Bone remodeling and bone regeneration are essential for preserving skeletal integrity and maintaining mineral homeostasis.T cells,as key members of adaptive immunity,play a pivotal role in bone remodeling and bone regeneration by producing a range of cytokines and growth factors.In the physiological state,T cells are involved in the maintenance of bone homeostasis through interactions with mesenchymal stem cells,osteoblasts,and osteoclasts.In pathological states,T cells participate in the pathological process of different types of osteoporosis through interaction with estrogen,glucocorticoids,and parathyroid hormone.During fracture healing for post-injury repair,T cells play different roles during the inflammatory hematoma phase,the bone callus formation phase and the bone remodeling phase.Targeting T cells thus emerges as a potential strategy for regulating bone homeostasis.This article reviews the research progress on related mechanisms of T cells immunity involved in bone remodeling and bone regeneration,with a view to providing a scientific basis for targeting T cells to regulate bone remodeling and bone regeneration.

Objective:To investigate the relationship between 21-gene recurrence risk score (21-Gene RS) and the prognosis and clinicopathological features of hormone receptor (HR) positive, HER2-negative early breast cancer patients who did not receive neoadjuvant therapy.Methods:A total of 469 patients with HR positive and HER2-negative early breast cancer who received surgical treatment in the First Affiliated Hospital, Zhejiang University School of Medicine from January 2014 to October 2017 were selected. Their clinicopathological data were retrospectively analyzed. Tumor tissue samples were collected from patients, and the expression of 21-gene was detected by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR). The 21-Gene RS was calculated according to the Trial Assigning Individualized Options for Treatment (TAILORx) RS grouping and National Surgical Adjuvant Breast and Bowel Project B-20 (NSABP B-20) RS grouping principles. Patients were divided into low (21-Gene RS<11 or 21-Gene RS<18), intermediate (11≤21-Gene RS<26 or 18≤21-Gene RS<31) and high (21-Gene RS≥26 or 21-Gene RS≥31) risk groups, and the clinicopathological features and prognostic differences of patients in different risk groups were compared. Statistical data were compared by chi-square test. Survival analysis was performed using Kaplan-Meier curve analysis and the differences between groups were compared using Log-rank test. Multivariate analysis was conducted by COX regression analysis.Results:Based on TAILORx RS grouping, the proportions of low-risk, intermediate-risk and high-risk groups among the 469 patients were 18.8% (88/469), 48.2% (226/469) and 33.0% (155/469), respectively. Based on NSABP B-20 RS grouping, the proportion of low-risk, intermediate-risk and high-risk groups were 43.1% (202/469), 37.5% (176/469) and 19.4% (91/469), respectively. The association of 21-Gene RS with histological grading, luminal typing, Ki-67 expression, and chemotherapy and treatment modalities were statistically significant ( P<0.05) regardless of TAILORx RS grouping or NSABP B-20 RS grouping. Kaplan-Meier survival curve suggested poor prognosis in high-risk group ( P<0.05, Log-rank test). Multivariate COX regression analysis showed that surgical method and 21-Gene RS were risk factors affecting the prognosis of patients. Conclusions:21-Gene RS is significantly associated with the prognosis of patients with HR-positive, HER2-negative, early-stage breast cancer not receiving neoadjuvant therapy, as well as with their clinicopathological characteristics such as patients′ histologic grade, luminal typing, Ki-67 expression, and whether or not they are treated with chemotherapy or other treatment modalities.The 21-Gene RS threshold of 11 and 26 or 18 and 31 can be used to grade the prognosis in Chinese patients with early-stage breast cancer. More researches are needed to guide the selection of postoperative adjuvant therapy for patients with HR-positive and HER2-negative early-stage breast cancer.

Objective:To investigate the feasibility of multi-slice spiral CT (MSCT) imaging feature of gastric stromal tumor (GST) in evaluating Ki-67 index expression .Methods:The clinical and CT imaging data of 501 patients with GST confirmed by surgery and pathology were retrospectively studied in Zhongshan Hospital affiliated to Fudan University and the Affiliated TCM Hospital of Southwest Medical University from Nov 2014 to Nov 2021. By immunohistochemical results, tumors were divided into Ki-67 low expression group (Ki-67≤6%, 335 lesions) and high expression group (Ki-67>6%, 168 lesions). Multivariate logistic regression analysis was conducted.Results:Between the two groups,there were statistical differences in the longest and shortest diameter of tumor, CT value on venous phase, CT attenuation value ( Z=4.80, 4.91, 3.21, 3.29, all P<0.01) and tumor location,morphology, necrosis, ulcer, feeding artery, vascular enhancement, positive fat sign around disease, gastrointestinal bleeding ( χ2=10.77, 13.49, 8.59, 22.87, 7.59, 7.23, 7.76, 8.58, all P<0.05). Tumor ulceration positive ( OR=1.88, 95%CI: 1.17-3.03) was independent risk factor of Ki-67 high expression ( P=0.009). Gastric antrum was used as the reference for tumor location, cardia ( OR=5.41, 95% CI:1.25-23.46) was independent risk factor of Ki-67 high expression ( P=0.024). Conclusion:MSCT has a definite predictive value for the expression in Ki-67 index of GST cases.

