There is an accumulating body of evidence implicating the muscarinic acetylcholine receptor 4 (M₄) in schizophrenia and dementia with Lewy bodies, however, a clinically validated M₄ positron emission tomography (PET) radioligand is currently lacking. As such, the aim of this study was to develop a suitable M₄ PET ligand that allows the non-invasive visualization of M₄ in the brain. Structure-activity relationship studies of pyrazol-4-yl-pyridine derivates led to the discovery of target compound 12 - a subtype-selective positive allosteric modulator (PAM). The radiofluorinated analogue, [¹⁸F] 12, was synthesized in 28 ± 10% radiochemical yield, >37 GBq/μmol and an excellent radiochemical purity >99%. Initial in vitro autoradiograms on rodent brain sections were performed in the absence of carbachol and showed moderate specificity as well as a low selectivity of [¹⁸F] 12 for the M₄-rich striatum. However, in the presence of carbachol, a significant increase in tracer binding was observed in the rat striatum, which was reduced by >60% under blocking conditions, thus indicating that orthosteric ligand interaction is required for efficient binding of [¹⁸F] 12 to the allosteric site. Remarkably, however, the presence of carbachol was not required for high specific binding in the non-human primate (NHP) and human striatum, and did not further improve the specificity and selectivity of [¹⁸F] 12 in higher species. These results pointed towards significant species-differences and paved the way for a preliminary PET study in NHP, where peak brain uptake of [¹⁸F] 12 was found in the putamen and temporal cortex. In conclusion, we report on the identification and preclinical development of the first radiofluorinated M₄ PET radioligand with promising attributes. The availability of a clinically validated M₄ PET radioligand harbors potential to facilitate drug development and provide a useful diagnostic tool for non-invasive imaging.

BACKGROUND: Preliminary researches conformed that neoadjuvant immunotherapy combined with chemotherapy had a significant short-term effect in resectable non-small cell lung cancer (NSCLC), but there were few clinical trials about neoadjuvant chemoimmunotherapy in China. We aimed to assess retrospectively the antitumour activity and safety of neoadjuvant chemoimmunotherapy for resectable stage Ib-IIIb NSCLC. METHODS: Twenty patients who had been diagnosed as stage Ib-IIIb NSCLC and received chemoimmunotherapy as neoadjuvant treatment between November 2019 and December 2020, in Beijing Chest Hospital, Capital Medical University were recruited. These patients received neoadjuvant treatment for 21 days as a cycle and antitumour activity and safety were evaluated every two cycles. RESULTS: Of 20 patients received neoadjuvant chemoimmunotherapy, 17 patients underwent surgical resection. 16 patients had R0 resection (no residual tumor resection) and 1 patient had R1 resection (microscopic residual tumor resection). Radiographic objective response rate (ORR) was 85.0% (4 complete response, 13 partial response). 5.0% (1/20) of patients had stable disease, and 10.0% (2/20) of patients had progression disease. The major pathologic response (MPR) was 47.1% (8/17), and complete pathologic response (CPR) was 29.4% (5/17). 1 case developed grade IV immune-related pneumonia (IRP) and 9 (45.0%) cases had grade III hematologic toxicity. CONCLUSIONS Immunotherapy combined with chemotherapy as neoadjuvant therapy has a better efficiency and tolerable adverse effects for patients with resectable NSCLC in stage Ib-IIIb.

