Objective:To explore the clinical phenotype and genetic characteristics of a patient with Progressive pseudorheumatoid dysplasia (PPRD) due to compound heterozygous variants of CCN6 gene. Methods:A patient who was admitted to Qilu Hospital of Shandong University due to " bilateral finger joint deformity, bilateral hip and knee joint movement limitation for 19 years" was selected as the study subject. Clinical data of the patient were retrospectively collected. Peripheral blood samples were collected from the patient and her parents and subjected to whole exome sequencing (WES). Long-read sequencing (LRS) and Sanger sequencing were used to verify the candidate variants. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of candidate variants was classified. This study was approved by the Medical Ethics Committee of Qilu Hospital of Shandong University (Ethics No.: KYLL-202502 061).Results:The patient, a 23-year-old female, presented with progressive polyarticular deformity, limited movement and abnormal growth and development since childhood. She was initially misdiagnosed as Ankylosing spondylitis and had poor response to sulphasalazine and etoricoxib treatment. WES revealed that she has harbored two heterozygous variants of the CCN6 gene (NM_198239.2), namely c. 348C>A and c. 676G>C. LRS confirmed that the two variants are located on two homologous chromosomes and constitute compound heterozygous variants. Based on the ACMG guidelines, both variants were rated as pathogenic (PVS1+ PM2_Supporting+ PM3; PM1+ PM2_Supporting+ PM3_Supporting+ PM5+ PP3_Strong). The c. 676G>C variant has not been recorded by the HGMD and ClinVar databases. Conclusion:The c. 348C>A and c. 676G>C compound heterozygous variants of the CCN6 gene probably underlay the pathogenesis of PPRD in this patient. Above finding has enriched the mutational spectrum of PPRD and provided a basis for the clinical diagnosis and genetic counseling.

Skeletal muscle is the largest organ in the human body and plays a crucial role in motor functions.With aging, skeletal muscle mass and function progressively decline, a phenomenon known as sarcopenia.This condition can result in various adverse health outcomes, including reduced muscle function, weakness, cognitive decline, increased medical expenses, and elevated mortality rates, thereby exerting significant social and lifestyle impacts.Several mechanisms contribute to the development of sarcopenia, including immune system alterations, inflammation, lipid accumulation, mitochondrial dysfunction, nicotinamide adenine dinucleotide metabolic disorders, and impaired muscle stem cell regeneration.Although lifestyle modifications, pharmacological therapies, mitochondrial transplantation, and stem cell therapy have shown promise in addressing sarcopenia, there remains a need for more effective and targeted interventions.This article aims to discuss the pathogenesis of sarcopenia and its interventions, providing new insights for clinical treatment.

OBJECTIVE: To explore the clinical phenotype and genetic characteristics of a patient with Progressive pseudorheumatoid dysplasia (PPRD) due to compound heterozygous variants of CCN6 gene. METHODS: A patient who was admitted to Qilu Hospital of Shandong University due to "bilateral finger joint deformity, bilateral hip and knee joint movement limitation for 19 years" was selected as the study subject. Clinical data of the patient were retrospectively collected. Peripheral blood samples were collected from the patient and her parents and subjected to whole exome sequencing (WES). Long-read sequencing (LRS) and Sanger sequencing were used to verify the candidate variants. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of candidate variants was classified. This study was approved by the Medical Ethics Committee of Qilu Hospital of Shandong University (Ethics No.: KYLL-202502 061). RESULTS: The patient, a 23-year-old female, presented with progressive polyarticular deformity, limited movement and abnormal growth and development since childhood. She was initially misdiagnosed as Ankylosing spondylitis and had poor response to sulphasalazine and etoricoxib treatment. WES revealed that she has harbored two heterozygous variants of the CCN6 gene (NM_198239.2), namely c.348C>A and c.676G>C. LRS confirmed that the two variants are located on two homologous chromosomes and constitute compound heterozygous variants. Based on the ACMG guidelines, both variants were rated as pathogenic (PVS1+PM2_Supporting+PM3; PM1+PM2_Supporting+PM3_Supporting+PM5+PP3_Strong). The c.676G>C variant has not been recorded by the HGMD and ClinVar databases. CONCLUSION The c.348C>A and c.676G>C compound heterozygous variants of the CCN6 gene probably underlay the pathogenesis of PPRD in this patient. Above finding has enriched the mutational spectrum of PPRD and provided a basis for the clinical diagnosis and genetic counseling.
Humans ; Female ; CCN Intercellular Signaling Proteins/genetics* ; Phenotype ; Heterozygote ; Young Adult ; Mutation ; Exome Sequencing ; Joint Diseases/congenital*

