs. sham acupuncture in controlling chemotherapy-induced nausea and vomiting (CINV) among patients with advanced cancer. METHODS: A total of 134 participants were randomly allocated into true acupuncture (TA) (n = 68) and sham acupuncture (SA) (n = 66) groups. Participants in both groups received acupuncture session twice on the first day of chemotherapy, and once consecutively on the following 4 days. The primary outcome was using the Common Terminology Criteria for Adverse Events (CTCAE) to assess CINV. The secondary outcome measures were the Eastern Cooperative Oncology Group score (ECOG), Simplified Nutritional Appetite Questionnaire (SNAQ), and Hospital Anxiety and Depression scale (HADS). RESULTS: Compared to the SA group, the TA group didn't show significant improvement in complete response rates of chemotherapy-induced nausea and vomiting (all P > 0.05). However, the TA group could modestly reduce the severity of nausea (from day-3 to day-21, P < 0.05) or vomiting (from day-4 to day-21, P < 0.05), which is notably superior to the control group. Besides, TA promoted the nutritional status of patients with a significantly higher score comparing to the SA group on day 14 (21.82 vs.20.12, P = 0.003) and day 21 (22.39 vs. 20.43, P = 0.001). No apparent differences were found in anxiety and depression assessment between these groups. Participants in both groups were well tolerant of acupuncture therapy. There was no adverse event occurs in our study. CONCLUSION: Acupuncture as an adjunctive approach could alleviate the severity of chemotherapy-induced nausea and vomiting compared to the sham control, even though the effect of acupuncture in preventing CINV occurring is relatively modest.

Combined navigated drilling and arthroscopy facilitate minimally invasive surgical treatment of ulnar-radial joint dislocation caused by epiphyseal premature closure: A case report.

RATIONALE: In this paper, the efficacy and safety of using navigated drilling and arthroscopy (NDA) to assist surgery for ulnar-radial joint dislocation caused by epiphyseal premature closure (EPC) are described. Deformity correction surgery was mentioned in the literature, but there were numerous complications, for example, poor correction, infection, neurovascular injury, osteofascial compartment syndrome, failure of internal fixation, and nonunion after osteotomy. In order to minimize surgical complications, we utilized navigated drilling to finish accuracy bone bridge resection and applied arthroscopy to assess wrist lesions. PATIENT CONCERNS: An 11-year-old male patient showed swelling and pain of the left wrist. DIAGNOSES: The patient was diagnosed with a postoperative of Kirschner wire internal fixation for epiphyseal injury, left lower ulnar-radial joint dislocation, left wrist deformity, and EPC. INTERVENTIONS: A NDA was used to assist the bone bridge resection in this patient. OUTCOMES: Pain was relieved clearly in the patient. Dorsiflexion increased from 60.8° to 85.3°, palmar flexion increased from 45.3° to 65.8°, supination increased from 41.3° to 69.5°, and pronation increased from 31.6° to 62.9°. The preoperative disabilities of the arm, shoulder, and hand (DASH) score was 86.1, which was increased to 16.4 postoperatively. Surgery designing lasted for 2 minutes, bone bridge resection lasted for 56 minutes, and fluoroscopic time was 2.4 minutes. Complications, for example, neurological injury, vascular injury, infection and deformity aggressive, were not found during the 5-month follow up. LESSONS: The outcome of the present study suggests that the NDA maximizes the bone bridge resection accuracy in EPC treatment, which is made efficient by reducing surgical trauma and avoiding neurovascular injury. An experience was gained that in the process of bone bridge removal, the bit of navigated drill should be continuously washed with normal saline to cool down, so as to avoid damage of nerve caused by heat conduction.

Effect of acupuncture in prevention and treatment of chemotherapy-induced nausea and vomiting in patients with advanced cancer: study protocol for a randomized controlled trial.

BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) is one of the most common and distressing side effects in patients with cancer. The introduction and development of antiemetic drugs have significantly improved the ability of clinicians to control CINV, but it is not easy to translate to practical application, owing to financial issues, provider-related barriers, and patient factors. Nondrug therapies are needed to alleviate the symptoms of CINV. Acupuncture is an appropriate adjunctive treatment for CINV, but additional evidence is needed. METHODS/DESIGN: This study is a multicenter, randomized, sham-controlled prospective clinical trial. A total of 136 participants will be randomly allocated into the intervention group (verum acupuncture) or the control group (sham acupuncture) in a 1:1 ratio. All treatment will be given for 5 days. Participants in both groups will receive acupuncture sessions twice on the first day of chemotherapy and once consecutively on the following 4 days. Each session takes approximately 30 minutes. The primary outcome measure will be the Common Terminology Criteria for Adverse Events to assess CINV. The secondary outcome measures will be the Eastern Cooperative Oncology Group score, Simplified Nutritional Appetite Questionnaire, and Hospital Anxiety and Depression scale. Safety will be assessed at each visit. DISCUSSION: The results of this trial will provide clinical evidence for the effect and safety of acupuncture for CINV. TRIAL REGISTRATIONS: ISRCTN Registry identifier: ISRCTN13287728 ). Registered on 28 February 2015. ClinicalTrials.gov identifier: NCT02369107 . Registered on 17 February 2015.

Granulomatous Lobular Mastitis Associated with Mycobacterium abscessus in South China: A Case Report and Review of the Literature.

Mycobacteria, which are known as rapidly growing bacteria, are pathogens that are responsible for cutaneous or subcutaneous infections that especially occur after injection, trauma, or surgery. In this report, we describe a species of Mycobacterium abscessus that was isolated from a breast abscess in a patient who was previously diagnosed with granulomatous lobular mastitis (GLM). This current case is the first ever presented case of GLM associated with M. abscessus documented in South China. The case presentation highlights the role of M. abscessus in GLM. The association of M. abscessus and GLM is discussed and a summary of breast infection due to Mycobacteria is given.

De-SUMOylation of FOXC2 by SENP3 promotes the epithelial-mesenchymal transition in gastric cancer cells.

The impact of cellular oxidative stress in promoting the epithelial-mesenchymal transition (EMT) has been noticed. Our previous study shows that SENP3, a redox-sensitive SUMO2/3-specific protease, accumulates in a variety of cancers, but whether SENP3 and SUMOylation involve in the regulation of EMT is unclear. The present study uncovers a novel role of SENP3 in promoting the EMT process in gastric cancer via regulating an EMT-inducing transcription factor, forkhead box C2 (FOXC2). We demonstrate that the expression of mesenchymal marker genes and cell migration ability are enhanced in SENP3-overexpressing gastric cancer cells and attenuated in SENP3-knockdown cells. A nude mouse model and a set of patient's specimens suggest the correlation between SENP3 and gastric cancer metastasis. Biochemical assays identify FOXC2 as a substrate of SENP3. Meanwhile N-cadherin is verified as a target gene of FOXC2, which is transcriptionally activated by a SUMO-less FOXC2. Additionally, reactive oxygen species-induced de-SUMOylation of FOXC2 can be blocked by silencing endogenous SENP3. In conclusion, SENP3, which is increased in gastric cancer cells, potentiates the transcriptional activity of FOXC2 through de-SUMOylation, in favor of the induction of specific mesenchymal gene expression in gastric cancer metastasis.

Does dynamic immobilization reduce chondrocyte apoptosis and disturbance to the femoral head perfusion?

