OBJECTIVE: To describe the characteristics of short arm deformity in patients with achondroplasia, and summarize the progress of its lenthening and reconstruction, so as to provide reference for clinical diagnosis and treatment. METHODS: The literature on the lenthening of upper limb with achondroplastic short arm deformity at home and abroad in recent years was reviewed, and the characteristics, extension methods, postoperative management, effectiveness evaluation, and related complications of short arm deformity were summarized. RESULTS: Achondroplastic short arm deformity affect the patient's daily perineal hygiene activities. Although the upper limb is proportionately shortened, the humerus is mainly short limb deformity. Bilateral humeral lengthening is a common treatment method, and the traditional lengthening tools are mainly external fixation, guided by Ilizarov distraction osteogenesis concept; intramedullary lengthening is the latest treatment method. Lengthening percentage and healing index are commonly used for clinical evaluation indexes, and complications such as nerve injury may occur during upper limb lengthening. CONCLUSION In addition to appearance improvement, achondroplastic short arm lengthening is of great significance in achieving self-management of individual perineal hygiene. Lenthening and reconstruction methods are constantly being innovated and improved.
Humans ; Achondroplasia/surgery* ; Osteogenesis, Distraction/methods* ; Bone Lengthening/methods* ; Plastic Surgery Procedures/methods* ; Humerus/abnormalities* ; Treatment Outcome ; Ilizarov Technique ; Arm/abnormalities*

OBJECTIVE: To explore the effectiveness of QIN Sihe's surgical strategy combined with Ilizarov technique in treating foot and ankle deformities on the verge of amputation. METHODS: A retrospective analysis was conducted on the clinical data of 56 patients (62 feet) with foot and ankle deformities on the verge of amputation treated with QIN Sihe's surgical strategy and Ilizarov technique between May 2010 and December 2020. Among them, there were 39 males and 17 females. The age ranged from 8 to 62 years (median, 27.5 years). QIN Sihe's surgical strategy: subcutaneous release or open lengthening of contracted Achilles tendons, limited correction of bony deformities through multiple osteotomies during surgery, tendon transfer to balance the power of the foot and ankle, simultaneous percutaneous osteotomy and correction of tibial torsion deformity to restore the weight-bearing line of the lower extremity, and installation of Ilizarov foot and ankle distraction devices for slow distraction and correction of residual foot and ankle deformities. After removal of external fixation, individualized braces were used for protection during exercise and walking. For patients with bilateral deformities, staged surgeries were performed. The effectiveness was evaluated according to the QIN Sihe's Postoperative Evaluation Criteria for Lower Limb (Foot and Ankle) Deformity Correction and Functional Reconstruction at last follow-up. RESULTS: All patients achieved the preoperative expected orthopedic and functional reconstruction goals. The postoperative wearing time of external fixator was 3-7 months, with an average of 5.5 months. The incidence of pin tract infection during the treatment period was 6.5% (4/62). All patients were followed up 25-132 months (median, 42 months). All 56 patients successfully retained their limbs. At last follow-up, foot and ankle deformities were corrected, the weight-bearing line was basically restored, and plantigrade feet were restored. At last follow-up, according to QIN Sihe's Postoperative Evaluation Criteria for Lower Limb (Foot and Ankle) Deformity Correction and Functional Reconstruction, the effectiveness was rated as excellent in 37 cases (39 feet), good in 18 cases (21 feet), and fair in 1 case (2 feet). The excellent and good rate was 96.8% (60/62). CONCLUSION The combination of QIN Sihe's surgical strategy and Ilizarov technique in treating foot and ankle deformities on verge of amputation is minimally invasive, safe, and the therapeutic effect is controllable. This combined approach has unique advantages in preserving limb function and restoring biomechanical balance.
Humans ; Ilizarov Technique ; Male ; Female ; Retrospective Studies ; Adult ; Middle Aged ; Adolescent ; Child ; Young Adult ; Amputation, Surgical ; Osteotomy/methods* ; Ankle/surgery* ; Treatment Outcome ; Foot Deformities/surgery* ; Tendon Transfer/methods* ; Achilles Tendon/surgery* ; Foot/surgery*

Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

ObjectiveTo investigate the therapeutic effect of Baihe Wuyaotang （BWT） on non-alcoholic fatty liver disease （NAFLD） and elucidate its underlying mechanism. MethodC57BL/6J mice were randomly assigned to six groups： normal control， model， positive drug （pioglitazone hydrochloride 1.95×10^-3 g·kg^-1）， and low-， medium-， and high-dose BWT （1.3，2.5 and 5.1 g·kg^-1）. Following a 12-week high-fat diet （HFD） inducement， the mice underwent six weeks of therapeutic intervention with twice-daily drug administration. Body weight was monitored weekly throughout the treatment period. At the fifth week， glucose tolerance （GTT） and insulin tolerance （ITT） tests were conducted. Subsequently， the mice were euthanized for the collection of liver tissue and serum， and the subcutaneous adipose tissue （iWAT） and epididymal adipose tissue （eWAT） were weighed. Serum levels of total triglycerides （TG） and liver function indicators，such as alanine aminotransferase （ALT） and aspartate aminotransferase （AST）， were determined. Histological examinations， including oil red O staining， hematoxylin-eosin （HE） staining， Masson staining， and transmission electron microscopy， were performed to evaluate hepatic lipid deposition， pathological morphology， and ultrastructural changes， respectively. Meanwhile， Western blot and real-time quantitative polymerase chain reaction （Real-time PCR） were employed to analyze alterations， at both gene and protein levels， the insulin signaling pathway molecules， including insulin receptor substrate 1/2/protein kinase B/forkhead box gene O1 （IRS1/2/Akt/FoxO1）， glycogen synthesis enzymes phosphoenolpyruvate carboxy kinase （Pepck） and glucose-6-phosphatase （G6Pase）， lipid metabolism-related genes stearoyl-coA desaturase-1 （SCD-1） and carnitine palmitoyltransferase-1 （CPT-1）， fibrosis-associated molecules α-smooth muscle actin （α-SMA）， type Ⅰ collagen （CollagenⅠ）， and the fibrosis canonical signaling pathway transforming growth factor-β₁/drosophila mothers against decapentaplegic protein2/3（TGF-β₁/p-Smad/Smad2/3）， inflammatory factors such as interleukin（IL）-6， IL-8， IL-11， and IL-1β， autophagy markers LC3B Ⅱ/Ⅰ and p62/SQSTM1， and the expression of mammalian target of rapamycin （mTOR）. ResultCompared with the model group， BWT reduced the body weight and liver weight of NAFLD mice（P<0.05， P<0.01）， inhibited liver lipid accumulation， and reduced the weight of white fat： it reduced the weight of eWAT and iWAT（P<0.05， P<0.01） as well as the serum TG content（P<0.05， P<0.01）. BWT improved the liver function as reflected by the reduced ALT and AST content（P<0.05， P<0.01）. It improved liver insulin resistance by upregulating IRS2， p-Akt/Akt， p-FoxO1/FoxO1 expressions（P<0.05）. Besides， it improved glucose and lipid metabolism disorders： it reduced fasting blood glucose and postprandial blood glucose（P<0.05， P<0.01）， improved GTT and ITT（P<0.05， P<0.01）， reduced the expression of Pepck， G6Pase， and SCD-1（P<0.01）， and increased the expression of CPT-1（P<0.01）. The expressions of α-SMA， Collagen1， and TGF-β₁ proteins were down-regulated（P<0.05， P<0.01）， while the expression of p-Smad/Smad2/3 was downregulated（P<0.05）， suggesting BWT reduced liver fibrosis. BWT inhibited inflammation-related factors as it reduced the gene expression of IL-6， IL-8， IL-11 and IL-1β（P<0.01） and it enhanced autophagy by upregulating LC3B Ⅱ/Ⅰ expression（P<0.05）while downregulating the expression of p62/SQSTM1 and mTOR（P<0.05）. ConclusionBWT ameliorates NAFLD by multifaceted improvements， including improving IR and glucose and lipid metabolism， anti-inflammation， anti-fibrosis， and enhancing autophagy. In particular， BWT may enhance liver autophagy by inhibiting the mTOR-mediated signaling pathway.

