Interactions between brain-resident and peripheral infiltrated immune cells are thought to contribute to neuroplasticity after cerebral ischemia. However, conventional bulk sequencing makes it challenging to depict this complex immune network. Using single-cell RNA sequencing, we mapped compositional and transcriptional features of peri-infarct immune cells. Microglia were the predominant cell type in the peri-infarct region, displaying a more diverse activation pattern than the typical pro- and anti-inflammatory state, with axon tract-associated microglia (ATMs) being associated with neuronal regeneration. Trajectory inference suggested that infiltrated monocyte-derived macrophages (MDMs) exhibited a gradual fate trajectory transition to activated MDMs. Inter-cellular crosstalk between MDMs and microglia orchestrated anti-inflammatory and repair-promoting microglia phenotypes and promoted post-stroke neurogenesis, with SOX2 and related Akt/CREB signaling as the underlying mechanisms. This description of the brain's immune landscape and its relationship with neurogenesis provides new insight into promoting neural repair by regulating neuroinflammatory responses.
Humans ; Ischemic Stroke ; Brain/metabolism* ; Macrophages ; Brain Ischemia/metabolism* ; Microglia/metabolism* ; Gene Expression Profiling ; Anti-Inflammatory Agents ; Neuronal Plasticity/physiology* ; Infarction/metabolism*

Objective:To investigate the risk factors for 1-year survival rate in patients with spinal metastasis secondary to lung cancer.Methods:The data of 343 patients with spinal metastases secondary to lung cancer from January 2011 to December 2018 were retrospectively studied. There were 188 males (54.8%) and 155 females (45.2%) with an average age of 59.47±10.21 years old (range 23-91 years). The patients were divided into operation group (150 cases, 43.7%) and non operation group (193 cases, 56.3%). The demographics, types of primary tumor, non spinal metastasis, visceral metastasis, spinal metastasis and segments, pathological fractures of vertebra, Frankel classification, physical function status (Karnofsky performance scale, KPS), visual analogue score (VAS), the spinal instability neoplastic score (SINS) were recorded and analyzed. The impact of different treatments on the survival prognosis of patients with spinal metastasis was evaluated. The independent factors affecting survival in those patients were analyzed by Cox proportional hazards regression model.Results:The peak incidence of spinal metastases was found in the age group of 46-60 years (43.7%, 150/343). 38.5% (132/343) of the patients had pathological fractures of the involved vertebral body. 58.3% (200/343) of the patients had extraspinal bone metastasis. 36.2% (124/343) of the patients had visceral metastasis. Among the primary tumors, adenocarcinoma was the most common tpye (61.5%, 211/343), followed by large cell lung cancer (12.5%, 43/343), small cell lung cancer (6.4%, 22/343), squamous cell cancer (6.1%, 21/343) and mixed cell lung cancer (5.3%, 18/343). The type of lung cancer cells in about 8.2 (28/343) patients was unknown. Among the surgical patients, 21 patients underwent minimally invasive surgery (14.0%), 28 patients underwent simple decompression surgery (18.7%), 76 patients underwent separation surgery (50.7%), and 25 patients underwent radical surgery (16.6%). 59.3% (89/150) of the patients had a better neurological function than before surgery. The average survival time of all patients was 9.88 months with the median survival time of 8 (5,14) months. The survival rates were 62.1% (213/343), 30.0% (103/343), and 3.8% (13/343) at 6, 12, and 24 months, respectively. The average survival time of patients in the operation group was 10.24 months with the median survival time of 9 (5, 15) months, and the average survival time of patients in the non operation group was 9.41 months with the median survival time of 7 (5, 13) months with no significant difference between the groups (χ 2=0.300, P=0.584). Multivariate Cox proportional hazard regression model analysis showed that radiotherapy [ HR=1.913, 95% CI(1.471, 2.488), P<0.001], chemotherapy [ HR=1.313, 95% CI(1.040, 1.658), P=0.022], targeted drug therapy [ HR=1.683, 95% CI(1.221, 2.319), P=0.001], KPS [ HR=1.593, 95% CI(1.140, 2.225), P=0.006] and pathological type (non-small cell lung cancer) were independent factors affecting the 1-year survival rate of patients with spinal metastasis secondary to lung cancer [ HR=0.322, 95% CI(0.225, 0.460), P<0.001] with significant difference. Conclusion:Surgical treatment can improve both the neurological function and general status of patients with spinal metastasis. Treatments of radiotherapy, chemotherapy, and targeted drug therapy can significantly improve 1-year survival rate, while a KPS less than 50 points and a primary lung cancer other than adenocarcinoma were independent risk factors reducing 1-year survival rate.

