Update on Immunotherapy Cardiotoxicity: Checkpoint Inhibitors, CAR T, and Beyond.

OPINION STATEMENT: Immunotherapy is an innovative approach to cancer treatment that involves using the body's immune system to fight cancer. The landscape of immunotherapy is constantly evolving, as new therapies are developed and refined. Some of the most promising approaches in immunotherapy include immune checkpoint inhibitors (ICIs): these drugs target proteins on the surface of T-cells that inhibit their ability to attack cancer cells. By blocking these proteins, checkpoint inhibitors allow T-cells to recognize and destroy cancer cells more effectively. CAR T-cell therapy: this therapy involves genetically modifying a patient's own T-cells to recognize and attack cancer cells. CAR T-cell therapy exhibits favorable response in many patients with refractory hematological cancers with growing clinical trials in solid tumors. Immune system modulators: these drugs enhance the immune system's ability to fight cancer by stimulating the production of immune cells or inhibiting the activity of immune-suppressing cells. While immunotherapy has shown great promise in the treatment of cancer, it can also pose significant cardiac side effects. Some immunotherapy drugs like ICIs can cause myocarditis, which can lead to chest pain, shortness of breath, and heart failure. Other cardiac side effects of ICIs include arrhythmias, pericarditis, vasculitis, and accelerated atherosclerosis. It is important for patients receiving immunotherapy to be monitored closely for these side effects, as prompt treatment can help prevent serious complications. Patients should also report any symptoms to their healthcare providers right away, so that appropriate action can be taken. CAR T-cell therapy can also illicit an exaggerated immune response creating cytokine release syndrome (CRS) that may precipitate cardiovascular events: arrhythmias, myocardial infarction, and heart failure. Overall, while immune modulating therapy is a promising and expanding approach to cancer treatment, it is important to weigh the potential benefits against the risks and side effects, especially in patients with high risk for cardiovascular complications.

The Association Between Pain and Fall Among Middle-Aged and Older Chinese.

BACKGROUND: Falls and fall-induced injuries in elderly people are common worldwide. However, few reports have examined the association between body pain and fall in middle-aged and older Chinese adults. The objective of this study is to access the association between pain and fall among middle-aged and older Chinese. METHODS: Data were drawn from the 2011 China Health and Retirement Longitudinal Study (CHARLS) from respondents who were middle-aged and older (over 45 years old). A logistic regression model was used to estimate the odds ratios (AOR) and 95% confidence interval (95% CI) of the association between body pain and fall, after controlling for confounders. RESULTS: After adjusting for demographic characteristics, socioeconomic status, lifestyle, health status and comorbidity, those participants who had pain were 73% more likely to report falls than those who did not have pain (AOR = 1.73, 95% CI 1.56-1.92). Elder age was associated with a higher risk of fall (AOR = 1.77, 95% CI 1.47-2.13). Comparing to female, male was associated with a lower risk of fall (AOR = 0.64, 95% CI 0.56-0.74). Lifestyle such as drinking status, self-reported health status, chronic diseases, vision impairment and disability were significantly associated with fall. CONCLUSION: Body pain is significantly associated with fall among middle-aged and older Chinese adults. Appropriate pain management programs and policies are needed in fall prevention.

The association between the socioeconomic status and body pain: A nationwide survey.

Pain is a significant burden among different communities, but little is known regarding the epidemiology of pain, particularly with respect to socioeconomic status (SES).The aim of the study was to estimate the prevalence of body pain and to identify risk factors of pain in middle-aged and older Chinese.The data were extracted from the 2008 Chinese Suboptimal Health Study that consisted of 18,316 Chinese subjects aged 18 to 65 years. Information on SES including occupation and education levels and body pain were collected. A Likert scale was used to evaluate reported body pain. We used the multiple logistic regression model to examine the association between SES and body pain.Overall, 65.34% reported body pain (male: 60.93%; female: 69.73%). After adjustments based on sex, age, education, area of residence, marital status, smoking, drinking and health status, the results showed that students (odds ratio [OR] = 1.51; 95% confidence interval [CI]: 1.32-1.74) and professionals (OR = 1.22; 95% CI: 1.08-1.37) had significant high risk for body pain, compared with civil servants and farmers (OR = 0.64; 95% CI: 0.55-0.75) who significantly lower risk of body pain. The study demonstrates there is a significant negative association between education and reported body pain.The results indicated an association between SES and body pain within the Chinese community. Body pain varied among different Chinese occupation-related population and people with higher education level are less like to have body pain.

