OBJECTIVE: To explore the clinical manifestations and genetic etiology of a child with Progressive familial intrahepatic cholestasis (PFIC2). METHODS: From April 2024 to June 2024, a child with jaundice, hepatomegaly and abnormal liver function who was repeatedly admitted to the First Department of Pediatrics of Qinzhou Maternal and Child Health Care Hospital was selected as the study subject. Clinical data of the child were collected. Peripheral blood samples were collected from the child and her parents. Genomic DNA was extracted for trio-whole exome sequencing, the candidate variant was verified by Sanger sequencing and bioinformatic analysis using REVEL, BLAST/BLAT, Swiss-Model and Swiss-Pdb Viewer software. This study was approved by the Medical Ethics Committee of the Qinzhou Maternal and Child Health Care Hospital (Ethics No.: L20240116). RESULTS: The child was a 1.5-month-old female. Her main clinical manifestations included jaundice, hepatomegaly, brownish urine and earth-like stool. Laboratory examination showed increased levels of bilirubin, mainly direct bilirubin, increased aminotransferase, especially glutamic oxalacetic aminotransferase, accompanied by increased bile acid. Genetic testing revealed that the she has harbored a homozygous c.3410T>G (p.V1137G) variant of the ABCB11 gene, for which both of her parents were heterozygous carriers. The variant was unreported previously, and was predicted to be pathogenic based on REVEL. Prediction with BLAST/BLAT software showed that the amino acids were highly conserved among different species. Swiss-Pdb Viewer software predicted that the variant has resulted in changes in hydrogen bonds between amino acids. According to the guidelines from the American Collage for Medical Genetics and Genomics (ACMG), the variant was determined to be likely pathogenic (PM1+PM2_Supporting+PM3_Supporting+PP3_Moderate). CONCLUSION The homozygous variant of the ABCB11 gene may be the genetic cause of this child. Genetic testing is helpful for confirming the diagnosis and enrich the mutational spectrum of the ABCB11 gene.
Humans ; Cholestasis, Intrahepatic/genetics* ; Female ; Infant ; ATP Binding Cassette Transporter, Subfamily B, Member 11/genetics* ; Homozygote ; Mutation

Objective:To explore the clinical manifestations and genetic etiology of a child with Progressive familial intrahepatic cholestasis (PFIC2).Methods:From April 2024 to June 2024, a child with jaundice, hepatomegaly and abnormal liver function who was repeatedly admitted to the First Department of Pediatrics of Qinzhou Maternal and Child Health Care Hospital was selected as the study subject. Clinical data of the child were collected. Peripheral blood samples were collected from the child and her parents. Genomic DNA was extracted for trio-whole exome sequencing, the candidate variant was verified by Sanger sequencing and bioinformatic analysis using REVEL, BLAST/BLAT, Swiss-Model and Swiss-Pdb Viewer software. This study was approved by the Medical Ethics Committee of the Qinzhou Maternal and Child Health Care Hospital (Ethics No.: L20240116).Results:The child was a 1.5-month-old female. Her main clinical manifestations included jaundice, hepatomegaly, brownish urine and earth-like stool. Laboratory examination showed increased levels of bilirubin, mainly direct bilirubin, increased aminotransferase, especially glutamic oxalacetic aminotransferase, accompanied by increased bile acid. Genetic testing revealed that the she has harbored a homozygous c. 3410T>G (p.V1137G) variant of the ABCB11 gene, for which both of her parents were heterozygous carriers. The variant was unreported previously, and was predicted to be pathogenic based on REVEL. Prediction with BLAST/BLAT software showed that the amino acids were highly conserved among different species. Swiss-Pdb Viewer software predicted that the variant has resulted in changes in hydrogen bonds between amino acids. According to the guidelines from the American Collage for Medical Genetics and Genomics (ACMG), the variant was determined to be likely pathogenic (PM1+ PM2_Supporting+ PM3_Supporting+ PP3_Moderate). Conclusion:The homozygous variant of the ABCB11 gene may be the genetic cause of this child. Genetic testing is helpful for confirming the diagnosis and enrich the mutational spectrum of the ABCB11 gene.

