Objective:To explore the clinical application effect of allogeneic acellular dermal matrix (ADM) in the repair of asymmetric nail fold deformity after complete syndactyly surgery in children.Methods:A retrospective analysis was conducted on the clinical data of children with secondary asymmetric nail fold deformity after complete syndactyly surgery treated at the Department of Burn and Plastic Surgery, Children’s Hospital of Nanjing Medical University, from January 2022 to December 2023. The patients required a secondary surgical repair due to insufficient soft tissue capacity with or without scar contracture, causing asymmetry of the nail fold after finger separation at the distal end following syndactyly surgery. During the operation, continuous Z-plasty was designed along the original surgical scar axis and incised towards the proximal end of the lateral nail fold, followed by thorough scar release. Scar debulking surgery was performed if there was significant local scar hyperplasia. A tunnel was created from the incision site near the lateral nail fold to reach the fingertip subcutaneously. ADM was filled into this tunnel until a satisfactory appearance of the lateral nail fold was achieved. The flaps were then closed by cross-suturing. Regular follow-up observations were conducted on the incision healing, scar, and appearance of the finger, and aesthetic evaluation according to Bulic’s standards was performed, classifying them into four grades: excellent, good, fair, and poor.Results:The study enrolled 12 patients, and nail fold asymmetry appeared 3 to 6 months after surgery, with 8 males and 4 females, ranging from 1 to 9 years old (average age 4.6 years). Affected digits included both hands in 7 cases and one hand in 5 cases, totaling 38 fingers. All 12 cases including 25 fingers presented with insufficient distal capacity in their fingers; seven cases including 16 fingers also had scar contracture resulting in poor appearance. All procedures were successfully performed. Post-operatively, one case of necrosis at the tip of the scar flap was observed after 12 days of removing the dressing but healed after dressing changes, and no infections or flap necrosis occurred in the remaining patients, with the incisions healing primarily. Follow-up periods ranged from 1 to 24 months, with an average duration of 13.6 months. All patients achieved the restoration of soft tissue capacity in the finger lateral nail fold, varying degrees of correction for asymmetrical nail fold deformities, and complete release for scar contracture, with 7 fingers in 4 cases rated as excellent, 12 fingers in 5 cases as good, 4 fingers in 2 cases as fair, and 2 fingers in one case as poor in evaluation of fingertip appearance.Conclusion:The use of ADM for filling is effective in restoring soft tissue capacity and correcting asymmetrical deformities caused by secondary nail fold abnormalities after complete syndactyly repair surgery in children. It has shown good clinical outcomes with minimal complications.

Objective:To explore the clinical application effect of allogeneic acellular dermal matrix (ADM) in the repair of asymmetric nail fold deformity after complete syndactyly surgery in children.Methods:A retrospective analysis was conducted on the clinical data of children with secondary asymmetric nail fold deformity after complete syndactyly surgery treated at the Department of Burn and Plastic Surgery, Children’s Hospital of Nanjing Medical University, from January 2022 to December 2023. The patients required a secondary surgical repair due to insufficient soft tissue capacity with or without scar contracture, causing asymmetry of the nail fold after finger separation at the distal end following syndactyly surgery. During the operation, continuous Z-plasty was designed along the original surgical scar axis and incised towards the proximal end of the lateral nail fold, followed by thorough scar release. Scar debulking surgery was performed if there was significant local scar hyperplasia. A tunnel was created from the incision site near the lateral nail fold to reach the fingertip subcutaneously. ADM was filled into this tunnel until a satisfactory appearance of the lateral nail fold was achieved. The flaps were then closed by cross-suturing. Regular follow-up observations were conducted on the incision healing, scar, and appearance of the finger, and aesthetic evaluation according to Bulic’s standards was performed, classifying them into four grades: excellent, good, fair, and poor.Results:The study enrolled 12 patients, and nail fold asymmetry appeared 3 to 6 months after surgery, with 8 males and 4 females, ranging from 1 to 9 years old (average age 4.6 years). Affected digits included both hands in 7 cases and one hand in 5 cases, totaling 38 fingers. All 12 cases including 25 fingers presented with insufficient distal capacity in their fingers; seven cases including 16 fingers also had scar contracture resulting in poor appearance. All procedures were successfully performed. Post-operatively, one case of necrosis at the tip of the scar flap was observed after 12 days of removing the dressing but healed after dressing changes, and no infections or flap necrosis occurred in the remaining patients, with the incisions healing primarily. Follow-up periods ranged from 1 to 24 months, with an average duration of 13.6 months. All patients achieved the restoration of soft tissue capacity in the finger lateral nail fold, varying degrees of correction for asymmetrical nail fold deformities, and complete release for scar contracture, with 7 fingers in 4 cases rated as excellent, 12 fingers in 5 cases as good, 4 fingers in 2 cases as fair, and 2 fingers in one case as poor in evaluation of fingertip appearance.Conclusion:The use of ADM for filling is effective in restoring soft tissue capacity and correcting asymmetrical deformities caused by secondary nail fold abnormalities after complete syndactyly repair surgery in children. It has shown good clinical outcomes with minimal complications.

