Abstract Adverse childhood experiences (ACEs) exposure is a pressing and severe global public health issue. Children and adolescents exposed to multiple ACEs are highly susceptible to toxic stress and impaired physiological functioning, which significantly jeopardize their physical and mental health. Effective prevention and intervention strategies can reduce the prevalence of ACEs and mitigate their severe impacts, thereby minimizing the long term detrimental consequences on future outcomes. The review provides a comprehensive review of intervention strategies across four dimensions: individual, family, school, and public services/policy, so as to establish a theoretical foundation for implementing effective interventions for children and adolescents exposed to adverse childhood experiences.

In surgery of patients with hypertensive intracerebral hemorrhage, precise positioning and minimally invasive operation provide a strong guarantee for overall curative effect. As an emerging visualization software, 3D-Slicer can optimize surgical approach, achieve precise intraoperative positioning, and accurately measure hematoma volume to guide treatment plan implementation. This article reviews the application of 3D-Slicer in surgery of patients with hypertensive intracerebral hemorrhage.

Objective:To prepare specific molecular probe 18F-AlF-1, 4, 7-triazacylononane-1, 4, 7-triacetic acid-(polyethylene glycol) 4-ZD2 ( 18F-AlF-NOTA-PEG 4-ZD2) for targeting extradomain-B fibronectin (EDB-FN), and evaluate its properties in vitro and in vivo. Methods:18F-AlF-NOTA-PEG 4-ZD2 was prepared by one-step chelation labeling with Al 18F. The radiochemical purity and in vitro stability were determined by high performance liquid chromatography (HPLC). The partition coefficient (logP) of 18F-AlF-NOTA-PEG 4-ZD2 was evaluated, and the cell uptake experiment was carried out (triple-negative breast cancer (MDA-MB-231) cells (1×10 6/tube) were divided into 3 groups ( n=3 per group); positive group, inhibition group, control group). MicroPET imaging was performed on MDA-MB-231 bearing nude mice ( n=3) after 18F-AlF-NOTA-PEG 4-ZD2 injection (30, 60, 90, 120 min) and compared with blocking group ( n=3, NOTA-PEG 4-ZQ 2 was preinjected at 0.5 h before 18F-AIF-NOTA-PEG a-ZD2 injection). Independent-sample t test was used to analyze the data. Results:18F-AlF-NOTA-PEG 4-ZD2 was successfully prepared. The optimized radiochemical yield was (33.8±2.1)% (undecay corrected, n=8) and the radiochemical purity was >96%. After incubating 120 min at 37 ℃, the radiochemical purity of 18F-AlF-NOTA-PEG 4-ZD2 in human serum and PBS was >93%, indicating its good stability in vitro. The specific activity was (11.1±3.2) GBq/μmol, and logP was -1.43±0.05. The uptake value of tumor cells was (1.77±0.28) percentage applied activity (%AR)/10 6 cells at 120 min post-injection in positive group, and the total uptake value of the inhibition group was (0.76±0.07) %AR/10 6 cells ( t=4.30, P=0.032). MicroPET imaging in tumor bearing nude mice showed that 18F-AlF-NOTA-PEG 4-ZD2 was mainly metabolized by the liver and kidneys. The tumor uptake value was (1.94±0.21) percentage activity of injection dose per gram of tissue (%ID/g) at 60 min post-injection and the tumor/muscle ratio was 3.80±0.25 at 90 min post-injection in the experimental group, while the tumor uptake value of tumor bearing nude mice in the blocking group was (0.43±0.09) %ID/g at 60 min post-injection ( t=3.18, P=0.006). Conclusions:18F-AlF-NOTA-PEG 4-ZD2 can be prepared simply with high labeling rate and good stability in vitro, with high tumor uptake and tumor/muscle ratio in microPET imaging, and good specificity and long tumor residence time. The probe has good application prospect in breast cancer with high expression of fibronectin subtype EDB-FN.