Autism spectrum disorder（ASD）is a heterogeneous group of neurodevelopmental disorders.The prevalence of ASD increases year by year.Sleep disorder is the common comorbidity of ASD.The pathogenesis is still unknown.The imbalance of excitation / inhibition（E/I）and neuroplasticity changes are the possible pathogenesis of ASD.Early childhood sleep is an important factor affecting E/I balance and neuroplasticity.ASD and sleep disorder may share common pathogenesis.Various genetic variants（such as Shank3，SynGAP，et al）and related chromosomal disease（such as 16p11.2 deletion）and their associated syndromes such as Rett syndrome，Smith-Magenis syndrome，and Angelman syndrome，ect，all manifest both ASD and sleep disorder phenotypes.In addition，melatonin，oxytocin，hypothalamic hormone，serotonin，etc，may participate in the neural pathways of sleep disorder，ASD pathology and neuroplasticity，promoting the incidence of ASD and sleep disorder.Some treatments such as supplementing with melatonin，oxytocin，zinc，iron，and dietary supplements can improve the clinical symptoms of ASD while treating sleep disorder in children with ASD.This article reviews the mechanism of comorbid sleep disorder in children with ASD to improve clinical diagnosis and treatment.

Background::Sentinel lymph node (SLN) biopsy is gradually accepted as the standard of care in breast cancer patients with down-staged axillary disease after neoadjuvant chemotherapy (NAC). However, it is still difficult to precisely define pre-NAC clinical node-positive (cN1) and post-NAC clinical node-negative (ycN0). This prospective single-center trial was designed to evaluate the feasibility and accuracy of standard targeted axillary dissection (TAD) after NAC in highly selective pre-NAC cN1 patients (not considering ultrasound-based axillary ycN staging).Methods::This prospective trial included patients with initial pre-NAC cT1–3N1M0 invasive breast cancer but with a rigorous definition of cN1 from the Affiliated Cancer Hospital of Zhengzhou University. When NAC was effective (including complete and partial responses) and preoperative axillary palpation was negative, preoperative ultrasound-based axillary staging was not considered, and all patients underwent TAD followed by axillary lymph node (LN) dissection. The detection rate (DR) and false-negative rate (FNR) of TAD were calculated.Results::A total of 82 patients were included, and 77 of them were eligible for data analysis. The DR for TAD was 94.8% (73/77). There were 26 patients with one abnormal LN at the time of diagnosis based on ultrasound, 45 patients with two, and 2 patients with three. One patient had one TAD LN, four patients had two TAD LNs, and 68 patients had three or more TAD LNs. Preoperative axillary palpation yielded negative results for all 73 patients who successfully underwent TAD. Preoperative ultrasound-based ycN0 and ycN+ conditions were detected for 52 and 21 cases, respectively. The FNR was 7.4% (2/27) for standard TAD (≥3 SLNs), which was lower than that of all successful TAD (≥1 SLN; 10.0%, 3/30).Conclusions::In rigorously defined pre-NAC cN1 breast cancer patients, standard TAD is feasible for those with negative axillary palpation after NAC, and FNR is also less than 10%.Registration::chictr.org.cn, ChiCTR2100049093

