OBJECTIVE: To evaluate the short-term effectiveness of Ilizarov technique combined with steel needle internal fixation in treating Charcot neuroarthropathy (CN) of the foot and ankle. METHODS: Between June 2020 and December 2023, 12 patients with Eichenholtz stage Ⅲ CN of the foot and ankle were treated with Ilizarov technique and steel needle internal fixation. There were 9 males and 3 females with an average age of 48.6 years (range, 19-66 years). The disease duration ranged from 1 to 16 months (mean, 6.8 months). Ankle joint involvement predominated in 7 cases, while midfoot involvement occurred in 5 cases; 3 cases presented with skin ulceration and soft tissue infection. Preoperative American Orthopedic Foot and Ankle Society (AOFAS) score was 31.2±9.0, 36-Item Short-Form Health Survey (SF-36)-Physical Component Summary (PCS) score was 32.6±6.8, and Mental Component Summary (MCS) score was 47.8±8.4. Postoperative assessments included wound healing, regular X-ray film/CT evaluations of fusion status, and effectiveness via AOFAS and SF-36-PCS, MCS scores. RESULTS: All operations were successfully completed without neurovascular complication. Two patients experienced delayed wound healing requiring intervention, and the others achieved primary healing. All patients were followed up 15-43 months (mean, 23.3 months). Imaging confirmed successful joint fusion within 13-21 weeks (mean, 16.8 weeks). At last follow-up, the AOFAS score was 72.5±6.4, and the SF-36-PCS and MCS scores were 63.2±8.4 and 76.7±5.3, respectively, all of which improved compared to preoperative levels, with significant differences ( P<0.05). CONCLUSION Ilizarov technique combined with steel needle internal fixation effectively restores walking function and achieves satisfactory short-term effectiveness in CN of the foot and ankle.
Humans ; Middle Aged ; Male ; Female ; Adult ; Ilizarov Technique ; Arthropathy, Neurogenic/surgery* ; Aged ; Ankle Joint/surgery* ; Treatment Outcome ; Needles ; Fracture Fixation, Internal/instrumentation* ; Steel ; Young Adult ; Foot Joints/surgery*

BACKGROUND:The Ilizarov technique is very effective in the treatment of congenital brachymetatarsia of the fourth,but there are still some complications.The optimal proportion of lengthening of the fourth metatarsal is still controversial.OBJECTIVE:To explore the clinical efficacy of Ilizarov technique in the treatment of congenital brachymetatarsia of the fourth and the optimal lengthening ratio.METHODS:Medical records of patients with congenital brachymetatarsia of the fourth treated with Ilizarov technique in Guangdong Provincial Hospital of Traditional Chinese Medicine from August 2021 to October 2023 were collected.American Orthopaedic Foot and Ankle Society scores before and after the treatment,length of the fourth metatarsal before and after surgery,and postoperative complications were evaluated.The prolongation ratio was analyzed by subgroups to assess the best suitable length for the operative conditions.RESULTS AND CONCLUSION:(1)A total of 16 patients were included.The length of the fourth metatarsal before treatment was(43.51±3.75)mm,and the shortening length was(12.53±2.82)mm;the lengthening time during the treatment period was(36.95±4.12)days,and the time with external fixation bracket was(102.30±32.74)days,and the lengthening length after the treatment was(13.90±3.47)mm,and the prolongation ratio was(32.30±9.10)％.(2)American Orthopaedic Foot and Ankle Society scores were significantly increased at the last follow-up compared with that before treatment(t=0.763,P＜0.01).(3)The main postoperative complications were bone nonunion,metatarsophalangeal joint dislocation,metatarsophalangeal joint narrowing,and excessive lengthening of the fourth metatarsal.All patients were free of infection and abnormal sensation in the toe.(4)Subgroup analysis based on prolongation ratio showed that the rate of complications in patients in the prolongation ratio ≤ 35.36％group(17％)was significantly lower than the prolongation ratio＞35.36％group(100％)(t=14.008,P＜0.01).Meanwhile,the postoperative American Orthopaedic Foot and Ankle Society score of patients in the prolongation ratio ≤ 35.36％group(90.25±3.01)was higher than that of patients in the prolongation ratio＞35.36％group(82.00±9.97)(t=2.254,P=0.037).(5)It is concluded that Ilizarov technique for the treatment of congenital brachymetatarsia of the fourth is less traumatic surgery,can significantly improve the foot deformity of patients,especially suitable for the treatment of patients whose prolongation ratio does not exceed 35.36％,with low complication rate and satisfactory results.

