Study of the optic nerve in patients with type 2 diabetic retinopathy by shear-wave elastography.

AIM: To investigate the clinical value of two-dimensional shear-wave elastography (2D-SWE) in detecting optic nerve elasticity and in-frame adipose tissue elasticity in patients with type 2 diabetic retinopathy (DR). MATERIALS AND METHODS: 2D-SWE was used to detect SWE values of the optic nerve and adipose tissue in adjacent optic nerve frames in 30 healthy participants, 30 patients with diabetic non-retinopathy (NDR), 35 patients with non-proliferative diabetic retinopathy (NPDR), and 30 patients with proliferative diabetic retinopathy (PDR). The correlation between SWE values and blood glucose, blood lipid, age, body mass index (BMI) was analysed. Receiver operating characteristic (ROC) curve analysis was performed for SWE values. RESULTS: The SWE values of the optic nerve and in-frame adipose tissue increased with the progression of DR, and analysis of variance was compared with groups: the SWE values of the optic nerve and in-frame adipose tissue in each group were significantly different (all p<0.001). The SWE values of the optic nerve and in-frame adipose tissue correlated positively with BMI, age, triglyceride, and fasting blood glucose, and correlated negatively with high-density lipoprotein. The SWE values of the optic nerve and in-frame adipose tissue had higher diagnostic efficacy. The combination of the two had higher diagnostic accuracy. CONCLUSION: The elastic modulus of optic nerve and in-frame adipose tissue can effectively predict and grade of DR, that is, 2D-SWE can be used as a non-invasive imaging diagnostic method for DR. The combined diagnostic efficacy of optic nerve SWE value and in-frame adipose tissue SWE value is significantly better than that of single use. This study found that increased BMI, age, triglyceride, and fasting blood glucose, and decreased high-density lipoprotein are risk factors for DR.

[Analysis of factors associated with futile recanalization after endovascular treatment for acute ischemic stroke with large vessels occlusion in anterior intracranial circulation].

Objective: To analyze the related factors of futile recanalization (FR) after emergency endovascular treatment of large artery occlusion in anterior circulation. Methods: Three studies on endovascular treatment of acute anterior circulation large vessels occlusion stroke were selected, and their data were merged for retrospective analysis. Patients were divided into the FR group and favorable prognosis group according to the functional prognosis. Risk factor analysis was conducted using multivariate logistic regression. Results: A total of 1 581 patients were finally included, with 858 (48.9%) patients in favorable prognosis group and 926 (51.91%) patients in FR group. Among them, there were 939 males and 642 females, with a mean age of (65±12) years. Multivariate logistic regression analysis showed that National Institute of Health Stroke Scale (NIHSS) score (OR=1.089,95%CI:1.066-1.113), puncture to recanalization time (OR=0.756, 95%CI:0.586-0.971), age (OR=1.04,95%CI:1.029-1.051), serum glucose (OR=1.101,95%CI:1.062-1.143), systolic blood pressure (OR=1.005,95%CI:1.001-1.010), passes≥3(OR=1.941,95%CI:1.294-2.941)Alberta stroke program early CT (ASPECT) score (OR=0.919,95%CI:0.847-0.996), occlusion site (M1 segment of middle cerebral artery, OR=0.744,95%CI:0.565-0.980) and collateral circulation [(2 points, OR=0.757, 95%CI:0.581-0.985); (3-4 points, adjusted OR=0.640, 95%CI: 0.472-0.866)] were independent factors of FR. Conclusion: The incidence of FR in patients with large artery occlusion in anterior circulation who achieve satisfied reperfusion after endovascular treatment is high. Higher NIHSS score, longer puncture to recanalization time, older age, higher serum glucose and systolic blood pressure are risk factors, while lower ASPECTS, occlusion in cerebral middle M1 segment, better collateral circulation are protective factors.

DWI-Based Radiomics Predicts the Functional Outcome of Endovascular Treatment in Acute Basilar Artery Occlusion.

