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*

BACKGROUND:Stem cell transplantation is a new way to prevent and cure intervertebral disc degeneration.However,whether the transplanted stem cells can survive,proliferate,differentiate,and restore the function of nucleus pulposus cells after transplantation,is the key and difficult point to overcome. OBJECTIVE:To explore the effects of Bushenhuoxue decoction on survival,proliferation,and nucleus pulposus-like differentiation of adipose-derived stem cells. METHODS:A Transwell chamber was used to construct a co-culture model of human adipose-derived stem cells and human degenerative nucleus pulposus cells.The experiment was divided into control group,model group,drug-containing serum group,and drug-free serum group.Except for the control group,the co-culture system of other groups was treated with 50 μmol/L tert-butyl hydrogen peroxide for 24 hours.The drug-containing serum group and drug-free serum group were treated with DMEM low-glucose complete culture medium containing drug-containing serum of Bushenhuoxue decoction or drug-free serum with 20％volume fraction for 48 hours.The sublayer adipose-derived stem cells were taken.Toluidine blue staining was used to detect proteoglycan synthesis levels.Real-time PCR method was used to detect mRNA expression of type Ⅱ collagen,proteoglycan and SRY-box transcription factor 9.The protein expression of SOX9 was detected by western blot assay.Lactate dehydrogenase assay was used to detect cytotoxicity.Flow cytometry was used to detect reactive oxygen species,and β-galactosidase staining was used to detect cell senescence. RESULTS AND CONCLUSION:(1)Compared with the control group,the proportion of necrotic cells in the model group increased;toluidine blue staining became lighter,and the expression levels of type Ⅱ collagen,proteoglycan,SOX9 mRNA and SOX9 protein decreased(P<0.05).Compared with the model group,the drug-containing serum of Bushenhuoxue decoction could significantly reduce cell injury and promote the expression of type Ⅱ collagen,proteoglycan,SOX9 mRNA,and SOX9 protein(P<0.05),but the improvement in the drug-free serum group was not significant(P>0.05).(2)Compared with the control group,the contents of cytotoxicity,reactive oxygen species,and cell senescence in the model group were significantly increased.Compared with the model group,the microenvironment of the coculture system was significantly improved by drug-containing serum of Bushenhuoxue decoction(P<0.05),while drug-free serum had no significant effect on the microenvironment of the co-culture system(P>0.05).(3)The results show that Bushenhuoxue decoction can promote the survival,proliferation,and nucleus pulposus-like differentiation of adipose-derived stem cells.

Objective To explore the therapeutic mechanism of Modified Lugen Formula(Phragmitis Rhizoma,Cicadae Periostracum,Batryticatus Bombyx,Lonicerae Japonicae Flos,Glycyrrhiza,Menthae Haplocalycis Herba,Notopterygii Rhizoma et Radix,Puerariae Lobatae Radix,Bupleuri Radix)in treating influenza from the virus-host interaction interface.Methods The phytocompounds were first collected from the HERB database,and then potential active compounds were screened out by Lipinski's rules of five.The targets of active compounds were further predicted through the SwissTargetPrediction platform.Differentially expressed genes(DEGs)were determined from the human H1N1 influenza dataset GSE90732 available in the Gene Expression Omnibus database(GEO).H1N1-Homo sapiens-related protein-protein interactions(PPIs)were gathered from the Pathogen-Host Interaction Search Tool(PHISTO).The above mentioned bioinformatic datasets were integrated.Then a PPI network and a Formula-virus-host interaction network were constructed using Cytoscape.Functional enrichment analyses were performed by using R software.Finally,molecular docking was carried out to evaluate the binding activities between the key compounds and targets.Results A total of 1 252 active compounds,1 415 targets,951 influenza-related DEGs,and 10 142 H1N1-Homo sapiens-related PPIs were obtained.There were 72 intersection targets between the Modified Lugen Formula and influenza.Functional enrichment analyses showed that these targets are closely related to host defense and programmed cell death.The network topological analysis showed that active compounds in the Modified Lugen Formula,such as oleanolic acid,γ-undecalactone,and longispinogenin,regulate viral proteins M2,NA,NS1,and HA and/or the host factors HSP90AA1,NRAS,and ITGB1,thus exert therapeutic effect.Molecular docking results confirmed that these compounds had a good binding ability with the targets.Conclusion Multiple active ingredients in Modified Lugen Formula directly target influenza virus proteins and/or host factors,thereby play an anti-influenza role in multiple dimensions,including inhibiting virus replication,regulating host defense and cell death.This study provides a theoretical basis for further experimental analysis of the action mechanism of the Modified Lugen Formula in treating influenza.