OBJECTIVE: To investigate the effectiveness of posterior minimally invasive approach in the treatment of posterior wall acetabular fractures. METHODS: The clinical data of 17 patients with posterior wall acetabular fractures treated with posterior minimally invasive approach between March 2019 and June 2023 were retrospectively analyzed. There were 14 males and 3 females with an average age of 41 years ranging from 28 to 57 years. The causes of injury were traffic accident in 12 cases and falling from height in 5 cases. There were 3 cases complicated with posterior hip dislocation and 2 cases complicated with sciatic nerve injury. According to AO/Orthopaedic Trauma Association (AO/OTA) classification, there were 11 cases of type A1.1 and 6 cases of type A1.2. The time from injury to operation was 5-8 days, with an average of 6.2 days. The incision length, intraoperative blood loss, and operation time were recorded. The quality of posterior wall fracture reduction were evaluated by Matta criteria, and hip function were evaluated by modified Merle d'Aubign-Postel score criteria at 6 months after operation and last follow-up. RESULTS: The operation was successfully completed in 17 cases. The length of incision ranged from 7 to 9 cm, with an average of 8.3 cm, and all incisions healed by first intention. The intraoperative blood loss ranged from 200 to 350 mL, with an average of 281 mL. The operation time ranged from 45 to 70 minutes, with an average of 57 minutes. Two patients had sciatic nerve injury before operation, and the sciatic nerve function recovered completely at 3 months after operation; the other 15 patients had no symptoms of sciatic nerve injury after operation. All the 17 patients were followed up 14-27 months, with an average of 19.5 months. At 1 week after operation, according to the Matta criteria, anatomical reduction was achieved in 12 cases and satisfactory reduction in 5 cases, with a satisfaction rate of 100%. According to the modified Merle d'Aubign-Postel scoring system, the hip function score was 13-18 (mean, 16.1) at 6 months after operation. Among them, 5 cases were excellent, 9 were good, and 3 were fair, with an excellent and good rate of 82.4%. At last follow-up, the hip function score was 7-18 (mean, 13.7), of which 3 cases were excellent, 9 were good, 3 were fair, and 2 were poor, with an excellent and good rate of 70.6%. During the follow-up, there was no infection, failure of internal fixation, and femoral head necrosis, and heterotopic ossification occurred in 2 cases. CONCLUSION The posterior minimally invasive approach has the advantages of less trauma, shorter operation time, less blood loss, without cutting off the external rotator muscle. Exposure through the gluteus medius-piriformis space and piriformis-supercilium space can provide sufficient safe exposure for the posterior wall acetabulum fracture, which is a reliable alternative approach for the posterior acetabular fracture.
Humans ; Acetabulum/surgery* ; Male ; Female ; Adult ; Middle Aged ; Minimally Invasive Surgical Procedures/methods* ; Retrospective Studies ; Fracture Fixation, Internal/instrumentation* ; Fractures, Bone/diagnostic imaging* ; Treatment Outcome ; Operative Time

