Optimal fibular tunnel direction for anterior talofibular ligament reconstruction: 45 degrees outperforms 30 and 60 degrees.

PURPOSE: There is currently no consensus on the optimal drilling direction of the fibular bone tunnel for anterior talofibular ligament (ATFL) reconstruction, and few studies have investigated the potential injury to the peroneus longus and brevis tendons and the possibility of fibular fractures during the drilling process. The aim of this study was to assess the potential risk of drilling the tunnel from different directions and determine the most appropriate tunnel direction. The hypothesis was that drilling the tunnel in the 45-degree direction would be the safest and most suitable for the fibular tunnel. METHODS: Forty-eight fibular tunnels were drilled on fresh ankle specimens using a K-wire guide and a 5.0 mm hollow drill. Three tunnel orientations were created, parallel to the sagittal plane of the long axis of the fibula and angled 30°, 45°, and 60° to the coronal plane. The length of the fibular tunnel and the distances from the outlet of the K-wire to the peroneus longus and brevis tendons were measured. The occurrence of a fibula fracture was also observed. RESULTS: The lengths of the bone tunnels in the three groups were 32.9 ± 6.1 mm (30°), 27.2 ± 4.4 mm (45°) and 23.6 ± 4.0 mm (60°). The length of the tunnel drilled at 30° was the longest when compared with that of the tunnels drilled at 45° and 60° (all p values < 0.05). The distances from the outlet of the K-wire to the peroneus longus tendon were 3.0 ± 3.8 mm (30°), 3.8 ± 3.2 mm (45°) and 5.3 ± 1.8 mm (60°), and the distances to the peroneus brevis tendon were 4.2 ± 4.0 mm (30°), 6.1 ± 3.8 mm (45°), 7.9 ± 3.5 mm (60°). In terms of protecting the peroneus longus and brevis tendons, drilling in the 60° direction was better than drilling in the 30° and 45° directions (all p values < 0.05). The risk of injury to the peroneal longus and brevis tendons was 62.5% (30°), 31.3% (45°), and 0% (60°). Although no fibular fractures were observed in any of the three directions, drilling the bone tunnel in the 60° direction disrupted the lateral cortex of the fibula. CONCLUSION: This study shows that drilling the tunnel in the 45° direction is less likely to cause injury to the peroneus longus and brevis tendons, while ensuring that the tunnel has a sufficient length and avoiding fracturing the distal fibula. Drilling a fibular bone tunnel in a 45° direction is safer and recommended for ATFL reconstruction.

Characterization of the immune cell infiltration landscape in lung adenocarcinoma.

Immune checkpoint inhibitors (ICIs) have played an important role in the treatment of lung adenocarcinoma (LUAD). However, their effectiveness is limited, and many patients exhibit a weak response. In this study, we propose a new and more effective immunophenotyping method for evaluating the prognosis and tumor microenvironment (TME) cellular infiltration characteristics in LUAD patients and their response to immunotherapy. Based on the transcriptomic and prognostic data of 584 patients with LUAD collected from TCGA cohort and GEO dataset, we combined tumor immune infiltration, the TME, and immune-related genes to score each sample using principal component analysis (PCA) and divided the patients into two subgroups with high and low tumor immune infiltration (TII) scores. The high-TII score group was characterized by increased immune activation and apoptosis signaling pathways. Moreover, clinical subgroup analysis demonstrated that the TII immune score was also applicable to different clinical groups and the high-TII score group still exhibited good prognosis and better response to ICIs. This study mapped the TII landscape in LUAD patients and confirmed that the TII score is helpful for predicting patient response to immunotherapy and may guide more effective immunotherapeutic strategies.

[Safety Analysis of Perioperative Period in Non-Small Cell Lung Cancer Patients with Comorbid Pneumoconiosis].