Objective:To compare the short-term efficacy and the safety of microwave ablation (MWA) and radiofrequency ablation (RFA) in the treatment of benign thyroid nodules (BTNs).Methods:This prospective randomized controlled trial, performed from December 2019 to September 2021, included 36 patients with solid or predominantly solid BTNs who met the eligibility criteria and provided written informed consent at the Nanjing sub-center (Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine). Patients were assigned to either the MWA group or the RFA group (18 patients in each group) at a ratio of 1∶1 using a block randomization design and allocation concealment using sealed envelope randomization. The independent-sample t-test and χ2 test were used to compare the volume reduction rates (VRRs), effective rates (VRRs≥50%), cosmetic scores, and complication rates at 1, 3, and 6 months after treatment between the two groups. Results:The clinical characteristics of the two groups of patients were comparable. After ablation, the nodule volume was significantly reduced in both groups. At 1, 3, and 6 months, there was no significant difference in the volume between the two groups (all P>0.05). At 3 months, the RFA group had a larger VRRs than that in the MWA group (62.08%±12.46% vs. 46.90%±23.16%, t=-2.45, P=0.021). However, at 1 and 6 months, no statistical significance was observed (both P>0.05). No significant difference was observed in the effective rates at the last follow-up (14/18 vs. 18/18, P=0.104). However, the RFA group had a lower cosmetic score than that in the MWA group (1.78±0.43 vs. 2.17±0.51, t=-2.47, P=0.019). There was no statistically significant difference in the complication rates between the two groups (all P>0.05). Conclusions:Both MWA and RFA were effective and safe treatments for BTNs, with no significant differences in short-term efficacy and safety. In addition, the RFA group showed slightly more favorable outcomes than the MWA group in terms of cosmetic improvement.

Objective The goals of this study were to identify early warning markers of severe dengue based on bioinformatics com-bined with machine learning,and explore the evaluation system of the risk of occurrence of severe dengue.Methods Based on the Gene Expression Omnibus database,the differentially expressed genes between dengue and severe dengue were analyzed,and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were conducted.Early warning genes of severe dengue were screened using a random forest model,and the accuracy of the genes was verified using receiver operating characteristic(ROC)curves.Finally,nomograms were constructed to quantify the warning genes and predict the risk of progression from dengue to severe dengue based on the expression level of these genes.Results A total of 817 differentially expressed genes were identified,along with the associated biolo-gical processes that may be closely related to the occurrence and development of severe dengue,namely,antimicrobial humoral response,humoral immune response,serine hydrolase activity,and arachidonic acid metabolism.Based on this analysis,five early warning genes were isolated:AZU1,PDCD4,COL4A3BP,TRPM4,and ATP4A.Among these,ATP4A,COL4A3BP,and TRPM4 showed low expression levels,whereas AZU1and PDCD4were highly expressed.The ROC curves indicated that these genes were accurate pre-dictors of severe dengue.The nomograms indicated good predictive accuracy,clinical benefit rate,and clinical effectiveness of the model.Conclusion Measuring the expression levels of five warning genes(AZU1,PDCD4,COL4A3BP,TRPM4,and ATP4A)may help to evaluate the risk of severe dengue.

Objective To evaluate the clinical efficacy and safety of modified Weijing Decoction in the treatment of stable stage of bronchiectasis(phlegm heat accumulating in the lung pattern).Methods A series of N-of-1 trials using bronchiectasis patients in stable stage with phlegm heat accumulation in the lung pattern were performed.Participants meeting inclusion criteria underwent two distinct treatment protocols during a therapy period.Modified Weijing Decoction was used in the experimental period and ambroxol tablets were used in the control period,washout periods were set.The medication-use order in the control period and experimental period is random.The visual analog scale(VAS)was used to assess symptom changes before and after treatment.24-hour sputum volume and COPD self-assessment test(CAT)scores were recorded,while adverse reactions were monitored during the study period.Statistical analysis and drawing were performed on SPSS 25.0 and GraphPad Prism 8.Comparison of inter-group differences before grouping was assessed by independent samples t-test.Analysis of symptom score,24-hour sputum volume and CAT scores in the experimental and control periods,as well as comparison of differences between the above two groups before and after treatment were performed using paired t-test,which enabled comprehensive exploration of clinical and statistical distinctions.Results A total of 9 patients participated in 16 rounds of analysis.Statistically significant differences(P＜0.05)before and after the treatment in the experimental period were noted in total Traditional Chinese Medicine(TCM)symptom scores,cough,sputum,sputum color,chest tightness and chest pain,bitter and dry mouth,fatigue and tiredness,24-hour sputum volume,and CAT score.Paired t-tests revealed significant variations(P＜0.05)in the total TCM symptom scores,sputum color scores,scores of chest tightness and pain,and 24-hour sputum volume between experimental and control periods.No adverse events related to the test methods or drugs occurred during the observation period.Conclusion Modified Weijing Decoction could comprehensively improve clinical symptoms of bronchiectasis patients in stable stage.It exhibits superior efficacy compared to ambroxol,and maintains a favorable safety profile.

