In randomized clinical trials, pharmacologically inactive placebos can induce positive physiological responses in the human body, thereby relieving disease symptoms, known as the placebo effect. This article summarizes the research progress on the mechanism of the placebo effect, introduces the integrative framework theory, and focuses on the study of placebomics and molecular mechanisms of placebo effects. Molecules in signal systems, such as dopamine, opiate substances, 5-hydroxytryptamine, and endogenous cannabinoids, may be involved in the placebo effect. These signal systems are also involved in the occurrence and development of mental illnesses such as depression. It suggests that there may be common molecular mechanisms between the placebo effect and depression, providing new insights for clinical treatment and drug design for depression. Personalized placebos can be applied to replace conventional active drugs for treating depression, and specific medications for depression can be developed by avoiding common molecular mechanisms with placebo effects during the development of antidepressants.

Biology-guided radiotherapy (BgRT) is a novel technique of external beam radiotherapy, combining positron emission tomography-computed tomography (PET-CT) with a linear accelerator (LINAC). The key innovation is to utilize PET signals from tracers in tumor tissues for real-time tracking and guiding beamlets. Compared with a traditional LINAC system, a BgRT system is more complex in hardware design, software algorithm, system integration and clinical workflow. RefleXion Medical has developed the world's first BgRT system. Nevertheless, its actively advertised function, PET-guided radiotherapy, is still in the research and development phase. In this review study, we presented a number of issues related to BgRT, including its technical advantages and potential challenges.
Positron Emission Tomography Computed Tomography ; Radiotherapy Planning, Computer-Assisted/methods* ; Algorithms ; Particle Accelerators ; Biology ; Radiotherapy, Image-Guided/methods* ; Radiotherapy Dosage

Objective: To investigate the safety and efficacy of laparoscopic surgery in locally advanced gastric cancer patients with neoadjuvant SOX chemotherapy combined with PD-1 inhibitor immunotherapy. Methods: Between November 2020 and April 2021, patients with locally advanced gastric cancer who were admitted to the Union Hospital of Tongji Medical College of Huazhong University of Science and Technology were prospectively enrolled in this study. Inclusion criteria were: (1) patients who signed the informed consent form voluntarily before participating in the study; (2) age ranging from 18 to 75 years; (3) patients staged preoperatively as cT3-4N+M0 by the TNM staging system; (4) Eastern Collaborative Oncology Group score of 0-1; (5) estimated survival of more than 6 months, with the possibility of performing R0 resection for curative purposes; (6) sufficient organ and bone marrow function within 7 days before enrollment; and (7) complete gastric D2 radical surgery. Exclusion criteria were: (1) history of anti-PD-1 or PD-L1 antibody therapy and chemotherapy; (2) treatment with corticosteroids or other immunosuppre- ssants within 14 days before enrollment; (3) active period of autoimmune disease or interstitial pneumonia; (4) history of other malignant tumors; (5) surgery performed within 28 days before enrollment; and (6) allergy to the drug ingredients of the study. Follow-up was conducted by outpatient and telephone methods. During preoperative SOX chemotherapy combined with PD-1 inhibitor immunotherapy, follow-up was conducted every 3 weeks to understand the occurrence of adverse reactions of the patients; follow-up was conducted once after 1 month of surgical treatment to understand the adverse reactions and survival of patients. Observation indicators were: (1) condition of enrolled patients; (2) reassessment after preoperative therapy and operation received (3) postoperative conditions and pathological results. Evaluation criteria were: (1) tumor staged according to the 8th edition of the American Joint Committee on Cancer (AJCC) TNM staging system; (2) tumor regression grading (TRG) of pathological results were evaluated with reference to AJCC standards; (3) treatment-related adverse reactions were evaluated according to version 5.0 of the Common Terminology Criteria for Adverse Events; (4) tumor response was evaluated by CT before and after treatment with RECIST V1.1 criteria; and (5) Clavien-Dindo complication grading system was used for postoperative complications assessment. Results: A total of 30 eligible patients were included. There were 25 males and 5 females with a median age of 60.5 (35-74) years. The primary tumor was located in the gastroesophageal junction in 12 cases, in the upper stomach in 8, in the middle stomach in 7, and in the lower stomach in 3. The preoperative clinical stage of 30 cases was III. Twenty-one patients experienced adverse reactions during neoadjuvant chemotherapy combined with immunotherapy, including four cases of CTCAE grade 3-4 adverse reactions resulting in bone marrow suppression and thoracic aortic thrombosis. All cases of adverse reactions were alleviated or disappeared after active symptomatic treatment. Among the 30 patients who underwent surgery, the time from chemotherapy combined with immunotherapy to surgery was 28 (23-49) days. All 30 patients underwent laparoscopic radical gastrectomy, of which 20 patients underwent laparoscopic-assisted radical gastric cancer resection; 10 patients underwent total gastrectomy for gastric cancer, combined with splenectomy in 1 case and cholecystectomy in 1 case. The surgery time was (239.9±67.0) min, intraoperative blood loss was 84 (10-400) ml, and the length of the incision was 7 (3-12) cm. The degree of adenocarcinoma was poorly differentiated in 18 cases, moderately differentiated in 12 cases, nerve invasion in 11 cases, and vascular invasion in 6 cases. The number lymph nodes that underwent dissection was 30 (17-58). The first of gas passage, the first postoperative defecation time, the postoperative liquid diet time, and the postoperative hospitalization time of 30 patients was 3 (2-6) d, 3 (2-13) d, 5 (3-12) d, and 10 (7-27) d, respectively. Postoperative complications occurred in 23 of 30 patients, including 7 cases of complications of Clavien-Dindo grade IIIa or above. Six patients improved after treatment and were discharged from hospital, while 1 patient died 27 days after surgery due to granulocyte deficiency, anemia, bilateral lung infection, and respiratory distress syndrome. The remaining 29 patients had no surgery-related morbidity or mortality within 30 days of discharge. Postoperative pathological examination showed TRG grades 0, 1, 2, and 3 in 8, 9, 4, and 9 cases, respectively, and the number of postoperative pathological TNM stages 0, I, II, and III was 8, 7, 8, and 7 cases, respectively. The pCR rate was 25.0% (8/32). Conclusion: Laparoscopic surgery after neoadjuvant SOX chemotherapy combined with PD-1 inhibitor immunotherapy for locally advanced gastric cancer is safe and feasible, with satisfactory short-term efficacy. Early detection and timely treatment of related complications are important.
Male ; Female ; Humans ; Middle Aged ; Aged ; Adolescent ; Young Adult ; Adult ; Stomach Neoplasms/pathology* ; Neoadjuvant Therapy ; Immune Checkpoint Inhibitors ; Gastrectomy/methods* ; Esophagogastric Junction/pathology* ; Laparoscopy ; Immunotherapy ; Postoperative Complications ; Retrospective Studies ; Treatment Outcome