Objective:To evaluate the efficacy and side effects of PD-1 monoclonal antibody in the treatment of advanced metastatic renal cell carcinoma in China.Methods:The clinical data of 117 patients with advanced metastatic renal cell carcinoma (mRCC) treated with PD-1 monoclonal antibody from October 2016 to February 2022 were retrospectively analyzed. There were 87 males (74.4%) and 30 females (25.6%), with an average age of (57.9±10.9) years old, BMI of (23.6±3.4) kg/m 2and smoking history of 79 (67.5%). There were 44 cases (37.6%) with hypertension, 19 (16.2%) cases of diabetes. The ECOG score of 59.8% (70/117) patients was 0, 33.3% (39/117) was 1, 4.3% (5/117) was 2, and 2.5% (3/117) was 3. The pathological type of 104 cases were renal clear cell carcinoma (ccRCC), 8 cases of papillary renal cell carcinoma, 2 cases of chromophobe cell carcinoma, 2 cases of collecting duct carcinoma and 1 case of eosinophilic cell carcinoma. The general condition of the overall population and the overall survival (OS) of relevant subgroups were analyzed. Secondary goals included progression free survival (PFS), objective response rate (ORR), adverse reactions, overall survival (OS), and progression free survival (PFS). Results:65.8% (77 / 117) of the patients chose targeted combined with PD-1 monoclonal antibody in the first-line treatment. The main targeted drugs were acitinib (81.8%, 63 / 77), tirelizumab (37.6%, 29 / 77) and cindilimab (25.9%, 20 / 77). After first-line treatment, 19.6.1% (23 / 117) patients needed to be converted to second-line treatment, and 15 patients changed the type of PD-1 antibody during treatment. In addition, the targeted drug of combined therapy was replaced by acitinib in 8 patients. The main causes of drug withdrawal were disease progression (70.7%, 29 / 41) and death (29.2%, 12 / 41). The median OS of the overall population was 35.6 (19-60) months and PFS was 12.1 (1-60) months. The ORR of the overall population was 47.8% (56 / 117). 4.2% (5/117) patients had complete remission, another 17.0% (20/117) patients were in stable condition, and 43.5% (51 / 117) patients were in partial remission. In the first-line treatment, the median PFS time of targeted combined with PD-1 monoclonal antibody was 12.6 (1-30) months, the median PFS time of PD-1 single drug immunotherapy was 10.5 (1-60) months. In the second-line treatment, the PFS of patients treated with PD-1 monoclonal antibody was 10.1 (4-19) months, and that of patients treated with PD-1 monoclonal antibody combined with targeted therapy was 11.7 (1-25) months. The most common adverse reactions were elevated blood pressure (18.5%, 23 / 124), followed by hypothyroidism (15.3%%, 19/124), rash (14.5%, 18 / 124), elevated transaminase (10.5%, 13 / 124) and bone marrow suppression (9.7%, 12/124). 9.4% (11 / 117) patients needed to reduce the related adverse reactions by interrupting the treatment control of PD-1 monoclonal antibody.Conclusions:The safety and efficacy of PD-1 monoclonal antibody in domestic patients are better, and the side effects are less. The efficacy and safety of PD-1 monoclonal antibody combined with targeted therapy in the real world population are consistent with many key clinical trials abroad. PD-1 monoclonal antibody combined with targeted drugs can be popularized in the domestic MRCC population.

Purpose: The incidence of adenocarcinoma of the esophagogastric junction (AEG) has increased in recent years, and the optimal surgical strategy for AEG remains highly controversial. We aimed to evaluate the safety and efficacy of proximal gastrectomy with double-tract reconstruction (PG-DT) for the treatment of patients with AEG. Materials and Methods: We retrospectively analyzed patients with Siewert type II/III AEG between January 2013 and July 2018. Clinicopathological characteristics, survival, surgical outcomes, quality of life (QOL), and nutritional status were compared between the PG-DT and total gastrectomy with Roux-en-Y anastomosis (TG-RY) groups. Results: After propensity score matching, 33 patients in each group were analyzed. There were no statistical differences between the 2 groups in terms of disease-free survival and overall survival. The surgical option was not an independent prognostic factor based on the multivariate analysis. In addition, no differences were found in terms of surgical complications. There were no significant differences in QOL assessed by the Visick grade, Gastrointestinal Symptom Rating Scale, or endoscopic findings. Furthermore, the long-term nutritional advantage of the PG-DT group was significantly greater than that of the TG-RY group. Conclusions PG-DT is a safe and effective procedure for patients with local Siewert type II/III AEG, regardless of the TNM stage.