Objective:To investigate the application value of joint friction sounds in diagnosing meniscus injury of the knee based on machine learning models.Methods:A case-control study was conducted to analyze the clinical data of 17 patients with meniscus injury of the knee (meniscus injury group) admitted to Sir Run Run Shaw Hospital Affiliated to Nanjing Medical University from August 2020 to October 2022, as well as 75 recruited healthy subjects without knee joint diseases (healthy group). The knee joint friction sounds of the subjects were collected in a relatively quiet environment (peak value below 40 dB). The sounds collected in a flexion-extension-flexion mode of exercise were split and divided randomly with a ratio of 4∶1 into the training set (125 segments from the meniscal injury group and 187 segments from the healthy group) and the test set (33 segments from the meniscal injury group and 47 segments from the healthy group). The sounds obtained in a sit-stand-sit mode of exercise were split and divided randomly with a ratio of 4∶1 into the training set (81 segments from the meniscal injury group and 164 segments from the healthy group) and the test set (20 segments from the meniscal injury group and 40 segments from the healthy group). Four machine learning models were built, including support vector machine with linear kernels, radial basis function support vector machine, random forest, and extremely randomized trees. The learning training of the model was performed on the training set, and its model performance was verified with the test set. The time required in a single collection of joint friction sound from the subjects and the interpretation of data analysis was recorded. Knee function of the subjects were scored according to the Lysholm Score before and at 1 day after the test. The accuracy rates of diagnosis of meniscus injury with friction sounds under the two modes of exercise were compared based on the test results to yield an optimal one. The effectiveness of the four models was compared to find the best machine learning model fitting the data frame of this study according to the test results such as accuracy, sensitivity, specificity, F1 score, and area under the receiver operating characteristic curve (AUC) obtained with the optimal mode of exercise. The diagnostic accuracy, misdiagnosis rate and missed diagnosis rate of joint friction sound for meniscal injury under the optimal machine learning model with the optimal mode of exercise were observed.Results:The time required in a single collection of joint friction sound ranged from 5 to 10 minutes [(7.1±1.3)minutes], when the time required for interpretation of data analysis was approximately 1 minute. The Lysholm Score before and after the test was (75.6±4.0)points and (77.7±3.7)points respectively in the meniscal injury group ( P>0.05), and (99.6±0.9)points and (99.5±1.0)points respectively in the healthy group ( P>0.05). The diagnosing accuracy rates for flexion-extension-flexion of exercise and sit-stand-sit modes of exercise were 0.775 and 0.817 under the support vector machine model with linear kernels; 0.813 and 0.900 under the radial basis function support vector machine model; 0.800 and 0.867 under the random forest model; 0.800 and 0.900 under the extremely randomized tree model. The accuracy rates for sit-stand-sit mode of exercise were all higher than those for flexion-extension-flexion mode of exercise. In the sit-stand-sit mode of exercise, the extremely randomized tree model had an accuracy rate of 0.900, sensitivity of 0.900, specificity of 0.950, F1 score of 0.900, and AUC of 0.942, which were higher than those under the remaining 3 models, showing better machine learning efficacy. Under the extremely randomized tree model in the sit-stand-sit mode of exercise, 22 (18 true positive and 4 false positive) were diagnosed as meniscal injury and 38 (36 true negative and 2 false negative) as healthy out of 60 segments in the test set (20 from the meniscal injury group and 40 from the healthy group). The diagnostic accuracy of joint friction sounds in diagnosing meniscus injury of the knee was 0.900, with the misdiagnosis rate of 0.100 and the missed diagnosis rate of 0.100. Conclusion:Diagnosis of meniscus injury of the knee with joint friction sounds can shorten time and enhance safety during the examination process. The diagnostic model using machine learning-based artificial intelligence is faster and more stable, which can be used as a diagnostic marker for such injury.

ObjectiveTo observe the effect of comprehensive intervention on the incidence of lactation galactostasis in communities from the perspective of preventive medicine， so as to prevent the occurrence of the mammary ducts obstruction disease. MethodsA total of 400 women in the early stage of pregnancy were selected from four communities. Those in two communities were set up as the intervention group. Comprehensive intervention for the prevention and treatment of mammary ducts obstruction disease during pregnancy and "Six-step recanalization manual therapy" practical guidance were conducted on the intervention group. The pregnant women from the other two communities were the control group， who received no intervention or guidance training. The two groups were followed up at 1 month， 3 months and 5 months postpartum， and the occurrence of mammary ducts obstruction disease was investigated and interventions were carried out. ResultsThe incidence of galactostasis in the intervention group was 26.0%， 10.6% and 5.1%， respectively at 1， 3 and 5 months after delivery， and the incidence of galactostasis in the control group was 38.0%， 22.2% and 8.3%， respectively. The incidence of galactostasis at 1 month and3 months after delivery was statistically different （P<0.05）， while the incidence of galactostasis 5 months after delivery was not statistically different （P>0.05）. The protection rates of comprehensive intervention on galactostasis were 31.58%， 52.25% and 38.55%， respectively. ConclusionPublicity and education work of prevention and control of the mammary ducts obstruction disease and "Six-step recanalization manual therapy" practical guidance can effectively reduce the occurrence of plugged mammary ducts， and therefore should be promoted.

