OBJECTIVE: To explore the corrective strategies and effectiveness of osteotomy surgery for severe lower limb deformities in hypophosphatemic rickets. METHODS: A retrospective analysis was conducted on 29 patients with severe lower limb deformities of hypophosphatemic rickets who underwent surgical treatment between February 2012 and August 2024. There were 9 males and 20 females. The age ranged from 13 to 53 years, with an average of 24.6 years. All patients were deformities of both lower limbs, presenting as 24 cases of O-shaped legs, 2 cases of wind-blown deformities, and 3 cases of X-shaped legs. Based on the full-length films of both lower limbs in the standing position before operation, the osteotomy planes of the femur, tibia, and fibula were designed. Among them, if both the same-sided thigh and leg were deformed, staged surgeries of both lower limbs were selected. If only the thigh or leg were deformed, simultaneous surgeries of both lower limbs were selected. The femur deformity was corrected immediately after osteotomy at the deformed plane; the osteotomy fragment was temporarily controlled with an external fixator, which was removed after perform internal fixation with a steel plate. After fibular osteotomy, the Ilizarov frame or Taylor frame was installed on the tibia and fibula. The threaded rods were removed and then tibial osteotomy was performed on the deformed plane. Patients using the Taylor frame did not undergo deformity correction during operation. The external fixators were adjusted starting 7 days after operation to correct the varus, valgus, and rotational deformities of the lower limb. Patients using the Ilizarov frame corrected the rotational deformity of the tibia during operation. The external fixator was adjusted starting 7 days after operation to correct the varus and valgus deformities of the lower limb. During the treatment period, the patient could walk with partial weight-bearing on the operated limb with crutches. The external fixator was removed after the bone healed. Before operation and at last follow-up, the medial proximal tibial angle (MPTA), lateral distal tibial angle (LDTA), posterior proximal tibial angle (PPTA), anterior distal tibial angle (ADTA), anatomic lateral distal femoral angle (aLDFA), posterior distal femoral angle (PDFA), and mechanical axis deviation (MAD), lower limb rotation, limb length discrepancy (LLD) were measured. The self-made scoring criteria were adopted to evaluate the degree of lower limb deformity of the patients. RESULTS: All operations were successfully completed, and no complications such as nerve or vascular injury occurred. The adjustment time of the external fixator of the lower limb after operation was 28-46 days, with an average of 37.4 days. The wearing time of the external fixator ranged from 134 to 398 days, with an average of 181.5 days. Mild pin tract infections occurred in 2 limbs. The osteofascial compartment syndrome occurred in 1 limb after operation. No complications related to orthopedic adjustment of the external fixator occurred in other patients. All patients were followed up 6-56 months, with an average of 28.2 months. At last follow-up, full-length films of both lower limbs in the standing position showed that the coronal mechanical axes of the lower limbs of all patients returned to the normal. At last follow-up, MPTA, LDTA, PPTA, aLDFA, PDFA, MAD, lower limb rotation, LLD, and the score of lower limb deformity significantly improved when compared with those before operation ( P<0.05). There was no significant difference in ADTA between pre- and post-operation ( P>0.05). The degree of lower limb deformity were rated as moderate in 2 cases and poor in 27 cases before operation and as excellent in 7 cases, good in 18 cases, and moderate in 4 cases at last follow-up, with an excellent and good rate of 86.2%. CONCLUSION For severe lower limb deformities in hypophosphatemic rickets, immediate correction of deformities with femoral osteotomy and internal plate fixation, as well as gradually correction of deformities with tibiofibular osteotomy and circular external fixation (Ilizarov frame or Taylor frame), have satisfactory therapeutic effects.
Humans ; Male ; Osteotomy/instrumentation* ; Female ; Adult ; Retrospective Studies ; Tibia/abnormalities* ; Adolescent ; Femur/abnormalities* ; Middle Aged ; Fibula/surgery* ; Rickets, Hypophosphatemic/complications* ; Young Adult ; Treatment Outcome ; External Fixators ; Bone Plates ; Lower Extremity Deformities, Congenital/etiology*

