Clinical-radiomics nomogram for the risk prediction of esophageal fistula in patients with esophageal squamous cell carcinoma treated with intensity-modulated radiation therapy or volumetric-modulated arc therapy.

Background: Esophageal fistula (EF) is a serious adverse event as a result of radiotherapy in patients with esophageal cancer (EC). We aimed to identify the predictive factors and establish a prediction model of EF in patients with esophageal squamous cell carcinoma (ESCC) who underwent intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT). Methods: Patients with ESCC treated with IMRT or VMAT from January 2013 to December 2020 at Xijing Hospital were retrospectively analyzed. Ultimately, 43 patients with EF and 129 patients without EF were included in the analysis and propensity-score matched in a 1:3 ratio. The clinical characteristics and radiomics features were extracted. Univariate and multivariate stepwise logistic regression analyses were used to determine the risk factors associated with EF. Results: The median follow-up time was 24.0 months (range, 1.3-104.9 months), and the median overall survival (OS) was 13.1 months in patients with EF. A total of 1,158 radiomics features were extracted, and eight radiomics features were selected for inclusion into a model for predicting EF, with an area under the receiver operating characteristic curve (AUC) value of 0.794. Multivariate analysis showed that tumor length, tumor volume, T stage, lymphocyte rate (LR), and grade IV esophagus stenosis were related to EF, and the AUC value of clinical model for predicting EF was 0.849. The clinical-radiomics model had the best performance in predicting EF with an AUC value of 0.896. Conclusions: The clinical-radiomics nomogram can predict the risk of EF in ESCC patients and is helpful for the individualized treatment of EC.

Diabetes-related Screw Loosening: The Distinction of Surgical Sites and the Relationship among Diabetes, Implant Stabilization and Clinical Outcomes.

OBJECTIVES: Diabetes mellitus (DM) is correlated with poor clinical outcomes in spinal surgery. However, the effect of it on screw stabilization has not been investigated. The aim of this study was to evaluate the screw loosening rate and postoperative outcomes in diabetic patients and to identify potential risk factors associated with loosening. METHODS: This was a retrospective study. Two hundred and forty-three patients who received cervical or lumbar internal fixation between 2015 and 2019 were enrolled. Screw loosening was assessed on radiography, and clinical outcomes were evaluated by the improvement of visual analogue scale (VAS), Oswestry disability index (ODI) or Japanese Orthopaedic Association (JOA) scores. The relationship of DM, screw loosening and clinical outcomes were analyzed with chi-square tests and regression analyses. RESULTS: One hundred and twenty-two patients (50.2%) with diabetes were included in this study. Diabetes led to the increase of the rate of screw loosening in the lumbar spine, while the loosening rate did not vary significantly in the cervical spine. The occurrence of screw loosening in the lumbar spine was more likely to be associated with clinical outcomes for motor performance including walking and sitting. However, no significant effect on JOA and VAS scores in the cervical spine of screw loosening was found. Moreover, the history of DM affected the outcomes of the patients who underwent spinal surgery. CONCLUSION: DM had an adverse effect on screw stabilization. The impaired improvement of clinical outcomes in diabetics after spinal surgery was related to screw loosening. In addition to the direct effects on operative wounds and neural function, the impact on the screws due to DM was also worth noting.

Re-irradiation for local primary-recurrence esophageal squamous cell carcinoma treated with IMRT/VMAT.

PURPOSE: Local primary-recurrence of esophageal squamous cell carcinoma (ESCC) after definitive treatment has the potential for increasing overall survival with re-irradiation (Re-RT), especially with advanced technique. This study aimed to evaluate the efficacy and toxicities of Re-RT using intensity-modulated radiotherapy (IMRT)/volumetric modulated arc therapy (VMAT) for local primary-recurrence of ESCC. MATERIALS AND METHODS: A total of 130 ESCC patients with local primary-recurrence from Xijing hospital between 2008 and 2021 were enrolled and 30 patients underwent IMRT/VMAT based salvage Re-RT. Cox regression analysis was used to analyze the prognostic factors for overall survival (OS) and after recurrence survival (ARS). The toxicities of 30 patients receiving Re-RT were also assessed. RESULTS: The median OS and ARS of the 130 recurrent patients were 21 months (1-164 months) and 6 months (1-142 months). The 1-, 2-, and 3-year OS rates were 81.5%, 39.2%, and 23.8%, respectively. Besides, the 1-, 2-, and 3-year ARS rates were 30.0%, 10%, and 6.2%. Multivariate analysis showed that Re-RT ± chemotherapy (p = 0.043) and chemotherapy alone (p < 0.001) and esophageal stents (p = 0.004) were independent prognostic factors for OS. The median OS of 30 patients treated with Re-RT were significantly better than that of 29 patients treated with chemotherapy (34.5 months vs. 22 months, p = 0.030). Among 30 ESCC patients treated with Re-RT, the median OS and ARS were 34.5 months (range 12-163 months) and 6 months (range 1-132 months), respectively. The recurrence-free interval (RFI) (> 12 months) and initial radiation dose (> 60 Gy) were significantly associated with improved OS. Radiation esophagitis (Grade 1-2) occurred in 16 patients and myelosuppression (Grade1-2) occurred in 10 patients. Grade 3 toxicities (radiation esophagitis and myelosuppression) were only 13.3%. There were no grade 4 toxicities. CONCLUSION: Our results demonstrated that IMRT/VMAT-based Re-RT was an effective therapeutic option for ESCC patients with local primary-recurrence compared with chemotherapy alone or without any treatment. Re-RT had improved OS but unfavorable ARS.