Objective: To explore the surgical safety of patients with comorbid non-small cell lung cancer (NSCLC) and pneumoconiosis. Methods: In this study, the clinical data of 165 NSCLC patients treated at West China Fourth Hospital, Sichuan University from August 2019 to May 2021 were collected. Among them, 21 patients with comorbid pneumoconiosis were included in the pneumoconiosis group, and the remaining 144 patients were included in the general group. Radical resection for lung cancer was performed in both groups. The perioperative clinical data, including preoperative, intraoperative and postoperative indicators, of the two groups were compared and analyzed. Results: There was no perioperative death in either group. The proportions of male patients and patients with smoking history in the pneumoconiosis group were significantly higher than those in the general group ( P<0.05). The body mass index (BMI), pulmonary ventilation function and diffusion function in the pneumoconiosis group were significantly lower than those in the general group ( P<0.05). There was no significant difference in the median operative time and the median volume of intraoperative blood loss between the pneumoconiosis group and the general group. In the pneumoconiosis group, the proportion of advanced tumors (stage Ⅱ/Ⅲ), incidence of postoperative complications, median duration of postoperative intubation, and postoperative length of hospital stay were higher/longer than those of the normal group ( P<0.05). Compared with the general group, the incidences of lymph node calcification, dense pleural adhesion and surgical method alteration (switching from thoracoscopic surgery to open surgery or video-assisted thoracoscopy) were also significantly higher in the pneumoconiosis group ( P<0.05). Univariate analysis showed that age, smoking history, pneumoconiosis, pulmonary ventilation dysfunction, lymph node calcification, dense pleural adhesion and the volume of intraoperative blood loss were the risk factors for postoperative complications. Further multivariate regression analysis demonstrated that smoking history ( OR=1.37, P<0.05), lymph node calcification ( OR=2.36, P<0.05) and pulmonary ventilation dysfunction ( OR=5.21, P<0.05) were independent risk factors for postoperative complications. Conclusion: NSCLC patients with comorbid pneumoconiosis face relatively greater risks during the perioperative period when they undergo radical resection for lung cancer. Therefore, the close attention of surgeons and the nursing staff should be raised accordingly.

All-Inside Arthroscopic Modified Broström Technique to Repair Anterior Talofibular Ligament Provides a Similar Outcome Compared With Open Broström-Gould Procedure.

PURPOSE: To introduce an all-inside modified Broström technique to suture the anterior talofibular ligament (ATFL) and inferior extensor retinaculum (IER) under arthroscopy and to compare its outcomes with those of the conventional open procedure. METHODS: All patients who underwent arthroscopic or open repair of the ATFL between June 2014 and December 2017 were included in this study. Visual analog scale (VAS), Karlsson and Peterson (K-P), American Orthopedic Foot and Ankle Society (AOFAS) ankle/hindfoot, and Tegner activity scores, as well as manual anterior drawer test (ADT), were used to evaluate the patients preoperatively and ≥2 years after surgery. The Sefton grading system was used to assess the level of satisfaction after surgery. Detailed surgical data and intraoperative findings were documented at the time of surgery. RESULTS: A total of 67 patients, 31 in the arthroscopic group and 36 in the open group, were included in this study (43 men and 24 women, mean body mass index 24.00, range 19.53 to 30.03). The surgical duration in the arthroscopic group (median, 34 minutes; range, 25 to 74) was significantly shorter than that in the open group (mean, 43.08 ± 8.11 minutes; 95% confidence interval [CI] 40.34 to 45.83) (P = .007). At the last follow-up, the subjective functional scores and ADT results improved significantly in both cohorts (P < .001). However, no significant difference was found in the VAS score (1.74 ± 1.24, 95% CI 1.29 to 2.2, in the open group versus 1.58 ± 1.2, 95% CI 1.18 to 1.99, in the arthroscopic group; P = .581), AOFAS score (91.71 ± 5.46, 95% CI 89.71 to 93.71, versus 90.67 ± 5.59, 95% CI 88.78 to 92.56; P = .444), K-P score (87.52 ± 7.59, 95% CI 84.73 to 90.3, versus 88.75 ± 5.56, 95% CI 86.87 to 90.63; P = .446), and ADT evaluation (normal: 96.77% versus 94.44%, P = .557) between the arthroscopic and open groups, respectively. In addition, 28 cases (90.32%) in the arthroscopic group and 32 (88.89%) in the open group achieved satisfactory results based on the Sefton grading system (P = .736). Seventeen patients (47.2%) in the open group and 18 patients (58.1%) in the arthroscopic group underwent Tegner evaluation after surgery, which showed no significant difference (5, interquartile range [IQR] 1 in the open group versus 5, IQR 3 in the arthroscopic group; P = .883). Complications were reported in 4 (11.1%) and 2 (6.5%) patients who underwent open and arthroscopic surgeries, respectively (P = .813). CONCLUSIONS: Both open and arthroscopic modified Broström surgeries generated favorable outcomes, with a significant improvement compared with the preoperative condition. Compared with the open Broström-Gould procedure, the all-inside arthroscopic modified Broström technique produced equivalent functional and clinical results at a minimum of 2 years after the operation, with a shorter surgical duration. Arthroscopic repair might be a safe and viable alternative to open surgery for lateral ankle stabilization. LEVEL OF EVIDENCE: III.