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*

OBJECTIVE T o explore the action mechanisms of Ganghuo Qingwen granules(GHQWG)in treatment of influenza based on network pharmacology and molecular docking technique.METHODS The TCMSP database was logged in to search for active compounds,targets of GHQWG and targets of influenza so as to screen out the intersected targets between HGQWG and influenza and establish a drug-ingredient-target network.The poten-tial mechanisms were analyzed by means of protein-protein interaction analysis,Gene Ontology(GO)function an-notation and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment,and the activity of binding the key targets with ingredients was validated by molecular docking.RESULTS GHQWG contained 90 types of po-tential active ingredients,312 active ingredient targets,1996 influenza targets and 134 intersection targets.The core ingredients included quercetin,kaempferol and luteolin;the key targets involved V-Rel reticuloendotheliosis viral oncogene homolog A(RELA),tumor protein 53(TP53),mitogen-activated protein kinase 3(MAPK3),tumor necrosis factor(TNF),serine/threonine kinase proteins 1(AKT1)and mitogen-activated protein kinase 1(MAPK1).The function enrichment showed that GHQWG could regulate the processes of gene expression,in-flammatory reaction and apoptosis.The result of KEGG indicated that GHQWG played therapeutic effect on influ-enza mainly through C type agglutinin receptor,TNF and in terleukin-17(IL-17)signaling pathway.The molecu-lar docking analysis showed that RELA,TP53,M APK3,TNF,AKT1 and M APK1 had strong activities of bind-ing with quercetin,kaempferol,luteolin,β-sitosterol,wogonin,stigmasterol,caffeic acid and isorhamnetin.CONCLUSION GHQWG may regulate the key targets of signaling pathways of C type agglutinin receptor,TNF and IL-17 through multiple ingredients-multiple targes-multiple pathway mechanisms so as to play the therapeutic effect on influenza.

Sepsis is a systemic inflammatory response triggered by infection and often leads to acute kidney injury(AKI).The pathogenesis of sepsis-associated AKI is complex,involving multiple factors such as renal ischemia,inflammation and oxidative stress.In recent years,pyroptosis,a pro-inflammatory form of programmed cell death,has gradually attracted the attention of researchers.Pyroptosis is activated by inflammasomes(e.g.,the NOD-like receptor pyrin domain-related protein 3 inflammasome,NLRP3 inflammasome),accompanied by Gas-dermin D(GSDMD)-mediated formation of cell membrane pores and release of cellular contents,which leads to exacerbation of local and systemic inflammatory responses.The mechanism of pyroptosis in sepsis-associated AKI has not been fully elucidated,but AKI is directly involved in the process of renal functional impairment by indu-cing the death of renal tubular epithelial cells and exacerbating the local inflammatory response.Blockade of key molecules in the pyroptosis pathway,such as GSDMD or NLRP3 inflammasome,can significantly alleviate renal injury,suggesting that the pyroptosis pathway may be a potential therapeutic target for sepsis-associated AKI.This review summarizes the recent research progress on pyroptosis in sepsis-associated AKI,and discuss its cen-tral role in the pathogenesis,particularly focusing on the inflammasome and GSDMD pathways.Additionally,this paper analyzes the potential of focal death inhibition as a therapeutic strategy and proposes future research direc-tions with the expectation of providing references for the treatment of sepsis-related AKI.

OBJECTIVE T o explore the action mechanisms of Ganghuo Qingwen granules(GHQWG)in treatment of influenza based on network pharmacology and molecular docking technique.METHODS The TCMSP database was logged in to search for active compounds,targets of GHQWG and targets of influenza so as to screen out the intersected targets between HGQWG and influenza and establish a drug-ingredient-target network.The poten-tial mechanisms were analyzed by means of protein-protein interaction analysis,Gene Ontology(GO)function an-notation and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment,and the activity of binding the key targets with ingredients was validated by molecular docking.RESULTS GHQWG contained 90 types of po-tential active ingredients,312 active ingredient targets,1996 influenza targets and 134 intersection targets.The core ingredients included quercetin,kaempferol and luteolin;the key targets involved V-Rel reticuloendotheliosis viral oncogene homolog A(RELA),tumor protein 53(TP53),mitogen-activated protein kinase 3(MAPK3),tumor necrosis factor(TNF),serine/threonine kinase proteins 1(AKT1)and mitogen-activated protein kinase 1(MAPK1).The function enrichment showed that GHQWG could regulate the processes of gene expression,in-flammatory reaction and apoptosis.The result of KEGG indicated that GHQWG played therapeutic effect on influ-enza mainly through C type agglutinin receptor,TNF and in terleukin-17(IL-17)signaling pathway.The molecu-lar docking analysis showed that RELA,TP53,M APK3,TNF,AKT1 and M APK1 had strong activities of bind-ing with quercetin,kaempferol,luteolin,β-sitosterol,wogonin,stigmasterol,caffeic acid and isorhamnetin.CONCLUSION GHQWG may regulate the key targets of signaling pathways of C type agglutinin receptor,TNF and IL-17 through multiple ingredients-multiple targes-multiple pathway mechanisms so as to play the therapeutic effect on influenza.