Objective Budd-Chiari syndrome is apt to be misdiagnosed,so we explore its diagnosis and treatment by liver transplantation.Methods We retrospectively analyzed the clinical data of two patients who underwent liver transplantation for Budd-Chiari syndrome.One patient was misdiagnosed before the transplantation and another was diagnosed correctly.Results Both patients were grouped to Child C category with decompensated liver cirrhosis.Patient 1 was diagnosed as recurrent hepatocellular carcinoma,but the etiology of liver disease was first unknown then suspected to be schistosomiasis.This patient underwent piggyback liver transplantation.Because there was significant swelling in the perineum and lower extremities after liver transplantation,we re-reviewed the preoperative imaging data and found communicant veins between hepatic veins,which proved that the patient was actually suffered from Budd-Chiari syndrome with hepatic vein and suprahepatic vena cava occlusion before the transplantation.After conservative treatment,the swelling of the lower body was alleviated,however,the long-term survival of the patient would be compromised.Learning from the first case,we found communicant veins between hepatic veins in imaging data of patient 2,resulting in correct diagnosis of Budd-Chiari syndrome with hepatic vein and retrohepatic vena cava diseases before the transplantation,so the patient underwent orthotopic liver transplantation,in which the liver and retrohepatic vena cava were resected,and recovered uneventfully.Liver function was normal during the follow up period of 7 months.Conclusion We should consider the possibility of Budd-Chiari syndrome in patients with unexplained end-stage liver diseases.Communicant veins between the hepatic veins shown in thin CT or MRI image are the characteristic sign for diagnosing Budd-Chiari syndrome.Simultaneously hepatic vein or cava vena disease determines the choice of various technique of liver transplantation.

Background and objective Small cell lung cancer (SCLC) accounts for nearly 15% of all cases of can-cer. As a type of highly invasive tumors, SCLC has high degree of malignancy, early and extensive metastasis, and is sensitive to chemotherapy and radiotherapy. The early treatment response rate of SCLC is high but it can also relapse rapidly without any treatment. Its median survival time is merely four to six months. Although many studies on SCLC have been conducted in re-cent years, its clinical treatment strategies have remained unchanged. The treatment of SCLC is still confined to chemotherapy regimens of etoposide plus cisplatin (EP) and other classic treatments because the surgical treatment of SCLC, particularly for Ⅲa treatment, has yet to reach a consensus. This study investigated the prognostic factors and clinical therapy effect in the comprehensive treatment of Ⅲa SCLC after surgical treatment.Methods This study was conducted through the retrospective analysis of the clinical data of 78 patients with SCLC who underwent surgical treatment in Beijing Chest Hospital affiliated to Capital Medical University between January 1995 and December 1995. Through follow-up, we performed statistical analysis of each patient's gender, age, tumor size, lymph node metastasis, tumor-node-metastasis (TNM) staging, surgical methods, and adjuvant radiation and chemotherapy.Results The median survival in this clinical trial team was 13.93 months. Among the participants, 47 patients accepted neoadjuvant chemotherapy and their median survival were 14.25 months. By contrast, 31 patients accepted postoperative adjuvant chemotherapy and their median survival were 13.83 months. No statistical difference was observed between the two groups. Moreover, 28 patients were of single Lymph node metastasis and their median survival was 17.1 months. By contrast, 50 patients were of multiple lymph node metastasis and their median survival was 11.9 months. Significant statistical difference was observed between the two groups (P<0.01).Conclusion In performing further evalua-tion of the status and value of surgical treatment in the comprehensive treatment of SCLC, several patients benefitted from Ⅲa SCLC surgery with comprehensive treatment.

Objective To investigate anatomic feature of variant right hepatic artery originating from the gastroduodenal artery.Methods We studied the anatomy of hepatic artery in 70 patients by 64-slice CT scans.If the right hepatic artery originated from the gastroduodenal artery,its relation to duodenum,common bile duct and portal vein was further investigated.Results Normal hepatic artery was found in 40 patients (57.1％).Variant hepatic artery can't be categorized to classic types in 8 patients (11.4％),among them 6 patients (8.6％) were with replaced (5 patients) or accessory (one patient) right hepatic artery arising from gastroduodenal artery.With the distance between original point of the right hepatic artery and that of the gastroduodenal artery growing further anatomic course of the variant right hepatic artery is more similar to that of the right hepatic artery originating from the superior mesenteric artery.Conclusions The variation of right hepatic artery originating from the gastroduodenal artery was not uncommon.This specific variant hepatic artery can exert impact on biliary blood supply,avoiding injury decreases the incidence of serious biliary complications in general surgery.