BACKGROUND:Multiple observational studies have suggested a potential association between telomere length and musculoskeletal diseases.However,the underlying mechanisms remain unclear. OBJECTIVE:To investigate the genetic causal relationship between telomere length and musculoskeletal diseases using two-sample Mendelian randomization analysis. METHODS:Genome-wide association study summary data of telomere length were obtained from the UK Biobank.Genome-wide association study summary data of 10 common musculoskeletal diseases(osteonecrosis,osteomyelitis,osteoporosis,rheumatoid arthritis,low back pain,spinal stenosis,gout,scapulohumeral periarthritis,ankylosing spondylitis and deep venous thrombosis of lower limbs)were obtained from the FinnGen consortium.Inverse variance weighting,Mendelian randomization-Egger and weighted median methods were used to evaluate the causal relationship between telomere length and 10 musculoskeletal diseases.Inverse variance weighting was the primary Mendelian randomization analysis method,and sensitivity analysis was performed to explore the robustness of the results. RESULTS AND CONCLUSION:(1)Inverse variance-weighted results indicated a negative causal relationship between genetically predicted telomere length and rheumatoid arthritis(odds ratio=0.78,95%confidence interval:0.64-0.95,P=0.015)and osteonecrosis(odds ratio=0.56,95%confidence interval:0.36-0.90,P=0.016).No causal relationship was found between telomere length and the other eight musculoskeletal diseases(all P>0.05).(2)Sensitivity analysis affirmed the robustness of these causal relationships,and Mendelian randomization-Egger intercept analysis found no evidence of potential horizontal pleiotropy(all P>0.05).(3)This Mendelian randomized study supports that telomere length has protective effects against rheumatoid arthritis and osteonecrosis.However,more basic and clinical research will be needed to support our findings in the future.

BACKGROUND:The Ilizarov technique is very effective in the treatment of congenital brachymetatarsia of the fourth,but there are still some complications.The optimal proportion of lengthening of the fourth metatarsal is still controversial.OBJECTIVE:To explore the clinical efficacy of Ilizarov technique in the treatment of congenital brachymetatarsia of the fourth and the optimal lengthening ratio.METHODS:Medical records of patients with congenital brachymetatarsia of the fourth treated with Ilizarov technique in Guangdong Provincial Hospital of Traditional Chinese Medicine from August 2021 to October 2023 were collected.American Orthopaedic Foot and Ankle Society scores before and after the treatment,length of the fourth metatarsal before and after surgery,and postoperative complications were evaluated.The prolongation ratio was analyzed by subgroups to assess the best suitable length for the operative conditions.RESULTS AND CONCLUSION:(1)A total of 16 patients were included.The length of the fourth metatarsal before treatment was(43.51±3.75)mm,and the shortening length was(12.53±2.82)mm;the lengthening time during the treatment period was(36.95±4.12)days,and the time with external fixation bracket was(102.30±32.74)days,and the lengthening length after the treatment was(13.90±3.47)mm,and the prolongation ratio was(32.30±9.10)％.(2)American Orthopaedic Foot and Ankle Society scores were significantly increased at the last follow-up compared with that before treatment(t=0.763,P＜0.01).(3)The main postoperative complications were bone nonunion,metatarsophalangeal joint dislocation,metatarsophalangeal joint narrowing,and excessive lengthening of the fourth metatarsal.All patients were free of infection and abnormal sensation in the toe.(4)Subgroup analysis based on prolongation ratio showed that the rate of complications in patients in the prolongation ratio ≤ 35.36％group(17％)was significantly lower than the prolongation ratio＞35.36％group(100％)(t=14.008,P＜0.01).Meanwhile,the postoperative American Orthopaedic Foot and Ankle Society score of patients in the prolongation ratio ≤ 35.36％group(90.25±3.01)was higher than that of patients in the prolongation ratio＞35.36％group(82.00±9.97)(t=2.254,P=0.037).(5)It is concluded that Ilizarov technique for the treatment of congenital brachymetatarsia of the fourth is less traumatic surgery,can significantly improve the foot deformity of patients,especially suitable for the treatment of patients whose prolongation ratio does not exceed 35.36％,with low complication rate and satisfactory results.