Objective:To investigate the clipping methods of ruptured posterior communicating artery (PCoA) aneurysms of medial posterior inferior type (aneurysms located at the medial posterior inferior part of internal carotid artery or occluded by the internal carotid artery) during conventional pterional craniotomy.Methods:Seven patients with ruptured PCoA aneurysms, admitted to our hospital from January 2004 to January 2020, were chosen in our study. The clinical data and surgical efficacies of these patients were retrospectively analyzed.Results:The anterior choroidal artery (AChA) was accidentally clipped in 2 patients during the surgery, of which one was released after adjustment and one was avoided after multiple adjustments. Due to severe acute brain swelling, the brain tissues of the anterior temporal lobe were removed for about 20 mm in 2 patients, and the anterior temporal lobe was retracted posteriorly by platens in 5 patients. All aneurysms disappeared in the postoperative CTA images, no residual neck was found, and the parent artery remained unobstructed. One patient had cerebral infarction in the AChA supplying area. All patients were followed up for 1-6 years, with an average of 27.6 months. Six patients recovered completely without neurological dysfunction. One patient had contralateral hemiplegia, with muscle strength grading III, walking on crutches, and basic living by himself.Conclusion:It's difficult to clip the ruptured PCoA aneurysms of medial posterior inferior type by conventional pterional craniotomy; so straight and curved aneurysm clips can be used to clip aneurysms by expanding the inter-cisternal space around the aneurysms.

Objective:To explore the surgical treatment efficacy and experience of intracranial malignant melanoma (IMM).Methods:Seven patients with IMM, including 3 with primary IMM and 4 with secondary IMM, admitted to our hospital from May 2013 to June 2018, were treated with minimally invasive transcranial surgery. The tumors were removed as much as possible during the operation; according to the postoperative condition of these patients, adjuvant therapies such as follow-up or radiotherapy/chemotherapy, or/and reoperation/comprehensive treatment were provided.Results:These 7 patients eventually died; among the 3 patients with primary IMM, one had total resection, one had subtotal resection, and one had partial resection, and the postoperative survival period was 10 months, 7 months and one month, respectively; among the 4 patients with secondary IMM, three had total resection, and one had partial resection, and the postoperative survival period was 32 months, 13 months, 12 months and 5 month, respectively.Conclusion:The overall prognosis of IMM patients is poor, and surgical removal of the primary and intracranial lesions is the key to prolong survival.

Objective:To investigate the relationship between Ki-67 and PD-L1 in patients with non-small cell lung cancer (NSCLC) and their effects on prognosis. Methods: A total of 401patients, who were pathologically diagnosed as NSCLC in Changhai Hospital from January 2012 toAugust 2018, were enrolled as study subjects; and the patients were immunohistochemically tested for PD-L1 and Ki-67. The clinical and pathological data were collected, and the follow-up was performed regularly. The correlation between Ki-67 and PD-L1 and their effects on postoperative DFS and post-chemotherapy PFS were statistically analyzed. Results: Positive rates of PD-L1 and Ki-67 in NSCLC tissues were 37.9% (152/401) and 96.3% (386/401), respectively. Univariate analysis showed that Ki-67 was an influencing factor for PD-L1 expression (OR=0.33, 95%CI=0.28-0.39, P<0.0001); Curve Fitting analysis showed a positive correlation between Ki-67 and PD-L1; threshold effect analysis, segmentation multivariate logistic and ROC curve analysis showed 14% is a relatively suitable threshold for Ki-67 to be combined with PD-L1. Kaplan-Meier analysis showed that patients in Ki-67 high expression group had a significantly shorter post-operative DFS than those in Ki-67 low expression group ([21.88±11.25] vs [41.22±16.25]m, P< 0.0001), patients in PD-L1 positive group had a significantly shorter DFS than those in PD-L1 negative group ([24.75±14.59] vs [38.27± 16.75]m, P<0.0001)], and patients in Ki-67 high/PD-L1 positive group had the shortest DFS as compared to the other three groups ([20.57±11.33] vs [24.11±10.79], [36.00±16.79], [42.91±15.77]m, P<0.0001).As for post-chemotherapy PFS, patients in Ki-67 high expression group was significantly longer than those in Ki-67 low expression group [(7.70±3.01) vs (5.80±2.99)m, P=0.016), but there was no significant difference between PD-L1 positive group and PD-L1 negative group [(7.04±3.21) vs (6.33±3.06)m, P=0.22); for combined evaluation with Ki-67 and PD-L1, the PFS of two Ki-67 high expression groups was significantly longer than the other two Ki-67 low expression groups [(7.74±3.25) vs (7.43±2.38) vs (4.91±1.97) vs (6.02±3.19)m, P=0.041). Conclusion: Ki-67 is positively correlated with PD-L1 in NSCLC patients, and Ki-67 14% is a suitable threshold for combined use with PD-L1. Both Ki-67 and PD-L1 are predictors of poor prognosis. The combination of the two has an "additive effect" on the prediction of poor prognosis, and patients with high Ki-67 expression are more sensitive to chemotherapy.

