Objective To establish a novel localization method for sacral nerve foramen puncture by analyzing the characteristic of sacral nerve foramen trying to help improve the success rate of sacral foramen puncture.Methods Clinical data and sacrococcyx CT and three-dimensional reconstruction imaging data of 158 patients who received sacral nerve modulation(SNM)during Jan.2019 and Aug.2022 in our hospital were retrospectively analyzed.The distance between inferior margin of articulatio sacroiliaca and the internal edge of the 3rd neural foramen(D1),and the distance between the internal edge of the 3rd neural foramen and sacral midline(D2)were measured,and the ratio of D1 and D2 was calculated for precise intraoperative positioning.The measurement data characteristic and puncture results were analyzed.Results A total of 89 males and 69 females were included,with an average age of(49.0±16.9)years.The average D1,D2,and D1/D2 were(29.6±4.9)mm,(13.8±3.2)mm,and(2.2±0.6),respectively.Female patients had greater D1[(30.7±5.5)mm vs.(28.7±4.2)mm,P=0.010]and D1/D2[(2.4±0.7)vs.(2.1±0.5),P=0.001]than male patients.Compared with adults,the adolescents had smaller D1[(29.8±4.7)mm vs.(25.7±5.4)mm,P=0.006].After precise intraoperative positioning using this positioning method,158 patients were successfully punctured,152(96.20％)had excellent intraoperative neural response,2(1.27％)had good response,and 4(2.53％)had average response.Conclusion The surface projection of sacral nerve was approximately at the middle-inner 1/3 of the inferior margin of articulatio sacroiliaca to sacral midline.Through measuring distance from inferior margin of articulatio sacroiliacato sacral midline via X-ray,sacral nerve situation could be performed in surface,which might be a secure way to accessorily situate electrode implantation site for sacral neuromodulation.

The management of antibiotic-resistant, bacterial biofilm infections in skin wounds poses an increasingly challenging clinical scenario. Pseudomonas aeruginosa infection is difficult to eradicate because of biofilm formation and antibiotic resistance. In this study, we identified a new benzothiazole derivative compound, SN12 (IC₅₀ = 43.3 nmol/L), demonstrating remarkable biofilm inhibition at nanomolar concentrations in vitro. In further activity assays and mechanistic studies, we formulated an unconventional strategy for combating P. aeruginosa-derived infections by targeting the two-component (Gac/Rsm) system. Furthermore, SN12 slowed the development of ciprofloxacin and tobramycin resistance. By using murine skin wound infection models, we observed that SN12 significantly augmented the antibacterial effects of three widely used antibiotics-tobramycin (100-fold), vancomycin (200-fold), and ciprofloxacin (1000-fold)-compared with single-dose antibiotic treatments for P. aeruginosa infection in vivo. The findings of this study suggest the potential of SN12 as a promising antibacterial synergist, highlighting the effectiveness of targeting the two-component system in treating challenging bacterial biofilm infections in humans.

Bipolar androgen therapy (BAT), as a new therapy, can effectively reduce the serum prostate specific antigen (PSA) level of a part of patients with castration resistant prostate cancer (CRPC), delay tumor progression, improve their quality of life and restore the sensitivity to drug therapy. This paper will review the background, possible mechanism, clinical research progress and development prospect of BAT.

Objective: The purpose of this study is to investigate the safety, tolerability and efficacy of titrating dose of rivastigmine oral solution in patients with mild to moderate Alzheimer’s disease (AD) in Taiwan. Methods: We recruited 108 mild to moderate AD patients with RivastⓇ (rivastigmine oral solution 2 mg/ml) treatment for 52 weeks. We recorded the demographic characteristics, initial cognition by mini-mental state examination (MMSE), initial global status by clinical dementia rating (CDR) with CDR-Sum of Boxes (CDR-SB), initial dose, and titrating dose at each visit. We investigated the adherence, proportion of possible side effects, optimal dose, and time to optimal dose. We demonstrated the proportion of cognitive decline and its possible risk factors. Results: During the course, 9 patients discontinued the rivastigmine oral solution due to poor compliance or preference. Twelve out of 99 patients (12.1%) reported possible side effects. Among 87 patients, the mean age was 77.2 ± 9.0 years ago with female predominant (65.2%). The optimal dose was 3.6 ± 1.4 ml in average and 4 ml (n = 31, 35.6%) in mode. The duration to optimal dose was 12.5 ± 10.2 weeks and 24 weeks (n = 35, 40.2%) in mode. It presented 25% with cognitive decline in MMSE, 27% with global function decline in CDR and 63% with global function decline in CDR-SB. Conclusion We demonstrated the clinical experience of rivastigmine oral solution in mild to moderate AD patients. It suggested rivastigmine oral solution 4ml is the optimal dose with 24 weeks to the optimal dose for at least one third of patients.