Drug-induced hyperglycemia/diabetes is a global issue. Some drugs induce hyperglycemia by activating the pregnane X receptor (PXR), but the mechanism is unclear. Here, we report that PXR activation induces hyperglycemia by impairing hepatic glucose metabolism due to inhibition of the hepatocyte nuclear factor 4-alpha (HNF4α)‒glucose transporter 2 (GLUT2) pathway. The PXR agonists atorvastatin and rifampicin significantly downregulated GLUT2 and HNF4α expression, and impaired glucose uptake and utilization in HepG2 cells. Overexpression of PXR downregulated GLUT2 and HNF4α expression, while silencing PXR upregulated HNF4α and GLUT2 expression. Silencing HNF4α decreased GLUT2 expression, while overexpressing HNF4α increased GLUT2 expression and glucose uptake. Silencing PXR or overexpressing HNF4α reversed the atorvastatin-induced decrease in GLUT2 expression and glucose uptake. In human primary hepatocytes, atorvastatin downregulated GLUT2 and HNF4α mRNA expression, which could be attenuated by silencing PXR. Silencing HNF4α downregulated GLUT2 mRNA expression. These findings were reproduced with mouse primary hepatocytes. Hnf4α plasmid increased Slc2a2 promoter activity. Hnf4α silencing or pregnenolone-16α-carbonitrile (PCN) suppressed the Slc2a2 promoter activity by decreasing HNF4α recruitment to the Slc2a2 promoter. Liver-specific Hnf4α deletion and PCN impaired glucose tolerance and hepatic glucose uptake, and decreased the expression of hepatic HNF4α and GLUT2. In conclusion, PXR activation impaired hepatic glucose metabolism partly by inhibiting the HNF4α‒GLUT2 pathway. These results highlight the molecular mechanisms by which PXR activators induce hyperglycemia/diabetes.

Objective:To analyze the clinical features and mutation of myeloid differentiation factor 88 (MYD88) L265P in patients with diffuse large B-cell lymphoma (DLBCL) of central nervous system (CNS).Methods:The clinicopathological materials of 45 cases of DLBCL of CNS were retrospectively collected in Xuanwu Hospital, Capital Medical University from September 2014 to February 2017. The clinicopathological data were retrospectively analyzed, combined with immunohistochemistry, EB virus in situ hybridization, imaging and medical history. The mutation of MYD88 L265P gene was detected by pyrosequencing and its clinical significance was analyzed. Results:The age of the patients ranged from 42 to 82 years [(57.6±8.8) years], including 24 males and 21 females. Totally 93.3% (42/45) of the patients had supratentorial tumours, which were single or multiple. The cerebral hemisphere (31/45, 68.9%) was the most common involved site, and 21 cases (21/45, 46.7%) had multiple lesions. Histologically, DLBCL in the CNS showed diffuse infiltration of tumor tissue, some of which grew around blood vessels in a "sleeve" arrangement. CD 20 and CD 79a were diffusely and strongly positive. Thirty-nine cases (39/45, 86.7%) were non-germinal center B cell (non-GCB) subtype and 6 cases (6/45, 13.3%) were germinal center B cell (GCB) subtype. MYD88 L265P mutation was found in 64.4% (29/45) patients. There was statistically significant difference between non-GCB type (71.8%, 28/39) and GCB type DLBCL (1/6, P=0.017). Compared with the operation/biopsy group without chemotherapy, operation+chemotherapy, biopsy+chemotherapy, operation/biopsy+chemotherapy+stem cell transplantation can improve the survival and prognosis ( HR=0.05, 95% CI 0.01-0.33 , P=0.002; HR=0.04, 95% CI 0.01-0.36 , P=0.004; HR=0.01, 95% CI 0.00-0.17 , P=0.001; respectively). Conclusions:DLBCL of the CNS is aggressive tumor with poor prognosis, the clinical manifestations are complex and diverse, and the diagnosis is challenging. MYD88 L265P is a common and specific gene mutation in primary CNS lymphoma(PCNSL), which is of great significance in the diagnosis and treatment of lymphoma. The MYD88 L265P mutation was more frequently detected in non-GCB than GCB subtype. Chemotherapy can improve the survival rate of PCNSL patients. If chemotherapy achieves complete remission and autologous hematopoietic stem cell transplantation is performed, there may be a chance of long-term survival.