The purpose of this study is to investigate whether the dynamic hip immobilization is more favourable for lessening ischemic injury to the immature femoral head than a static immobilization. 152 Japanese white rabbits were divided into four groups randomly, and the hips were immobilized into "human" position (group A), "frog leg" position (group B) and "dynamic frog leg" position (group C). Group D was used as control. Ten rabbits in each group were killed, and the hip specimens were harvested at 1, 2, and 3 weeks after immobilization. Bcl-2/Bax expression balance and chondrocytes apoptosis were analyzed. The remaining eight rabbits in each group were used to measure the blood supply of capital femoral epiphysis by selective vascular perfusion with Indian ink. The Bcl-2/Bax expression ratio in group C was significantly increased than that in group A and B (p<0.001), while that was not significantly different from control group (p=0.0592). At three weeks after immobilization, the average apoptotic ratio was 36.7%, 45.8%, and 26.7% in group A, B and C, respectively (p<0.01). There was no significant difference between group C and normal control (p=0.0597). The perfusion ratio was 0.03±0.03, 0.03±0.02, and 0.08±0.03 in group A, B and C respectively, and 0.12±0.04 in control group (p<0.05). Thus, the dynamic immobilization model exhibited a relatively less chondrocytes apoptosis and disturbance to the femoral head perfusion than other immobilizations in vivo, which therefore may be useful for reducing avascular necrosis following the treatment of developmental dysplasia of the hip.

Characterization of cancer stem-like cells derived from a side population of a human gallbladder carcinoma cell line, SGC-996.

The cancer stem cell (CSC) hypothesis proposes that CSCs, which can renew themselves proliferate infinitely, and escape chemotherapy, become the root of recurrence and metastasis. Previous studies have verified that side population (SP) cells, characterized by their ability to efflux lipophilic substrate Hoechst 33342, to share many characteristics of CSCs in multiplying solid tumors. The purpose of this study was to sort SP cells from a human gallbladder carcinoma cell line, SGC-996 and to preliminarily identify the biological characteristics of SP cells from the cell line. Using flow cytometry we effectively sorted SP cells from the cell line SGC-996. SP cells not only displayed higher proliferative, stronger clonal-generating, more migratory and more invasive capacities, but showed stronger resistance. Furthermore, our experiments demonstrated that SP cells were more tumorigenic than non-SP counterparts in vivo. Real-time PCR analysis and immunocytochemistry showed that the expression of ATP-binding cassette subfamily G member 2 (ABCG2) was significantly higher in SP cells. Hence, these results collectively suggest that SP cells are progenitor/stem-like cells and ABCG2 might be a candidate marker for SP cells in human gallbladder cancer.

Clinical features and treatment of the hip in multiple epiphyseal dysplasia in childhood.

Multiple epiphyseal dysplasia is a rare congenital osteochondrodysplasia disorder characterized by a delay in the appearance of the epiphyses; irregular, symmetric epiphyseal formation; mild short stature; and early-onset osteoarthritis. Peripheral weight-bearing and nonweight-bearing joints can be affected. Treatment of the hip deformity in multiple epiphyseal dysplasia is a challenge for orthopedic surgeons.We reviewed the clinical features and treatment options of hip joints affected by multiple epiphyseal dysplasia in 6 young patients (4 boys and 2 girls). Average patient age was 8.8 years (range, 5-14 years). The spectrum of hip joint deformity ranged from mild to severe. Surgical procedures included intertrochanteric extension osteotomy of the femur in 2 patients (4 hips), Staheli acetabular augmentation in 1 patient (2 hips), and trochanter arthroplasty associated with Dega osteotomy in 2 patients (4 hips). One patient did not undergo surgical treatment. All patients were followed up for an average 7.2 years. Joint function improved in the patients treated surgically. The coxa vara deformity was corrected satisfactorily, and the femoral head was covered completely by the acetabulum.Good mid-term outcomes were obtained for the treatment of severe hip deformity by using intertrochanteric extension osteotomy and trochanter arthroplasty. However, because of the inherent nature of this disorder, long-term follow-up of the patients is required.

[Gene mapping of developmental dysplasia of the hip in chromosome 17q21 region].