Spatiotemporal Regulation of Injectable Heterogeneous Silk Gel Scaffolds for Accelerating Guided Vertebral Repair.

Osteoporotic vertebral fracture is jeopardizing the health of the aged population around the world, while the hypoxia microenvironment and oxidative damage of bone defect make it difficult to perform effective tissue regeneration. The balance of oxidative stress and the coupling of vessel and bone ingrowth are critical for bone regeneration. In this study, an injectable heterogeneous silk gel scaffold which can spatiotemporally and sustainedly release bone mesenchymal stem cell-derived small extracellular vesicles, HIF-1α pathway activator, and inhibitor is developed for bone repair and vertebral reinforcement. The initial enhancement of HIF-1α upregulates the expression of VEGF to promote angiogenesis, and the balance of reactive oxygen species level is regulated to effectively eliminate oxidative damage and abnormal microenvironment. The subsequent inhibition of HIF-1α avoids the overexpression of VEGF and vascular overgrowth. Meanwhile, complex macroporous structures and suitable mechanical support can be obtained within the silk gel scaffolds, which will promote in situ bone regeneration. These findings provide a new clinical translation strategy for osteoporotic vertebral augmentation on basis of hypoxia microenvironment improvement.

Safety and efficacy of C-arm CT laser-guided percutaneous renal pelvic catheter drainage under DSA in the treatment of hydronephrosis caused by pelvic malignancy / 中华泌尿外科杂志

Objective:To investigate the safety and efficacy of C-arm CT laser-guided puncture combined with digital subtraction angiography (DSA)for percutaneous renal pelvic catheter drainage in the treatment of hydronephrosis caused by pelvic malignancy.Methods:A retrospective analysis was performed on the data of 56 patients with ureteral obstruction caused by pelvic malignancy admitted to the Affiliated Cancer Hospital of Zhengzhou University from February 2020 to August 2021, including 10 males and 46 females. The mean age of the patients was (54.0±10.1)years old. The causes were colorectal cancer (7 cases), bladder cancer (3 cases), cervical cancer (36 cases), endometrial cancer (3 cases), ovarian cancer (2 cases), pelvic metastasis of gastric cancer (4 cases) and pelvic sarcoma (1 case). There were 71 sides of renal pelvis dilation in 56 patients, with the degree of dilation ranging from 1.2cm to 5.0cm.The degree of hydronephrosis was mild on 36 sides, moderate on 27 sides, and severe on 8 sides. Preoperative blood urea nitrogen(9.90±6.22)mmol/L and creatinine (155.80±146.83)μmol/L.During the puncture and catheter drainage, the patient was placed in the prone position, the C-arm CT scan was used to plan the puncture path, and the laser positioning of the DSA flat panel detector was used to determine the skin puncture point. With local anesthesia, the puncture direction of the puncture needle was adjusted to make the skin puncture point, the tail of the puncture needle, and the laser fixation point present a state of "three-points in one-line" when the patient stopped breathing temporarily at the end of expiratory breath in a non-fluoroscopic state, so as to achieve the preset puncture angle. Subsequently, pyelocentesis was completed according to the planned puncture depth. After successful pyelocentesis, percutaneous external renal drainage tube insertion or ureteral stents were performed under DSA. The number of renal pelvis puncture, puncture time, radiation dose, deviation of external renal drainage tube insertion angle from puncture angle, as well as postoperative hemoglobin changes, renal function recovery and complications were recorded.Results:In this group, 56 cases of 71 sides of renal pelvis puncture and catheter drainage were successfully completed, and the success rate of the operation was 100.0% (71/71). The success rate of the first needle puncture was 97.2% (69/71). Those who failed the first needle puncture succeeded in the second puncture during the operation. The puncture time of renal pelvis was (1.9±1.8) min.The intraoperative radiation dose was (2.7±1.5) mSV. The external drainage tube of the renal pelvis was placed on 53 sides, and the external drainage tube was placed on 29 sides with the same angle as the preset angle, and 24 sides with a deviation within 3°.On the first day after operation, there was no significant difference in hemoglobin compared with that before operation, urea nitrogen (5.31±1.99) mmol/L and creatinine (62.25±16.72) μmol/L were re-examined after operation, and the differences were statistically significant compared with those before operation ( P=0.008, P=0.002). No serious surgery-related complications occurred in any patient. Conclusion:C-arm CT laser-guided puncture combined with DSA percutaneous renal pelvic catheter drainage could be safe and effective in the treatment of ureteral obstruction caused by pelvic malignancy.