H-Plasty Repair Technique Improved Tibiofemoral Contact Mechanics After Repair for Adjacent Radial Tears of Posterior Lateral Meniscus Root: A Biomechanical Study.

PURPOSE: To compare the time-zero tibiofemoral contact mechanics among the 4 different suturing repairs: transtibial pullout suture repair, suture anchor repair, side-to-side repair, and H-plasty repair. METHODS: Twenty-four human cadaveric knees were included. Each lateral meniscus condition (intact, radial tear, and repair) was tested under a 1000-N axial compressive load at 0°, 30°, 60°, and 90° of flexion. Four different repair techniques, transtibial pullout, suture anchor, side-to-side, and H-plasty repair technique, were tested. Tibiofemoral mean and peak contact pressure and contact area in the lateral and medial compartments were measured by Tekscan sensors. RESULTS: Radial tears adjacent to the posterior lateral meniscus root produced significantly decreased contact area and increased mean and peak contact pressures in the lateral compartment across all angles (P < .05). All repair groups could improve the contact mechanics relative to the torn condition (P < .05), but only H-plasty repair showed no significant difference in the mean and peak contact pressure and contact area compared with that of the intact state at all flexion angles (P > .05). CONCLUSIONS: The results showed that the tibiofemoral contact mechanics after adjacent radial tears of the posterior lateral meniscal root were improved to the intact level by H-plasty repair at time-zero. The additional vertical mattress sutures act as "stabilizers" to provide a more stable environment in distributing vertical tibiofemoral pressure. The other 3 repair techniques also significantly improved lateral tibiofemoral contact mechanics relative to the corresponding tear conditions. CLINICAL RELEVANCE: The results of this study suggest that H-plasty repair can restore the biomechanical properties to the intact state. Since it was a time-zero cadaveric study, the results should be carefully used in clinical practices.

Tibiofemoral Contact Mechanics After Horizontal or Ripstop Suture in Inside-Out and Transtibial Repair for Meniscus Radial Tears in a Porcine Model.

PURPOSE: To compare tibiofemoral contact mechanics after horizontal or ripstop (horizontal plus vertical) sutures in inside-out and transtibial repair for meniscal radial tears with 10 porcine knees in each group. METHODS: Ten matched pairs of porcine knees were tested under a 1500-N axial compressive load at 0°, 30°, 60°, and 90° of knee flexion. Each knee underwent 4 testing conditions consecutively: (1) intact, (2) medial meniscal radial tear, (3) horizontal suture repair configuration, and (4) ripstop suture repair configuration. Tekscan sensors measured tibiofemoral contact pressure and contact area in the medial and lateral compartments. RESULTS: All repair groups improved their contact mechanics when compared with the tear state among all flexion angles analyzed (all P < .05). Furthermore, ripstop sutures with both inside-out and transtibial repairs restored intact knee contact area and pressures (peak and mean) in the medial compartment at all flexion angles, whereas the horizontal sutures alone failed to do so for contact pressures at 60° and 90° and for contact surface areas at all flexion angles. However, the aforementioned parameters were not significantly different between inside-out sutures and transtibial sutures, regardless of horizontal or ripstop configuration (P > .05). CONCLUSIONS: Radial tears of the meniscus in a porcine model significantly decreased medial contact area and increased mean and peak contact pressure. Both inside-out and transtibial ripstop repairs for radial tears aid in restoring intact tibiofemoral contact mechanics at all assessed knee flexion angles. CLINICAL RELEVANCE: Our results suggest that both inside-out and transtibial ripstop repairs for radial tears can restore tibiofemoral contact mechanics to the intact state. Since the study were performed in an open fashion porcine model, the results should be carefully used in clinical practices, and the efficacy of the techniques through arthroscopic method should be further explored.

[Hyperhomocysteinemia and kidney diseases].