Objective:To explore the clinical phenotype and genetic characteristics of a patient with Progressive pseudorheumatoid dysplasia (PPRD) due to compound heterozygous variants of CCN6 gene. Methods:A patient who was admitted to Qilu Hospital of Shandong University due to " bilateral finger joint deformity, bilateral hip and knee joint movement limitation for 19 years" was selected as the study subject. Clinical data of the patient were retrospectively collected. Peripheral blood samples were collected from the patient and her parents and subjected to whole exome sequencing (WES). Long-read sequencing (LRS) and Sanger sequencing were used to verify the candidate variants. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of candidate variants was classified. This study was approved by the Medical Ethics Committee of Qilu Hospital of Shandong University (Ethics No.: KYLL-202502 061).Results:The patient, a 23-year-old female, presented with progressive polyarticular deformity, limited movement and abnormal growth and development since childhood. She was initially misdiagnosed as Ankylosing spondylitis and had poor response to sulphasalazine and etoricoxib treatment. WES revealed that she has harbored two heterozygous variants of the CCN6 gene (NM_198239.2), namely c. 348C>A and c. 676G>C. LRS confirmed that the two variants are located on two homologous chromosomes and constitute compound heterozygous variants. Based on the ACMG guidelines, both variants were rated as pathogenic (PVS1+ PM2_Supporting+ PM3; PM1+ PM2_Supporting+ PM3_Supporting+ PM5+ PP3_Strong). The c. 676G>C variant has not been recorded by the HGMD and ClinVar databases. Conclusion:The c. 348C>A and c. 676G>C compound heterozygous variants of the CCN6 gene probably underlay the pathogenesis of PPRD in this patient. Above finding has enriched the mutational spectrum of PPRD and provided a basis for the clinical diagnosis and genetic counseling.

Skeletal muscle is the largest organ in the human body and plays a crucial role in motor functions.With aging, skeletal muscle mass and function progressively decline, a phenomenon known as sarcopenia.This condition can result in various adverse health outcomes, including reduced muscle function, weakness, cognitive decline, increased medical expenses, and elevated mortality rates, thereby exerting significant social and lifestyle impacts.Several mechanisms contribute to the development of sarcopenia, including immune system alterations, inflammation, lipid accumulation, mitochondrial dysfunction, nicotinamide adenine dinucleotide metabolic disorders, and impaired muscle stem cell regeneration.Although lifestyle modifications, pharmacological therapies, mitochondrial transplantation, and stem cell therapy have shown promise in addressing sarcopenia, there remains a need for more effective and targeted interventions.This article aims to discuss the pathogenesis of sarcopenia and its interventions, providing new insights for clinical treatment.

Chronic osteomyelitis is a serious clinical problem with repeated courses and high disability rate, which seriously affects the physical and mental health of patients. Through continuous learning and summary in the process of using traditional therapies, the innovative improvements and changes had made in the treatment of osteomyelitis: Radical debridement of lesions was performed by applying the basic principles of modern bone tumor surgery. The application of microsurgical technique to transfer composite tissue flap can provide guarantee for tissue defect repair and wound closure without tension. Combined with bone grafting, local antibiotics and bone fixation, an one-stage operation has significantly improve the therapeutic effect of chronic complex osteomyelitis.

Objective To investigate the expression of hsa_circ_0018574 in colorectal cancer tissues and human colon cancer HT29 cell line, as well as its effect on the proliferation and apoptosis of colorectal cancer cells. Methods The circPrimer 1.2 software was used to draw the circRNA sequence structure. Meanwhile, the circRNA microarray was used to screen differentially-expressed circRNA in colorectal cancer tissues and adjacent tissues, and RNA was extracted from tissue samples. The expression of hsa_circ_0018574 in human colorectal tumors was detected by RT-qPCR. The si-circ_0018574 was transfected into HT29 cells, and the expression of CDK2, CDK4, CDK6, cyclinD1, and cyclinE cyclins were detected by colony formation assay, flow cytometry, and Western blot, respectively. Results The expression of hsa_circ_0018574 in human colorectal tumor tissues was significantly higher than that in adjacent tissues (P < 0.01). Meanwhile, the si-circ_0018574 in HT29 cells could significantly inhibit the proliferation of cancer cells, reduce clone formation and colony formation ability (P < 0.01), and induce tumor cell apoptosis (P < 0.01). The expressions of CDK2, CDK4, CDK6, cyclinD1 and cyclinE cyclins were decreased. Conclusion The hsa_circ_0018574 is highly expressed in colorectal tumors, and si-circ_0018574 could significantly inhibit the proliferation of HT29 cells, reduce cell division, and induce apoptosis.