OBJECTIVETo investigate the current status of social support for HIV/AIDS patients under antiretroviral treatment (ART) and related factors in Wuhan.

METHODSSocial Support Rating Scale (SSRS) was used to analyze the current status of social support for HIV/AIDS patients under ART in Wuhan. Student's t test, analysis of variance (ANOVA) and multiple linear regression model were used to identify the related factors.

RESULTSThe scores of subjective support, objective support, utilization of social support, and overall social support for 330 HIV/AIDS patients were significant lower than the national norm (P < 0.05). Multiple linear regression analysis showed that the subjective support (β' = -0.260), objective support (β' = -0.196) and overall social support (β' = -0.141) for the patients who were unmarried, divorced or widowed were worse than those for the patients who were married (P < 0.05). The patients with higher educational level had more objective support (β' = 0.250) and utilization of social support (β' = 0.232) than those with lower educational level (P < 0.05). The subjective support for patients without HIV related symptoms in the past two weeks was better than those with HIV related symptoms (β' = 0.232, P < 0.05).

CONCLUSIONThe current status of social support for HIV/AIDS patients under ART in Wuhan was worse than that for healthy people. More attention should be paid to HIV/AIDS patients with worse social support.

Acquired Immunodeficiency Syndrome ; drug therapy ; Anti-Retroviral Agents ; therapeutic use ; China ; Educational Status ; HIV Infections ; drug therapy ; Humans ; Linear Models ; Marital Status ; statistics & numerical data ; Regression Analysis ; Social Support

Objective To investigate the current status of social support for HIV/AIDS patients under antiretroviral treatment(ART)and related factors in Wuhan. Methods Social Support Rating Scale(SSRS)was used to analyze the current status of social support for HIV/AIDS patients under ART in Wuhan. Student’s t test,analysis of variance(ANOVA)and multiple linear regression model were used to identify the related factors. Results The scores of subjective support,objective support,utilization of social support,and overall social support for 330 HIV/AIDS patients were significant lower than the national norm(P<0.05). Multiple linear regression analysis showed that the subjective support(β′=-0.260),objective support(β′=-0.196)and overall social support(β′=-0.141) for the patients who were unmarried,divorced or widowed were worse than those for the patients who were married(P<0.05). The patients with higher educational level had more objective support(β′=0.250)and utilization of social support(β′=0.232)than those with lower educational level (P<0.05). The subjective support for patients without HIV related symptoms in the past two weeks was better than those with HIV related symptoms(β′=0.232,P<0.05). Conclusion The current status of social support for HIV/AIDS patients under ART in Wuhan was worse than that for healthy people. More attention should be paid to HIV/AIDS patients with worse social support.

OBJECTIVETo analyze absentees due to injury among primary school pupils in Hubei, 2012-2013; and to provide theoretical basis for the prevention and control of injuries.

METHODSA total of 32 primary schools in Qianjiang city and Shayang county were sampled to conduct injury absenteeism surveillance, and the total number of students was 21 493. The surveillance contents included absent dates, genders, grades, initial or return absent, and the detailed absent reasons. The classification of injury was based on the 10th Revision of the international classification of diseases developed by WHO. Data from 2012-2013 school-year were extracted from the surveillance system for analysis. The total surveillance period was 182 days, of which the fall semester was 98 days and the spring semester was 84 days. The absenteeism rate and injury rate in different characteristics of primary school students were compared by χ² test, and the possible risk factors of injury were preliminary explored by calculating the RR (95% CI) value.

RESULTSThe total daily injury absenteeism rate was 8.26/100 100 during 2012-2013 school-year in 32 primary schools in Hubei province, which was higher in fall semester (9.16/100 000), Qianjiang area (9.63/100 000), rural primary schools (13.44/100 000), boys (9.57/100 000), 1-2 grades (10.41/100 000), and the differences were significant (P < 0.05). The total injury rate was 0.46%. Rural primary schools (RR = 2.32, 95% CI: 1.46-3.70), boys (RR = 1.88, 95% CI: 1.23-2.87), and 3-4 grades (RR = 1.85, 95% CI: 1.10-3.09) were identified as high-risk factors, while using city primary schools, girls, and 5-6 grades as references, respectively.