Aim To investigate the effect of vanillin on the regulation of cyclic guanylate adenylate synthetase(cGAS)/stimulator of interferon gene(STING)signa-ling pathway on hepatic tissue injury in rats with intra-hepatic cholestasis(IC).Methods SD rats were randomly divided into normal group,IC group,vanillin group,cGAS overexpression group,and vanillin+cGAS overexpression group,with continuous adminis-tration for seven days.The body weight,liver weight and liver to body weight ratio of rats were measured.Liver function(ALT,AST,ALP,LDH),IC(TBIL,TBA)and liver fibrosis(HA,LN,PC Ⅲ)index were determined by ELISA.Liver pathology and fibrosis were observed using HE and Masson staining,and col-lagen volume fraction was calculated.The expression of cGAS/STING pathway related proteins in liver tissue was detected by Western blot.Results Vanillin could improve liver pathology and fibrosis,increase body weight,and decrease liver weight,ALT,AST,ALP,LDH,TBIL,TBA,HA,LN,PC Ⅲ,collagen volume fraction,cGAS,STING protein in IC rats(P＜0.05).Overexpression of cGAS could reverse the effects of vanillin on the above indicators in IC rats(P＜0.05).Conclusions Vanillin may improve liver function,IC,liver fibrosis,and liver tissue damage in IC rats by downregulating the cGAS/STING signaling pathway.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.

Objective: To evaluate the efficacy and safety of neoadjuvant chemotherapy combined with programmed death-1 (PD-1) antibody in operable, borderline or potentially resectable locally advanced esophageal squamous cell carcinoma(ESCC) in the real world. Methods: The study retrospectively analyzed 28 patients with operable or potentially resectable locally advanced ESCC patients treated with preoperative chemotherapy combined with PD-1 inhibitor in Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School from April 2020 to March 2021. According to the clinical TNM staging system of the 8th edition of the American Joint Committee on Cancer, there were 1, 15, 10, 1 and 1 case of stage Ⅱ, Ⅲ, ⅣA, ⅣB and unknown stage respectively. The treatment was two cycle of dual drug chemotherapy regimen including taxane plus platinum or fluorouracil combined with PD-1 antibody followed by tumor response assessment and surgery if the patient was eligible for resection. Results: Of the 28 patients, 1, 2, 3 and 4 cycles of chemotherapy combined with PD-1 antibody treatment completed in 1, 21, 5, and 1 patient, respectively. Objective response rate (ORR) was 71.4% (20/28), and disease control rate (DCR) was 100% (28/28). The incidence of adverse events exceeding grade 3 levels was 21.4% (6/28), including 3 neutropenia, 1 leukopenia, 1 thrombocytopenia and 1 immune hepatitis. There was no treatment-related death. Of the 23 patients underwent surgery, R0 resection rate was 87.0% (20/23), 13 patients had down staged to the T1-2N0M0 I stage, the pCR rate was 17.3% (4/23), and the pCR rate of primary tumor was 21.7% (5/23). Four patients received definitive chemoradiotherapy. One patient rejected surgery and other treatment after achieved PR response. Conclusion: Neoadjuvant chemotherapy combined PD-1 inhibitor is safe and has high efficacy in operable, borderline or potentially resectable locally advanced ESCC, and it is a promising regimen.
Humans ; Antibodies/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols ; Carcinoma, Squamous Cell/surgery* ; Cisplatin ; Esophageal Neoplasms/surgery* ; Esophageal Squamous Cell Carcinoma/drug therapy* ; Immune Checkpoint Inhibitors/therapeutic use* ; Neoadjuvant Therapy ; Programmed Cell Death 1 Receptor/therapeutic use* ; Retrospective Studies ; Treatment Outcome

This study explored a new model of Prostate Imaging Reporting and Data System (PIRADS) and adjusted prostate-specific antigen density of peripheral zone (aPSADPZ) for predicting the occurrence of prostate cancer (PCa) and clinically significant prostate cancer (csPCa). The demographic and clinical characteristics of 853 patients were recorded. Prostate-specific antigen (PSA), PSA density (PSAD), PSAD of peripheral zone (PSADPZ), aPSADPZ, and peripheral zone volume ratio (PZ-ratio) were calculated and subjected to receiver operating characteristic (ROC) curve analysis. The calibration and discrimination abilities of new nomograms were verified with the calibration curve and area under the ROC curve (AUC). The clinical benefits of these models were evaluated by decision curve analysis and clinical impact curves. The AUCs of PSA, PSAD, PSADPZ, aPSADPZ, and PZ-ratio were 0.669, 0.762, 0.659, 0.812, and 0.748 for PCa diagnosis, while 0.713, 0.788, 0.694, 0.828, and 0.735 for csPCa diagnosis, respectively. All nomograms displayed higher net benefit and better overall calibration than the scenarios for predicting the occurrence of PCa or csPCa. The new model significantly improved the diagnostic accuracy of PCa (0.945 vs 0.830, P < 0.01) and csPCa (0.937 vs 0.845, P < 0.01) compared with the base model. In addition, the number of patients with PCa and csPCa predicted by the new model was in good agreement with the actual number of patients with PCa and csPCa in high-risk threshold. This study demonstrates that aPSADPZ has a higher predictive accuracy for PCa diagnosis than the conventional indicators. Combining aPSADPZ with PIRADS can improve PCa diagnosis and avoid unnecessary biopsies.
Male ; Humans ; Prostate/pathology* ; Prostate-Specific Antigen/analysis* ; Prostatic Neoplasms/diagnostic imaging* ; Biopsy ; Nomograms ; Retrospective Studies