Clinical efficacy of radiofrequency ablation guided by CT hepatic arteriography in the treatment of multiple nodular liver metastases of colorectal cancer / 中华肝胆外科杂志

Objective:To evaluate the safety and efficacy of radiofrequency ablation guided by CT hepatic arteriography (CTHA) in the treatment of multiple nodular liver metastases of colorectal cancer.Methods:Clinical data of 32 patients with liver metastasis of colorectal cancer who underwent femoral arterial catheterization and percutaneous radiofrequency ablation guided by CT hepatic arteriography (CTHA) at the Affiliated Cancer Hospital of Zhengzhou University from March 2020 to September 2021 were retrospectively analyzed, including 21 males and 11 females, aged (53.2±9.9) years old. Before ablation, the angiography catheter were placed in the common or proper hepatic artery under the digital subtraction angiography (DSA). The patients were then transferred to a CT operating room. Under general anesthesia, contrast agent was injected into the indwelling angiography catheter and percutaneous radiofrequency ablation guided by CTHA was performed. The presentation of lesions, the dosage of contrast agent and complications during ablation were analyzed, and the treatment outcome was followed up outpatient or inpatient review.Results:All 32 patients uneventfully underwent DSA-guided angiography catheter placement, and CTHA-guided radiofrequency ablation was successfully performed in 97 lesions, with a technical success rate of 100% (97/97). The difference between CT values at the lesion enhancement site and peri-tumor hepatic parenchyma were greater than 25 HU. The total amount of contrast agent used during the procedure was 63.9±14.7 ml. All ablation-related complications were graded as A or B according to the Society of Interventional Radiology classification system. The complete ablation rate assessed by CTHA after the ablation was 100% (97/97). The rate of lesion necrosis was 100% evaluated by MRI one month after ablation. All patients were followed up and no recurrence was observed in 97 ablated lesions by the end of follow-up period.Conclusion:Radiofrequency ablation guided by CTHA is safe and feasible for the treatment of multiple nodular liver metastases of colorectal cancer, which could reduce the local recurrence of lesions after ablation.

Short-term effectiveness of calcaneal lateral displacement osteotomy with lateral ligament repair in treatment of Takakura stage Ⅱ varus-type ankle arthritis / 中国修复重建外科杂志

OBJECTIVE@#To investigate the short-term effectiveness of calcaneal lateral displacement osteotomy with lateral ligament repair in the treatment of Takakura stage Ⅱ varus-type ankle arthritis.@*METHODS@#A retrospective analysis was performed on the clinical data of 13 patients with Takakura stage Ⅱ varus-type ankle arthritis treated with calcaneal lateral displacement osteotomy with lateral ligament repair between January 2016 and December 2020. There were 6 males and 7 females aged 31-65 years, with an average age of 53.6 years. The preoperative tibial-ankle surface angle (TASA) was (88.13±1.01)°, medial distal tibial angle (MDTA) was (86.36±1.49)°, tibial talar surface angle (TTSA) was (6.03±1.63)°, talar tilting angle (TTA) was (81.95±2.15)°, and tibiocalcaneal axis angle (TCAA) was (-5.74±6.81)°. The preoperative American Orthopedic Foot and Ankle Society (AOFAS) score was 56.3±7.1 and the pain visual analogue scale (VAS) score was 3.7±0.5. AOFAS scores, VAS scores, TTSA, TTA, and TCAA were compared between pre- and post-operatively.@*RESULTS@#All 13 patients were followed up 14-41 months, with an average of 28.7 months. The osteotomies healed in all patients. The last follow-up revealed TTA, TTSA, and TCAA to be (88.27±1.19)°, (-0.13±1.37)°, and (2.09±5.10)° respectively, the AOFAS score was 84.3±4.2 and the VAS score was 0.7±0.5, all showing significant improvement when compared to preoperative values ( P<0.05).@*CONCLUSION@#For patients with Takakura stage Ⅱ varus-type ankle arthritis, calcaneal lateral displacement osteotomy with lateral ligament repair can correct the lower limb force line, regain ankle stability, and achieving good short-term effectiveness.