OBJECTIVE: To explore the effectiveness of additional anti-rotation steel plate assisted intramedullary nail technology in treatment of aseptic femoral non-union patients. METHODS: A retrospective analysis was conducted on 21 patients with aseptic femoral non-union who admitted between September 2020 and October 2024 and treated with additional anti-rotation steel plate assisted intramedullary nail technology. There were 17 males and 4 females, aged 25-67 years (mean, 44 years). There were 19 cases of femoral anterograde intramedullary nail fixation, 1 case of femoral retrograde intramedullary nail fixation, and 1 case of steel plate fixation with fatigue fracture. There were 9 cases of hypertrophic non-union and 12 cases of atrophic non-union. All patients had varying degrees of fracture end atrophy/sclerosis. Among them, 20 patients who were fixed with intramedullary nails underwent removal of soft tissue and hardened bone at the fracture end, and cortical treatment resulted in the appearance of "chili sign" at the fracture end. Iliac bone grafting and anti-rotation steel plate fixation were performed. One patient with steel plate fixation was removed the steel palte and fixed with a retrograde intramedullary nail, while the hardened bone at the fracture end was removed, iliac bone grafting and anti-rotation steel plate fixation were performed. Postoperative follow-up observation included the incision healing, maximum knee flexion range of motion, bone healing, length of lower limbs, and subjective satisfaction. The lower extremity functional scale (LEFS) score was used to evaluate the lower limb function. RESULTS: All incisions healed by first intention. All patients were followed up 7-26 months (mean, 15.5 months). At last follow-up, the femoral fracture healed with the obvious callus formation at the fracture end; the maximum knee flexion range of motion was 95°-127° (mean, 112.67°). The LEFS score increased from 29.9±6.7 before operation to 75.9±3.0 at last follow-up, and the difference was significant (t=-29.622, P<0.001). Except for 1 patient who underwent intramedullary nail dynamic treatment before operation and had a lower limb shortening of about 0.9 cm, the other patients had bilateral lower limbs of equal length. All patients had no postoperative infections, mal-union of fractures, deep vein thrombosis, joint stiffness, or other complications. CONCLUSION The use of additional anti-rotation steel plate assisted intramedullary nail technology in the treatment of aseptic femoral non-union not only overcomes the drawbacks of insufficient stability at the fracture end of intramedullary nails, but also overcomes the shortcomings of biased fixation with steel plates. It has the advantages of minimal trauma, effective maintenance of fracture stability, and ideal postoperative functional recovery, making it an effective treatment for aseptic femoral non-union.
Humans ; Male ; Fracture Fixation, Intramedullary/instrumentation* ; Female ; Bone Plates ; Middle Aged ; Adult ; Femoral Fractures/surgery* ; Retrospective Studies ; Bone Nails ; Aged ; Fractures, Ununited/surgery* ; Treatment Outcome ; Bone Transplantation/methods* ; Steel ; Fracture Healing

Objective To establish a scheme of immunosuppressant(tacrolimus)tube administration after lung transplantation and evaluate the effect.Methods Utilizing evidence summary and the Delphi method with the Structure-Process-Outcome(SPO)model,a tacrolimus administrating via feeding tubes scheme was established for lung transplantations,incorporating 5 aspects"medication management""risk assessment""enteral feeding implementation""process monitoring"and"evaluation and feedback"from July to September 2023.A convenience sampling method was employed to select patients with lung transplant surgery of a tertiary hospital in Zhejiang Province from November 2023 to June 2024.Among them,18 patients admitted from March to June 2024 were designated as an experimental group,receiving the developed tacrolimus enteral feeding administration plan;18 patients admitted from November 2023 to February 2024 were designated as a control group,receiving standard enteral feeding administration measures.The standard trough concentration of tacrolimus,the coefficient of variation of tacrolimus trough concentration,the daily dosage of tacrolimus and its coefficient of variation,and the rate of achieving the target trough concentration of tacrolimus were compared between the 2 groups.Results Of the initially recruited subjects,15 in the experimental group and 18 in the control group were included in the final analysis.After intervention,the coefficient of variation of trough concentrations and daily doses of tacrolimus in the experimental group were lower than those in the control group,while the rate of achieving target trough concentrations was higher,with all differences being statistically significant(P＜0.05).There was no statistically significant difference in the comparison of standardized blood drug concentrations and the coefficient of variation of daily doses between the 2 groups(P＞0.05).Conclusion The tacrolimus administrating via feeding tubes scheme for lung transplantations based on the SPO model is scientific and practical,providing clinical references for the use of tacrolimus enteral medication after lung transplantation,in order to promote the standardization of tacrolimus enteral administration.