BACKGROUND AND PURPOSE: Endovascular treatment is a reference treatment for acute basilar artery occlusion (ABAO). However, no established and specific methods are available for the preoperative screening of patients with ABAO suitable for endovascular treatment. This study explores the potential value of DWI-based radiomics in predicting the functional outcomes of endovascular treatment in ABAO. MATERIALS AND METHODS: Patients with ABAO treated with endovascular treatment from the BASILAR registry (91 patients in the training cohort) and the hospitals in the Northwest of China (31 patients for the external testing cohort) were included in this study. The Mann-Whitney U test, random forests algorithm, and least absolute shrinkage and selection operator were used to reduce the feature dimension. A machine learning model was developed on the basis of the training cohort to predict the prognosis of endovascular treatment. The performance of the model was evaluated on the independent external testing cohort. RESULTS: A subset of radiomics features (n = 6) was used to predict the functional outcomes in patients with ABAO. The areas under the receiver operating characteristic curve of the radiomics model were 0.870 and 0.781 in the training cohort and testing cohort, respectively. The accuracy of the radiomics model was 77.4%, with a sensitivity of 78.9%, specificity of 75%, positive predictive value of 83.3%, and negative predictive value of 69.2% in the testing cohort. CONCLUSIONS: DWI-based radiomics can predict the prognosis of endovascular treatment in patients with ABAO, hence allowing a potentially better selection of patients who are most likely to benefit from this treatment.

Adaptive Hybrid Optimization Learning-Based Accurate Motion Planning of Multi-Joint Arm.

Motion planning is important to the automatic operation of the manipulator. It is difficult for traditional motion planning algorithms to achieve efficient online motion planning in a rapidly changing environment and high-dimensional planning space. The neural motion planning (NMP) algorithm based on reinforcement learning provides a new way to solve the above-mentioned task. Aiming to overcome the difficulty of training the neural network in high-accuracy planning tasks, this article proposes to combine the artificial potential field (APF) method and reinforcement learning. The neural motion planner can avoid obstacles in a wide range; meanwhile, the APF method is exploited to adjust the partial position. Considering that the action space of the manipulator is high-dimensional and continuous, the soft-actor-critic (SAC) algorithm is adopted to train the neural motion planner. By training and testing with different accuracy values in a simulation engine, it is verified that, in the high-accuracy planning tasks, the success rate of the proposed hybrid method is better than using the two algorithms alone. Finally, the feasibility of directly transferring the learned neural network to the real manipulator is verified by a dynamic obstacle-avoidance task.

Particle-sounding of the spatial structure of kinetic Alfvén waves.

Kinetic Alfvén waves (KAWs) are ubiquitous throughout the plasma universe. Although they are broadly believed to provide a potential approach for energy exchange between electromagnetic fields and plasma particles, neither the detail nor the efficiency of the interactions has been well-determined yet. The primary difficulty has been the paucity of knowledge of KAWs' spatial structure in observation. Here, we apply a particle-sounding technique to Magnetospheric Multiscale mission data to quantitatively determine the perpendicular wavelength of KAWs from ion gyrophase-distribution observations. Our results show that KAWs' perpendicular wavelength is statistically 2.4[Formula: see text] times proton thermal gyro-radius. This observation yields an upper bound of the energy the majority proton population can reach in coherent interactions with KAWs, that is, roughly 5.76 times proton perpendicular thermal energy. Therefore, the method and results shown here provide a basis for unraveling the effects of KAWs in dissipating energy and accelerating particles in a number of astrophysical systems, e.g., planetary magnetosphere, astrophysical shocks, stellar corona and wind, and the interstellar medium.

[The correlation between No. 6 and No. 14v lymph node metastasis and the value of dissecting these lymph nodes in radical gastrectomy].

Radical gastrectomy with D2 lymphadenectomy has been widely performed as the standard surgery for patients with gastric cancer in major medical centers in China and abroad. However, the exact extent of lymph node dissection is still controversial. In the latest version of the Japanese Gastric Cancer Treatment Guidelines, No. 14v lymph nodes (along the root of the superior mesenteric vein) are again defined as loco-regional lymph nodes, and it is clarified that distal gastric cancer presenting with infra-pyloric regional lymph node (No.6) metastasis is recommended for D2+ superior mesenteric vein (No. 14v) lymph node dissection. To explore the relevance and clinical significance of No.6 and No.14v lymphadenectomy in radical gastric cancer surgery, a review of the national and international literature revealed that No.6 lymph node metastasis was associated with No.14v lymph node metastasis, that No.6 lymph node status was a valid predictor of No.14v lymph node negative status and false negative rate, and that for gastric cancer patients with No. 14v lymph node negative and No.6 lymph node positive, the dissection of No.14v lymph node may also have some significance. The addition of No. 14v lymph node dissection in radical gastrectomy is safe, but it is more important to distinguish the patients who can benefit from it. Professor Liang Han of Tianjin Medical University Cancer Hospital is currently leading a multicenter, large-sample, prospective clinical trial (NCT02272894) in China, which is expected to provide higher level evidence for the clinical significance of lymph node dissection in No.14v.