Homocysteine (Hcy) is an intermediate metabolite of methionine metabolism. Hyperhomocysteinemia (HHcy) is defined as a condition characterized by plasma Hcy level above 16 µmol/L which can result from abnormal Hcy metabolism. HHcy has been confirmed to be related to cardio-cerebrovascular disease, peripheral vascular disorders, neurodegenerative diseases, diabetes, pregnancy-induced hypertension syndrome, liver cirrhosis and kidney diseases. In this review, we summarize the correlation between HHcy and kidney diseases. Elucidating the role of HHcy in kidney diseases may provide a new strategy to prevent and treat kidney diseases.

Whole-brain CT Perfusion at Admission and During Delayed Time-window Detects the Delayed Cerebral Ischemia in Patients with Aneurysmal Subarachnoid Hemorrhage.

OBJECTIVE: To evaluate the utility of computed tomography perfusion (CTP) both at admission and during delayed cerebral ischemia time-window (DCITW) in the detection of delayed cerebral ischemia (DCI) and the change in CTP parameters from admission to DCITW following aneurysmal subarachnoid hemorrhage. METHODS: Eighty patients underwent CTP at admission and during DCITW. The mean and extreme values of all CTP parameters at admission and during DCITW were compared between the DCI group and non-DCI group, and comparisons were also made between admission and DCITW within each group. The qualitative color-coded perfusion maps were recorded. Finally, the relationship between CTP parameters and DCI was assessed by receiver operating characteristic (ROC) analyses. RESULTS: With the exception of cerebral blood volume (P=0.295, admission; P=0.682, DCITW), there were significant differences in the mean quantitative CTP parameters between DCI and non-DCI patients both at admission and during DCITW. In the DCI group, the extreme parameters were significantly different between admission and DCITW. The DCI group also showed a deteriorative trend in the qualitative color-coded perfusion maps. For the detection of DCI, mean transit time to the center of the impulse response function (Tmax) at admission and mean time to start (TTS) during DCITW had the largest area under curve (AUC), 0.698 and 0.789, respectively. CONCLUSION: Whole-brain CTP can predict the occurrence of DCI at admission and diagnose DCI during DCITW. The extreme quantitative parameters and qualitative color-coded perfusion maps can better reflect the perfusion changes of patients with DCI from admission to DCITW.

Parental involvement in postoperative pain management among children in a urology ward: A best practice implementation project.

AIM: Postoperative pain has adverse effects on children with urological problems, including sleep disturbances, incision dehiscence, bleeding and delayed recovery. Accurate parental assessment of children's behaviours and responses could help to manage postoperative pain. We aimed to implement evidence-based practice for parental involvement in a urology ward, to increase parents' participation in children's postoperative pain management. DESIGN: The project was conducted in a paediatric urology ward using the framework and methods of the Fudan University Evidence-Based Nursing Center's Evidence-based Continuous Quality Improvement Model. METHODS: Fifteen audit criteria were used to represent best practice recommendations for parental involvement in postoperative pain management. A pre-implementation audit was conducted with 211 randomly sampled children and parents. Obstacles, promoting factors and key strategies were analysed, and evidence-based interventions implemented to improve compliance. A follow-up audit using the same audit criteria was conducted with 202 children and parents to assess the effect of targeted strategies on compliance with best practice. The SQUIRE guidelines were followed. RESULTS: At the baseline audit, compliance with the evidence-based criteria was 0%-71.5%; only five audit criteria achieved a compliance rate > 60%. After best practice implementation, the follow-up audit showed compliance improvements for all criteria; compliance for three criteria improved to 100%. PATIENT OR PUBLIC CONTRIBUTION: This best practice implementation project improved parents' participation in children's postoperative pain management. The findings demonstrate how audits can promote best practice in postoperative pain management for children. Additional studies will be conducted to address children's postoperative life quality based on best practice.

Role of macrophages in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a severe cardiopulmonary vascular disease characterized by progressive pulmonary artery pressure elevation, increased pulmonary vascular resistance and ultimately right heart failure. Studies have demonstrated the involvement of multiple immune cells in the development of PAH in patients with PAH and in experimental PAH. Among them, macrophages, as the predominant inflammatory cells infiltrating around PAH lesions, play a crucial role in exacerbating pulmonary vascular remodeling in PAH. Macrophages are generally polarized into (classic) M1 and (alternative) M2 phenotypes, they accelerate the process of PAH by secreting various chemokines and growth factors (CX3CR1, PDGF). In this review we summarize the mechanisms of immune cell action in PAH, as well as the key factors that regulate the polarization of macrophages in different directions and their functional changes after polarization. We also summarize the effects of different microenvironments on macrophages in PAH. The insight into the interactions between macrophages and other cells, chemokines and growth factors may provide important clues for the development of new, safe and effective immune-targeted therapies for PAH.