Objective: To investigate the clinicopathological characteristics, immunohistochemical profiles, molecular features, and prognosis of subungual melanoma in situ (SMIS). Methods: Thirty cases of SMIS were collected in Fudan University Shanghai Cancer Center, Shanghai, China from 2018 to 2022. The clinicopathological characteristics and follow-up data were retrospectively analyzed. Histopathologic evaluation and immunohistochemical studies were carried out. By using Vysis melanoma fluorescence in situ hybridization (FISH) probe kit, combined with 9p21(CDKN2A) and 8q24(MYC) assays were performed. Results: There were 8 males and 22 females. The patients' ages ranged from 22 to 65 years (median 48 years). All patients presented with longitudinal melanonychia involving a single digit. Thumb was the most commonly affected digit (16/30, 53.3%). 56.7% (17/30) of the cases presented with Hutchinson's sign. Microscopically, melanocytes proliferated along the dermo-epithelial junction. Hyperchromatism and nuclear pleomorphism were two of the most common histological features. The melanocyte count ranged from 30 to 185. Most cases showed small to medium nuclear enlargement (29/30, 96.7%). Pagetoid spread was seen in all cases. Intra-epithelial mitoses were identified in 56.7% (17/30) of the cases. Involvement of nailfold was found in 19 cases, 4 of which were accompanied by cutaneous adnexal extension. The positive rates of SOX10, PNL2, Melan A, HMB45, S-100, and PRAME were 100.0%, 100.0%, 96.0%, 95.0%, 76.9%, and 83.3%, respectively. FISH analysis was positive in 6/9 of the cases. Follow-up data were available in 28 patients, and all of them were alive without disease. Conclusions: SMIS mainly shows small to medium-sized cells. High melanocyte count, hyperchromatism, nuclear pleomorphism, Pagetoid spreading, intra-epithelial mitosis, nailfold involvement, and cutaneous adnexal extension are important diagnostic hallmarks. Immunohistochemistry including SOX10 and PRAME, combined with FISH analysis, is valuable for the diagnosis of SMIS.
Male ; Female ; Humans ; Young Adult ; Adult ; Middle Aged ; Aged ; Skin Neoplasms/pathology* ; Prognosis ; Retrospective Studies ; In Situ Hybridization, Fluorescence ; China ; Melanoma/diagnosis* ; Nail Diseases/pathology* ; Antigens, Neoplasm