Objective To establish a scheme of immunosuppressant(tacrolimus)tube administration after lung transplantation and evaluate the effect.Methods Utilizing evidence summary and the Delphi method with the Structure-Process-Outcome(SPO)model,a tacrolimus administrating via feeding tubes scheme was established for lung transplantations,incorporating 5 aspects"medication management""risk assessment""enteral feeding implementation""process monitoring"and"evaluation and feedback"from July to September 2023.A convenience sampling method was employed to select patients with lung transplant surgery of a tertiary hospital in Zhejiang Province from November 2023 to June 2024.Among them,18 patients admitted from March to June 2024 were designated as an experimental group,receiving the developed tacrolimus enteral feeding administration plan;18 patients admitted from November 2023 to February 2024 were designated as a control group,receiving standard enteral feeding administration measures.The standard trough concentration of tacrolimus,the coefficient of variation of tacrolimus trough concentration,the daily dosage of tacrolimus and its coefficient of variation,and the rate of achieving the target trough concentration of tacrolimus were compared between the 2 groups.Results Of the initially recruited subjects,15 in the experimental group and 18 in the control group were included in the final analysis.After intervention,the coefficient of variation of trough concentrations and daily doses of tacrolimus in the experimental group were lower than those in the control group,while the rate of achieving target trough concentrations was higher,with all differences being statistically significant(P＜0.05).There was no statistically significant difference in the comparison of standardized blood drug concentrations and the coefficient of variation of daily doses between the 2 groups(P＞0.05).Conclusion The tacrolimus administrating via feeding tubes scheme for lung transplantations based on the SPO model is scientific and practical,providing clinical references for the use of tacrolimus enteral medication after lung transplantation,in order to promote the standardization of tacrolimus enteral administration.

Objective:To explore the clinical manifestations and genetic etiology of a child with Progressive familial intrahepatic cholestasis (PFIC2).Methods:From April 2024 to June 2024, a child with jaundice, hepatomegaly and abnormal liver function who was repeatedly admitted to the First Department of Pediatrics of Qinzhou Maternal and Child Health Care Hospital was selected as the study subject. Clinical data of the child were collected. Peripheral blood samples were collected from the child and her parents. Genomic DNA was extracted for trio-whole exome sequencing, the candidate variant was verified by Sanger sequencing and bioinformatic analysis using REVEL, BLAST/BLAT, Swiss-Model and Swiss-Pdb Viewer software. This study was approved by the Medical Ethics Committee of the Qinzhou Maternal and Child Health Care Hospital (Ethics No.: L20240116).Results:The child was a 1.5-month-old female. Her main clinical manifestations included jaundice, hepatomegaly, brownish urine and earth-like stool. Laboratory examination showed increased levels of bilirubin, mainly direct bilirubin, increased aminotransferase, especially glutamic oxalacetic aminotransferase, accompanied by increased bile acid. Genetic testing revealed that the she has harbored a homozygous c. 3410T>G (p.V1137G) variant of the ABCB11 gene, for which both of her parents were heterozygous carriers. The variant was unreported previously, and was predicted to be pathogenic based on REVEL. Prediction with BLAST/BLAT software showed that the amino acids were highly conserved among different species. Swiss-Pdb Viewer software predicted that the variant has resulted in changes in hydrogen bonds between amino acids. According to the guidelines from the American Collage for Medical Genetics and Genomics (ACMG), the variant was determined to be likely pathogenic (PM1+ PM2_Supporting+ PM3_Supporting+ PP3_Moderate). Conclusion:The homozygous variant of the ABCB11 gene may be the genetic cause of this child. Genetic testing is helpful for confirming the diagnosis and enrich the mutational spectrum of the ABCB11 gene.

Epigenomic imbalance drives abnormal transcriptional processes,promoting the onset and progression of cancer.Although defective gene regulation generally affects carcinogenesis and tumor suppression networks,tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes,which may have significant implications for the development and application of epigenetic therapy,cancer immunotherapy,and their combinations.Herein,we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes,DNA methylation,histone post-translational modification,and chromatin structure in tumor immunogenicity,and introduce these epigenetic research methods.We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immuno-therapy through the complex interaction between cancer epigenetics and cancer immunology.