Objective To investigate the relationship between expression levels of epidermal growth factor receptor(EGFR),proliferation marker protein Ki-67(Ki-67),P53 and circulating tumor cell(CTC)and the prognosis of triple negative breast cancer.Methods A total of 95 patients with triple negative breast cancer were selected.The expression levels of EGFR,Ki-67 and P53 in pathological tissue specimens were detected by immunohistochemistry.All patients underwent 8 cycles of chemotherapy,and the expression of CTC was detected before and after chemotherapy by isolation epithelial tumor cells(ISET).The relationship between CTC expression before and after chemotherapy and efficacy of chemotherapy was analyzed.The correlation between CTC and expression levels of EGFR,Ki-67 and P53 was analyzed.Patients were followed up for progression free survival(PFS).Risk factors of progression for triple negative breast cancer were analyzed by COX regression.Results The positive detection rates of EGFR,Ki-67 and P53 were 44.21%(42/95),63.16%(60/95)and 56.84%(54/95).The positive detection rate of CTC was lower in patients after chemotherapy than that before chemotherapy(14.74%vs.61.05%,P＜0.05).The efficacy of chemotherapy was negatively correlated with the positive expression of CTC after chemotherapy(P＜0.001).COX regression analysis found that clinical stage Ⅲ,positive EGFR and CTC after chemotherapy were independent risk factors of progression of triple negatively breast cancer(P＜0.05).PFS of patients at clinical stage Ⅰ,stage Ⅱ,and stage Ⅲ decreased in order(P＜0.05).PFS of EGFR positive patients was shorter than that of EGFR negative patients(P＜0.05).PFS of CTC positive patients after chemotherapy was shorter than that of CTC negative patients after chemotherapy(P＜0.05).Conclusion The positive expression of EGFR before chemotherapy and the positive expression of CTC after chemotherapy are related to the poor survival prognosis of patients with triple negative breast cancer.The lower the positive detection rate of CTC after chemotherapy,the better the efficacy of chemotherapy.

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 evaluate the feasibility, safety, treatment outcome, and the individualized surgical procedure selection of the interventional treatments of chylous leakage.Methods:From July 2019 to January 2022, the clinical data of 60 consecutive patients with chylous leakage underwent interventional treatment were respectively analyzed. The cases included chylothorax ( n=37), chylous ascites ( n=10), chyluria ( n=4), chylothorax combined with chylous ascites ( n=5), chylothorax combined with chylopericardium ( n=2), and pelvic chylous effusion ( n=2). Conservative treatment was considered to have failed for all patients. The lymphangiography was firstly performed to detect chylous leakage, then an individualized procedure was selected according to the lymphangiography results. The treatment outcomes and complications were recorded, and follow-up was performed. Results:Lymphangiography was technically successful in 55 of 60 patients (91.7%), and no cisterna chyli and thoracic duct opacification was observed in 5 patients. The procedures for the patients included lymphangiography alone ( n=23), thoracic duct embolization ( n=23), thoracic duct disruption ( n=5), lymphatic embolization for pelvic chylous effusion ( n=4), and balloon plasty for thoracic duct ( n=5). Clinical success was achieved in 53 of 60 cases (88.3%). The complication rate was 8.3% (5/60), and all complications were minor. The median follow-up time was 11 months (range 0.5-30 months) for 56 patients, and 4 patients were lost to follow-up. There was one patient presenting the reoccurrence of symptom, and 8 patients died. Conclusions:The interventional treatment of chylous leakage is safe with good outcomes and low complication rate. Individualized treatment procedures based on the lymphangiography findings is feasible and with good curative effect.

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