Objective To study the clinical efficacy of transnasal transsphenoidal surgery in acromegaly caused by pituitary adenoma and the clinical characteristics of patients achieved early biochemical remission after surgery. Methods Thirty-three patients with acromegaly caused by pituitary adenoma, admitted to and underwent transnasal transsphenoidal surgery in our hospital from September 2014 to June 2017, were chosen in our study. Clinical data and treatment efficacy of these patients were analyzed retrospectively. The patients were divided into biochemical remission group and non-biochemical remission group according to serum growth hormone (GH) trough value and insulin-like growth factor-1 (IGF-1) levels after oral glucose tolerance test (OGTT) 3 months after surgery, and endocrinology test results of the two groups were compared. Results Thirty-three acromegaly patients underwent microscopic transnasal pituitary surgery. For these patients, 24 achieved total resection, two achieved subtotal resection, 5 achieved massive resection, and two achieved partial resection. Patients were followed up for an average of 13.2 (3-36) months. At 3 months after surgery, blood sugar of two patients with diabetes were restored to normal level; reduction or restoration of hypertension was observed in most patients with preoperative hypertension (81.8％ , 9/11); improvement of cardiac hypertrophy or cardiac enlargement was observed in about 1/3 patients with preoperative cardiac organic changes; heart enlargement was improved in 4 patients; one patient had normal sinus arrhythmia. The average interventricular septum thickness of the patients after surgery was significantly reduced as compared with that before surgery ([8.36±1.56] mm vs. [9.22±1.24] mm, P<0.05). The early biochemical remission was achieved in 19 patients (57.6％); as compared with the 14 patients failed to achieve early biochemical remission, those patients achieved early biochemical remission had significantly smaller adenoma diameters and volumes, lower percentages of patients with degrees of adenoma packaging internal carotid artery<135° and Knosp grading 0-2, and higher extent of surgical resection, lower IGF-1 level at one week and three months after surgery, lower GH level one, two and three d, one week and three months after surgery, and lower GH trough value after OGTT before surgery, one week and 3 months after surgery, with significant differences (P<0.05). Conclusions Transsphenoidal surgery is effective treatment for acromegaly caused by pituitary adenoma. Most patients could achieve biochemical remission three months after surgery. And the surgery could help in improving the cardiovascular complications of patients. The patients who are able to achieve early biochemical remission may have the features of smaller adenoma, lower GH trough value after OGTT before and one week after surgery, and lower GH and IGF-1 levels after surgery.