Background and Objectives: Cancer stem cells (CSCs) with tumorigenic potential are reported as the crucial factors of hepatocellular carcinoma (HCC) recurrence and therapy resistance. Bone mesenchymal stem cells (BMSCs) are documented to play an important role in the protection of hepatocytes. Bie Jia Jian pill (BJJP), a Traditional Chinese Medicine, has been used to treat liver fibrosis and liver cancer. This study aimed to explore the potential role of combined use of BJJP with BMSCs in HCC cell lines. Methods: and Results: Flow cytometry was used to identify BMSCs isolated from BALB/c mice and CSCs enriched from Huh7 cells by measuring CD24, CD133, CD44, CD73, CD105, CD166, CD29, CD14 and CD34. Differentiation potential of BMSCs was also determined. Cell viability and proliferation ability of CSCs were determined by CCK-8 assay and clone formation assay. The expressions of CSCs biomarkers and Wnt/β-catenin signal pathway related proteins were determined by PCR and western blot. TOP-Flash/FOP-Flash luciferase assay was applied to measure the activity of β-catenin/TCF. Compared with untreated CSCs, BJJP or BMSCs treatment alone on CSCs lead to increased miR-140 expression and cell apoptosis, as well as decreased expressions of CD24, CD133, EpCAM and cell viability.Downregualted expressions of Wnt/β-catenin signal pathway related proteins, Wnt3a and β-catenin were found in response to BJJP or BMSCs treatment alone. The combination of BJJP＋BMSCs treatment on CSCs could further enhance the suppressive effect on CSCs. Down-regulation of miR-140 in CSCs partially blocked the effects of BMSCs or BMSCs＋BJJP on the expressions of Wnt3a and β-catenin as well as the cell viability and apoptosis of CSCs.Reversed expression pattern was found in CSCs transfected with miR-140 overexpression. Conclusions Taken together, we demonstrate that BJJP＋BMSCs together could further enhance the suppressive effect on CSCs through regulating miR-140 and suppressing Wnt/β-catenin signal pathway. This study demonstrated the potential of BJJP＋BMSCs in therapeutic treatment of HCC.

Objective:To investigate the effects of calcium sulfate on the proliferation of osteoblast-like MG-63 cells and the osteoprotegerin/receptor activator of NF-κB ligand/receptor activator of NF-κB (OPG/RANKL/RANK) system.Methods:The extract of calcium sulfate was prepared. The osteoblast-like MG-63 cells were cultured for 24 hours in the medium containing calcium sulfate (the calcium sulfate group) and in the normal medium without calcium sulfate (the blank group), respectively. The growth of osteoblast-like MG-63 cells was observed and their proliferation detected by CCK-8. The mRNA and protein expression levels of OPG/RANKL were detected.Results:The growth of osteoblast-like MG-63 cells was fine in both groups. The CCK-8 test showed that the absorbance value at 24 h was 0.997±0.008 for the calcium sulfate group, significantly higher than that for the blank group (0.640±0.003) ( P<0.001). Respectively, the mRNA expression levels of OPG were 2.834±0.176 and 1.005±0.102 and the mRNA expression levels of RANKL 0.355±0.035 and 1.002±0.068 for the calcium sulfate group and the blank control group, showing statistically significant differences ( P<0.001). The results of Western blot showed that compared with the blank control group, the protein expression of OPG in osteoblast-like MG-63 cells was promoted but the protein expression of RANKL inhibited in the calcium sulfate group. Conclusion:Calcium sulfate may have a positive effect on bone formation, because it can promote the proliferation and activity of osteoblast-like MG-63 cells and regulate the OPG/RANKL/RANK system.

Objective: The purpose of this study is to investigate the safety, tolerability and efficacy of titrating dose of rivastigmine oral solution in patients with mild to moderate Alzheimer’s disease (AD) in Taiwan. Methods: We recruited 108 mild to moderate AD patients with RivastⓇ (rivastigmine oral solution 2 mg/ml) treatment for 52 weeks. We recorded the demographic characteristics, initial cognition by mini-mental state examination (MMSE), initial global status by clinical dementia rating (CDR) with CDR-Sum of Boxes (CDR-SB), initial dose, and titrating dose at each visit. We investigated the adherence, proportion of possible side effects, optimal dose, and time to optimal dose. We demonstrated the proportion of cognitive decline and its possible risk factors. Results: During the course, 9 patients discontinued the rivastigmine oral solution due to poor compliance or preference. Twelve out of 99 patients (12.1%) reported possible side effects. Among 87 patients, the mean age was 77.2 ± 9.0 years ago with female predominant (65.2%). The optimal dose was 3.6 ± 1.4 ml in average and 4 ml (n = 31, 35.6%) in mode. The duration to optimal dose was 12.5 ± 10.2 weeks and 24 weeks (n = 35, 40.2%) in mode. It presented 25% with cognitive decline in MMSE, 27% with global function decline in CDR and 63% with global function decline in CDR-SB. Conclusion We demonstrated the clinical experience of rivastigmine oral solution in mild to moderate AD patients. It suggested rivastigmine oral solution 4ml is the optimal dose with 24 weeks to the optimal dose for at least one third of patients.