Objective:To investigate the treatment of autologous fat grafting (AFG) for breast reconstruction of soft tissue defects in pediatric Poland syndrome (PS) with computer-assisted calculation.Methods:Patients with PS were recruited in Children’s Hospital of Nanjing Medical University from January 2016 to January 2021. The children were divided into two groups: CT-assisted group and control group. CT-assisted group were examined by CT scan before operation. The imaging data were imported to 3D Slicer Software. Three -dimensional (3D) reconstruction of thoracis soft tissue in defected side were created in the software with the healthy side served as controls. The obtained 3D image was divided into six sections and the volume of each section was calculated. The interest 3D model was fabricated by using a 3D resin printer. The autologous fat grafting was made in PS patients under the 3D printing model guidance. Patients in control group for AFG that the volume of fat determined by surgeon experience without CT scan. The following outcomes were studied: postoperative breast contour, local complications and major systemic complications. Patients were reviewed at six months postoperatively. The satisfaction scores were made by physicians and patient’s guardians, respectively. The scores were analyzed by the independent samples t-test. P< 0.05 was considered statistically significant. Results:18 patients is in CT-assisted group, 8 males, 12 females, the age range from 3-12 years, mean age: 8.3 years. 10 cases underwent once injection, 6 cases underwent twice injections and 3 times in 2 cases, the average is 1.5 times. 18 patients are in control group, 4 males, 14 females, the age range from 4-14 years, mean age: 8.1 years. 8 cases underwent once injection, twice in 5 cases, and 3 times in 5 cases, the average is 1.8 times. The follow-up ranged from 1 to 2 years. The chests were essentially symmetrical and upper limb and thoracic functions were unaffected, no serious local and systematic complications were observed in the CT-assisted group. Thoracic deformities were improved to various degrees in control group. There was chest induration in two cases at 6-month follow-up, which disappeared at 1-year follow-up without any treatment. The physician satisfaction score grades in the control group and CT-assisted group: very satisfied 7 and l2 cases, satisfied 8 and 6 cases, general 3, respectively. The patient’s satisfaction score grades in the control group and CT-assisted group: very satisfied 7 and l2 cases, satisfied 10 and 6cases, general 1 , respectively. The physician satisfaction scores in the CT-assisted group and control group were 83.56±7.90, 75.67±13.63, respectively, which showing statistically significant differences ( t=2.13, P=0.041). Furthermore, the patient’s guardian satisfaction scores in the CT-assisted group and control group are 84.39±7.77, 78.28±9.82, respectively, which showing statistically significant differences ( t=2.07, P=0.046). Conclusions:AFG under computer guidance is an individualized surgical method based on children’s own characteristics in improving chest deformity of PS patients, following with high postoperative satisfaction.