Sepsis is a systemic inflammatory response triggered by infection and often leads to acute kidney injury(AKI).The pathogenesis of sepsis-associated AKI is complex,involving multiple factors such as renal ischemia,inflammation and oxidative stress.In recent years,pyroptosis,a pro-inflammatory form of programmed cell death,has gradually attracted the attention of researchers.Pyroptosis is activated by inflammasomes(e.g.,the NOD-like receptor pyrin domain-related protein 3 inflammasome,NLRP3 inflammasome),accompanied by Gas-dermin D(GSDMD)-mediated formation of cell membrane pores and release of cellular contents,which leads to exacerbation of local and systemic inflammatory responses.The mechanism of pyroptosis in sepsis-associated AKI has not been fully elucidated,but AKI is directly involved in the process of renal functional impairment by indu-cing the death of renal tubular epithelial cells and exacerbating the local inflammatory response.Blockade of key molecules in the pyroptosis pathway,such as GSDMD or NLRP3 inflammasome,can significantly alleviate renal injury,suggesting that the pyroptosis pathway may be a potential therapeutic target for sepsis-associated AKI.This review summarizes the recent research progress on pyroptosis in sepsis-associated AKI,and discuss its cen-tral role in the pathogenesis,particularly focusing on the inflammasome and GSDMD pathways.Additionally,this paper analyzes the potential of focal death inhibition as a therapeutic strategy and proposes future research direc-tions with the expectation of providing references for the treatment of sepsis-related AKI.

Post-amputation pain causes great suffering to amputees, but still no effective drugs are available due to its elusive mechanisms. Our previous clinical studies found that surgical removal or radiofrequency treatment of the neuroma at the axotomized nerve stump effectively relieves the phantom pain afflicting patients after amputation. This indicated an essential role of the residual nerve stump in the formation of chronic post-amputation pain (CPAP). However, the molecular mechanism by which the residual nerve stump or neuroma is involved and regulates CPAP is still a mystery. In this study, we found that nociceptors expressed the mechanosensitive ion channel TMEM63A and macrophages infiltrated into the dorsal root ganglion (DRG) neurons worked synergistically to promote CPAP. Histology and qRT-PCR showed that TMEM63A was mainly expressed in mechanical pain-producing non-peptidergic nociceptors in the DRG, and the expression of TMEM63A increased significantly both in the neuroma from amputated patients and the DRG in a mouse model of tibial nerve transfer (TNT). Behavioral tests showed that the mechanical, heat, and cold sensitivity were not affected in the Tmem63a^-/- mice in the naïve state, suggesting the basal pain was not affected. In the inflammatory and post-amputation state, the mechanical allodynia but not the heat hyperalgesia or cold allodynia was significantly decreased in Tmem63a^-/- mice. Further study showed that there was severe neuronal injury and macrophage infiltration in the DRG, tibial nerve, residual stump, and the neuroma-like structure of the TNT mouse model, Consistent with this, expression of the pro-inflammatory cytokines TNF-α, IL-6, and IL-1β all increased dramatically in the DRG. Interestingly, the deletion of Tmem63a significantly reduced the macrophage infiltration in the DRG but not in the tibial nerve stump. Furthermore, the ablation of macrophages significantly reduced both the expression of Tmem63a and the mechanical allodynia in the TNT mouse model, indicating an interaction between nociceptors and macrophages, and that these two factors gang up together to regulate the formation of CPAP. This provides a new insight into the mechanisms underlying CPAP and potential drug targets its treatment.
Animals ; Mice ; Amputation, Surgical ; Chronic Pain/pathology* ; Disease Models, Animal ; Ganglia, Spinal/pathology* ; Hyperalgesia/etiology* ; Ion Channels/metabolism* ; Macrophages ; Neuroma/pathology*