Clinical study of the CT hepatic arteriography guided percutaneous radiofrequency ablation of hypervascular hepatocellular carcinoma / 中华放射学杂志

Objective:To investigate the feasibility of CT hepatic arteriography(CTHA) guided percutaneous radiofrequency ablation of hepatocellular carcinoma (HCC).Methods:Forty-four patients diagnosed with hepatocellular carcinomas were enrolled in this prospective study from September 2019 to May 2021 in Henan Cancer Hospital. Thirty-three out of the 44 patients were treatment naive, 8 cases recurred after radiofrequency ablation, and the other 3 patients recurred after surgery. The mean size of HCC nodules was 5-44(17±8)mm measured on enhanced MRI images. Each patient was implanted a 5-French Cobra catheter or a 5-French RH angiographic catheter, then was catheterized into common hepatic artery or proper hepatic artery, under DSA monitoring via right femoral artery. Then the patient was transferred to CT operation room. Percutaneous radiofrequency ablation was performed by CTHA guidance using contrast agent injected via the catheter indwelled in hepatic artery. The endpoint of a complete ablation was a non-enhancing ablation necrosis zone in the target tumor and the target tumor margin at least 5 mm on CTHA. At the end of the procedure, the probe was retracted using tract ablation, and the arterial catheter and sheath were removed. The number of HCC lesions showed on the enhanced MRI and CTHA imaging were compared using Wilcoxon rank-sum test. The technical success rate and volume of contrast agent used during the CTHA ablation procedures were summarized.Results:Additional tumors were founded in 13 out of the 44 patients during the CT hepatic arteriography compared with enhanced MRI. The tumors founded by enhanced MRI and CTHA were 64 and 91 respectively, with statistical significance ( Z=-3.24, P=0.001). One patient dropped out of the study after palliative ablation and was transferred to transaterial chemoembolization treatment because the number of lesions showed by CTHA scan was more than 5. The other 43 patients got complete ablation verified by immediate postoperative assessment using CTHA. The technical success rate was 100%. The average volume of contrast agent used in CTHA guided radiofrequency ablation was 30-80(42±14)ml. There was no complications occurred related to the CTHA guided percutaneous radiofrequency ablation procedures. Conclusions:CTHA can demonstrate additional lesions that can not be detected by the enhanced MRI images, which improves the lesion conspicuity and verifies the optimal position of radiofrequency probe. The complete tumor ablation can be verified by CTHA performed immediately after ablation.

An Intelligent Arch Diagnostic Method Based on Principal Component Analysis of Plantar Pressure Distribution / 医用生物力学

Objective According to clinical demand of quantification evaluation on flat foot and high arch, an intelligent and rapid method to diagnose arch shape based on principal component analysis (PCA) of plantar pressure is proposed, and its clinic validity is tested. Methods Volunteers diagnozed as abnormal arch and healthy arch were included in this study, and a portable intelligent arch test system was designed and developed. By adopting thin-firm piezoresistive sensor array with 44 rows, 52 columns of sensing units, the system could collect plantar pressure distribution data from the subjects under static standing. Foot axis could be fitted automatically by using the self-programmed PCA, so that foot diagnosis was completed with diagnostic report. The plantar pressure results from the system were compared with those from the existing plantar pressure acquisition device, so as to verify precision of collected data. The accuracy of the diagnosis algorithm for flat foot, high arch and healthy foot was verified through comparison with clinical diagnosis. Results The result of the system had a good correlation with that of the existing plantar pressure acquisition device, the deviation of contact area acquired by the system was smaller than 3.2%, and the angle deviation of the fitted foot axis with clinically defined angel was less than 1°. The system was capable of making diagnosis on arch shape that was 92.6% consistent with the clinical diagnosis. Conclusions PCA is introduced to automatically fit foot axis to achieve the purpose of fast and accurate extraction of foot arch information. The method can be used to assist clinical diagnosis of flat foot and high arch foot, and contribute to quantative analysis on foot arch deformity and its pathogenesis study.

Impact of probiotics supplement on the gut microbiota in neonates with antibiotic exposure: an open-label single-center randomized parallel controlled study.