Background and Objectives: Cancer stem cells (CSCs) with tumorigenic potential are reported as the crucial factors of hepatocellular carcinoma (HCC) recurrence and therapy resistance. Bone mesenchymal stem cells (BMSCs) are documented to play an important role in the protection of hepatocytes. Bie Jia Jian pill (BJJP), a Traditional Chinese Medicine, has been used to treat liver fibrosis and liver cancer. This study aimed to explore the potential role of combined use of BJJP with BMSCs in HCC cell lines. Methods: and Results: Flow cytometry was used to identify BMSCs isolated from BALB/c mice and CSCs enriched from Huh7 cells by measuring CD24, CD133, CD44, CD73, CD105, CD166, CD29, CD14 and CD34. Differentiation potential of BMSCs was also determined. Cell viability and proliferation ability of CSCs were determined by CCK-8 assay and clone formation assay. The expressions of CSCs biomarkers and Wnt/β-catenin signal pathway related proteins were determined by PCR and western blot. TOP-Flash/FOP-Flash luciferase assay was applied to measure the activity of β-catenin/TCF. Compared with untreated CSCs, BJJP or BMSCs treatment alone on CSCs lead to increased miR-140 expression and cell apoptosis, as well as decreased expressions of CD24, CD133, EpCAM and cell viability.Downregualted expressions of Wnt/β-catenin signal pathway related proteins, Wnt3a and β-catenin were found in response to BJJP or BMSCs treatment alone. The combination of BJJP＋BMSCs treatment on CSCs could further enhance the suppressive effect on CSCs. Down-regulation of miR-140 in CSCs partially blocked the effects of BMSCs or BMSCs＋BJJP on the expressions of Wnt3a and β-catenin as well as the cell viability and apoptosis of CSCs.Reversed expression pattern was found in CSCs transfected with miR-140 overexpression. Conclusions Taken together, we demonstrate that BJJP＋BMSCs together could further enhance the suppressive effect on CSCs through regulating miR-140 and suppressing Wnt/β-catenin signal pathway. This study demonstrated the potential of BJJP＋BMSCs in therapeutic treatment of HCC.

Objective To investigate the efficacy of three-dimensional (3D) printing used to assist the treatment of pilon fracture combined with ipsilateral tibial shaft fracture.Methods From May to July 2016,3 patients with pilon fracture combined with ipsilateral tibial shaft fracture were treated at Department of Traumatic Orthopedics,The Second Affiliated Hospital,University of South China.They were all male,aged from 26 to 47 years.They all had preoperative 3D CT scan.Their CT data were imported to Mimics software for 3D reconstruction.After their fracture 3D models were manufactured by 3D printing,precise patient-specific surgical plans were made to guide their actual operations.Postoperatively,Johner-Wruhs scores were used to evaluate the treatment of tibial shaft fracture,Burwell-Charnley scores to evaluate the treatment of pilon fracture and Tornetta scores to evaluate the therapeutic outcomes.Results All the operations were performed according to the patient-specific surgical plans designed preoperatively.All the fractures achieved bony union without any infection,exposure of bone or internal fixation,osteofascial compartment syndrome or neurovascular injury.The outcomes of tibial shaft fracture were excellent by Johner-Wruhs scoring,anatomic reduction was achieved for pilon fractures by Burwell-Charnley scoring and the therapeutic outcomes were excellent by Tornetta scoring.Conclusion In the treatment of pilon fracture combined with ipsilateral tibial shaft fracture,3D printing can help making of precise and patient-specific surgical plans to promote clinical efficacy.

Objective To explore the relationship between MRI and VEGF&CerbB-2 expression in atypical breast cancer.Methods 82 cases of atypical breast cancer confirmed by pathology were analyzed retrospectively.The relationship between MRI and VEGF &CerbB-2 expression were compared and analyzed.Results In total patients,57 cases were VEGF positive expression(69.5%,57/82),50 cases were CerbB-2 positive expression(61.0%,50/82).The VEGF positive expression rate was 78.8% in maximum diameter ≥2.0 cm group,which was obviously higher than < 2.0 cm group(P<0.05).Internal necrosis,ADC value and VEGF positive expression were positively correlated (P<0.05).There were not positively correlated relationships between internal reinforcement method,TIC and VEGF positive expression(P>0.05).There were positively correlated relationships between internal necrosis,ADC value and CerbB-2 positive expression (P<0.05).There were not positively correlated relationships between maximum diameter,internal reinforcement method, TIC and CerbB-2 positive expression(P>0.05).Conclusion There are relationships between the maximum diameter,internal necrosis,ADC value and molecular biology (VEGF,CerbB-2)of the atypical breast cancer.