In randomized clinical trials, pharmacologically inactive placebos can induce positive physiological responses in the human body, thereby relieving disease symptoms, known as the placebo effect. This article summarizes the research progress on the mechanism of the placebo effect, introduces the integrative framework theory, and focuses on the study of placebomics and molecular mechanisms of placebo effects. Molecules in signal systems, such as dopamine, opiate substances, 5-hydroxytryptamine, and endogenous cannabinoids, may be involved in the placebo effect. These signal systems are also involved in the occurrence and development of mental illnesses such as depression. It suggests that there may be common molecular mechanisms between the placebo effect and depression, providing new insights for clinical treatment and drug design for depression. Personalized placebos can be applied to replace conventional active drugs for treating depression, and specific medications for depression can be developed by avoiding common molecular mechanisms with placebo effects during the development of antidepressants.

Metastatic triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer. Combination of systemic chemotherapy and immune checkpoint blockade is effective but of limited benefit due to insufficient intratumoral infiltration of cytotoxic T lymphocytes (CTLs) and the accumulation of immunosuppressive cells. Herein, we designed a lenvatinib- and vadimezan-loaded synthetic high-density lipoprotein (LV-sHDL) for combinational immunochemotherapy of metastatic TNBC. The LV-sHDL targeted scavenger receptor class B type 1-overexpressing 4T1 cells in the tumor after intravenous injection. The multitargeted tyrosine kinase inhibitor (TKI) lenvatinib induced immunogenic cell death of the cancer cells, and the stimulator of interferon genes (STING) agonist vadimezan triggered local inflammation to facilitate dendritic cell maturation and antitumor macrophage differentiation, which synergistically improved the intratumoral infiltration of total and active CTLs by 33- and 13-fold, respectively. LV-sHDL inhibited the growth of orthotopic 4T1 tumors, reduced pulmonary metastasis, and prolonged the survival of animals. The efficacy could be further improved when LV-sHDL was used in combination with antibody against programmed cell death ligand 1. This study highlights the combination use of multitargeted TKI and STING agonist a promising treatment for metastatic TNBC.

Heavy metal is one of pollutants existed widely in the environment, its relationship with cardiovascular disease has attracted more and more attention. In this review, the concentrations of heavy metals, including lead, cadium and asenic, in the body from several national surveillance networks and the epidemiological studies on the effects of the exposure of three heavy metals on cardiovascular system were summarized. It is suggested to strengthen nationwide surveillance for body concentrations of heavy metals in general population in order to provide baseline data for quantitative evaluation of the risk of heavy metal exposure on cardiovascular disease.
Cadmium ; Cardiovascular Diseases/chemically induced* ; Environmental Exposure/adverse effects* ; Environmental Pollutants/toxicity* ; Epidemiologic Studies ; Humans ; Lead/toxicity* ; Metals, Heavy/toxicity* ; Neoplasms ; Research/trends*

Objective: To analyze the spatial distribution of tuberculosis (TB) and identify the clustering areas in Qinghai province from 2014 to 2016, and provide evidence for the prevention and control of TB. Methods: The data of pulmonary TB cases confirmed by clinical and laboratory diagnosis in Qinghai during this period were collected from National Disease Reporting Information System. The visualization of annual reported incidence, three-dimensional trend analysis and local Getis-Ord G(i)(*) spatial autocorrelation analysis of TB were performed by using software ArcGIS 10.2.2, and global Moran's I spatial autocorrelation analysis were analyzed by using software OpenGeoDa 1.2.0 to describe and analyze the spatial distribution characteristics and high incidence areas of TB in Qinghai from 2014 to 2016. Results: A total of 20 609 pulmonary TB cases were reported in Qinghai during this period. The reported incidences were 101.16/100 000, 123.26/100 000 and 128.70/100 000 respectively, an increasing trend with year was observed (trend χ(2)=187.21, P<0.001). The three-dimensional trend analysis showed that the TB incidence increased from northern area to southern area, and up-arch trend from the east to the west. Global Moran's I spatial autocorrelation analysis showed that annual reported TB incidence in different areas had moderate spatial clustering (Moran's I values were 0.631 3, 0.605 4, and 0.587 3, P<0.001). And local G(i)(*) analysis showed that there were some areas with high TB incidences, such as 10 counties of Yushu and Guoluo prefectures (Gande, Banma and Dari counties, etc., located in the southwest of Qinghai), and some areas with low TB incidences, such as Huangzhong county, Chengdong district and Chengbei district of Xining city and Dachaidan county of Haixi prefecture, and the reported TB incidences in the remaining areas were moderate. Conclusion: The annual reported TB incidence increased year by year in Qinghai from 2014 to 2016. The distribution of TB cases showed obvious spatial clustering, and Yushu and Guoluo prefectures were the key areas in TB prevention and control. In addition, the spatial clustering analysis could provide the important evidence for the development of TB prevention and control measures in Qinghai.
China/epidemiology* ; Cluster Analysis ; Disease Notification/statistics & numerical data* ; Female ; Geographic Information Systems ; Humans ; Incidence ; Male ; Spatial Analysis ; Spatio-Temporal Analysis ; Tuberculosis/microbiology* ; Tuberculosis, Pulmonary/ethnology*