Baicalein ameliorates Alzheimer's disease via orchestration of CX3CR1/NF-κB pathway in a triple transgenic mouse model.

Alzheimer's disease (AD) is a common chronic neurodegenerative disease. Some studies have suggested that dysregulation of microglia activation and the resulting neuroinflammation play an important role in the development of AD pathology. Activated microglia have both M1 and M2 phenotypes and inhibition of M1 phenotype while stimulating M2 phenotype has been considered as a potential treatment for neuroinflammation-related diseases. Baicalein is a class of flavonoids with anti-inflammatory, antioxidant and other biological activities, but its role in AD and the regulation of microglia are limited. The purpose of this study was to investigate the effect of baicalein on the activation of microglia in AD model mice and the related molecular mechanism. Our results showed that baicalein significantly improved the learning and memory ability and AD-related pathology of 3 × Tg-AD mice, inhibited the level of pro-inflammatory factors TNF-α, IL-1ß and IL-6, promoted the production of anti-inflammatory factors IL-4 and IL-10, and regulated the microglia phenotype through CX3CR1/NF-κB signaling pathway. In conclusion, baicalein can regulate the phenotypic transformation of activated microglia and reduce neuroinflammation through CX3CR1/NF-κB pathway, thereby improving the learning and memory ability of 3 × Tg-AD mice.

Novel, chimeric, cancer-specific, and radiation-inducible gene promoters for suicide gene therapy of cancer.

BACKGROUND: Although the promoter of the human telomerase reverse transcriptase (hTERT) gene has been widely used in gene therapy for targeted cancer cells, it has some limitations for clinical use because of its low activity and potential toxicity to certain normal cells. To overcome these defects, the authors generated novel chimeric hTERT promoters that contained the radiation-inducible sequence CC(A/T)(6) GG (known as CArG elements). METHODS: Chimeric hTERT promoters were synthesized that contained different numbers of CArG elements, and the activity of chimeric promoters was assessed in different cancer cell lines and normal cells. The potential of selected promoters to successfully control horseradish peroxidase (HRP) and prodrug indole-3-acetic acid (IAA) suicide gene therapy was tested in vitro and in vivo. RESULTS: The promoter activity assays indicated that the synthetic promoter that contained 6 repeating CArG units had the best radiation inducibility than any other promoters that contained different numbers of CArG units, and the chimeric promoters retained their cancer-specific characteristics. The chimeric promoter was better at driving radiation-inducible gene therapy than the control promoters. The sensitizer enhancement ratio of the chimeric promoter system determined by clonogenic assay was higher, and the chimeric promoter system resulted in a significantly higher apoptotic level compared with other promoter systems. The combination of chimeric/promoter-mediated gene therapy and radiotherapy significantly inhibited tumor volume in a xenograft mouse model and resulted in a significant prolongation of survival in mice. CONCLUSIONS: The current results indicated that a combinational cancer-specific promoter system that is responsive to irradiation has great potential for improving the efficacy of cancer treatment.

Meniscus Regeneration With Multipotent Stromal Cell Therapies.

Meniscus is a semilunar wedge-shaped structure with fibrocartilaginous tissue, which plays an essential role in preventing the deterioration and degeneration of articular cartilage. Lesions or degenerations of it can lead to the change of biomechanical properties in the joints, which ultimately accelerate the degeneration of articular cartilage. Even with the manual intervention, lesions in the avascular region are difficult to be healed. Recent development in regenerative medicine of multipotent stromal cells (MSCs) has been investigated for the significant therapeutic potential in the repair of meniscal injuries. In this review, we provide a summary of the sources of MSCs involved in repairing and regenerative techniques, as well as the discussion of the avenues to utilizing these cells in MSC therapies. Finally, current progress on biomaterial implants was reviewed.

[Analysis on "the essence of tuina, arrival of qi ensuring curative effect"].

