Integrin α _v β ₃ is overexpressed in various tumor cells and angiogenesis. To date, no drug has been proven to target it for therapy. A first-in-human study was designed to investigate the safety, pharmacokinetics, and dosimetry of ¹⁷⁷Lu-AB-3PRGD2, a novel integrin α _v β ₃-targeting radionuclide drug with an albumin-binding motif to optimize the pharmacokinetics. Ten patients (3 men, 7 women; aged 45 ± 16 years) with integrin α _v β ₃-avid tumors were recruited to accept ¹⁷⁷Lu-AB-3PRGD2 injection in a dosage of 1.57 ± 0.08 GBq (42.32 ± 2.11 mCi), followed by serial scans to obtain its dynamic distribution in the body. Safety tests were performed before and every 2 weeks after the treatment for 6-8 weeks. No adverse event over grade 3 was observed. ¹⁷⁷Lu-AB-3PRGD2 was excreted mainly through the urinary system, with intense radioactivity in the kidneys and bladder. Moderate distribution was found in the liver, spleen, and intestines. The estimated blood half-life was 2.85 ± 2.17 h. The whole-body effective dose was 0.251 ± 0.047 mSv/MBq. The absorbed doses were 0.157 ± 0.032 mGy/MBq in red bone marrow and 0.684 ± 0.132 mGy/MBq in kidneys. This first-in-human study of ¹⁷⁷Lu-AB-3PRGD2 treatment indicates its promising potential for targeted radionuclide therapy of integrin α _v β ₃-avid tumors. It merits further studies in more patients with escalating doses and multiple treatment courses.

The anterior cingulate cortex (ACC) has recently been proposed as a key player in the representation of itch stimuli. However, to date, little is known about the contribution of specific ACC interneuron populations to itch processing. Using c-Fos immunolabeling and in vivo Ca²⁺ imaging, we reported that both histamine and chloroquine stimuli-induced acute itch caused a marked enhancement of vasoactive intestinal peptide (VIP)-expressing interneuron activity in the ACC. Behavioral data indicated that optogenetic and chemogenetic activation of these neurons reduced scratching responses related to histaminergic and non-histaminergic acute itch. Similar neural activity and modulatory role of these neurons were seen in mice with chronic itch induced by contact dermatitis. Together, this study highlights the importance of ACC VIP⁺ neurons in modulating itch-related affect and behavior, which may help us to develop novel mechanism-based strategies to treat refractory chronic itch in the clinic.
Animals ; Pruritus/physiopathology* ; Vasoactive Intestinal Peptide/metabolism* ; Interneurons/metabolism* ; Gyrus Cinguli/metabolism* ; Mice ; Male ; Mice, Inbred C57BL ; Histamine ; Chloroquine ; Optogenetics ; Mice, Transgenic

Following the principles of evidence-based medicine,in accordance with the structure and drafting rules of standardized documents,based on literature research,according to the characteristics of chronic cough in children and issues that need to form a consensus,the TCM Guidelines for Diagnosis and Treatment of Chronic Cough in Children was formulated based on the Delphi method,expert discussion meetings,and public solicitation of opinions.The guideline includes scope of application,terms and definitions,eti-ology and diagnosis,auxiliary examination,treatment,prevention and care.The aim is to clarify the optimal treatment plan of Chinese medicine in the diagnosis and treatment of this disease,and to provide guidance for improving the clinical diagnosis and treatment of chronic cough in children with Chinese medicine.

Objective:To analyze the ultrasonic features of tonsillar lymphoma to improve the diagnostic accuracy.Methods:The clinical, pathological and ultrasonic data of nine patients with tonsillar lymphoma confirmed by pathology at Tianjin Medical University Cancer Institute and Hospital during June 2015 and June 2022 were analyzed retrospectively, and the characteristics of their ultrasonic images were summarized.Results:All 9 cases of tonsil lymphoma were unilateral tonsil disease, including 4 cases on the left side and 5 cases on the right side. The average maximum diameter of tonsil lymphoma in 9 cases was 4.32 cm. There were 3 cases with simultaneous involvement of tonsil and cervical lymph nodes, all of which were ipsilateral lymph nodes. Gray scale ultrasound showed that the lesions were hypoechoic, with clear boundaries in 7 cases and unclear boundaries in 2 cases. The shape was full and irregular in 5 cases and oval in 4 cases. The echo was uniform in 7 cases and uneven in 2 cases. Color Doppler ultrasonography showed abundant internal blood flow signal in 1 case, a little dotted linear internal blood flow signal in 5 cases, and no obvious internal blood flow signal in 3 cases.Conclusions:The ultrasonic features of tonsillar lymphoma include hypoechoic area, clear boundary, full shape, irregular and uniform internal echo, no or low linear signal of internal blood flow. Ultrasonography is of great value in the diagnosis of this disease and can help clinical decision-making.