Cost-effectiveness analysis of five drugs for treating postmenopausal women in the United States with osteoporosis and a very high fracture risk.

PURPOSE: Five strategies were recommended by the American Association of Clinical Endocrinologists/American College of Endocrinology (AACE/ACE) guidelines for the treatment of postmenopausal osteoporosis (PMO) patients with a very high fracture risk. We aimed to assess their cost-effectiveness in the United States (US). METHODS: A microsimulation Markov model was created to compare the cost-effectiveness of five treatment strategies, including zoledronate, denosumab, abaloparatide, teriparatide, and romosozumab in PMO patients with a recent fracture from the healthcare perspective of the US. The data used in the model were obtained from published studies or online resources. Base-case analysis, one-way deterministic sensitivity analysis (DSA) and probability sensitivity analysis (PSA) were conducted for 65-, 70-, 75-, and 80-year-old patients. RESULTS: In base case, at 65 years, zoledronate was the cheapest strategy. The incremental cost-effectiveness ratios (ICER, which represent incremental costs per QALY gained) of denosumab, teriparatide, abaloparatide, and romosozumab against zoledronate were $13,020/QALY (quality-adjusted years), $477,331 /QALY, $176,287/QALY, and $98,953/QALY, respectively. Under a willing-to-pay (WTP, which means the highest price a consumer will pay for one unit of a good of service) threshold of $150,000/QALY, denosumab and romosozumab were cost-effective against zoledronate. The PSA results showed that denosumab was the most cost-effective option with WTP thresholds of $50,000/QALY, $100,000/QALY and $150,000/QALY. The results were similar in other age groups. The DSA results indicated that the most common parameters that have important influence on the outcome were drug persistence, incidence of adverse events, the efficacy of drugs on hip fractures and the cost of the drug. CONCLUSION AND RELEVANCE: Among PMO patients with a very high fracture risk in the US, zoledronate is the cheapest strategy and denosumab is the most cost-effective choice among these five strategies.

Micro-LED with red-green-blue super-pixel integration for simultaneous display and optical near field communication.

This work presents a novel all-in-one Micro-LED pixel (µLEDP) technology by integrating red-green-blue super-pixels (RGBSP) in a single unit cell. Measurement results show that the proposed µLEDP delivers excellent optical and electrical characteristics, including wide color gamut (109% NTSC), wide correlated color temperature range (2831.7-10016.8 K), and high modulation system bandwidth (58-62 MHz). To the best of our knowledge, the proposed integrated µLEDP achieves the highest data rate compared to published results based on other multi-color low-capacitance high-bandwidth LEDs. The maximum simulated non-return-to-zero (NRZ) and 4-level pulse-amplitude-modulation (PAM-4) data rates of 0.3-Gb/s and 1.1-Gb/s, respectively.

Simultaneous macroscale and microscale wave-ion interaction in near-earth space plasmas.

Identifying how energy transfer proceeds from macroscales down to microscales in collisionless plasmas is at the forefront of astrophysics and space physics. It provides information on the evolution of involved plasma systems and the generation of high-energy particles in the universe. Here we report two cross-scale energy-transfer events observed by NASA's Magnetospheric Multiscale spacecraft in Earth's magnetosphere. In these events, hot ions simultaneously undergo interactions with macroscale (~[Formula: see text] km) ultra-low-frequency waves and microscale ([Formula: see text] km) electromagnetic-ion-cyclotron (EMIC) waves. The cross-scale interactions cause energy to directly transfer from macroscales to microscales, and finally dissipate at microscales via EMIC-wave-induced ion energization. The direct measurements of the energy transfer rate in the second event confirm the efficiency of this cross-scale transfer process, whose timescale is estimated to be roughly ten EMIC-wave periods about (1 min). Therefore, these observations experimentally demonstrate that simultaneous macroscale and microscale wave-ion interactions provide an efficient mechanism for cross-scale energy transfer and plasma energization in astrophysical and space plasmas.