CONCLUSIONThe injury absenteeism rate and injury rate were more higher in rural primary schools, boys and low or middle grades in Hubei province during 2012 to 2013 school year, so monitoring and preventive measures should be focused on those students.

Absenteeism ; Adolescent ; Child ; Female ; Humans ; Male ; Risk Factors ; Rural Population ; Schools ; Sex Factors ; Students ; Wounds and Injuries

Objective To analyze absentees due to injury among primary school pupils in Hubei , 2012-2013;and to provide theoretical basis for the prevention and control of injuries.Methods A total of 32 primary schools in Qianjiang city and Shayang county were sampled to conduct injury absenteeism surveillance , and the total number of students was 21 493.The surveillance contents included absent dates , genders, grades, initial or return absent , and the detailed absent reasons.The classification of injury was based on the 10th Revision of the international classification of diseases developed by WHO.Data from 2012-2013 school-year were extracted from the surveillance system for analysis.The total surveillance period was 182 days, of which the fall semester was 98 days and the spring semester was 84 days.The absenteeism rate and injury rate in different characteristics of primary school students were compared by χ2 test, and the possible risk factors of injury were preliminary explored by calculating the RR ( 95%CI ) value.Results The total daily injury absenteeism rate was 8.26/100 100 during 2012-2013 school-year in 32 primary schools in Hubei province , which was higher in fall semester ( 9.16/100 000 ) , Qianjiang area ( 9.63/100 000), rural primary schools (13.44/100 000), boys (9.57/100 000), 1-2 grades (10.41/100 000), and the differences were significant ( P<0.05 ).The total injury rate was 0.46%.Rural primary schools (RR=2.32, 95%CI:1.46-3.70), boys (RR=1.88, 95%CI:1.23-2.87), and 3-4 grades (RR=1.85, 95%CI:1.10-3.09) were identified as high-risk factors, while using city primary schools , girls, and 5-6 grades as references , respectively.Conclusion The injury absenteeism rate and injury rate were more higher in rural primary schools , boys and low or middle grades in Hubei province during 2012 to 2013 school year, so monitoring and preventive measures should be focused on those students .

Objective To analyze absentees due to injury among primary school pupils in Hubei , 2012-2013;and to provide theoretical basis for the prevention and control of injuries.Methods A total of 32 primary schools in Qianjiang city and Shayang county were sampled to conduct injury absenteeism surveillance , and the total number of students was 21 493.The surveillance contents included absent dates , genders, grades, initial or return absent , and the detailed absent reasons.The classification of injury was based on the 10th Revision of the international classification of diseases developed by WHO.Data from 2012-2013 school-year were extracted from the surveillance system for analysis.The total surveillance period was 182 days, of which the fall semester was 98 days and the spring semester was 84 days.The absenteeism rate and injury rate in different characteristics of primary school students were compared by χ2 test, and the possible risk factors of injury were preliminary explored by calculating the RR ( 95%CI ) value.Results The total daily injury absenteeism rate was 8.26/100 100 during 2012-2013 school-year in 32 primary schools in Hubei province , which was higher in fall semester ( 9.16/100 000 ) , Qianjiang area ( 9.63/100 000), rural primary schools (13.44/100 000), boys (9.57/100 000), 1-2 grades (10.41/100 000), and the differences were significant ( P<0.05 ).The total injury rate was 0.46%.Rural primary schools (RR=2.32, 95%CI:1.46-3.70), boys (RR=1.88, 95%CI:1.23-2.87), and 3-4 grades (RR=1.85, 95%CI:1.10-3.09) were identified as high-risk factors, while using city primary schools , girls, and 5-6 grades as references , respectively.Conclusion The injury absenteeism rate and injury rate were more higher in rural primary schools , boys and low or middle grades in Hubei province during 2012 to 2013 school year, so monitoring and preventive measures should be focused on those students .