In reference with the systematic review of the thought of deqi (arrival of qi) put forward in Huangdi Neijing (Internal Classic of Yellow Emperor) and other classic books of traditional Chinese medicine, in view of detecting qi and identifying qi before treatment, as well as the prerequisites of deqi in tuina, meaning the accurate syndrome differentiation and manipulations, the importance of deqi in treatment with tuina is expounded. In association with clinical experience, the specific manifestations of deqi in patients during tuina are summarized, e.g. soreness, distention, pain, numbness, warm feeling and slight sweating, local changes in intestinal sound and skin color, as well as mind regulation. It is anticipated that deqi of tuina may be drawn the attention in clinical practice, and the relevant study be expanded.

Cornuside Is a Potential Agent against Alzheimer's Disease via Orchestration of Reactive Astrocytes.

Cornuside is an iridoid glycoside from Cornus officinalis, with the activities of anti-inflammatory, antioxidant, anti-mitochondrial dysfunction, and neuroprotection. In the present research, a triple-transgenic mice model of AD (3 × Tg-AD) was used to explore the beneficial actions and potential mechanism of cornuside on the memory deficits. We found that cornuside prominently alleviated neuronal injuries, reduced amyloid plaque pathology, inhibited Tau phosphorylation, and repaired synaptic damage. Additionally, cornuside lowered the release of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and nitric oxide (NO), lowered the level of malondialdehyde (MDA), and increased the activity of superoxide dismutase (SOD) and the level of glutathione peroxidase (GSH-Px). Cornuside also significantly reduced the activation of astrocytes and modulated A1/A2 phenotypes by the AKT/Nrf2/NF-κB signaling pathway. We further confirmed that LY294002 and Nrf2 silencing could block the cornuside-mediated phenotypic switch of C6 cells induced by microglia conditioned medium (MCM) in response to lipopolysaccharide (LPS), which indicated that the effects of cornuside in astrocyte activation are dependent on AKT/Nrf2/NF-κB signaling. In conclusion, cornuside may regulate the phenotypic conversion of astrocytes, inhibit neuroinflammation and oxidative stress, improve synaptic plasticity, and alleviate cognitive impairment in mice through the AKT/Nrf2/NF-κB axis. Our present work provides an experimental foundation for further research and development of cornuside as a candidate drug for AD management.

Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy improves survival of gastric cancer with peritoneal carcinomatosis: evidence from an experimental study.

BACKGROUND: Cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) has been considered as a promising treatment modality for gastric cancer with peritoneal carcinomatosis (PC). However, there have also been many debates regarding the efficacy and safety of this new approach. Results from experimental animal model study could help provide reliable information. This study was to investigate the safety and efficacy of CRS + HIPEC to treat gastric cancer with PC in a rabbit model. METHODS: VX2 tumor cells were injected into the gastric submucosa of 42 male New Zealand rabbits using a laparotomic implantation technique, to construct rabbit model of gastric cancer with PC. The rabbits were randomized into control group (n = 14), CRS alone group (n = 14) and CRS + HIPEC group (n = 14). The control group was observed for natural course of disease progression. Treatments were started on day 9 after tumor cells inoculation, including maximal removal of tumor nodules in CRS alone group, and maximal CRS plus heperthermic intraperitoneal chemoperfusion with docetaxel (10 mg/rabbit) and carboplatin (40 mg/rabbit) at 42.0 ± 0.5°C for 30 min in CRS + HIPEC group. The primary endpoint was overall survival (OS). The secondary endpoints were body weight, biochemistry, major organ functions and serious adverse events (SAE). RESULTS: Rabbit model of gastric cancer with PC was successfully established in all animals. The clinicopathological features of the model were similar to human gastric PC. The median OS was 24.0 d (95% confidence interval 21.8 - 26.2 d ) in the control group, 25.0 d (95% CI 21.3 - 28.7 d ) in CRS group, and 40.0 d (95% CI 34.6 - 45.4 d ) in CRS + HIPEC group (P = 0.00, log rank test). Compared with CRS only or control group, CRS + HIPEC could extend the OS by at least 15 d (60%). At the baseline, on the day of surgery and on day 8 after surgery, the peripheral blood cells counts, liver and kidney functions, and biochemistry parameters were all comparable. SAE occurred in 0 animal in control group, 2 animals in CRS alone group including 1 animal death due to anesthesia overdose and another death due to postoperative hemorrhage, and 3 animals in CRS + HIPEC group including 1 animal death due to anesthesia overdose, and 2 animal deaths due to diarrhea 23 and 27 d after operation. CONCLUSIONS: In this rabbit model of gastric cancer with PC, CRS alone could not bring benefit while CRS + HIPEC with docetaxel and carboplatin could significantly prolong the survival with acceptable safety.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy improves survival of patients with peritoneal carcinomatosis from gastric cancer: final results of a phase III randomized clinical trial.