BACKGROUND: Antibiotics, a common strategy used for neonatal infection, show consistent effect on the gut microbiota of neonates. Supplementation with probiotics has become increasingly popular in mitigating the loss of the gut microbiota. However, no clear consensus recommending the use of probiotics in the infection of neonates currently exists. This study examined the effects of probiotics on the gut microbiota of infectious neonates when used concurrently with or during the recovery period following antibiotic therapy. METHODS: Fifty-five full-term neonates diagnosed with neonatal infections were divided into the following groups: NI (no intervention, antibiotic therapy only), PCA (probiotics used concurrently with antibiotics), and PAA (probiotics used after antibiotics). The NI group received antibiotic treatment (piperacillin-tazobactam) for 1 week and the PCA group received antibiotic treatment together with probiotics (Bifidobacterium longum, Lactobacillus acidophilus, and Enterococcus faecalis) for 1 week. The PAA group received antibiotic treatment for 1 week followed by probiotics for 1 week. Fecal samples were collected at four time nodes: newborn, 1 week, 2 weeks, and 42 days after birth. The composition of the gut microbiota was determined by the high-throughput sequencing of 16S rRNA amplicons. RESULTS: Antibiotic exposure was found to dramatically alter gut microbiota, with a significant decrease of Bifidobacterium and Lactobacillus. The use of probiotics did not restore the overall diversity of the gut microbiota. However, using probiotics simultaneously with the antibiotics was found to be beneficial for the gut microbiota as compared to delaying the use of probiotics to follow treatment with antibiotics, particularly in promoting the abundance of Bifidobacterium. CONCLUSIONS: These results suggest that the early use of probiotics may have a potential ability to remodel the gut microbiota during recovery from antibiotic treatment. However, further study is required to fully understand the long-term effects including the clinical benefits.

Verification of SARS-CoV-2-Encoded small RNAs and contribution to Infection-Associated lung inflammation

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus that causes coronavirus disease 2019 (COVID-19), the respiratory illness responsible for the COVID-19 pandemic. SARS-CoV-2 is a positive-stranded RNA virus belongs to Coronaviridae family. The viral genome of SARS-CoV-2 contains around 29.8 kilobase with a 5'-cap structure and 3'-poly-A tail, and shows 79.2% nucleotide identity with human SARS-CoV-1, which caused the 2002-2004 SARS outbreak. As the successor to SARS-CoV-1, SARS-CoV-2 now has circulated across the globe. There is a growing understanding of SARS-CoV-2 in virology, epidemiology, and clinical management strategies. In this study, we verified the existence of two 18-22 nt small viral RNAs (svRNAs) derived from the same precursor in human specimens infected with SARS-CoV-2, including nasopharyngeal swabs and formalin-fixed paraffin-embedded (FFPE) explanted lungs from lung transplantation of COVID-19 patients. We then simulated and confirmed the formation of these two SARS-CoV-2-Encoded small RNAs in human lung epithelial cells. And the potential pro-inflammatory effects of the splicing and maturation process of these two svRNAs in human lung epithelial cells were also explored. By screening cytokine storm genes and the characteristic expression profiling of COVID-19 in the explanted lung tissues and the svRNAs precursor transfected human lung epithelial cells, we found that the maturation of these two small viral RNAs contributed significantly to the infection associated lung inflammation, mainly via the activation of the CXCL8, CXCL11 and type I interferon signaling pathway. Taken together, we discovered two SARS-CoV-2-Encoded small RNAs and investigated the pro-inflammatory effects during their maturation in human lung epithelial cells, which might provide new insight into the pathogenesis and possible treatment options for COVID-19.

Effects of high-flux hemodialysis combined with levocarnitine on vascular calcification, microinflammation, hepcidin, and malnutrition of elderly patients on maintenance hemodialysis.

BACKGROUND: This study was to investigate the effect of high-flux hemodialysis (HD) combined with levocarnitine on vascular calcification, microinflammation, hepcidin, and malnutrition in elderly patients on maintenance HD (MHD). METHODS: 75 MHD elderly patients admitted to hospital between 1st September 2017 and 31st August 2019 were selected as the study subjects. They were randomly divided by digital table into three groups: low-flux group (n=25), high-flux group (n=25) and joint group (n=25). In the low-flux group, dialyzer had an ultrafiltration coefficient 12 mL/(h·mmHg) and effective surface area of 1.4 m2 compared with 59 mL/(h·mmHg) and 1.8 m2 in the high-flux group. After treatment, the calcification of blood vessels was examined by lateral X-ray, pelvic plain film and bilateral positive position. For patients in all groups, the concentrations of parathyroid hormone (PTH) and ß 2-microglobulin (ß 2-MG) in serum were measured by automatic chemiluminescence; levels of interleukin-6, C-reactive protein (CRP), and tumor necrosis factor alpha (TNF-α) were measured by ELISA before and after treatment; and the level of hepcidin was measured by ELISA. Before and 12 weeks after the treatment, the nutritional status of the patients was evaluated by modified quantitative subjective global assessment (MQSGA), hemoglobin (Hb) and red blood cell count (RBC). Complications in the three groups were recorded, including nausea, chest pain, hypotension, hypertension, pruritus, dry heat, muscle spasm, arrhythmia, and restless legs. RESULTS: Vascular calcification in the joint group was better than the low-flux and high-flux groups (P<0.05). After treatment, the serum PTH and ß 2-mg concentrations in the joint group were lower than those in the other two groups (P<0.05), and the levels of IL-6, CRP, TNF-α and hepcidin in the joint group were significantly lower than those before treatment (P<0.05). After treatment, the MQSGA scores in the joint group were lower than those in the low-flux and high-flux groups (P<0.05), and Hb and RBC were higher (P<0.05). CONCLUSIONS: The combination of high-flux HD and levocarnitine in elderly patients on MHD can increase the clearance of medium and large molecular toxins, effectively correct malnutrition, alleviate microinflammation, delay the progress of vascular calcification, and is safe.