[The level distribution of serum AMH in different clinical manifestations of women of childbearing age].

To investigate the distribution and diagnostic value of serum anti-Müllerian hormone (AMH) in healthy women of childbearing age, women with polycystic ovary syndrome (PCOS), ovarian dysfunction (DOR) and premature ovarian failure (POF). This study retrospectively selected female patients of childbearing age who were treated in the affiliated Obstetrics and Gynecology Hospital of Fudan University from January to December 2019. According to different clinical manifestations, they were divided into 133 cases in PCOS group, 120 cases in DOR group and 134 cases in POF group. 125 healthy women in the same period were selected as the control group. The values of serum AMH, estradiol (E2), follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone (T) were measured in the four groups. Single sample Kolmogorov-Smirnov test, one-way ANOVA, independent sample t-test, Kruskal-Wallis H test, Mann-Whitney U test, logistic regression analysis and ROC curve were used for comparative analysis. The serum AMH levels of PCOS group, DOR group, POF group and control group were 9.10 (6.67, 11.49) ng/ml, 0.11 (0.05, 0.29) ng/ml, 0.03 (0.02, 0.06) ng/ml and 2.99 (1.57, 4.98) ng/ml, respectively [M(Q1,Q3)], the differences were statistically significant (P<0.001). The basal endocrine levels including E2, FSH, LH and T also had significant differences between groups (P<0.001). The results of multiple comparisons showed that there were significant differences in AMH and LH between DOR, POF and PCOS groups and the control group. The T level of PCOS group was significantly higher than that of the control group, the E2, LH and T levels of DOR group were significantly higher than that of the control group, and the FSH level of POF group was significantly higher than that of the control group (P<0.05). The area under the curve (AUC) of AMH and AMH+LH in the diagnosis of PCOS were 0.905 and 0.922, the sensitivity was 82.7% and 85.0%, and the specificity was 88.0% and 88.8%. The AUC of DOR was 0.861 and 0.971, the sensitivity was 89.0% and 92.5%, and the specificity was 63.0% and 92.0%. The AUC of POF was 0.950 and 0.998, the sensitivity was 98.3% and 99.2%, and the specificity was 75.9% and 97.0%, respectively. The AUC of AMH and AMH+LH combined indexes in the differential diagnosis of DOR and POF were 0.768 and 0.937, the sensitivity was 70.3% and 95.5%, and the specificity was 73.9% and 80.8%.

[Surgical management of nipple areola complex in central breast cancer].

Objective: To explore the surgical strategy of nipple areola complex (NAC) management in central breast cancer. Methods: A retrospective analysis was conducted on 164 cases of central breast cancer who underwent surgery treatment from December 2017 to December 2020 in the Breast Center of Beijing Tongren Hospital, Capital Medical University. Prior to the surgery, the tumor-nipple distance (TND) and the maximum diameter of the tumor were measured by magnetic resonance imaging (MRI). The presence of nipple invagination, nipple discharge, and nipple ulceration (including nipple Paget's disease) were recorded accordingly. NAC was preserved in patients with TND≥0.5 cm, no signs of NAC invasion (nipple invagination, nipple ulceration) and negative intraoperative frozen pathological margin. All patients with signs of NAC involvement, TND<0.5 cm or positive NAC basal resection margin confirmed by intraoperative frozen pathology underwent NAC removal. χ(2) test or Fisher exact test was used to analyze the influencing factors. Results: Of the 164 cases of central breast cancer, 73 cases underwent breast-conserving surgery, 43 cases underwent nipple-areola complex sparing mastectomy (NSM), 34 cases underwent total mastectomy, and the remaining 14 cases underwent skin sparing mastectomy (SSM). Among the 58 cases of NAC resection (including 34 cases of total mastectomy, 14 cases of SSM, and 10 cases of breast-conserving surgery), 25 cases were confirmed tumor involving NAC (total mastectomy in 12 cases, SSM in 9 cases, and breast-conserving surgery in 4 cases). The related factors of NAC involvement included TND (P=0.040) and nipple invagination (P=0.031). There were no correlations between tumor size (P=0.519), lymph node metastasis (P=0.847), bloody nipple discharge (P=0.742) and NAC involvement. During the follow-up period of 12 to 48 months, there was 1 case of local recurrence and 3 cases of distant metastasis. Conclusions: For central breast cancer, data suggest that patients with TND≥0.5cm, no signs of NAC invasion (nipple invagination, nipple ulceration) and negative NAC margin in intraoperative frozen pathology should be treated with NAC preservation surgery, whereas for those with TND<0.5 cm or accompanied by signs of NAC invasion, NAC should be removed. In addition, nipple reconstruction can be selected to further improve the postoperative appearance of patients with central breast cancer.