Purpose: Patients with human epidermal growth factor receptor 2 (HER2)–low advanced breast cancer can benefit from trastuzumab deruxtecan. Given the unclear prognostic characteristics of HER2-low breast cancer, we investigated the prognostic characteristics of HER2-low expression from primary tumor to residual disease after neoadjuvant chemotherapy (NACT). Materials and Methods: The data of HER2-negative patients receiving NACT at our center were collected. Pathological complete response (pCR) rate were compared between HER2-0 and HER2-low patients. The evolution of HER2 expression from primary tumor to residual disease and its impact on disease-free survival (DFS) were examined. Results: Of the 690 patients, 494 patients had HER2-low status, of which 72.3% were hormone receptor (HR)–positive (p < 0.001). The pCR rates of HER2-low and HER2-0 patients (14.2% vs. 23.0%) showed no difference in multivariate analysis regardless of HR status. No association was observed between DFS and HER2 status. Of the 564 non-pCR patients, 57 (10.1%) changed to HER2-positive, and 64 of the 150 patients (42.7%) with HER2-0 tumors changed to HER2-low. HER2-low (p=0.004) and HR-positive (p=0.010) tumors before NACT were prone to HER2 gain. HER2 gain patients had a better DFS compared with HER2-negative maintained patients (87.9% vs. 79.5%, p=0.048), and the DFS of targeted therapy group was better than that of no targeted therapy group (92.4% vs. 66.7%, p=0.016). Conclusion Although HER2-low did not affect the pCR rate and DFS, significant evolution of HER2-low expression after NACT creates opportunities for targeted therapy including trastuzumab.

Objective:To evaluate the value of preoperative prediction of vessel invasion (VI) of locally advanced gastric cancer by machine learning model based on the venous phase enhanced CT radiomics features.Methods:A retrospective analysis of 296 patients with locally advanced gastric cancer confirmed by pathology in the First Affiliated Hospital of Zhengzhou University from July 2011 to December 2020 was performed. The patients were divided into VI positive group ( n=213) and VI negative group ( n=83) based on pathological results. The data were divided into training set ( n=207) and test set ( n=89) according to the ratio of 7∶3 with stratification sampling. The clinical characteristics of patients were recorded, and the independent risk factors of gastric cancer VI were screened by multivariate logistic regression. Pyradiomics software was used to extract radiomic features from the venous phase enhanced CT images, and the minimum absolute shrinkage and selection algorithm (LASSO) was used to screen the features, obtain the optimal feature subset, and establish the radiomics signature. Four machine learning algorithms, including extreme gradient boosting (XGBoost), logistic, naive Bayes (GNB), and support vector machine (SVM) models, were used to build prediction models for the radiomics signature and the screened clinical independent risk factors. The efficacy of the model in predicting gastric cancer VI was evaluated by the receiver operating characteristic curve. Results:The degree of differentiation (OR=13.651, 95%CI 7.265-25.650, P=0.003), Lauren′s classification (OR=1.349, 95%CI 1.011-1.799, P=0.042) and CA199 (OR=1.796, 95%CI 1.406-2.186, P=0.044) were independent risk factors for predicting the VI of locally advanced gastric cancer. Based on the venous phase enhanced CT images, 864 quantitative features were extracted, and 18 best constructed radiomics signature were selected by LASSO. In the training set, the area under the curve (AUC) of XGBoost, logistic, GNB and SVM models for predicting gastric cancer VI were 0.914 (95%CI 0.875-0.953), 0.897 (95%CI 0.853-0.940), 0.880 (95%CI 0.832-0.928) and 0.814 (95%CI 0.755-0.873), respectively, and in the test set were 0.870 (95%CI 0.769-0.971), 0.877 (95%CI 0.788-0.964), 0.859 (95%CI 0.755-0.961) and 0.773 (95%CI 0.647-0.898). The logistic model had the largest AUC in the test set. Conclusions:The machine learning model based on the venous phase enhanced CT radiomics features has high efficacy in predicting the VI of locally advanced gastric cancer before the operation, and the logistic model demonstrates the best diagnostic efficacy.