Objective:To investigate the clinical value of early gastroscopy for patients with hypopharyngeal cancer.Methods:A total of 231 cases of hypopharyngeal cancer diagnosed and treated in the First Affiliated Hospital of Xiamen University from January 2010 to December 2014 were included in the retrospective analysis. The 5-year survival rate of hypopharyngeal cancer and patients accompanied with synchronous esophageal cancer (including early and advanced esophageal cancer), as well as the detection rate of synchronous esophageal cancer by gastroscopy and systemic PET-CT examination were statistically analyzed.Results:The 5-year survival rate of hypopharyngeal cancer was 38.96% (90/231). The 5-year survival rates of 62 patients accompanied with synchronous esophageal cancer and 169 patients without were 27.42% (17/62) and 43.20% (73/169), respectively, with statistic difference ( χ2=4.747, P=0.029). The 5-year survival rate of 49 patients accompanied with synchronous early esophageal cancer was 30.69% (17/49). Among the 13 patients with synchronous progressive esophageal cancer, none had a survival period of 5 years, which was significantly different compared with the patients with synchronous early esophageal cancer ( P=0.013). The detection rates of synchronous esophageal carcinoma by gastroscopy and by systemic PET-CT were 26.84% (62/231) and 14.29% (33/231), respectively, with statistic difference ( χ2=11.14, P<0.01). The detection rates of synchronous early esophageal carcinoma by gastroscopy and by systemic PET-CT were 21.21% (49/231) and 8.66% (20/231), respectively, and the difference was also statistically significant ( χ2=14.328, P<0.01). Conclusion:Hypopharyngeal cancer accompanied with synchronous esophageal cancer is of high risk, which affects the survival rate of patients. Early gastroscopy in hypopharyngeal cancer patients can significantly improve the detection rate of synchronous esophageal cancer, which helps to design individualized regimen to improve the survival rate of patients.

Objective    To explore the feasibility and clinical value of free-of-puncture positioning in three-dimension-guided anatomical segmentectomy for ground-glass nodule (GGN) compared with percutaneous positioning. Methods    Clinical data of 268 enrolled patients undergoing anatomical pulmonary segmentectomy from October 2018 to June 2019 were retrospectively collected, including 75 males and 193 females with an average age of 56.55±12.10 years. The patients were divided into two groups, including a percutaneous positioning group (n=89) and a free-of-puncture positioning group (n=179). Perioperative data of the two groups were compared. Results    The average CT scan times of the percutaneous positioning group was 3.01±0.98 times, and the numerical rating scale (NRS) score of puncture pain was 3.98±1.61 points. Pulmonary compression pneumothorax (≥30%) occurred in 7 (7.87%) patients and intercostal vascular hemorrhage occurred in 8 (8.99%) patients after puncture. Lung nodules were successfully found and removed in both groups. There was no statistically significant difference between the two groups in the location of nodules (P=0.466), operation time (151.83±39.23 min vs. 154.35±33.19 min, P=0.585), margin width (2.07±0.35 cm vs. 1.98±0.28 cm, P=0.750), or the number of excised subsegments (2.83±1.13 vs. 2.73±1.16, P=0.530). Conclusion    Anatomical segmentectomy with three-dimensional navigation avoids the adverse consequences of puncture, which has the same clinical efficacy and meets the requirements of oncology compared with percutaneous positioning. The free-of-puncture positioning method can be used for GGN located in the central region of pulmonary segment/subsegment or adjacent to   intersegment veins instead of percutaneous positioning.

The lateral hypothalamic area (LHA) plays a pivotal role in regulating consciousness transition, in which orexinergic neurons, GABAergic neurons, and melanin-concentrating hormone neurons are involved. Glutamatergic neurons have a large population in the LHA, but their anesthesia-related effect has not been explored. Here, we found that genetic ablation of LHA glutamatergic neurons shortened the induction time and prolonged the recovery time of isoflurane anesthesia in mice. In contrast, chemogenetic activation of LHA glutamatergic neurons increased the time to anesthesia and decreased the time to recovery. Optogenetic activation of LHA glutamatergic neurons during the maintenance of anesthesia reduced the burst suppression pattern of the electroencephalogram (EEG) and shifted EEG features to an arousal pattern. Photostimulation of LHA glutamatergic projections to the lateral habenula (LHb) also facilitated the emergence from anesthesia and the transition of anesthesia depth to a lighter level. Collectively, LHA glutamatergic neurons and their projections to the LHb regulate anesthetic potency and EEG features.