Impairment of type H vessels by NOX2-mediated endothelial oxidative stress: critical mechanisms and therapeutic targets for bone fragility in streptozotocin-induced type 1 diabetic mice.

Rationale: Mechanisms underlying the compromised bone formation in type 1 diabetes mellitus (T1DM), which causes bone fragility and frequent fractures, remain poorly understood. Recent advances in organ-specific vascular endothelial cells (ECs) identify type H blood vessel injury in the bone, which actively direct osteogenesis, as a possible player. Methods: T1DM was induced in mice by streptozotocin (STZ) injection in two severity degrees. Bony endothelium, the coupling of angiogenesis and osteogenesis, and bone mass quality were evaluated. Insulin, antioxidants, and NADPH oxidase (NOX) inhibitors were administered to diabetic animals to investigate possible mechanisms and design therapeutic strategies. Results: T1DM in mice led to the holistic abnormality of the vascular system in the bone, especially type H vessels, resulting in the uncoupling of angiogenesis and osteogenesis and inhibition of bone formation. The severity of osteopathy was positively related to glycemic levels. These pathological changes were attenuated by early-started, but not late-started, insulin therapy. ECs in diabetic bones showed significantly higher levels of reactive oxygen species (ROS) and NOX 1 and 2. Impairments of bone vessels and bone mass were effectively ameliorated by treatment with anti-oxidants or NOX2 inhibitors, but not by a NOX1/4 inhibitor. GSK2795039 (GSK), a NOX2 inhibitor, significantly supplemented the insulin effect on the diabetic bone. Conclusions: Diabetic osteopathy could be a chronic microvascular complication of T1DM. The impairment of type H vessels by NOX2-mediated endothelial oxidative stress might be an important contributor that can serve as a therapeutic target for T1DM-induced osteopathy.

In Situ Regulation of Macrophage Polarization to Enhance Osseointegration Under Diabetic Conditions Using Injectable Silk/Sitagliptin Gel Scaffolds.

As a chronic inflammatory disease, diabetes mellitus creates a proinflammatory microenvironment around implants, resulting in a high rate of implant loosening or failure in osteological therapies. In this study, macroporous silk gel scaffolds are injected at the bone-implant interface for in situ release of sitagliptin that can regulate macrophage response to create a prohealing microenvironment in diabetes mellitus disease. Notably, it is discovered that sitagliptin induces macrophage polarization to the M2 phenotype and alleviates the impaired behaviors of osteoblasts on titanium (Ti) implants under diabetic conditions in a dose-dependent manner. The silk gel scaffolds loaded with sitagliptin elicite a stronger recruitment of M2 macrophages to the sites of Ti implants and a significant promotion of osteointegration, as compared to oral sitagliptin administration. The results suggest that injectable silk/sitagliptin gel scaffolds can be utilized to modulate the immune responses at the bone-implant interface, thus enhancing bone regeneration required for successful implantation of orthopedic and dental devices in diabetic patients.

Promotion of osteointegration under diabetic conditions by a silk fibroin coating on 3D-printed porous titanium implants via a ROS-mediated NF-κB pathway.

Clinical evidence indicates the compromised application of titanium implants (TIs) in diabetics, associated with reactive oxygen species (ROS) overproduction at the bone-implant interface. Silk fibroin (SF) has displayed impressive biocompatibility in the application of biomedical material and optimal anti-diabetic effects in oriental medicine. We proposed that SF-coated titanium implants (STIs) could alleviate diabetes-induced compromised osteointegration, which has rarely been reported before. To confirm this hypothesis and explore the underlying mechanisms, rat osteoblasts cultured on 3-dimensional (3D) -printed titanium implants (TIs) and STIs were subjected to normal serum (NS), diabetic serum (DS), DS with N-acetyl-L-cysteine (a ROS inhibitor) or SN50 (an NF-κB inhibitor). Anin vivostudy was performed on diabetic sheep with TIs or STIs implanted into bone defects on thecrista iliaca. The results demonstrated that ROS overproduction induced by diabetes lead to osteoblast dysfunctions and cellular apoptosis on the TI substrate, associated with the activation of an NF-κB signaling pathway in osteoblasts. Importantly, the STI substrate significantly attenuated ROS production and NF-κBp65 phosphorylation, thereby ameliorating the osteoblast biological dysfunctions. These results were further confirmedin vivoby the improved osteointegration of the STIs, as evidenced by Micro-CT and histological examinations compared with those of TIs. These results demonstrated that the ROS-mediated NF-κB signaling pathway played a crucial role in diabetes-induced implant destabilization. Importantly, the SF coating, as a promising material for biomaterial-engineering, markedly improved the clinical treatment effect of TIs under diabetic conditions, possibly associated with the suppression of the NF-κB pathway.