Objective:To investigate surgical methods and clinical effects of tibial pseudarthrosis due to neurofibromatosis type I (NF1) in adult using Ilizarov technique combined with intramedullary nail.Methods:A total of 12 adult with tibial pseudarthrosis due to NF1 treated by Ilizarov technique combined with intramedullary nail from October 2009 to December 2017 were retrospectively included. There were 6 males and 6 females with an average age of 27±8.3 years (range 17-44). All cases presented severe anterior arch in varus or valgus deformity with shortening in an average of 10.8±3.7 cm (range 5.6-16.5 cm). The in-volved levels were at the middle and lower part of tibia. All cases suffered from more than one treatment with failed surgery. One male patient with 5 times of unsuccessful operations. There were 4 cases with severe limping gait and 8 cases with walking with the help of brace (or single crutch) preoperatively. Regarding the family history, seven cases were inherited by father and 5 cases by mother. During surgery, the part of tibial pseudarthrosis and thickened fibrous tissue surroundings like periosteal were removed. The contracture achilles tendon was elongated in open way, and intramedullary nailing cross the ankle joint was applied when the tibial medullary cavity opened. Further, iliac bone grafting and proximal tibial osteotomy were performed with Ilizarov fixator application finally. The tibia was lengthened at a rate of 0.5-1 mm/d at 7 days postoperatively. The healing rate of pseudarthrosis and the length and alignment of limb were evaluated by X-ray routinely. The lower limb function and complications were assessed by self-made table for lower limb deformity correction and functional reconstruction.Results:All patients were followed up for 31-80 months with an average of 47.6±14.7 months. Bone union of pseudarthrosis in all cases was eventually achieved. The tibia was lengthened 5-12 cm with an average of 8.4±2.5 cm. There were 9 cases underwent second surgeries to promote bone healing and to correct residual deformities. The external fixator was used for 25-37 months with an average of 31.5±3.7 months. There was no complication, including neurovascular injury, severe soft tissue or bone infection affecting the clinical effects. All intramedullary nails were not removed finally. The limb function and gait in full weight bearing in 12 patients recovered at the latest follow-up. The evaluation score was 2.4±0.3 (range 2.1-2.8), of which 9 cases were excellent 3 were good. Thus, the excellent and good rate was 100%.Conclusion:The satisfactory clinical effects, including angular deformity correction, pseudarthrosis healing and short limb lengthening, can be achieved in adult with tibial pseudarthrosis due to NF1 by using the combination method of Ilizarov technique and intramedullary nail. However, the treatment duration could be longer.

Lower leg lengthening has a history of more than 100 years. However, serious complications occurred in the early stage due to the immature device and technical conditions. The emergence of Ilizarov technology making limb lengthening is a kind of controlled operation. Based on the "Ilizarov effect", the results of limb regeneration and lengthening were obtained by slow, stable and continuous distraction of living tissues. The regeneration of bone and soft tissue is like limb development in children. Currently, the traditional Ilizarov external fixation is still the dominated method for leg lengthening. The Chinese Ilizarov external fixator and the lower leg Achilles tendon elastic lengthening external fixator are the representatives of domestic application. Other limb lengthening methods, including computer hexapod assisted orthopedic surgery (CHAOS), lengthening over nail (LON), lengthening and then nailing (LATN) and intramedullary nail lengthening system, have not been developed in China. Percutaneous transverse osteotomy at 5-6 cm below the tibial plateau is a common osteotomy method in China. This method can maximize the retention of periosteum and intramedullary blood circulation. Limb lengthening more than 4 cm is recommended by leg Achilles tendon elastic synchronous lengthening fixator with calcaneal wire fixation. Following the principle of tension-stress, the lengthening is carried out slowly. Further, the lengthening device is removed step by step according to the principle of dynamic adjustment of fixed stiffness.