Human Bone Marrow Stromal Cell Exosomes Ameliorate Periodontitis.

Human bone marrow stromal cell (hBMSC)-derived exosomes are promising therapeutics for inflammatory diseases due to their unique microRNA (miRNA) and protein cargos. Periodontal diseases often present with chronicity and corresponding exuberant inflammation, which leads to loss of tooth support. In this study, we explored whether hBMSC exosomes can affect periodontitis progression. hBMSC exosomes were isolated from cell culture medium through sequential ultracentrifugation. miRNAs and proteins that were enriched in hBMSC exosomes were characterized by RNA sequencing and protein array, respectively. hBMSC exosomes significantly suppressed periodontal keystone pathogen Porphyromonas gingivalis-triggered inflammatory response in macrophages in vitro. Transcriptomic analysis suggested that exosomes exerted their effects through regulating cell metabolism, differentiation, and inflammation resolution. In vivo, weekly exosome injection into the gingival tissues reduced the tissue destruction and immune cell infiltration in rat ligature-induced periodontitis model. Collectively, these findings suggest that hBMSC-derived exosomes can potentially be used as a host modulation agent in the management of periodontitis.

Observational evidence of ring current in the magnetosphere of Mercury.

The magnetic gradient and curvature drift of energetic ions can form a longitudinal electric current around a planet known as the ring current, that has been observed in the intrinsic magnetospheres of Earth, Jupiter, and Saturn. However, there is still a lack of observational evidence of ring current in Mercury's magnetosphere, which has a significantly weaker dipole magnetic field. Under such conditions, charged particles are thought to be efficiently lost through magnetopause shadowing and/or directly impact the planetary surface. Here, we present the observational evidence of Mercury's ring current by analysing particle measurements from MErcury Surface, Space Environment, GEochemistry, and Ranging (MESSENGER) spacecraft. The ring current is bifurcated because of the dayside off-equatorial magnetic minima. Test-particle simulation with Mercury's dynamic magnetospheric magnetic field model (KT17 model) validates this morphology. The ring current energy exceeds [Formula: see text] J during active times, indicating that magnetic storms may also occur on Mercury.

[Clinicopathological characteristics of SMARCB1(INI1)-deficient sinonasal carcinoma].