All-Aqueous-Processed Injectable In Situ Forming Macroporous Silk Gel Scaffolds for Minimally Invasive Intracranial and Osteological Therapies.

Hydrogels are widely utilized in regenerative medicine for drug delivery and tissue repair due to their superior biocompatibility and high similarity to the extracellular matrix. For minimally invasive therapies, in situ forming gel scaffolds are desirable, but technical challenges remain to be overcome to achieve the balance between tissue-like strength and cell-sized porosity, especially for intracranial and osteological therapies. Here, a new method-inspired by the liquid crystalline spinning process in natural silk fibers-is reported for preparing injectable silk gel scaffolds with favorable preclinical efficacy and unique characteristics including 1) in situ gelling for minimally invasive surgeries, 2) controllable porosity for efficient cellular infiltration and desirable degradation, 3) resilient and tunable mechanical properties that are compatible with the modulus regime of native soft tissues, and 4) all-aqueous processing that avoids toxic solvents and enables facile loading of bioactive agents. Moreover, hierarchically structured heterogeneous silk gel scaffolds with variable porosity and bioactive agent gradients within 3D matrices can be achieved for sustained drug release and guided tissue regeneration. Preclinical efficacy studies in rodent models show efficient bacterium and glioma inhibition and positive effects on bone regeneration and vascularization.

The impact of sitagliptin on macrophage polarity and angiogenesis in the osteointegration of titanium implants in type 2 diabetes.

BACKGROUND: Clinical evidence indicates that sitagliptin treatment improves bone quality in diabetic patients, but the mechanisms involved remain elusive. Here, we studied the role of angiogenesis with sitagliptin treatment in diabetes-induced poor osteointegration of titanium implants and the underlying mechanisms. METHODS: In vitro, Human Umbilical Vein Endothelial Cells (HUVECs) incubated on titanium (Ti) surface were subjected to 1) normal milieu (NM); 2) diabetic milieu (DM); 3) DM + sitagliptin; 4) NM + macrophage; 5) DM + macrophage; or 6) DM + macrophage + sitagliptin. Microphage and HUVECs were cultured alone or co-cultured in a Transwell system. In vivo, DM was induced by high-fat diet and administration of streptozotocin (STZ) in rats. Titanium screws were implanted in the femurs of rats in three groups: Control, DM, Sitagliptin-treated DM. RESULTS: In vitro, when cells were incubated alone, DM caused M1 polarization of macrophage, evidenced by the increased iNOS and decreased CD206 expressions, and obvious dysfunctions of HUVECs. The DM-induced injury of endothelial cells were significantly worsened when the two cells were co-cultured. The addition of sitagliptin markedly reversed the changes of macrophage but not of HUVECs in DM when cells were cultured alone. When cells co-cultured, however, both the abnormal macrophage polarization and the endothelial impairment in DM was significantly alleviated by sitagliptin. In vivo, compared with normal animals, DM animals showed imbalanced M1/M2 polarization, angiogenesis inhibition and poor bone formation on the bone-implant interface (BII), which were significantly ameliorated by sitagliptin treatment. CONCLUSION: Our results demonstrate macrophage polarization imbalance as a crucial mechanism underlying the impaired angiogenesis and bone healing in diabetes, and provide sitagliptin as a promising novel drug for biomaterial-engineering to improve the osteointegration of titanium implants in diabetic patients.

Expert consensus on integration program for cervical cancer screening and management measures for abnormal population / 医学研究生学报

Cervical cancer is a kind of malignant tumor that seriously endangers women's health. Cervical cancer has a clear etiology and easy sampling, which can be early detected by screening, and its development can be blocked by early intervention. Cervical cancer screening has been launched for rural women since 2009 in China in order to reduce the incidence of cervical cancer. However, the incidence of cervical cancer has not significantly reduced after ten years. There are three common pain points in the current cervical cancer screening program, including inaccurate sampling, invalid management and no integrated technology. The resolution of these problems will promote the development of cervical cancer screening and the establishment of the long-term mechanism of the prevention and treatment system in China. On the basis of previous studies and in combination with our innovative technologies, we put the observation function of colposcope on the first step for the screening of cervical cancer, which not only ensures accurate sampling, but also further integration of VIA/VILI, HPV typing, liquid-based cytology (TCT) and p16/ki-67 to improve the detection rate of cervical cancer and reduce false negatives. Those women in high-risk groups found by screening can be automatically followed up and given medical advices in the intelligent medical and health management platform for cervical cancer screening. Through repeatedly discussion by expert committee, we put forward expert consensus (2019) for early cervical cancer screening and abnormal crowd management in China. This expert consensus can help doctors in scientific research, clinical practice and the establishment of national policy of cervical cancer screening. We will continuously provide more data to improve cervical cancer screening process in the future.