OBJECTIVE: To investigate the effectiveness of sequential plate internal fixation in the correction of Madelung deformity after ulnar osteotomy and shortening. METHODS: The clinical data of 13 patients with Madelung deformity admitted between September 2015 and July 2021 were retrospectively analyzed. There were 5 males and 8 females with an average age of 18.3 years ranging from 17 to 23 years. The disease duration ranged from 12 to 24 months, with an average of 17 months. Three cases had a clear history of trauma. All patients had external radial deviation deformity and limited movement of the ulnar deviation, and the ulnar impact pain was significant during ulnar deviation movement; 9 patients had limited wrist joint supination movement, and the supination movement was normal. In the first stage, ulnar osteotomy and shortening combined with external fixator were used to correct wrist deformity in 13 patients. After operation, bone transfer was performed 6 times per day, with adjustments made every 4 hours, which was 1 mm per day. After the osteotomy was in place, the ulnar plate internal fixation was performed to reconstruct the ulnar stability in the second stage. The Cooney wrist joint score was used to assess the pain, function, range of motion, flexion and extension range of motion, and grip strength of the wrist joint before operation and before the removal of internal fixator. The subjective feeling and appearance satisfaction of patients were recorded. RESULTS: After the second-stage operation, all the 13 patients were followed up 10-22 months, with an average of 15 months. The deformity of wrist joint disappeared after operation, and the flexion, extension, and ulnar deviation were basically normal. There was no complication such as ulnar impingement sign, nonunion or infection. Wrist function, pain, and range of motion were significantly improved after operation, except for 1 patient who had no significant improvement in rotation and pain. The ulnar internal fixator was removed at 10-18 months after the second-stage operation. The scores of pain, function, range of motion, flexion and extension range of motion, and grip strength in the Cooney wrist score before removal of internal fixator significantly improved when compared with those before operation ( P<0.05). Subjective and appearance satisfaction of patients were excellent in 9 cases, good in 3 cases, and fair in 1 case. CONCLUSION Ulnar osteotomy and shortening with sequential plate internal fixation for correction of Madelung deformity, with mild postoperative pain, can effectively avoid bone nonunion, improve wrist joint function, and have significant effectiveness.
Male ; Female ; Humans ; Adolescent ; Retrospective Studies ; Ulna/surgery* ; Osteochondrodysplasias ; Radius Fractures/surgery* ; Wrist Joint/surgery* ; Osteotomy ; Range of Motion, Articular ; Treatment Outcome

Objective:To evaluate the clinical effects of anatomical reconstruction of the deltoid ligament and medial migration calcaneal osteotomy in the treatment of chronic ankle instability after trauma.Methods:A retrospective study was conducted to analyze of the clinical data of 16 patients with chronic post-traumatic instability of the medial malleolus who had been treated at The Eighth Department of Orthopedics, Foshan Hospital of Traditional Chinese Medicine from December 2015 to February 2017. There were 14 males and 2 females with an age of (28.1±4.2) years. Seven left sides and 9 right sides were affected; the time from injury to operation was (8.9±2.4) months. Before operation, X-rays (anteroposterior, lateral and Saltzman views) and MRI of weight-bearing ankle were taken. All patients were treated by anatomical reconstruction of the deltoid ligament using the autologous semitendinosus and medial migration osteotomy of the calcaneus. The time for injury healing and occurrence of complications were recorded. The talus tilt angle, Meary angle, hindfoot valgus angle, visual analogue scale (VAS), and the American Orthopedic Foot & Ankle Society (AOFAS) ankle-hindfoot function score were compared between the preoperation and the last follow-up. The Sefton evaluation for efficacy in ankle ligament reconstruction was used to assess stability of the ankle joint.Results:Of this cohort, 14 patients were followed up for (16.4±4.9) months after operation and 2 patients lost to follow-up. The 14 patients all returned to normal physical activities 3 months after operation. All incisions healed at the first stage with no infection. One patient experienced pain at the site for harvest of the semitendinosus but the symptoms were relieved after rehabilitation treatment like massage and physical therapy. At the last follow-up, the talus tilt angle [1.0 (0.0, 2.0)°], Meary angle (1.4°±4.2°), hindfoot valgus angle (3.2°±2.4°), VAS score [0.5 (0.0, 1.0) points], and AOFAS ankle-hindfoot score [(89.2±6.1) points] were all significantly improved compared with the preoperative values [8.3°±1.8°, 0.8°±3.8°, 9.9°±3.4°, (5.7±2.5) points, and (49.6±9.8) points] (all P<0.05). According to the Sefton evaluation, the stability of the ankle joint was excellent in 9 cases, good in 4 cases, and fair in 1 case. Conclusion:In the treatment of chronic ankle instability after trauma, anatomical reconstruction of the deltoid ligament and medial migration calcaneal osteotomy is safe and effective, resulting in limited complications.