Objective: To investigate the clinicopathological characteristics, diagnosis, differential diagnosis and prognostic factors of SMARCB1 (INI1)-deficient sinonasal carcinoma (SDSC). Methods: Sixteen cases of SDSC diagnosed in the Department of Pathology, Beijing Tongren Hospital from January 2016 to September 2020 were enrolled. Ninety-nine cases of small round cell malignant tumors of the head and neck were selected as the control, including poorly-differentiated squamous cell carcinoma (n=10), poorly-differentiated adenocarcinoma (n=5), undifferentiated carcinoma (SNUC, n=4), NUT carcinoma (n=5), neuroendocrine carcinoma (n=10), and other non-epithelial tumors [olfactory neuroblastoma (n=10), rhabdomyosarcoma (n=10), NK/T-cell lymphoma (n=10), malignant melanoma (n=10), Ewing's sarcoma/primitive neuroectodermal tumor (EWS/PNET, n=5)] and non-keratinizing undifferentiated nasopharyngeal carcinoma (n=20). The clinical and pathologic characteristics of SDSC, and immunohistochemical (IHC) expression of broad-spectrum CKpan, CK7, CK8/18, CK5/6, p63, p40, p16, INI1, NUT and neuroendocrine markers (Syn, CgA, CD56) were evaluated. In situ hybridization (ISH) was used to detect EBER and fluorescence in situ hybridization (FISH) to detect INI1 gene deletion. Results: The 16 cases of SDSC accounted for 1.3% (16/1 218) of all malignant sinonasal tumors in the author's unit during this time period, and 2.4% (16/657) of all malignant epithelial tumors. Microscopically, there was no clear squamous and adenomatous differentiation, but "rhabdoid-like" cells, are often seen. All SDSC cases were positive for CKpan and CK8/18, negative for INI1; Epstein-Barr virus was not detected by ISH; and INI1 gene deletion was observed in all 11 SDSC patients with FISH. Twelve cases were followed up for 3-47 months. One died of tumor-related diseases half a year after diagnosis, and the remaining patients were alive with tumor, the longest survival time was 47 months. Conclusion: SDSC should be differentiated from a variety of poorly-differentiated tumors in the sinonasal area. Histologically, SDSC has no clear differentiation, but the tumor cells are characteristically basal-like or rhabdoid-like, with non-specific vacuoles, translucent or vacuolar nuclei, prominent nucleoli and necrotic foci. They are negative for INI1 IHC staining, and FISH demonstrates INI1 gene deletion. The clinical prognosis is still unclear, further studies on its biologic behavior and treatment methods are warranted.

Pathogenic ATM Mutations in Cancer and a Genetic Basis for Radiotherapeutic Efficacy.

BACKGROUND: Radiation therapy is one of the most commonly used cancer therapeutics but genetic determinants of clinical benefit are poorly characterized. Pathogenic germline variants in ATM are known to cause ataxia-telangiectasia, a rare hereditary syndrome notable for marked radiosensitivity. In contrast, somatic inactivation of ATM is a common event in a wide variety of cancers, but its clinical actionability remains obscure. METHODS: We analyzed 20 107 consecutively treated advanced cancer patients who underwent targeted genomic sequencing as part of an institutional genomic profiling initiative and identified 1085 harboring a somatic or germline ATM mutation, including 357 who received radiotherapy (RT). Outcomes of irradiated tumors harboring ATM loss-of-function (LoF) mutations were compared with those harboring variants of unknown significance. All statistical tests were 2-sided. RESULTS: Among 357 pan-cancer patients who received 727 courses of RT, genetic inactivation of ATM was associated with improved radiotherapeutic efficacy. The 2-year cumulative incidence of irradiated tumor progression was 13.2% vs 27.5% for tumors harboring an ATM LoF vs variant of unknown significance allele, respectively (hazard ratio [HR] = 0.51, 95% confidence interval [CI] = 0.34 to 0.77, P = .001). The greatest clinical benefit was seen in tumors harboring biallelic ATM inactivation (HR = 0.19, 95% CI = 0.06 to 0.60, P = .005), with statistically significant benefit also observed in tumors with monoallelic ATM inactivation (HR = 0.57, 95% CI = 0.35 to 0.92, P = .02). Notably, ATM LoF was highly predictive of outcome in TP53 wild-type tumors but not among TP53-mutant tumors. CONCLUSIONS: We demonstrate that somatic ATM inactivation is associated with markedly improved tumor control following RT. The identification of a radio-sensitive tumor phenotype across multiple cancer types offers potential clinical opportunities for genomically guided RT.

Sirt7 protects chondrocytes degeneration in osteoarthritis via autophagy activation.