Objective To compare the therapeutic efficacy of giant nonfunctioning pituitary adenomas (GNPAs) of different imaging types,and to explore the surgical treatment strategies of GNPAs.Methods The pre-and post-operative images,clinical data and follow-up results of 69 patients with GNPAs,admitted to our hospital from July 2011 to October 2016,were analyzed retrospectively.According to the morphology and growth patterns of tumors on MR imaging,they were divided into GNPAs of vertical type,cystic type,deviation Ⅰ/Ⅱ type,lateral extension type,sinus type,laryngeal type,isolated type,and mixed type.The tumor resection results of GNPAs of different types were compared by different surgical treatment strategies.Results Fifty-one patients,with total resection rate of 31.37％,were treated by transsphenoidal approach,and 18 patients,total resection rate of 44.44％,were treated by craniotomy.The overall total resection rate of GNPAs was 36.23％ (n=25).Total resection rate and subtotal resection rate was 71.01％ (n=49).The surgery resection rates of GNPAs of different types were different,and the GNPAs of mixed type enjoyed the worst efficacy.Fifty-three patients were followed-up for one-66 months with an average of 17 months;in patients with total resection,18 (72％) were without recurrence,one (4％) was with recurrence;X knife treatment was performed in 14 patients.Postoperative residual reduction,control,and increase were noted in 4,26 and 4 patients.Two patients died after surgery.Conclusions The total reduction rate of GNPAs is low and the operation is difficult;however,favorable prognosis can be achieved.Transsphenoidal surgery is the first choice for elimination of occupying effect.According to different types,appropriate procedures can be used to reduce the tumor residue and improve the total resection or subtotal rates.

Objective To explore the role of 3D venous-fusion models in the resection of meningiomas.Methods The study included 19 patients with meningiomas,admitted to our hospital from March 2015 to July 2015.The preoperative and postoperative contrast enhancement MR venography (CE-MRV) data were imported into the neuronavigator system.The establishment of 3D venous-fusion models was performed;reconstruction,cropping,fusion of the intracranial venae and tumors were performed.3D venous-fusion models were used to evaluate the intracranial venous circulation,and the positions of venae and tumors were navigated in real-time.Results 3D venous-fusion models showed good results.The position relationship of tumors and their surrounding venous was perfectly assessed in operation.Nineteen patients underwent craniotomy using neuronavigator to locate venous position,and no postoperative venous complications occurred.The contrast of preoperative and postoperative 3D venous-fusion models prompted that the venous protection was in line with expectations.Conclusions The 3D venous-fusion models established by neuronavigator can accurately evaluate the relationship between cerebral venous and the tumors.These models help the operator making a better understanding of tumors and their peripheral venous imaging data from 3D perspective.It is benefit for the operator to make a more reasonable venous protect strategy.

Objective To analyze the correlative factors of hypopituitarism in patients with intracranial non-sellar tumors.Methods Eighty-three patients with intracranial non-sellar tumors,admitted to our hospital from May 2014 to April 2015,were included in our study;their clinical data were retrospectively analyzed.The status of pituitary function was assessed according to the level of preoperative serum hormone.Univariate and multivariate Logistic regression analyses were employed to analyze the correlations of preoperative hypopituitarism with age,gender,hypertension,epilepsy history,course of disease,mass effect of tumor,tumor location,intracranial pressure (ICP),and composition of cerebrospinal fluid.Results Before surgery,30 showed hypopituitarism,accounting for 36.14％:23 had deficiency in one pituitary axe and 7 had multi-axial deficiency.Univariate analysis showed that high ICP (ICP＞200 mmH2O),acute or sub-acute course (≤ 3 months) and presence of mass effect by non-sellar brain tumor were the risk factors of hypopituitarism (P＜0.05).Multivariate Logistic regression analysis revealed that intracranial mass effect in patients with non-sellar brain tumor was an independent risk factor (OR=3.197,95％CI=1.085-9.423,P=0.035).Conclusion Hypopituitarism has high morbidity in patients with non-sellar brain tumor;intracranial mass effect is an independent risk factor for hypopituitarism.