Objective:To investigate the clinical efficiency of gastrocnemius muscle flap combined with antibiotics loaded calcium sulfate in the treatment of postoperative infection and plate exposure of tibial plateau fracture in elderly patients.Methods:From January, 2015 to May, 2019, 21 elderly patients with postoperative infection and plate exposure of tibial plateau fracture were treated, including 14 males and 7 females with an average age of 72.6 years, ranging from 61 to 82 years. The average course of disease was 22.7 days, ranging from 6 to 91 days. The site of wound infection was at medial in 8 cases, lateral in 9 cases and bilateral in 4 cases. The size of wound ranged from 2.0 cm×3.5 cm to 5.0 cm×12.0 cm. All wounds were implanted with antibiotics loaded calcium sulfate and repaired by gastrocnemius muscle flap combined with skin graft after debridement. Muscle flap survival, wound healing, inflammatory index, fracture healing and knee joint function were recorded. The curative effect was evaluated by McKee infection treatment criteria and the knee joint function was evaluated by HSS scoring criteria.Results:All 21 muscle flaps survived. In 1 case, skin graft necrosis occurred in a small area, and the wound healed well after dressing change. One case had exudation which was clear and the bacterial culturing was negative, and the wound healed after 2 weeks of dressing change. The other incisions were healed in stage I, and the healing rate was 90%. All patients were followed-up for an average of 28.7(16-39) months. The redness and swelling occurred in 1 case without exudation after 2 months which disappeared after anti-infection treatment and didn't recur again. The infection recurred in 1 case after 5 months, and it which was controlled after debridement and plate removal. According to McKee criteria, 19 cases were cured, 1 improved and 1 recurred with an effective rate of 95.2%. The fracture healing time was from 3 to 7 months, with an average of 4.6 months. According to HSS scoring criteria, the knee joint function was excellent in 12 cases, good in 7 cases and moderate in 2 cases.Conclusion:After thorough debridement, gastrocnemius muscle flap combined with antibiotic loaded calcium sulfate can effectively control the infection, repair the wound, promote fracture union and restore limb function in the treatment of postoperative infection and plate exposure of tibial plateau fracture in elderly patients.

To investigate the effect and application value of transplantation of the free cutaneous fibular flap combined with antibiotic-loaded calcium sulfate artificial bone graft for the treatment of antibrachial chronic osteomyelitis of Cierny-Mader type IV. Methods From August, 2013 to May, 2017, 12 cases of ulna or (and) radius chronic osteomyelitis of Cierny-Mader type IV were treated by transplantation of the free cutaneous fibu-lar flap combined with antibiotic-loaded calcium sulfate artificial bone graft. There were 7 males and 5 females, with an average age of 36.3 (21-47) years.Pure ulnar osteomyelitis in 7 cases, radius osteomyelitis in 4 cases, and both ul-nar and radius osteomyelitis in 1 case. The average range of osteomyelitis lesions was 6.3 (3.0-9.0) cm. The area of soft tissue defect (including bone scar) ranged from 8.0 cm×2.0 cm to 15.0 cm×5.0 cm. The area of the flap was 10.0 cm×3.5cm-17.0 cm×7.0 cm.The average length of the fibular flap was 8.8 (5.0-12.0) cm.Locking plate internal fixa-tion was used in 9 cases, external fixator in 2 cases, and plate combined with external fixator in 1 case. Vancomycin/gentamicin, an effective component of calcium sulfate artificial bone, averaged 0.64 g/102.7 kU (0.4 g/64 kU-1.0 g/160 kU).Routine postoperative treatment.And monthly outpatient review in the first half year after operation, and outpatient review every 3 months after half a year.One year after operation, comprehensive evaluation of elbow, forearm and wrist function with Mayo Elbow Function Index, Anderson Forearm Double Fracture Evaluation System and Cooney Wrist Function Score. Results Vascular crisis occurred in 1 case after operation, prompt surgical exploration, and ultimately all flaps survived completely.The donor sites healed well in all cases.The lower extremity functions of donor sites had no change compared with that before operation.Followed-up of an average of 22.7 months, there were 2 cases who had sen-sory disturbance in the ulnar nerve innervation area and returned to normal 3 months after operation. The fibular flaps healed satisfactorily with an average healing time of 4.7 (3-6) months.No calcium sulphate artificial bone granules were seen on X-ray at 3 months after operation.One year after operation, bone healing, forearm appearance and wrist function recovered well, but elbow and forearm motor function recovered unsatisfactorily. Conclusion On the basis of master-ing the applied anatomy and vascular anastomosis techniques of microsurgery, this method of transplantation of the free cutaneous fibular flap combined with antibiotic-loaded calcium sulfate artificial bone graft for the treatment of an-tibrachial chronic osteomyelitis of Cierny-Mader type IV has achieved satisfactory results.The recipient area is beautiful. The bone healing is reliable.And it has little influence on the recipient area and the donor area.It is worthy of clinical application.

Objective: To summarize and explore the clinical effect and application of L-shaped flap pedicled with peroneal artery perforator in the treatment of unhealed lateral L-shaped incision after calcaneal fractures. Methods: From October 2013 to March 2015, 17 patients with unhealed L-shaped incision after calcaneal fractures were treated with one-stage thorough debridement, artificial bone filling with antibiotics-laden calcium sulphate and L-shaped flap pedicled with peroneal artery. Flap areas ranged from 8 cm × 2 cm to 11 cm × 3 cm. Donor sites are primarily sutured. Results: All 17 patients were followed up for 6 to 18 months with an average of 11.5 months. All patients with infection were cured effectively, demonstrating well survived flaps with normal elasticity and pigmentation, no scar contracture, satisfactory appearance and normal ankle joint motility. Conclusions L-shaped flap pedicled with peroneal artery perforator was an effective method in the treatment of unhealed lateral L-shaped incision after calcaneal fractures. It was suitable for coverage of the unhealed wound and worthy of being popularized.