: Autophagy is a strictly regulated process which degrades and recycles long-lived or misfolded proteins and damaged organelles for the maintenance of energy and function homeostasis of cells. Insufficient oxygen and glucose supply caused by cerebral ischemia leads to higher ratio of AMP/ATP, which will activate AMPK pathway to initiate the process of autophagy. Accumulating evidence shows that autophagy participates in the pathogenesis of ischemic stroke as a doubleedge sword. However, the exact role of autophagy in the pathogenesis of ischemic stroke is controversial and yet to be elucidated. In this review, we expounded the autophagy pathway both in physiological condition and in ischemic stroke. We also focused on discussing the double-edge sword effect of autophagy in brain ischemia and its underlying mechanisms. In addition, we reviewed potential therapeutic strategies for ischemic stroke targeting autophagy pathway.

Osteosarcoma (OS) is a mesenchymal-origin tumor that constitutes the most common primary malignant bone tumor. The survival rate of the patients has significantly improved since the introduction of neoadjuvant chemotherapy and extensive resection, but it has stagnated in recent 40 years. Tyrosine kinase inhibitors (TKIs) have played a key part in the treatment of malignant tumors. In advanced OS, TKIs including anlotinib, apatinib, sorafenib, etc. have significantly improved the progression-free survival of patients, while the overall survival remains unchanged. The main reason is the rapid and inevitable progress of acquired drug resistance of OS. However, as the application of TKIs in OS and other tumors is still in the exploratory phase, its drug resistance mechanism and corresponding solutions are rarely reported. Hence, in this review, we summarize knowledge of the applications of TKIs, the mechanism of TKIs resistance, and the attempts to overcome TKIs resistance in OS, which are the three potentially novel insights of TKIs in OS. Because most evidence is derived from studies using animal and cell models, we also reviewed clinical trials and related bioinformatics data available in public databases, which partially improved our understanding of TKIs applications.

Background Most previous studies focused on the minimum interval between surgery and radiotherapy in spinal metastases, leaving the maximum interval under-investigated. However, in real world, limited radiotherapist and equipment cannot meet the needs of a large patient population to obtain timely radiotherapy after the index spine surgery in developing countries. This study aimed to estimate the clinical risks of delayed radiotherapy after surgery in patients with spinal metastases in developing country. Methods Data from 89 patients who underwent surgery and postoperative radiotherapy at a single site in a developing country were retrospectively reviewed. Patients were divided into the progression before radiotherapy (PBR) and no progression before radiotherapy (NPBR) groups. Kaplan–Meier analysis and log-rank tests were used to compare the local control (LC) and overall survival (OS) between groups. Results Within 1 month after surgery, only 20.2% of patients underwent radiotherapy. Risk of local progression before radiotherapy at 1, 3, and 6 months was 1.2%, 24.1%, and 45.1%, respectively. The LC rate at 1 year was lower in the PBR group than in the NPBR group (53.3% vs. 76.3%, P = 0.040). The OS rate at 1 year was 61.9% and 79.6% in the PBR and NPBR groups, respectively (P = 0.001). The Karnofsky performance status significantly improved only in the NPBR group (52.5 ± 17.6 vs. 66.8 ± 26.3, P < 0.001). The sphincter dysfunction significantly improved in the NPBR group (0.3 ± 0.5 vs. 0.1 ± 0.3, P = 0.007) but it tended to be deteriorated in the PBR group (0.1 ± 0.4 vs. 0.3 ± 0.5, P = 0.500). Conclusions In real world, about 80% of patients had delayed radiotherapy 1 month after spine surgery for metastases in our developing country. Patients had a higher risk for radiographic local progression before radiotherapy and poorer LC, OS, and quality of life as time to radiotherapy increased.