The Soviet Union orthopedic doctor Ilizarov invented the ring external fixator which could be assembled into more than 800 configurations, and created a new minimally invasive external fixation technology system called Ilizarov technology which was different from the western classical orthopedic technique. The theoretical basis of this technique is to imitate nature, by controlling and transforming the stress of life movement in vitro, to cure the complex trauma fracture, bone and soft tissue defect, infection and severe deformity of limbs, and to save some endangered amputation complex trauma and limb deformity. From theoretical guidance, surgical indications, medical models and postoperative management, it differs from the modern technique of internal fixation (AO) fracture treatment theory in trauma orthopedics. It can achieve fracture reduction and fixation by the most minimally invasive or even bloodless operation, and control bone growth in vitro. It can not only complete the fixation requirements of most fractures in trauma orthopedics, but also solve complex problems such as bone nonunion, bone defect, soft tissue defect of limbs and associated malformation without bone graft and loss of bone length. Ilizarov technology was introduced into China mainland for more than 30 years, but the application of this technology in the field of orthopaedics in China is still not extensively spreaded because of many reasons, In this article, the authors review the application of Ilizarov technology in the field of trauma orthopedics in China for domestic Orthopaedic surgeon to better understand this technology.

Objective: To explore the effectiveness of the first-stage debridement and Ilizarov metatarsal bone lengthening in treatment of diabetic foot ulcer complicated with chronic osteomyelitis of metatarsal head. Methods: Between January 2015 and October 2018, 8 cases (9 feet, 11 sites) of diabetic foot ulcer complicated with chronic osteomyelitis of metatarsal head were treated by first-stage debridement and Ilizarov metatarsal bone lengthening. There were 3 males (4 feet, 5 sites) and 5 females (5 feet, 6 sites), with an average age of 57.5 years (range, 44-65 years). According to diabetic foot Wagner grade, 6 cases (7 feet) were grade 3 and 2 cases (2 feet) were grade 4. The chronic osteomyelitis located at left foot in 4 cases, right foot in 3 cases, and bilateral feet in 1 case. The duration of chronic osteomyelitis was 1-5 years (mean, 3.1 years). The chronic osteomyelitis site was the 1st metatarsal head in 3 feet, the 3rd metatarsal head in 1 foot, the 4th metatarsal head in 1 foot, and the 5th metatarsal head in 6 feet. Two patients had chronic osteomyelitis at 2 sites on 1 foot. The length of lengthened metatarsal bone, lengthening time, and the time of wearing external fixation frame were recorded, and the external fixation frame index was calculated. The healing conditions of foot ulcer and lengthening bone segment were observed, the healing time was recorded, and the healing index of lengthening bone was calculated. The ankle function was evaluated according to the American Orthopedic Foot and Ankle Society (AOFAS) score criteria. Results: All patients were followed up 9-26 months with an average of 15.0 months. Except pin tract infection during the bone lengthening period, there was no complications such as skin necrosis and vascular or nerve injury occurred during treatment. The length of lengthened metatarsal bone was 12-35 mm with an average of 20.5 mm; the metatarsal bone lengthening time were 21-84 days with an average of 57.8 days. The average time of wearing external fixation frame was 14.6 weeks (range, 10.4-21.1 weeks) and the external fixation frame index was 54.3 days/cm (range, 42.9-59.2 days/cm). The ulcer wound healed with an average healing time of 30.5 days (range, 19-70 days) and no ulcer recurrence was observed during follow-up. Bone healing was obtained in all bone lengthening segments, and the average healing index was 42.5 days/cm (range, 37-51 days/cm). The average AOFAS score was 91.7 (range, 87-95); 5 feet were excellent and 4 feet were good. The excellent and good rate was 100%. Conclusion: The metatarsal bone lengthening under Ilizarov law of tension-stress after debridement can promote diabetic foot ulcers healing and reconstructing the length of metatarsal to retain the function of metatarsal load and avoid amputation. This is an effective method for the treatment of diabetic foot ulcer complicated with chronic osteomyelitis of metatarsal head.