Objective:To investigate the feasibility and early clinical efficacy of spherical motion axis hinge knee prosthesis to reconstruct distal femoral bone defects.Methods:A retrospective analysis was performed on 16 patients admitted to PLA 960th Hospital and Tianjin Hospital from October 2019 to November 2021, including 8 males and 8 females, with an average age of 43.3±17.8 years (range, 15-71 years). There were 13 patients of primary tumors of the distal femur and 3 patients of postoperative revision of knee joint prostheses. Among the 13 patients with distal femur tumors, there were 6 cases of osteosarcoma, 5 cases of giant cell tumor of bone, 1 case of leiomyosarcoma and 1 case of chondrosarcoma. The reasons for revision after prosthesis replacement in 3 cases were: 2 cases of aseptic loosening after tumor-type prosthesis and 1 case of periphery fracture of surface artificial knee prosthesis. A spherical shaft rotary hinged knee prosthesis was designed and fabricated to reconstruct postoperative femoral defects in 16 patients. Follow up regularly after the operation, recheck the X-ray film to evaluate the lower limb force line, evaluate the quality of life after the operation with the Chinese version of 36-item short-form (SF-36), and evaluate the postoperative limb function with the Musculoskeletal Tumor Society (MSTS) 93 evaluation system.Results:All 16 patients were successfully placed with prostheses, and except for 2 patients undergoing total femoral replacement, the length of bone defects was 18.2±11.7 cm (range, 8.6-47.1 cm) in other 14 patients, and the operation time was 138±19 min (range, 110-170 min), the intraoperative blood loss was 211±118 ml (range, 100-500 ml). The postoperative full length orthostatic X-ray film of the lower limbs showed that the distance between the mechanical axis of the lower limb and the center of the knee joint was 0.1 (0, 0.7) cm in 16 patients, and the hip-knee ankle angle was 179.0°±2.3°(range, 173.3°-182.2°). The patients were followed up for 12-36 months. No prosthesis complications were found in 16 patients. The SF-36 score was 56.7±7.0 (range, 42.7-67.4) for physiological function and 54.1±7.6 (range, 40.5-66.3) for psychological function. The maximum knee flexion angle was 120.0°±15.6° (range, 95°-130°). The MSTS 93 score of 15 patients with tumor was 25.0±1.7 (range, 22-28), including 7 excellent and 8 good. One patient developed liver and lung metastases 10 months after surgery and died 18 months after surgery. The remaining patients, as of the last follow-up, were alive and had no local recurrence or distant metastases. Tumor-free survival time was 25.8±8.4 months (range, 12-36 months).Conclusion:The spherical motion axis hinge knee prosthesis reconstruction for distal femoral bone defects is simple and fast in intraoperative prosthesis installation, and there are no prosthetic related complications during short-term follow-up. The clinical efficacy is satisfactory.