Objective:To investigate the treatment of autologous fat grafting (AFG) for breast reconstruction of soft tissue defects in pediatric Poland syndrome (PS) with computer-assisted calculation.Methods:Patients with PS were recruited in Children’s Hospital of Nanjing Medical University from January 2016 to January 2021. The children were divided into two groups: CT-assisted group and control group. CT-assisted group were examined by CT scan before operation. The imaging data were imported to 3D Slicer Software. Three -dimensional (3D) reconstruction of thoracis soft tissue in defected side were created in the software with the healthy side served as controls. The obtained 3D image was divided into six sections and the volume of each section was calculated. The interest 3D model was fabricated by using a 3D resin printer. The autologous fat grafting was made in PS patients under the 3D printing model guidance. Patients in control group for AFG that the volume of fat determined by surgeon experience without CT scan. The following outcomes were studied: postoperative breast contour, local complications and major systemic complications. Patients were reviewed at six months postoperatively. The satisfaction scores were made by physicians and patient’s guardians, respectively. The scores were analyzed by the independent samples t-test. P< 0.05 was considered statistically significant. Results:18 patients is in CT-assisted group, 8 males, 12 females, the age range from 3-12 years, mean age: 8.3 years. 10 cases underwent once injection, 6 cases underwent twice injections and 3 times in 2 cases, the average is 1.5 times. 18 patients are in control group, 4 males, 14 females, the age range from 4-14 years, mean age: 8.1 years. 8 cases underwent once injection, twice in 5 cases, and 3 times in 5 cases, the average is 1.8 times. The follow-up ranged from 1 to 2 years. The chests were essentially symmetrical and upper limb and thoracic functions were unaffected, no serious local and systematic complications were observed in the CT-assisted group. Thoracic deformities were improved to various degrees in control group. There was chest induration in two cases at 6-month follow-up, which disappeared at 1-year follow-up without any treatment. The physician satisfaction score grades in the control group and CT-assisted group: very satisfied 7 and l2 cases, satisfied 8 and 6 cases, general 3, respectively. The patient’s satisfaction score grades in the control group and CT-assisted group: very satisfied 7 and l2 cases, satisfied 10 and 6cases, general 1 , respectively. The physician satisfaction scores in the CT-assisted group and control group were 83.56±7.90, 75.67±13.63, respectively, which showing statistically significant differences ( t=2.13, P=0.041). Furthermore, the patient’s guardian satisfaction scores in the CT-assisted group and control group are 84.39±7.77, 78.28±9.82, respectively, which showing statistically significant differences ( t=2.07, P=0.046). Conclusions:AFG under computer guidance is an individualized surgical method based on children’s own characteristics in improving chest deformity of PS patients, following with high postoperative satisfaction.

Objective:To evaluate the value of the indocyanine green lymphography in diagnosing cystic lymphatic malformations (cLM) in children.Methods:Between October 2019 and August 2020, patients with cLM were treated in the Department of Burns and Plastic Surgery of Children’s Hospital of Nanjing Medical University. After preoperative intracutaneous and subcutaneous injection of indocyanine green, a near-infrared fluorescence imaging system was performed to observe the lymph flow. The number, morphology, contraction frequency of afferent lymph vessels, as well as dermal backflow, were recorded.Results:Thirty-two cases of cLM were enrolled in this study. The male-to-female ratio was 18∶14, with age ranging from 3 months to 8 years. All cLMs were histologically categorized as macro-cystic (16 cases), micro-cystic (six cases), and mixed-cystic (ten cases). Only one afferent lymph vessel was detected in most of the macro-cystic cases (14/16) and mixed-cystic cases (8/10), while all micro-cystic cases (6/6) had more than two inflows. The afferent lymph vessel in macro-cystic cases and mixed-cystic cases demonstrated the normal structure. In contrast, the inflow vessels in micro-cystic LM were tortuous and small, and a dermal backflow was recorded in one case. The contraction frequency of the afferent lymphatic vessels ranged from 0.40 to 1.50 times per min, with an average of 0.80 times per min. Another two cases were confirmed not lymphangiogenic by indocyanine green lymphography and postoperative pathology.Conclusions:Indocyanine green lymphography renders a reliable, safe, and useful approach for diagnosing cLM. The application of this technique is considered effective for exploring the cLM pathogenesis, evaluation of differential diagnosis, and appropriate selection of surgical intervention.

Objective:To evaluate the value of the indocyanine green lymphography in diagnosing cystic lymphatic malformations (cLM) in children.Methods:Between October 2019 and August 2020, patients with cLM were treated in the Department of Burns and Plastic Surgery of Children’s Hospital of Nanjing Medical University. After preoperative intracutaneous and subcutaneous injection of indocyanine green, a near-infrared fluorescence imaging system was performed to observe the lymph flow. The number, morphology, contraction frequency of afferent lymph vessels, as well as dermal backflow, were recorded.Results:Thirty-two cases of cLM were enrolled in this study. The male-to-female ratio was 18∶14, with age ranging from 3 months to 8 years. All cLMs were histologically categorized as macro-cystic (16 cases), micro-cystic (six cases), and mixed-cystic (ten cases). Only one afferent lymph vessel was detected in most of the macro-cystic cases (14/16) and mixed-cystic cases (8/10), while all micro-cystic cases (6/6) had more than two inflows. The afferent lymph vessel in macro-cystic cases and mixed-cystic cases demonstrated the normal structure. In contrast, the inflow vessels in micro-cystic LM were tortuous and small, and a dermal backflow was recorded in one case. The contraction frequency of the afferent lymphatic vessels ranged from 0.40 to 1.50 times per min, with an average of 0.80 times per min. Another two cases were confirmed not lymphangiogenic by indocyanine green lymphography and postoperative pathology.Conclusions:Indocyanine green lymphography renders a reliable, safe, and useful approach for diagnosing cLM. The application of this technique is considered effective for exploring the cLM pathogenesis, evaluation of differential diagnosis, and appropriate selection of surgical intervention.