OBJECTIVE: To map the susceptibility gene of developmental dysplasia of the hip(DDH) in chromosome 17q21 region. METHODS: According to the number of alleles (≥ 5), heterozygosity (≥ 0.70) and polymorphic information content (PIC≥ 0.5), 11 STR markers in the 17q21 region were chosen for transmission disequilibrium test (TDT). STR markers were amplified by PCR and genotypes were analyzed by capillary electrophoresis in 103 trio families. TDT was used to locate the susceptibility gene in 17q21 region. RESULTS: Because of a low genetic polymorphism, D17S810 and D17S931 loci were removed from the TDT. Transmission disequilibrium was detected at D17S855, D17S858, D17S806, D17S1877, D17S941, D17S752 and D17S790, which overlapped 11.7 cM in 17q21. However, no transmission disequilibrium was found at D17S1787 and D17S787. Thus, the susceptibility gene for DDH was located in the chromosome region between D17S855 and D17S790. CONCLUSION: The susceptibility gene for DDH is narrowed to an 11.7 cM region of 17q21.31-17q22, between STR loci D17S855 and D17S790.

Pediatric synovial sarcoma of the sacrum: a case report.

We reported a rare synovial sarcoma arising within sacrum of a 12-year-old boy. A plain radiograph, magnetic resonance imaging performed before surgery, and the intraoperative findings showed that the tumor was S2 and below. Immunohistochemically, desmin and CD34 were negative. CK, CK7, CK1, CK3, CK8, CK19, Bcl-2, E-cadherin, ki-67, P53, SMA, CD99, CD56, S-100, vimentin, and epithelial membrane antigen were positive. Some were focal positively reactive to S-100, P53, and ki-67. The spindle cells were strongly positive for vimentin and CK3. The immunohistochemical findings confirmed its diagnosis of synovial sarcoma.

[A clinical study of bile cultures and antibiotic susceptibility test in the patients with operation on biliary tract].

OBJECTIVE: To illustrate the bacteriology and their susceptibility to antibiotics in patients with biliary tract diseases and provide information for antibiotic choices. METHODS: The bile specimens were cultured and pathogens' susceptibility to antibiotics was obtained intraoperatively from 195 patients undergoing operations on biliary tract and 24 healthy liver donors from June 2007 to March 2008. RESULTS: Among 195 bile specimens collected from the patients intraoperatively, 44 ones were found bacterial growth by culture (22.6%), in which 11 ones were mixed infections (25.0%). Fifty-five bacterial strains belonging to 16 species were identified from these bile specimens. They included 34 Gram negative strains (61.8%), 19 Gram positive strains (34.6%) and 2 fungal strains (3.6%). The commonest pathogens were Escherichia coli (27.3%), Enterobacter cloacae (12.7%), Enterococcus faecalis (12.7%) and Enterococcus faecium (10.9%). Among 24 bile specimens collected from the healthy liver donors, one was found Escherichia coli growth by culture (4.2%). The results of susceptibility test showed that the resistant rates of Gram negative strains to Meropenem was 2.8%, followed by Imipenem (5.6%), Sulperazone (22.8%) and Amikacin (28.7%). In this study Gram negative strains were highly resistant to Penicillins, Quinolones, some third generation Cephalosporins and so on (>50.0%). None of Gram positive strains were resistant to Vancomycin and Teicoplanin. They were highly resistant to Penicillins, Quinolones, Clindamycin and so on (>40.0%). CONCLUSIONS: (1) Gram negative strains remain the commonest pathogens in biliary tract infection in Renji Hospital and the commonest pathogen is Escherichia coli. The infection of enterococcus is going up. The mixed infection cases happen mostly in acute biliary infection. (2) To treat biliary infection the broad-spectrum antibiotics which are effective to Escherichia coli are optimal choices. Ceftazidime or Ciprofloxacin may be used in mild biliary infection. Sulperazone or Amikacin may be used in severe biliary infection. Imipenem and Vancomycins may be used as second choice to treat the infection which other drugs are ineffective to.

Deformity correction with external fixator in pseudoachondroplasia.