Objective:To explore the reasons for revision of tumor prosthesis of knee joint and summarize the experience of revision surgery.Methods:We conducted a retrospective study of 33 patients who underwent revision surgery for tumor prosthesis of knee joint in Tianjin Hospital and the 960th Hospital of the People's Liberation Army Hospital from June 2004 to June 2018. There were 25 male and 8 female patients, the mean age was 45±13.1 years (range 19-64 years) at the time of revision. Histological diagnosis was giant cell tumor in 17 patients, osteosarcoma in 9 patients, malignant fibrous histiocytoma in 3 patients and one for each of chondrosarcoma, peripheral schwannoma, ligamentoid fibroma and bone metastases. The reasons for revision were aseptic loosening in 23 cases, dislocation, stem breakage and periprosthetic fracture in 2 cases, infection in 3 cases, and local recurrence in 1 case. The general outcome, oncological outcome, reasons for prosthesis revision, postoperative limb function, and complications were summarized.Results:The median follow-up of the 33 patients was 48.0 (24.0, 107.0) months. The most common reason for revision was aseptic loosening (88%, 29/33), followed by infection (9%, 3/33) and local recurrence (3%, 1/33). The MSTS of 32 patients with survival more than 1 year was 24.28±4.74 points (range 9-30 points), which was statistically different from preoperative 11.78±5.23 points (range 4-21 points) ( t=10.02, P<0.001). The postoperative median TESS score of 32 patients with survival more than 1 year was 86.67(80.00, 91.67) points, and the preoperative median score was 56.0(43.17, 65.33) points, which was statistically significant ( Z=6.78, P<0.001). Postoperative complications occurred in 12 patients, most commonly mechanical problems (15%, 5/33) and infection (15%, 5/33), followed by local recurrence (6%, 2/33), with an overall complication rate of 36% (12/33). Conclusion:The main reason for revision of tumor prosthesis of knee joint is aseptic loosening. Revision surgery can achieve ideal postoperative function and should be the first choice for failure of prosthesis after initial replacement.

Objective:To retrospectively analyze the patients with spinal metastases who received surgical intervention and summarize the evolution of their clinical and pathological characteristics and surgical methods.Methods:The data of 703 patients with spinal metastases from January 2007 to December 2018 were collected retrospectively. There were 395 males (56.19%, 395/703) and 308 females (43.81%, 308/703) with an average age of 58.14±11.46 years (range 13-84 years). According to the degree of invasion and thoroughness of tumor resection, the surgical methods could be divided into minimally invasive surgery, decompression surgery, separation surgery, piecemeal resection and total en-bloc spondylectomy surgery. The operative methods were minimally invasive surgery in 89 cases (12.66%), decompression surgery in 96 cases (13.66%), separation surgery in 303 cases (43.10%), piecemeal resection in 182 cases (25.89%) and total en-bloc spondylectomy in 33 cases (4.69%). To analyze the trend of the clinical, pathological types and surgical treatment of patients with spinal metastases over the years, and determine the relevant factors affecting the decision-making of surgical methods by multivariate logistic regression.Results:The ratio of male to female was 1.28:1. 39.54% (278/703) of patients with single-segment involvement in 703 patients, 24.04% (169/703) of patients with double-segment metastasis and 36.42% (256/703) of patients with multi-segment metastasis. The most common type of primary tumor was lung cancer (34.57%, 243/703), followed by breast cancer (8.25%, 58/703), myeloma (8.11%, 57/703), gastrointestinal tumor (6.82%, 48/703) and renal malignant tumor (6.40%, 45/703). From 2007 to 2018, there was no significant difference in the percentage change of different age, gender and primary tumor source composition (age: χ 2=14.01, P=0.233; gender: χ 2=35.73, P=0.341; primary tumor: χ 2=120.09, P=0.074). The percentage of patients with sacrococcygeal metastasis decreased from 20.00% in 2008 to 1.89% in 2017 and the difference was statistically significant (χ 2=8.09, P=0.005). The percentage of patients with multi-level metastasis increased from 26.67% in 2008 to 52.83% in 2017, and the difference was statistically significant (χ 2=7.23, P=0.007). The percentage of patients with minimally invasive surgery decreased from 25.00% in 2007 to 5.88% in 2018, and the percentage of patients with segmented resection decreased from 53.33% in 2008 to 10.29% in 2018. The proportion of the two surgical methods showed a significant downward trend, and the differences were statistically significant (minimally invasive surgery: χ 2=1.46, P=0.026; segmented resection surgery: χ 2=19.56, P<0.001). The percentage of patients undergoing separation surgery increased from 13.33% in 2008 to 64.71% in 2018, and the proportion of patients undergoing total en-bloc spondylectomy increased from 0 in 2007 to 10.29% in 2018. Both surgical methods showed a significant growth trend and the differences were statistically significant (separation surgery: χ 2=27.09, P<0.001; χ 2=4.16, P=0.042). Multivariate Logistic regression analysis showed that age, metastatic site, number of metastatic segments, pathological vertebral fractures, Frankel grade, SINS score and VAS score were independent factors influencing surgical decision-making ( P<0.05). Conclusion:With different time and age, the invasiveness and thoroughness of surgery are increasing, which shows that the percentage of patients who underwent separation surgery and to-tal en-bloc spondylectomy is significantly increasing. Age, metastatic site, number of metastatic segments, pathological vertebral fractures, Frankel grade, SINS score and VAS score are independent factors affecting surgical decision-making.