Purpose: Accumulating evidence has suggested that toll-like receptor 4 (TLR4) is critically involved in the pathogenesis of asthma. The aim of this study was to investigate the role of TLR4 in toluene diisocyanate (TDI)-induced allergic airway inflammation. Methods: TLR4−/− and wild-type (WT) C57BL/10J mice were sensitized and challenged with TDI to generate a TDI-induced asthma model. B-cell lymphoma 2 (Bcl-2) inhibitors, ABT-199 (4 mg/kg) and ABT-737 (4 mg/kg), were intranasally given to TDI-exposed TLR4−/− mice after each challenge. Results: TDI exposure led to increased airway hyperresponsiveness (AHR), granulocyte flux, bronchial epithelial shedding and extensive submucosal collagen deposition, which were unexpectedly aggravated by TLR4 deficiency. Following TDI challenge, TLR4−/− mice exhibited down-regulated interleukin-17A and increased colony-stimulating factor 3 in bronchoalveolar lavage fluid (BALF), while WT mice did not. In addition, TLR4 deficiency robustly suppressed the expression of NOD-like receptor family pyrin domain containing 3 and NLR family CARD domain containing 4, decreased caspase-1 activity in TDI-exposed mice, but had no effect on the level of high mobility group box 1 in BALF. Flow cytometry revealed that TDI hampered both neutrophil and eosinophil apoptosis, of which neutrophil apoptosis was further inhibited in TDI-exposed TLR4−/− mice, with marked up-regulation of Bcl-2. Moreover, inhibition of Bcl-2 with either ABT-199 or ABT-737 significantly alleviated neutrophil recruitment by promoting apoptosis. Conclusions These data indicated that TLR4 deficiency promoted neutrophil infiltration by impairing its apoptosis via up-regulation of Bcl-2, thereby resulting in deteriorated AHR and airway inflammation, which suggests that TLR4 could be a negative regulator of TDI-induced neutrophilic inflammation.

Purpose: Accumulating evidence has suggested that toll-like receptor 4 (TLR4) is critically involved in the pathogenesis of asthma. The aim of this study was to investigate the role of TLR4 in toluene diisocyanate (TDI)-induced allergic airway inflammation. Methods: TLR4−/− and wild-type (WT) C57BL/10J mice were sensitized and challenged with TDI to generate a TDI-induced asthma model. B-cell lymphoma 2 (Bcl-2) inhibitors, ABT-199 (4 mg/kg) and ABT-737 (4 mg/kg), were intranasally given to TDI-exposed TLR4−/− mice after each challenge. Results: TDI exposure led to increased airway hyperresponsiveness (AHR), granulocyte flux, bronchial epithelial shedding and extensive submucosal collagen deposition, which were unexpectedly aggravated by TLR4 deficiency. Following TDI challenge, TLR4−/− mice exhibited down-regulated interleukin-17A and increased colony-stimulating factor 3 in bronchoalveolar lavage fluid (BALF), while WT mice did not. In addition, TLR4 deficiency robustly suppressed the expression of NOD-like receptor family pyrin domain containing 3 and NLR family CARD domain containing 4, decreased caspase-1 activity in TDI-exposed mice, but had no effect on the level of high mobility group box 1 in BALF. Flow cytometry revealed that TDI hampered both neutrophil and eosinophil apoptosis, of which neutrophil apoptosis was further inhibited in TDI-exposed TLR4−/− mice, with marked up-regulation of Bcl-2. Moreover, inhibition of Bcl-2 with either ABT-199 or ABT-737 significantly alleviated neutrophil recruitment by promoting apoptosis. Conclusions These data indicated that TLR4 deficiency promoted neutrophil infiltration by impairing its apoptosis via up-regulation of Bcl-2, thereby resulting in deteriorated AHR and airway inflammation, which suggests that TLR4 could be a negative regulator of TDI-induced neutrophilic inflammation.