OBJECTIVE: Osteoarthritis (OA) is associated with decreased autophagy activity and imbalance of cell homeostasis in chondrocytes (CHs). Sirtuin 7 (Sirt7) is claimed to have the ability to activate the autophagy response. The aim of this study was to explore the function of Sirt7 in the development of OA involving autophagy by culturing human chondrocytes (CHs). PATIENTS AND METHODS: We collected knee joint cartilage from patients undergoing traumatic amputation and arthroscopic knee replacement. Protein and mRNA levels of collagen II, Sirt7, ULK1, Lc3, and Beclin1 were analyzed by Western blot and RT-PCR. CHs were isolated from the traumatic cartilage as a control group, and IL-1ß was used to induce CHs degeneration. The expression of Sirt7 gene was silenced by siRNA and upregulated by recombinant human Sirt7 protein (rh-Sirt7). An autophagy activator Tat-beclin 1 (Tat) was used to activate autophagy in cultural CHs. Expression of collagen II, Sirt7, ULK1, Lc3, and Beclin1 was determined by immunofluorescence, Western blot, and RT-PCR, respectively. RESULTS: The protein and mRNA levels of Collagen II, Sirt7, ULK1, Lc3-II, and Beclin1 expressions were decreased in OA cartilage compared with those in healthy cartilage. IL-1ß degenerated the CHs resulting in a reduction of collagen II, which also downregulated Sirt7, ULK1, Lc3-II, and Beclin1. Sirt7 deficiency accelerated the catabolism of collagen II and weakened the expression of ULK1, Lc3-II, and Beclin1. On the contrary, exogenous rh-Sirt7 played a positive role in these gene expressions. Finally, Tat alleviated the CHs degeneration by upregulating collagen II and activating ULK1, Lc3-II, and Beclin1, but incapable to mediate Sirt7 expression. CONCLUSIONS: Overall, these findings suggested that Sirt7 was suppressed in the degenerated cartilage. Sirt7 deficiency does harm to the autophagy level, affecting CHs metabolism, while the upregulation of Sirt7 activated autophagy and protected CHs degeneration. An appropriate increase in autophagy can protect CHs but has no effect on Sirt7 expression.

[Application of indocyanine green in complex upper urinary tract repair surgery].

OBJECTIVE: To evaluate the clinical application of indocyanine green (ICG) visualization by near infrared fluorescence laparoscopy (NIFL) in complex upper urinary tract reconstructions surgery. METHODS: This was a retrospective study of 7 patients who underwent complex surgeries of ureteral reconstruction between May 2019 and October 2019. There were 6 males and 1 female with the age ranging from 24 to 57 years (median age was 47 years). There were 5 cases of right ureteral strictures, of which 3 were proximal ureteral strictures and 2 were multiple and long ureteral strictures caused by radiotherapy. There were 2 cases of left ureteral strictures, of which 1 was ureteropelvic junction stricture and 1 was proximal ureteral stricture. There were 4 cases of secondary repair operations and 3 cases of primary operations. All the patients underwent laparoscopic surgery via the abdominal approach. ICG was injected into the ureter via nephrostomy tube during the operations, and the diseased ureter was identified by NIFL. Among the patients, 2 cases underwent IUPU (Institute of Urology, Peking University) modified ileal ureter replacement, 2 cases underwent ureteroureterostomy, 2 cases underwent appendiceal onlay flap ureteroplasty, and 1 case underwent lingual mucosa onlay flap ureteroplasty. RESULTS: All the operations were successfully completed without open conversion. The localization and separation of ureteral lesions were completed under NIFL. The mean operative time was 187 (135-300) min. The duration of ureteral separation was 15-27 min, and the mean time was 18 min. The estimated blood loss was 15-200 mL, the mean estimated blood loss was 50 mL. There was one patient with ileal ureter replacement who had fever after surgery and responded well to antibiotics. The mean (range) length of postoperative hospital stay was 7 (6-10) days and no postoperative complications of a high grade (Clavien-Dindo Ⅲ and Ⅳ) occurred. Up to now, the mean follow-up duration was 9 (6-11) months, and no indocyanine green toxicity occurred. All D-J stents and nephrostomy were removed successfully 2 months after the operation. Ultrasound showed no obvious hydronephrosis, and CTU (computed tomography urography) showed that the urinary tract was unobstructed and the kidney function was normal. CONCLUSION: The application of ICG in the complex upper urinary tract reconstructive surgery is a safe and easy method to help surgeon to identify the ureter which may reduce the risk of iatrogenic damage and protect the ureteral blood supply.

Loss of TNR causes a nonprogressive neurodevelopmental disorder with spasticity and transient opisthotonus.