Objective:To evaluate the clinical value of the New England spinal metastasis score (NESMS) in predicting the prognosis of patients with spinal metastases by retrospectively analyzing the medical records of multicenter spinal metastases in China.Methods:The data of 179 patients with spinal metastases from January 2008 to December 2018 were retrospectively collected. There were 108 males (60.3%) and 71 females (39.7%) with an average age of 59.79±10.88 years old (range 27-84 years). The patient demographic characteristics, primary tumor type, spinal metastases and segments, vertebral pathological fractures, neurological Frankel classification, physical function status, Karnofsky performance scale (KPS), visual analogue score (VAS), the spinal instability neoplastic score (SINS), modified Bauer score, NESMS score, Tomita score and modified Tokuhashi score were collected. The clinical value of NESMS score, Tomita score and modified Tokuhashi score in predicting the survival of patients with spinal metastases were compared. The independent factors affecting survival in these patients were analyzed by Cox proportional hazards regression model.Results:Among the 179 patients, the peak incidence of spinal metastases was in the age group of 61-75 years (45.3%, 81/179) of all patients. Lung cancer was the most common primary tumor (46.9%, 84/179). 40.8% (73/179) of patients had multi-segment metastasisand thoracic spine was the most common site with single-site metastasis (26.3%, 47/179). 28.5% (51/179) of the patients had visceral metastases and 52.0% (93/179) of the patients had extraspinal bone metastases. 31.3% (56/179) of the patients had pathological fractures of the involved vertebral bodies.114 patients received surgical treatment (63.4%). The mortality rates in 3-months, 6-months and 1-year were 22.4% (40/179), 51.4% (92/179) and 77.1% (138/179), respectively. The median survival time of patients with NESMS score of 0-3 was 3, 4, 8, and 10 months respectively with the mean survival time was 3.60±2.10, 6.77±3.39, 9.69±5.71 and 10.53±6.25 months. The 1-year mortality rates were 100% (13/13), 87.5% (42/48), 71.6% (63/88) and 66.7% (20/30) respectively. The consistency of NESMS score, Tomita score and modified Tokuhashi score in predicting survival of all patients was 0.63, 0.58 and 0.55, respectively. For patients with spinal metastases, the NESMS score was better than the Tomita score and modified Tokuhashi score in predicting survival at 3-months (AUC=1.00, 0.63, 0.42) and 6-months (AUC=0.71, 0.63, 0.45). But the accuracy of Tomita score was best in predicting survival at 1-year (AUC=0.66, 0.61, 0.38). Multivariate Cox proportional hazards regression model analysis showed that growth rate of primary tumor, neurological function Frankel score, albumin level and surgical treatment were independent factors affecting the survival time of patients with spinal metastases ( P<0.05). Conclusion:The consistency and accuracy of NESMS score in predicting survival of patients with spinal metastases are better than Tomita score and modified Tokuhashi score, especially in predicting 3- and 6-month survival. The growth rate of primary tumor, Frankel classification, albumin level and surgical treatment were independent factors affecting the survival time of patients with spinal metastases.