Objective: To understand the related risk behaviors, knowledge and status of HIV/AIDS infection among rural adults of Derung minority, to provide relevant messages for the development of HIV/AIDS intervention strategy in this minority group. Methods: We used system sampling method to conduct a cross-sectional survey in 6 administration villages of Derung Township, Gongshan Derung and Nu Autonomous County in Nujiang Lisu Autonomous Prefecture of Yunnan Province, with a sample size estimated as 383. Adult residents with Derung minority in six villages of Gongshan County were involved, with relevant information collected through door-to-door visit. HIV antibody was tested and SPSS 17.0 was used for statistical analysis. Results: Information on 394 valid respondents was collected, with age as between 18 and 65 (34.39±9.74), 80.7% (318/394) as married, 54.0% (213/394) having had primary school education, 13.2% (52/394) as migrant workers. In this population, the overall HIV infection rate appeared as 0.5% (2/400), mainly through sexually transmission. The rate of awareness on HIV/AIDS was 69.8% (275/394), mainly through free publicized materials 50.0% (197/394). Rates on premarital sexual behavior on multiple sexual partners in the past year, on temporary sexual partners in the past year, having commercial sexual experiences in the past year and ever used condoms when engaging in casual sex, were 6.4% (60/366), 18.0%(66/366), 5.7%(21/366), 1.9%(7/366) and 8.0%(25/311), respectively. Conclusions: Few numbers of HIV infections were identified among the migrating workers with Derung minority, with sexual transmission as the major route, along with the increased number of rural migrant workers and the low rates both on AIDS knowledge and condom use, accompanied by the high risk sexual behavior appeared in this rural adult residents of Derung minority. Relative strategies on HIV/AIDS intervention and control should be developed.
Acquired Immunodeficiency Syndrome ; Adult ; China/epidemiology* ; Condoms ; Cross-Sectional Studies ; HIV Infections/epidemiology* ; Health Knowledge, Attitudes, Practice ; Humans ; Infections ; Risk-Taking ; Rural Population/statistics & numerical data* ; Sexual Behavior ; Sexual Partners ; Surveys and Questionnaires ; Transients and Migrants

Objective: To explore the characteristics of distribution on Chinese adult body mass index (BMI) in different age groups and genders and to provide reference related to obesity and related chronic diseases. Methods: Data from the China Health and Nutrition Survey in 2009 were used. Sequential sample cluster method was used to analyze the characteristics of BMI distribution in different age groups and genders by SAS. Results: Our results showed that the adult BMI in China should be divided into 3 groups according to their age, as 20 to 40 years old, 40 to 65 years old, and> 65 years old, in females or in total when grouped by difference of 5 years. For groupings in male, the three groups should be as 20 to 40, 40 to 60 years old and>60 years old. There were differences on distribution between the male and female groups. When grouped by difference of 10 years, all of the clusters for male, female and total groups as 20-40, 40-60 and>60 years old, became similar for the three classes, respectively, with no differences of distribution between gender, suggesting that the 5-years grouping was more accurate than the 10-years one, and BMI showing gender differences. Conclusions: BMI of the Chinese adults should be divided into 3 categories according to the characteristics of their age. Our results showed that BMI was increasing with age in youths and adolescents, remained unchanged in the middle-aged but decreasing in the elderly.
Adolescent ; Adult ; Age Distribution ; Aged ; Asian People/statistics & numerical data* ; Body Mass Index ; China/epidemiology* ; Female ; Humans ; Male ; Middle Aged ; Nutrition Surveys ; Obesity/ethnology* ; Sex Distribution ; Sex Factors ; Young Adult