OBJECTIVE: To investigate the effectiveness of single Taylor external fixator combined with biplanar osteotomy on correction of tibial multiplanar deformities. METHODS: Between October 2016 and December 2021, 11 patients with tibial multiplanar deformities (20 sides) were treated with single Taylor external fixator and biplanar osteotomy. Of them, 4 were male and 7 were female; the average age ranged from 13 to 33 years (mean, 21.9 years). Diagnosis included rickets severe genu varum deformity (7 cases, 14 sides), rickets severe genu valgum deformity (2 cases, 4 sides), multiple osteochondromatosis calf deformity (1 case, 1 side), neurofibromatosis medial lower leg anterior arch deformity with short of leg (1 case, 1 side). After fibular osteotomy and tibial multiplanar osteotomy, a Taylor external fixator was installed. After operation, the deformities were corrected successively and fixed completely. The osteotomy healed, then the external fixator was removed. Before operation and at 12 months after operation, the full-length X-ray films were taken. The leg-length discrepancy, medial proximal tibial angle (MPTA), lateral distal tibial angle (LDTA), posterior proximal tibial angle (PPTA), anterior distal tibial angle (ADTA), and tibial rotation angle were measured. The degree of lower limb deformity was scored with reference to a customized tibial mechanical axis scoring table. RESULTS: Osteotomy was successfully completed without neurovascular injury and other complications. The external fixator was adjusted for 28-46 days, with an average of 37 days, and the external fixator was worn for 136-292 days, with an average of 169 days. Mild needle infection during the fixation period occurred in 3 sides, refracture at the distal tibial osteotomy in 1 side after removing the external fixator, and nonunion of the distal fibular osteotomy in 1 side. All patients were followed up 369-397 days (mean, 375 days). At 12 months after operation, the lower limb discrepancy decreased, but there was no significant difference ( P>0.05). MPTA, LDTA, PPTA, ADTA, and tibial rotation angle improved, and the differences in LDTA, ADTA, and tibial rotation angle were significant ( P<0.05). The score of lower limb deformity was significantly higher than that before operation ( P<0.05), and the results were excellent in 9 sides, good in 8 sides, fair in 3 sides, with the excellent and good rate of 85%. CONCLUSION Single Taylor external fixator combined with biplanar osteotomy is effective in the correction of tibial multiplanar deformities.
Humans ; Male ; Female ; Adolescent ; Young Adult ; Adult ; Tibia/surgery* ; Osteotomy/methods* ; Rickets ; External Fixators ; Retrospective Studies ; Treatment Outcome

Humans ; Lymphoma, T-Cell, Cutaneous/complications* ; Neuroglia ; Pruritus/pathology* ; Skin Neoplasms/complications* ; Spinal Cord/pathology* ; Sympathetic Nervous System

Objective To summarize the clinical efficacy of renal transplantation from donors of donation after brain death (DBD) complicated with acute kidney injury (AKI). Methods Fifty-nine DBD donors successfully undergoing renal transplantation were recruited in this investigation. According to the Scr level upon admission of intensive care unit (ICU), DBD donors were divided into the AKI group (n=14) and control group (n=45). A total of 101 recipients were assigned into the AKI group (n=23) and control group (n=78) correspondingly. The organ donation conditions of 59 donors were summarized. Main parameters of the donors before organ procurement were statistically compared between two groups. Postoperative kidney function, hospitalization condition and clinical outcomes of the recipients were statistically compared between two groups. Results Among 59 donors, 14 cases (24%) suffered from AKI. Two donors received continuous renal replacement therapy during organ maintenance. Compared with the donors in the control group, the APACHE Ⅱ score of the donors was significantly higher (P<0.05), the incidence of central diabetes insipidus was considerably higher (P<0.01), the Scr levels at admission of ICU and before organ procurement were significantly higher (both P<0.01) and the amount of urine at 24 h before organ procurement was dramatically less in the AKI group (P<0.01).Compared with the recipients in the control group, the Scr levels at postoperative 2 and 3 d were significantly higher (both P<0.05), the length of hospital stay was considerably longer (P<0.01) and the hospitalization expanse was significantly higher in the AKI group (P<0.05). No statistical significance was observed in the postoperative delayed recovery of renal graft function, incidence of acute rejection, infection and rehabilitation dialysis in the recipients between two groups (all P>0.05). At 3 months after transplantation, the recipients in two groups were discharged and the graft survival rate was 100%. Conclusions For renal transplantation from DBD donors complicated with AKI, active measures should be taken to maintain the organ and relieve the AKI, which yields similar clinical efficacy to renal transplantation from non-AKI donors and widens the origin of kidney graft.