BACKGROUND: This randomized phase III study was to evaluate the efficacy and safety of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of peritoneal carcinomatosis (PC) from gastric cancer. METHODS: Sixty-eight gastric PC patients were randomized into CRS alone (n = 34) or CRS + HIPEC (n = 34) receiving cisplatin 120 mg and mitomycin C 30 mg each in 6000 ml of normal saline at 43 ± 0.5°C for 60-90 min. The primary end point was overall survival, and the secondary end points were safety profiles. RESULTS: Major clinicopathological characteristics were balanced between the 2 groups. The PC index was 2-36 (median 15) in the CRS + HIPEC and 3-23 (median 15) in the CRS groups (P = 0.489). The completeness of CRS score (CC 0-1) was 58.8% (20 of 34) in the CRS and 58.8% (20 of 34) in the CRS + HIPEC groups (P = 1.000). At a median follow-up of 32 months (7.5-83.5 months), death occurred in 33 of 34 (97.1%) cases in the CRS group and 29 of 34 (85.3%) cases of the CRS + HIPEC group. The median survival was 6.5 months (95% confidence interval 4.8-8.2 months) in CRS and 11.0 months (95% confidence interval 10.0-11.9 months) in the CRS + HIPEC groups (P = 0.046). Four patients (11.7%) in the CRS group and 5 (14.7%) patients in the CRS + HIPEC group developed serious adverse events (P = 0.839). Multivariate analysis found CRS + HIPEC, synchronous PC, CC 0-1, systemic chemotherapy ≥ 6 cycles, and no serious adverse events were independent predictors for better survival. CONCLUSIONS: For synchronous gastric PC, CRS + HIPEC with mitomycin C 30 mg and cisplatin 120 mg may improve survival with acceptable morbidity.

[Anti-tumor effect of suicide gene therapy using chimeric promoter plus radiotherapy on cancer cell lines].

OBJECTIVE: To explore the synergistic anti-tumor effect of radiotherapy and horseradish peroxidase/prodrug indole-3-acetic acid (HRP/IAA) gene therapy system using chimeric hTERT promoter responsive to ionizing radiation. METHODS: The synthetic hTERT promoters containing four tandem-repeat copies of radio-inducible CArG elements, and the chimeric promoter containing cytomegalovirus (CMV) early promoter were both constructed. The activities of the chimeric promoters in cancer cell lines (HeLa, A549, and MHCC97) and normal cell line (MRC-5) were detected using luciferase reporter gene expression analysis after a (60)Co γ-irradiation treatment at a series of doses(a single dose of 0 to 10 Gy). The anti-tumor effect of combining irradiation with HRP/IAA gene-directed enzyme prodrug therapy system controlled by the chimeric promoter was tested by colony formation assay, cell counting and apoptosis analysis. RESULTS: The chimeric promoters were ineffective in normal human cells, even after irradiation, but the expression of luciferase gene in tumor cells was significantly higher. The activity of the chimeric promoter in MRC-5 cells was 22.3%, 12.9% and 13.6% of that in HeLa, A549 and MHCC97 cells, respectively. After irradiation, the ratios were 11.7%, 8.7% and 8.8%, respectively. Furthermore, the chimeric promoters could successfully induce the expression of luciferase gene following different doses of radiation, with maximal inducible activity seen after 6 Gy irradiation. The chimeric promoter containing four tandem-repeat copies of radio-inducible CArG elements and CMV early promoter showed the highest activity with 6 Gy irradiation. The relative luciferase activities in HeLa, A549 and MHCC97 cells were 1.7 ± 0.2, 2.3 ± 0.2 and 2.3 ± 0.1, respectively. The chimeric promoter mediated suicide gene therapy system could increase radio-sensitivity in different cancer cells. Compared with the control system, it plus irradiation showed stronger cell proliferation inhibition, 67.3% vs. 26.1% in HeLa, 69.0% vs. 28.3% in A549, 64.6% vs. 20.8% in MHCC97 cells, and also higher apoptosis-inducing effect, 39.6% vs. 14.2% in HeLa, 33.0% vs. 12.4% in A549, and 33.2% vs. 14.2% in MHCC97 cells. CONCLUSIONS: Chimeric promoter containing hTERT promoter, CArG elements and CMV promoter preserve the tumor-specificity in telomerase-positive tumor cells, and irradiation-responsive to low dose of radiation. The suicide gene therapy using this promoter plus radiotherapy show a strong anti-tumor effect in vitro. It is expected to have a good potential for future application in gene radiotherapy.