Investigation of the replacement of obstructed double J tube in ureter under X-ray guidance / 中华放射学杂志

Objective:To investigate the feasibility and safety of the X-ray guided obstructive double J tube replacement in ureter.Methods:The clinical data of 44 patients with double J tube obstruction who underwent double J tube replacement from April 2016 to August 2019 were analyzed retrospectively. Among the 44 cases, there were 3 males and 41 females, aged from 27.0 to 70.0 (54.6±11.2) years. The time since last double J tube placement, the method of transurethral remove of double J tube, the method of double J tube replacement, the location of double J tube obstruction and postoperative complications were collected, and the success rate of operation was calculated. According to the different positions of calcium salt deposition in double J tubes, the obstructive double J tubes were divided into bladder end type, renal pelvis end type, two-end type and whole partial type. The replacement method was differentiated according to different types of double J tube obstruction. The cut-off end method was to cut off the obstructed bladder end of double J tube by scissors, and the internal unobstructed double J tube could be seen. The guide wire could be introduced into the renal pelvis through the double J tube, and the new double J tube could be replaced. This method was only used for bladder end type double J tube obstruction. The thine guide wire method was to replace the common guide wire which could not pass through the renal pelvis end obstruction with the microguide wire, so that it could pass through the end of the double J tube of the renal pelvis end obstruction or through the side hole, enter into the renal pelvis, withdraw the original double J tube, and then replace the new double J tube. This method was suitable for renal pelvis end type double J tube obstruction, or combined with cut-off end method for two-end type double J tube obstruction. In the auxiliary sheath method, the obstructed double J tube was used as the support, the vascular sheath tube was sent into the ureter, and the guide wire was sent to the renal pelvis through the sheath tube to replace the new double J tube. This method was suitable for all types of double J tube obstruction.Results:A total of 47 X-ray-guided double J tube replacements were performed in 44 patients. In the removal of double J tube, 37 cases of direct method and 10 cases of indirect method were used, and the overall success rate of double J tube removal was 100% (47/47). The time from the last double J tube placement was (4.2±1.3) months. There were 23 cases of bladder end type obstruction, 8 cases of renal pelvis end obstruction, 5 cases of two-end type obstruction, and 11 cases of whole partial type obstruction.The success rate of replacing double J tubes by cut-off end method, thin guide wire method and auxiliary sheath method was 76.0% (19/25), 50.0% (2/4) and 77.8% (14/18), respectively. After the failure of the cut-off end method or the thin guide wire method, 4 cases were further replaced by the thin guide wire method or auxiliary sheath method, and 3 cases were successful. Therefore, the overall success rate of double J tube replacement was 80.9% (38/47). The double J tubes were inserted by percutanous pyelostomy in 9 patients who failed to replace double J tube successfully. Among the 44 cases, there were 4 cases of urethral orifice pain and discomfort, and 2 cases of gross hematuria, all of which relieved spontaneously.Conclusion:It is feasible and safe to replace the obstructive double J tube in ureter under X-ray guidance.

Nail Gun Injury of the Spine: Case Report and Review of the Literature.

BACKGROUND: Since the first report about nail gun injuries in 1959, there has been an average of approximately 37,000 patients hurt by nail guns and treated in emergency departments. Carotid arterial injury by nail gun has been reported, but vertebral artery damage is extremely rare. CASE DESCRIPTION: A 42-year-old man was transported to the emergency department after suffering an accidental self-inflicted nail gun injury to the left lateral aspect of his neck. Radiographic imaging of the cervical spine revealed a 3.1-cm metallic nail in the C5 region. A computed tomography (CT) angiogram revealed the nail passing through the left C5 transverse foramen and compressing the left vertebral artery. He was immediately brought to the operating room for removal of the nail. At 1-month follow-up, the patient did not have any neck complaints and postoperative CT angiogram indicated the patient was asymptomatic with no signs of complication or infection. CONCLUSIONS: Based on our experience and a review of the literature, in terms of treating a nail gun injury to the cervical spine, we would like emphasize that preoperative CT scan or CT angiogram is necessary to assess the location and shape of the nail, especially nails with barbers or washers. Improving awareness of the risk from accidental nail gun trauma may lead to better prevention of this rare but potentially life-threatening injury.