Objective: To explore the network structure characteristics and core items of rural middle school students suffering from campus bullying and anxiety symptoms, so as to provide a reference basis for the precise prevention and intervention of the comorbidity of campus bullying and anxiety symptoms. Methods: From September 2021 to March 2022, a multi stage random cluster sampling method was used to select 1 920 rural middle school students from Xuzhou. The Chinese version of the Olweus Bully/Victim Questionnaire was used to investigate the situation of campus bullying, and the Chinese version of the Generalized Anxiety Disorder (GAD-7) was used to assess anxiety symptoms. The network analysis method was used to construct the network between suffering from campus bullying and anxiety symptoms of rural middle school students to evaluate the centrality, bridge strength, stability and accuracy of each item. Results: The total score of suffering from campus bullying symptoms of rural middle school students was (10.42±3.26) points, and the total score of anxiety symptoms was (11.47±4.93) points. The symptom with the highest strength and expected influence was "unable to stop or control one s worry emotions", and the node strength and expected influence value was 1.041 7. The nodes "feel nervous, anxious or irritable" and "unable to stop or control one s worry emotions" were most closely related. The symptoms with the highest bridge strength were "others give me ugly nicknames to scold me or make fun of and satirize me" and "unable to stop or control one s worry emotions". Conclusions Rural middle school students suffering from campus bullying is related to anxiety symptoms. Accurate intervention according to the intervention targets may minimize the negative impact of suffering from campus bullying and anxiety symptoms on rural middle school students.

Objective:To analyze the ultrasonic features of tonsillar lymphoma to improve the diagnostic accuracy.Methods:The clinical, pathological and ultrasonic data of nine patients with tonsillar lymphoma confirmed by pathology at Tianjin Medical University Cancer Institute and Hospital during June 2015 and June 2022 were analyzed retrospectively, and the characteristics of their ultrasonic images were summarized.Results:All 9 cases of tonsil lymphoma were unilateral tonsil disease, including 4 cases on the left side and 5 cases on the right side. The average maximum diameter of tonsil lymphoma in 9 cases was 4.32 cm. There were 3 cases with simultaneous involvement of tonsil and cervical lymph nodes, all of which were ipsilateral lymph nodes. Gray scale ultrasound showed that the lesions were hypoechoic, with clear boundaries in 7 cases and unclear boundaries in 2 cases. The shape was full and irregular in 5 cases and oval in 4 cases. The echo was uniform in 7 cases and uneven in 2 cases. Color Doppler ultrasonography showed abundant internal blood flow signal in 1 case, a little dotted linear internal blood flow signal in 5 cases, and no obvious internal blood flow signal in 3 cases.Conclusions:The ultrasonic features of tonsillar lymphoma include hypoechoic area, clear boundary, full shape, irregular and uniform internal echo, no or low linear signal of internal blood flow. Ultrasonography is of great value in the diagnosis of this disease and can help clinical decision-making.

Objective:To evaluate the efficacy and safety of θ short burst rapid pulse stimulation(TBS)in treating schizophrenia by meta-analysis.Methods:Randomized controlled trials(RCTS)on TBS in the treatment of schizophrenia were searched from CNKI,Wanfang,VIP,China Biomedicine,Web of science,PubMed,Embase and Cochrane Library databases to December 2022.The main study indicator was the Positive and Negative Symptoms Scale(PANSS).Risk quality assessment of the included literatures was performed by two reviewers and statistical analysis was performed using RevMan5.3.Results:A total of 13 RCTS with 641 patients were included.Meta-anal-ysis showed that TBS targeting the left dorsolateral prefrontal cortex(DLPFC)with intervention duration longer than 2 weeks decreased the PANSS total scores(WMD=-4.63,95％CI:-5.75--3.51,P＜0.001),positive symptom scores(WMD=-1.13,95％CI:-2.00--0.26,P＜0.05),negative symptom scores(WMD=-2.51,95％CI:-2.77--1.53,P＜0.001)and general psychopathological symptom scores(WMD=-1.20,95％CI:-1.80--0.60,P＜0.001).The adverse reactions of TBS included dizziness,and no serious adverse e-vents were reported.Conclusion:TBS has high safety,and stimulation of left dorsolateral prefrontal cortex targets for more than 2 weeks could effectively improve psychiatric symptoms in patients with schizophrenia.