We aimed to compare the demographic, clinical and laboratory characteristics between IgG4-related kidney disease (IgG4-RKD+) and extrarenal IgG4-related disease (IgG4-RKD−) in a large Chinese cohort, as well as describing the radiological and pathological features of IgG4-RKD+. We retrospectively analyzed the medical records of 470 IgG4-related disease (IgG4-RD) patients at Peking University People’s Hospital from January 2004 to January 2020. The demographic, clinical, laboratory, radiological and pathological characteristics between IgG4-RKD+ and IgG4-RKD− were compared. Twenty IgG4-RD patients who had definite etiology of renal impairment including diabetes, hypertension and etc. were excluded. Among the remained 450 IgG4-RD patients, 53 were diagnosed with IgG4-RKD+ . IgG4-RKD+ patients had older age at onset and at diagnosis. Male to female ratio of IgG4-RKD+ patients is significantly higher. In the IgG4-RKD+ group, the most commonly involved organs were salivary gland, lymph nodes and pancreas. It was found that renal function was impaired in approximately 40% of IgG4-RKD+ patients. The most common imaging finding is multiple, often bilateral, hypodense lesions. Male sex, more than three organs involved, and low serum C3 level were risk factors for IgG4-RKD+ in IgG4-RD patients. These findings indicate potential differences in pathogenesis of these two phenotypes.

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In clinical practice, we found that IgG4-related disease (IgG4-RD) patients complicated with allergic rhinitis (AR)/chronic rhinosinusitis (CRS) seemed to have unique characteristics different from patients with IgG4-RD alone. In this study, demographic, clinical and laboratory characteristics of IgG4-RD patients complicated with AR/CRS were investigated. We retrospectively analyzed 756 IgG4-RD patients who were recruited in four medical centers from 2009 to 2021. We divided 756 IgG4-RD patients into 2 groups: the case group included IgG4-RD patients complicated with AR/CRS, and the control group included IgG4-RD patients without AR/CRS. 411 patients were complicated with AR/CRS among 756 IgG4-RD patients. Multiple organs involvement (≥ 3, p < 0.0001, OR 3.585 (95% CI 2.655–4.839)) and other types of allergic disease (p < 0.0001, OR 2.007 (95% CI 1.490–2.693)) were more common in the case group. Patients in the case group had a higher level of serum IgG4 (650 mg/dL vs 385 mg/dL, p < 0.0001), IgE (347 mg/dL vs 98 mg/dL, p < 0.0001) and ESR (14 mm/h vs 12 mm/h, p < 0.05). High IgE level (p < 0.01, OR 1.003 (95% CI 1.001–1.005)) and other types of allergic disease (p < 0.05, OR 3.196 (95% CI 1.146–8.908)) were risk factors for patients in the case group, in which most patients had nasal manifestations before the diagnosis of IgG4-RD. The median time interval from nasal symptoms appearance to IgG4-RD diagnosis was − 120 and − 90 months for patients complicated with AR and CRS, respectively. IgG4-RD patients are often complicated with AR/CRS and have distinct characteristics, which appear to be a subgroup of IgG4-RD. The data suggests a pathogenic association of IgG4-RD and AR/CRS.

Objective. In the present study, the authors aimed to optimize the workflow of utilizing a 3D printing technique during surgical treatment for malignant sacral tumors, mainly on preparation of patient-specific surgical jigs and ready-made 3D-printed total sacral endoprosthesis. Methods. Three patients with a malignant sacral tumor received total sacrectomy with preoperative design of a patient-specific 3D-printed cutting jig and endoprosthetic reconstruction. Size of ready-made 3D-printed endoprosthesis was determined based on preoperative images, planned surgical margin, and size of the endoprosthesis. A patient-specific cutting jig was designed with a bilateral cutting slot matching the bilateral planes of the implant precisely. The tumor was removed en bloc through a single posterior approach only, being followed by reconstruction with ready-made total sacral endoprosthesis. Results. The mean time for preoperative design and manufacture of the surgical jig was 6.3 days. Surgical jigs were successfully used during surgery and facilitated the osteotomy. The mean operation time was 177 minutes (range 150-190 minutes). The mean blood loss was 3733 ml (range 3600-4000 ml). R0 resections were achieved in all the three cases proven by pathology. Evaluation of osteotomy accuracy was conducted by comparing preoperative plans and postoperative CT scans. The mean osteotomy deviation was 2.1 mm (range 0-4 mm), and mean angle deviation of osteotomy was 3.2° (range 0-10°). At a mean follow-up of 18.7 months, no local recurrence was observed. One patient had lung metastasis 15 months after surgery. Two patients were alive with no evidence of the disease. Conclusions. The patient-specific surgical jig and ready-made 3D-printed total sacral endoprosthesis can shorten the surgical preparation time preoperatively, facilitating accurate osteotomy and efficient reconstruction intraoperatively. The workflow seems to be feasible and practical.

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