Patients with pseudoachondroplasia have complex, difficult to correct deformities including angular deformity, rotational deformity, and ligament laxity. We retrospectively reviewed seven patients (two children, five adults) with 26 segmental deformities (12 femora, 14 tibiae). We performed bilateral femoral and tibial osteotomies in six patients and bilateral tibial osteotomies in one patient. Distraction osteogenesis was used in 20 segments and acute deformity correction was done in six segments. External fixation was applied to all segments. Of 26 segments, there were five good, 12 fair, and nine poor radiographic results with nine major and 12 minor complications. Recurrent deformity in children and refracture in adults were related to poor results. Of 14 limbs, there were four good, five fair, and five poor clinical results with five major and 14 minor complications. Knee stiffness was the most common complication related to poor results in our series, and occurred particularly in patients with simultaneous correction of the ipsilateral tibial and femoral deformities. Therefore, two-stage surgery including bilateral tibial osteotomies first and then bilateral femoral osteotomies is recommended instead of simultaneous correction of the ipsilateral tibial and femoral deformities to avoid knee stiffness.

[Association analysis on the polymorphisms of PCOL2 and Sp1 binding sites of COL1A1 gene and the congenital dislocation of the hip in Chinese population].

OBJECTIVE: To investigate the polymorphism distribution of the PCOL2 and Sp1 binding sites of the collagen type I alpha 1(COL1A1) gene in Chinese population and explore their relationship with congenital dislocation of the hip (CDH). METHODS: The PCOL2 polymorphism (-1997 G/T) in COL1A1 promoter and the Sp1 polymorphism (1546 G/T) in intron 1 were genotyped in 243 members from 81 CDH nuclear family trios by the technique of polymerase chain reaction-restriction fragment length polymorphism, and then transmission disequilibrium test was used to analyze the data of genotypes. RESULTS: No statistically significant association was observed between CDH and PCOL2 polymorphism. Significant differences of genotype and allele frequency distributions were detected between the Chinese population and the Caucasian population in Spain, and between the Chinese population and the Caucasian population in America. The allele at the Sp1 site that has been found to be polymorphic in other populations was not found in Chinese. CONCLUSION: There exists racial difference in the distribution of the PCOL2 and Sp1 polymorphisms of COL1A1 gene. The results suggest that the PCOL2 and Sp1 polymorphisms may not be the major susceptibility gene of CDH in Chinese population.

Mesomelic dwarfism in pseudoachondroplasia.

Pseudoachondroplasia (PSACH) is associated with mutations in the cartilage oligomeric matrix protein (COMP) gene and the clinical characteristics include short stature, deformities of the extremities involving the epiphyses and metaphyses, early onset arthritis, and ligament laxity. PSACH has been considered a rhizomelic form of dwarfism. So far no previous report has described mesomelic shortening of the limbs in PSACH. We reviewed nine patients with a diagnosis of PSACH based on clinical and radiographic examination and mutation analysis of the COMP gene. The mean height in the adults was 116 cm. All patients showed mesomelic dwarfism. The average ratios of radial length to humeral length and tibial length to femoral length were 0.62 and 0.63, respectively. The tibia and the radius showed more severe bony deformity than the femur and humerus. The degree of short stature was related to the site of the mutation in the COMP gene, but there was no correlation between bony deformity and height or gene mutation.

Spondyloepiphyseal dysplasia congenita with absent femoral head.

Spondyloepiphyseal dysplasia congenita (SEDC), an inherited chondrodysplasia, occurs through a mutation in the COL2A1 gene encoding the type II procollagen alpha1 chain, proalpha1 (II). Recently, the authors studied two Korean patients with SEDC. Both these patients had short stature, os odontoideum with or without atlantoaxial instability, platyspondyly, and epiphyseal dysplasia limited to the femoral heads. The more seriously affected patient had shorter height (125 cm), atlantoaxial instability associated with os odontoideum, flat feet, and cleft palate, absence of the femoral head on radiographic and magnetic resonance imaging (MRI), and dislocated proximal femur. The less seriously affected patient was taller (145 cm) and had no atlantoaxial instability, absence of the femoral head on radiography with visible cartilage anlage on MRI, and subluxated cartilaginous femoral head. A mutation analysis was performed using direct sequencing. Two novel dominant mutations were found in the COL2A1 gene of these two patients: G277V and G238S, respectively. Although glycine was substituted with valine and serine in the proalpha1 (II) of these two patients, their phenotypes were significantly different in physical and radiologic evaluations.