Objective To evaluate the predictive values of serum neutrophil gelatinase-associated lipocalin (NGAL), urine NGAL, serum cystatin C (Cys-C) and serum creatinine (Scr) for early delayed graft function (DGF) in kidney transplant recipients. Methods Clinical data, blood and urine samples of 159 kidney transplant recipients were collected. All recipients were divided into the DGF group (n=42) and immediate graft function (IGF) group (n=117) according to the incidence of DGF. Clinical data of all recipients were analyzed. The changes of serum NGAL, urine NGAL, Cys-C and Scr levels were statistically compared between two groups. The predictive values of different markers for early DGF were assessed. Results Among 159 kidney transplant recipients, DGF occurred in 42 cases with an incidence rate of 26.4%. There were statistically significant differences in donor age, cold ischemia time of donor kidney and complement-dependent cytoxicity (CDC) between the two groups(all P < 0.05). Within postoperative 2 weeks, the serum NGAL levels in the DGF group were higher than those in the IGF group (all P < 0.05). The Cys-C, Scr and urine NGAL levels in the DGF group were higher compared with those in the IGF group within 3 weeks after kidney transplantation(all P < 0.001). Serum NGAL, urine NGAL, Cys-C and Scr levels had certain predictive values for early DGF in kidney transplant recipients. Cys-C yielded the highest predictive value with a cut-off value of 4.73 mg/L, sensitivity of 0.833, specificity of 0.812 and area under the curve (AUC) of 0.895. Conclusions Cys-C has higher predictive value for early DGF in kidney transplant recipients compared with serum NGAL, urine NGAL and Scr.

OBJECTIVE: To investigate the effects of co-expression of sodium iodide symporter (NIS) reporter gene on the proliferation and cytotoxic activity of chimeric antigen receptor (CAR)-T cells in vitro. METHODS: T cells expressing CD19 CAR (CAR-T cells), NIS reporter gene (NIS-T cells), and both (NIS-CAR-T cells) were prepared by lentiviral infection. The transfection rates of NIS and CAR were determined by flow cytometry, and the cell proliferation rate was assessed using CCK-8 assay at 24, 48 and 72 h of routine cell culture. The T cells were co-cultured with Nalm6 tumor cells at the effector-target ratios of 1∶2, 1∶1, 2∶1 and 4∶1 for 24, 48 and 72 h, and the cytotoxicity of CAR-T cells to the tumor cells was evaluated using lactate dehydrogenase (LDH) assay. ELISA was used to detect the release of IFN-γ and TNF-β in the co-culture supernatant, and the function of NIS was detected with iodine uptake test. RESULTS: The CAR transfection rate was 91.91% in CAR-T cells and 99.41% in NIS-CAR-T cells; the NIS transfection rate was 47.83% in NIS-T cells and 50.24% in NIS- CAR-T cells. No significant difference in the proliferation rate was observed between CAR-T and NIS-CAR-T cells cultured for 24, 48 or 72 h (P> 0.05). In the co-cultures with different effector-target ratios, the tumor cell killing rate was significantly higher in CAR-T group than in NIS-CAR-T group at 24 h (P < 0.05), but no significant difference was observed between the two groups at 48 h or 72 h (P>0.05). Higher IFN-γ and TNF-β release levels were detected in both CAR-T and NIS-CAR-T groups than in the control group (P < 0.05). NIS-T cells and NIS-CAR-T cells showed similar capacity of specific iodine uptake (P>0.05), which was significantly higher than that in the control T cells (P < 0.05). CONCLUSION The co-expression of the NIS reporter gene does not affect CAR expression, proliferation or tumor cell-killing ability of CAR-T cells.
Antineoplastic Agents ; Cell Line, Tumor ; Cell Proliferation ; Iodine ; Lymphotoxin-alpha ; Receptors, Chimeric Antigen ; Symporters ; T-Lymphocytes