In recent years,cortisol has been used as a biomarker to assess stress in dogs.To evaluate the welfare of dogs,we reviewed cortisol levels and changes in dogs under various stresses.We explored the influential factors that relieve stress in accordance with variations in cortisol levels,to improve the measures which reduce stress in dogs.It is recommended to apply cortisol measurement and behavioral observation comprehensively to evaluate stress in dogs more accurately.

Objective:To analyze the differences in clinical outcomes and toxicities between postoperative radiotherapy alone and postoperative radiochemotherapy for soft tissue sarcoma (STS), as well as the related factors affecting clinical prognosis of STS patients.Methods:Retrospective analysis of patients diagnosed with primary STS admitted to Zhejiang Cancer Hospital from May 2012 to May 2019 was performed, who received adjuvant radiotherapy after surgery, combined with or without postoperative chemotherapy. A total of 100 patients were enrolled and divided into postoperative radiotherapy group ( n=52) and postoperative radiochemotherapy group ( n=48). The median follow-up time was 65 months (24-124 months). The local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), overall survival (OS), and treatment-related toxicities were recorded in two groups. The survival rate was calculated by Kaplan-Meier analysis. Log-rank test was used for univariate analysis, and Cox model was used for multivariate analysis. Results:In multivariate analysis, the maximum tumor diameter was an independent predictor of local tumor recurrence ( HR=4.80, 95% CI=1.16-19.85, P=0.031), distant metastasis ( HR=4.67, 95% CI=1.53-14.26, P=0.007) and OS ( HR=4.10, 95% CI=1.35-12.48, P=0.013). In addition, the degree of myelosuppression in patients in postoperative radiochemotherapy was significantly higher than that in their counterparts in postoperative radiotherapy group ( P<0.001). Conclusions:In the limited number of patients, radiochemotherapy has no advantages over radiotherapy alone in distant metastasis or survival rate. Besides, it increases toxicities, but the overall tolerability is favorable. It is necessary to conduct prospective randomized studies in a large population and subgroup analysis of histological subtypes, aiming to obtain results with better reference value.

Objective:This study aimed to investigate the risk features of postoperative tumor recurrence of medullary thyroid carcinoma.Methods:One hundred and seventy two patients with medullary thyroid carcinoma diagnosed at Tianjin Cancer Hospital between Jan 2010 and Jan 2018 were enrolled in this study. Based on the follow-up results, patients were divided into tumor recurrence and non-tumor recurrence group. US features,clinicopathological characteristics and somatic RET mutations were evaluated between the two groups. The cut-off values of pre-and post-operative serum calcitonin were calculated by ROC curve.Univariate and multivariate analysis were adopted between the two groups to determine independent risk factors for tumor recurrence of MTC.Tumor-free survival was determined by Kaplan-Meier analysis.Results:Univariate analysis showed that preoperative serum calcitonin≥1 367 pg/ml ( χ2=18.909, P=0.000), postoperative serum calcitonin ≥61 pg/ml ( χ2=72.278, P=0.000), mulifocality ( χ2=11.787, P=0.001),lesions in both lobes ( χ2=10.452, P=0.003), extrathyroidal invasion ( χ2=14.511, P=0.000), T3+T4-staging ( χ2=11.920, P=0.001)、TNMⅢ+Ⅳ-staging ( χ2=18.915, P=0.000), ACR TI-RADS 5 ( χ2=7.162, P=0.006) and RET mutation ( χ2=10.937, P=0.001) were significantly related to tumor recurrence of medullary thyroid carcinoma. Multivariate analysis demonstrated that postoperative serum calcitonin≥61 pg/ml ( OR=22.323, 95%CI: 6.370-78.236) and RET mutation ( OR=4.054, 95%CI: 1.354-12.139) were the independent factors related to tumor recurrence of medullary thyroid carcinoma.The survival curves of MTC patients showed a significantly lower percentage of surviving patients in the group with postoperative serum calcitonin ≥61 pg/ml ( P=0.000) or RET mutations ( P=0.001). Conclusions:Postoperative serum calcitonin ≥61 pg/ml and oncogenic RET mutation were the independent risk factors for tumor recurrence of MTC.Patients with postoperative serum calcitonin ≥61 pg/ml or a RET mutation tended to have a shorter tumor-free survival.