[CT imaging characteristics of incomplete and complete myocardial bridges-mural coronary artery].

OBJECTIVE: To evaluate the CT imaging characteristics of incomplete and complete myocardial bridges-mural coronary artery (MB-MCA). METHODS: Fifty subjects with dual source coronary CT angiography (DSCTA) evidenced MB were included. The subjects were divided into incomplete MB-MCA and complete MB-MCA groups. The diameter of MCA in best systole phase and diastole phase, the MCA stenosis rate, the presence of atheromatous change proximal to the MB were evaluated. RESULTS: There were 58 MB, the average length was (2.02 ± 1.02) cm, 23 were incomplete MB and 35 were complete MB. Thirty-two MB were in the middle segments of left anterior descending artery (55.2%); 17 MB were in the distal segment of the left anterior descending artery (29.3%); 1 MB was in the proximal segment of left anterior descending artery; 3 MB in diagonal branch; 4 MB in obtuse marginal branch, 1 MB in distal right coronary artery. It was statistically significant difference between the incomplete MB-MCA and the complete MB-MCA of the diameter change in diastole and systole phase [(1.93 ± 0.49) mm, (1.71 ± 0.45) mm vs. (2.21 ± 0.41) mm, (1.63 ± 0.52) mm, P = 0.008] and stenosis rate (10.38% ± 20.2% vs. 25.12% ± 21.02%, P = 0.01). Atherosclerotic finding was evidenced in 8 incomplete MB (34.78%) and 15 complete MB (42.86%) at the proximal vessel of mural coronary artery (P > 0.05). CONCLUSION: DSCTA can vividly display the incomplete and complete myocardial MB, accurately evaluate the shape change of MB-MCA in diastole and systole phase and detect the atherosclerotic change in the proximal vessel of MB.

Comparison of Function- and Activity-Related Outcomes After Anterior Talofibular Ligament Repair With 1 Versus 2 Suture Anchors.

BACKGROUND: Few studies have compared the clinical outcomes of using 1 versus 2 suture anchors for anterior talofibular ligament (ATFL) repair. PURPOSE: To compare the function and activity-related outcomes of arthroscopic ATFL repair using 1 versus 2 suture anchors. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: This retrospective study involved 46 patients (22 patients in the 1-anchor group, 24 patients in the 2-anchor group) who underwent ATFL repair between January 2015 and December 2017. American Orthopaedic Foot & Ankle Society score, Karlsson and Peterson score, and Tegner activity level were evaluated preoperatively and ≥2.5 years postoperatively. At follow-up, patients were also asked about time to return to sport as well as level and intensity of physical fitness. Satisfaction was evaluated with the Sefton grading system. RESULTS: After ≥2.5 years of follow-up (30 months in the 1-anchor group, 33 months in the 2-anchor group), patients in the 2-anchor group had a higher Tegner activity level than those in the 1-anchor group (mean ± SD, 4.75 ± 1.07 vs 4.05 ± 1.17; P = .039). As compared with patients in the 2-anchor group, fewer patients in the 1-anchor group returned to their preoperative activity level (54.2% vs 22.9%; P = .029); the rate of activity at the same or higher intensity as preinjury was also lower in the 1-anchor group (50% vs 79.2%; P = .038). However, there were no differences between the groups in terms of American Orthopaedic Foot & Ankle Society and Karlsson and Peterson scores, time to return to work/sport, duration of activity participation, level of physical fitness, or satisfaction according to Sefton grading. CONCLUSION: Arthroscopic ATFL repair appears to be an effective treatment regardless of whether 1 or 2 suture anchors are used. The techniques had similar functional outcome scores, but 1-anchor repair produced inferior activity-related outcomes.