Poly(ADP-ribose) polymerase 1 (PARP1) is a multifunctional protein involved in diverse cellular functions, notably DNA damage repair. Pharmacological inhibition of PARP1 has therapeutic benefits for various pathologies. Despite the increased use of PARP inhibitors, challenges persist in achieving PARP1 selectivity and effective blood-brain barrier (BBB) penetration. The development of a PARP1-specific positron emission tomography (PET) radioligand is crucial for understanding disease biology and performing target occupancy studies, which may aid in the development of PARP1-specific inhibitors. In this study, we leverage the recently identified PARP1 inhibitor, AZD9574, to introduce the design and development of its ¹⁸F-isotopologue ([¹⁸F]AZD9574). Our comprehensive approach, encompassing pharmacological, cellular, autoradiographic, and in vivo PET imaging evaluations in non-human primates, demonstrates the capacity of [¹⁸F]AZD9574 to specifically bind to PARP1 and to successfully penetrate the BBB. These findings position [¹⁸F]AZD9574 as a viable molecular imaging tool, poised to facilitate the exploration of pathophysiological changes in PARP1 tissue abundance across various diseases.

Radical gastrectomy with D2 lymphadenectomy has been widely performed as the standard surgery for patients with gastric cancer in major medical centers in China and abroad. However, the exact extent of lymph node dissection is still controversial. In the latest version of the Japanese Gastric Cancer Treatment Guidelines, No. 14v lymph nodes (along the root of the superior mesenteric vein) are again defined as loco-regional lymph nodes, and it is clarified that distal gastric cancer presenting with infra-pyloric regional lymph node (No.6) metastasis is recommended for D2+ superior mesenteric vein (No. 14v) lymph node dissection. To explore the relevance and clinical significance of No.6 and No.14v lymphadenectomy in radical gastric cancer surgery, a review of the national and international literature revealed that No.6 lymph node metastasis was associated with No.14v lymph node metastasis, that No.6 lymph node status was a valid predictor of No.14v lymph node negative status and false negative rate, and that for gastric cancer patients with No. 14v lymph node negative and No.6 lymph node positive, the dissection of No.14v lymph node may also have some significance. The addition of No. 14v lymph node dissection in radical gastrectomy is safe, but it is more important to distinguish the patients who can benefit from it. Professor Liang Han of Tianjin Medical University Cancer Hospital is currently leading a multicenter, large-sample, prospective clinical trial (NCT02272894) in China, which is expected to provide higher level evidence for the clinical significance of lymph node dissection in No.14v.
Humans ; Stomach Neoplasms/pathology* ; Lymphatic Metastasis/pathology* ; Prospective Studies ; Retrospective Studies ; Lymph Nodes/pathology* ; Lymph Node Excision ; Gastrectomy ; Multicenter Studies as Topic

Intestinal adaptation is a spontaneous compensation of the remanent bowel after extensive enterectomy, which improves the absorption capacity of the remanent bowel to energy, fluid and other nutrients. Intestinal adaptation mainly occurs within 2 years after enterectomy, including morphological changes, hyperfunction and hyperphagia. Intestinal adaptation is the key factor for patients with short bowel syndrome to weaning off parenteral nutrition dependence and mainly influenced by length of remanent bowel, type of surgery and colon continuity. In addition, multiple factors including enteral feeding, glucagon-like peptide 2 (GLP-2), growth hormone, gut microbiota and its metabolites regulate intestinal adaptation via multi-biological pathways, such as proliferation and differentiation of stem cell, apoptosis, angiogenesis, nutrients transport related protein expression, gut endocrine etc. Phase III clinical trials have verified the safety and efficacy of teduglutide (long-acting GLP-2) and somatropin (recombinant human growth hormone) in improving intestinal adaptation, and both have been approved for clinical use. We aim to review the current knowledge about characteristics, mechanism, evaluation methods, key factors, clinical strategies of intestinal adaptation.
Humans ; Adaptation, Physiological ; Glucagon-Like Peptide 2/therapeutic use* ; Intestines/surgery* ; Parenteral Nutrition ; Short Bowel Syndrome/surgery*

Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Chlorpromazine ; Humans ; Lymphoma ; Sphingosine-1-Phosphate Receptors

Hearing Loss, High-Frequency ; Hearing Loss, Noise-Induced/epidemiology* ; Humans ; Manufacturing Industry ; Noise, Occupational/adverse effects* ; Occupational Exposure

Hearing ; Hearing Loss, Noise-Induced/etiology* ; Humans ; Male ; Manufacturing Industry ; Noise, Occupational/adverse effects* ; Occupational Exposure/adverse effects* ; Surveys and Questionnaires

Humans ; Interior Design and Furnishings ; Manufacturing Industry ; Noise, Occupational ; Occupational Exposure ; Textile Industry

Cross-Sectional Studies ; Depression/epidemiology* ; Humans ; Job Satisfaction ; Occupational Stress/epidemiology* ; Oil and Gas Fields ; Stress, Psychological ; Surveys and Questionnaires

Investigating the pathophysiological mechanisms underlying brain disorders is a priority if novel therapeutic strategies are to be developed. In vivo studies of animal models and in vitro studies of cell lines/primary cell cultures may provide useful tools to study certain aspects of brain disorders. However, discrepancies among these studies or unsuccessful translation from animal/cell studies to human/clinical studies often occur, because these models generally represent only some symptoms of a neuropsychiatric disorder rather than the complete disorder. Human brain slice cultures from postmortem tissue or resected tissue from operations have shown that, in vitro, neurons and glia can stay alive for long periods of time, while their morphological and physiological characteristics, and their ability to respond to experimental manipulations are maintained. Human brain slices can thus provide a close representation of neuronal networks in vivo, be a valuable tool for investigation of the basis of neuropsychiatric disorders, and provide a platform for the evaluation of novel pharmacological treatments of human brain diseases. A brain bank needs to provide the necessary infrastructure to bring together donors, hospitals, and researchers who want to investigate human brain slices in cultures of clinically and neuropathologically well-documented material.
Brain ; drug effects ; physiopathology ; Brain Diseases ; drug therapy ; physiopathology ; Humans ; Tissue Culture Techniques

Objective: To understand the characteristics of HIV infected persons without long term disease progress [also known as long term non-progressors (LTNPs)], and related factors in Guangxi Zhuang Autonomous Region (Guangxi). Methods: Data of persons living with HIV and receiving no antiretroviral therapy in Guangxi by the end of 2016 were collected from the national HIV/AIDS comprehensive control and prevention information system of China. Results: By the end of 2016, there were 313 LTNPs in Guangxi, accounting for 2.3% of those being reported for more than 10 years, 5.4% of those being reported for more than 10 years and surviving, and 26.6% of those being reported for more than 10 years, surviving and receiving no antiretroviral therapy. Among the LTNPs, 87.2%(273) were men, 94.9% (297) were aged ≤ 40 years, 32.3% (101) were farmers, 55.6% (174) were single, divorced or widowed, 69.3% (217) were of Han ethnic group, 68.1% (213) were injecting drug users, and 52.1% (163) were from custody facilities. Multiple logistic regression analysis indicated that factors associated with delayed disease progression included age ≤40 years (compared with age >40 years, aOR=1.55, 95%CI: 1.31-3.12) and injection drug use (compared with sexual transmission, aOR=1.23, 95%CI: 1.10-1.74). Conclusions: A number of LTNPs existed in HIV-infected individuals in Guangxi. Further research are needed to identify the related factors, and it is necessary to conduct large sample size studies on host immunology, genetics and the virology of HIV to explore the related mechanism.
Adolescent ; Adult ; Age Distribution ; China/epidemiology* ; Drug Users/statistics & numerical data* ; Ethnicity/statistics & numerical data* ; HIV Infections/ethnology* ; Humans ; Male ; Socioeconomic Factors