Objective:To analyse the MRI features of hilar schwannomas and pathology.Methods:The MRI and pathological features of 5 patients with hilar schwannomas which were confirmed histopathologically at Zhongshan Hospital, Fudan University from January 2012 to August 2019 were retrospectively analyzed. There were 3 males and 2 females, with age ranging from 47 to 67 years (median age 59 years). Contrast-enhanced MRI scans were performed in these 5 patients. The site, shape, size, edge, signal and enhancement pattern of these lesions and pathologicl findings were analysed.Results:All the lesions were single, located in and around the perihilar region. Four lesions were oval or roundish, and 1 lesion was sausage-shaped. Two lesions were solid while 3 lesions were cystic solid. All lesions had clear borders with intact capsules. The solid parts in all the lesions showed isointensity or slightly hypointensity on T 1 weighted imaging, hyperintensity on fat-suppression T 2 weighted imaging (T 2WI), hyperintensity on diffusion weighted imaging, slightly hyperintensity / isointensity / slightly hypointensity on apparent diffusion coefficient maping with progressive mild to moderate enhancement. Thick septum was observed in the cystic part. The septum and capsule showed mild to moderate delayed enhancement. Fluid-fluid level was seen in one lesion. The cystic solid lesion in one patient showed the " target sign" on fat-suppression T 2WI. All the 5 tumors were close to blood vessels, and their long axes followed the shape of the portal vein. In 1 patient, the lesion slightly compressed the adjacent bile ducts. Pathological examination showed that all the tumors in the 5 patients had complete fibrous envelopes, and the solid parts of the tumor showed mainly spindle cells. Conclusions:The MRI features of hilar schwannomas were oval or sausage-shaped lesions, with the long axis along the portal vein. They were prone to develop cystic changes, and a"target sign"could be shown on fat-suppression T 2WI. The solid parts, septa and capsules of the lesions showed mild to moderate progressive enhancement after contrast-injection.

BACKGROUND: For early-stage lung cancer, segmentectomy can get the same oncological benefits as lobectomy. Accurate identification of the intersegmental border is the key to segmentectomy. This study used extended segmentectomy and extended subsegmentectomy to treat lung intersegmental and intersubsegmental ground-glass nodules (GGN) by utilizing modified inflation-deflation methods to distinguish the intersegmental and intersubsegmental borders. The accuracy of modified inflation-deflation methods and the effectiveness of extended resection to guarantee a safe surgical margin were evaluated. METHODS: A retrospective analysis of 83 cases of extended segmentectomy and extended subsegmentectomy was conducted. Preoperative three-dimensional computed tomography bronchography and angiography (3D-CTBA) revealed that nodules were involved in intersegmental or intersubsegmental veins. Based on preoperative three-dimensional reconstruction, the surgery was designed to extendedly remove the dominant lung segment or subsegment with nodules involved. When the dominant lung segment or subsegment could not be identified, the simpler lung segment or subsegment was selected for the resection. After the target vessel and bronchus were cut off during the operation, modified inflation-deflation method was used to determine the border, and a stapler was used to resect the adjacent lung segment or subsegment tissue by 2 cm-3 cm around the inflation-deflation boundary line. Then, the relationship between the inflation-deflation boundary line and the nodule and the width of the surgical margin were measured. Clinical data were collected during the perioperative period. RESULTS: 56 extended segmentectomies and 27 extended subsegmentectomies were performed. The average diameter of pulmonary nodules was (0.9±0.3) cm. There were 79 cases with clearly inflation-deflation boundary lines. The average time needed for the appearance of the lines was (13.6±6.5) min. In 55 cases, the nodules were involved with the inflation-deflation boundary lines. Meanwhile, the remaining 24 cases revealed an average minimum distance of (0.6±0.3) cm between nodules and the boundary lines. The average width of surgical margin was (2.1±0.3) cm in these 79 cases. No deaths or major complications appeared during 30 d after operation. CONCLUSIONS The modified inflation-deflation method can effectively define the intersegmental and intersubsegmental borders, and guarantee the safe surgical margins of extended segmentectomy and extended subsegmentectomy to treat intersegmental and intersubsegmental small lung tumors.