PURPOSE: TNR, encoding Tenascin-R, is an extracellular matrix glycoprotein involved in neurite outgrowth and neural cell adhesion, proliferation and migration, axonal guidance, myelination, and synaptic plasticity. Tenascin-R is exclusively expressed in the central nervous system with highest expression after birth. The protein is crucial in the formation of perineuronal nets that ensheath interneurons. However, the role of Tenascin-R in human pathology is largely unknown. We aimed to establish TNR as a human disease gene and unravel the associated clinical spectrum. METHODS: Exome sequencing and an online matchmaking tool were used to identify patients with biallelic variants in TNR. RESULTS: We identified 13 individuals from 8 unrelated families with biallelic variants in TNR sharing a phenotype consisting of spastic para- or tetraparesis, axial muscular hypotonia, developmental delay, and transient opisthotonus. Four homozygous loss-of-function and four different missense variants were identified. CONCLUSION: We establish TNR as a disease gene for an autosomal recessive nonprogressive neurodevelopmental disorder with spasticity and transient opisthotonus and highlight the role of central nervous system extracellular matrix proteins in the pathogenicity of spastic disorders.

Absence of iron-responsive element-binding protein 2 causes a novel neurodegenerative syndrome.

Disruption of cellular iron homeostasis can contribute to neurodegeneration. In mammals, two iron-regulatory proteins (IRPs) shape the expression of the iron metabolism proteome. Targeted deletion of Ireb2 in a mouse model causes profoundly disordered iron metabolism, leading to functional iron deficiency, anemia, erythropoietic protoporphyria, and a neurodegenerative movement disorder. Using exome sequencing, we identified the first human with bi-allelic loss-of-function variants in the gene IREB2 leading to an absence of IRP2. This 16-year-old male had neurological and haematological features that emulate those of Ireb2 knockout mice, including neurodegeneration and a treatment-resistant choreoathetoid movement disorder. Cellular phenotyping at the RNA and protein level was performed using patient and control lymphoblastoid cell lines, and established experimental assays. Our studies revealed functional iron deficiency, altered post-transcriptional regulation of iron metabolism genes, and mitochondrial dysfunction, as observed in the mouse model. The patient's cellular abnormalities were reversed by lentiviral-mediated restoration of IRP2 expression. These results confirm that IRP2 is essential for regulation of iron metabolism in humans, and reveal a previously unrecognized subclass of neurodegenerative disease. Greater understanding of how the IRPs mediate cellular iron distribution may ultimately provide new insights into common and rare neurodegenerative processes, and could result in novel therapies.

Individualization of Clinical Target Volume Delineation Based on Stepwise Spread of Nasopharyngeal Carcinoma: Outcome of More Than a Decade of Clinical Experience.

PURPOSE: Radiation-related toxicity in nasopharyngeal carcinoma (NPC) is common. There are no well-established guidelines for clinical target volume (CTV) delineation with long-term follow-up. Current consensus continues to rely heavily on bony landmarks and fixed margins around the gross tumor volume (GTV), an approach used to define fields in the conventional 2- and 3-dimensional radiation therapy era. METHODS AND MATERIALS: We retrospectively evaluated patients with newly diagnosed nonmetastatic NPC treated with definitive radiation therapy using a technique of CTV delineation based on individual tumor extent and the orderly stepwise pattern of tumor spread. Dosimetric comparisons were made between national protocol HN001 and our contouring strategies on a representative early- and advanced-stage NPC. The primary endpoints were patterns of failure and local control; secondary endpoints included regional control and survival, estimated using the Kaplan-Meier method. RESULTS: Between 1999 and 2013, 73 patients (88% with stage 3-4 disease) were treated with median follow-up of 90 months for surviving patients. Median dose to GTV was 70 Gy. Four patients developed local recurrence and 1 patient developed regional recurrence. All locoregional recurrences occurred within the high-dose GTV. The 5-year local control, regional control, and overall survival was 94% (95% confidence interval [CI], 85%-98%), 99% (95% CI, 90%-100%), and 84% (95% CI, 73%-91%), respectively. Compared with HN001, our contouring strategy resulted in 62% and 36% reduction in CTV for T1 and T4 disease, respectively. In the T1 tumor, the reduction of doses to the contralateral parotid, optic nerve, and cochlea were 54%, 50%, 34% respectively. In the T4 case, there was a decrease of optic chiasm dose of 46% and contralateral optic nerve of 37%. There were 10 grade 3 toxicities. There was no grade 2 or higher xerostomia and no grade 4/5 toxicity. CONCLUSIONS: Our long-term experience with individualized CTV delineation based on stepwise patterns of spread results in excellent local control, with no recurrence outside the GTV.