Cystathionine beta synthase-hydrogen sulfide system in paraventricular nucleus reduced high fatty diet induced obesity and insulin resistance by brain-adipose axis.

Hydrogen sulfide (H2S) is an essential neuromodulator, generates by cystathionine ß synthase (CBS) or 3-mecaptopyruvate sulfurtransferase (3MST) in the brain. H2S can mediate paraventricular nucleus (PVN) neuron activity, and regulate neuroendocrine hormones secretion. On the other hand, CBS deficiency caused metabolic disorder and body weight reduction. However, whether CBS/H2S of PVN regulates neuroendocrine hormones to mediate energy metabolism is unknown. Here, we first identified the CBS co-localization with thyrotropin-releasing hormone (TRH) and corticotropin releasing hormone (CRH) positive neurons. In HFD induced obese rats, CBS protein of hypothalamus decreased. By contrast, overexpression CBS in PVN via lentivirus, lowered food uptake, body weight and fat mass, and reduced blood glucose, lipid disorders and insulin resistance. Intriguingly, CBS overexpression increased the pre-TRH expression, slightly elevated plasma thyroxine and thyrotropin level, but decreased the plasma ACTH and corticosterone level. Then, we found that mTOR activation contributed to pre-TRH up-regulation by CBS/H2S system. In db/db obese mice, hypothalamus CBS/H2S system also down-regulated association with reduction pre-TRH expression; in contrast, CBS overexpression in PVN slightly elevated plasma leptin. Next, leptin stimulated FOXO3a nuclear translocation, increased FOXO3a binding activity to two binding sites of CBS promoter, and then enhanced CBS protein expression. In conclusion, leptin activates neuron CBS-H2S system by FOXO3a, regulates neuroendocrine hormones to modulate the energy homeostasis, thus highlights a new brain-adipose feedback axis in energy metabolism.

In vivo therapeutic applications of cell spheroids.

Spheroids are increasingly being employed to answer a wide range of clinical and biomedical inquiries ranging from pharmacology to disease pathophysiology, with the ultimate goal of using spheroids for tissue engineering and regeneration. When compared to traditional two-dimensional cell culture, spheroids have the advantage of better replicating the 3D extracellular microenvironment and its associated growth factors and signaling cascades. As knowledge about the preparation and maintenance of spheroids has improved, there has been a plethora of translational experiments investigating in vivo implantation of spheroids into various animal models studying tissue regeneration. We review methods for spheroid delivery and how they have been utilized in tissue engineering experiments. We break down efforts in this field by organ systems, discussing applications of spheroids to various animal models of disease processes and their potential clinical implications. These breakthroughs have been made possible by advancements in spheroid formation, in vivo delivery and assessment. There is unexplored potential and room for further research and development in spheroid-based tissue engineering approaches. Regenerative medicine and other clinical applications ensure this exciting area of research remains relevant for patient care.

Induced Abortion among Chinese Women with Living Child-A National Study.

OBJECTIVE: Induced abortion is widely practiced in China. However, the information on induced abortion is limited. A national cross-sectional survey was designed to determine the risk factors of induced abortion among Chinese women with one child. METHODS: We sampled 16,881 Chinese women with one living child for the study. A structured questionnaire was used to collect induced abortion and related health information. The National Research Institute for Family Planning of China conducted a cross-sectional study among women who had delivered a baby between 2006 and 2008. Information was collected in relation to demographic characteristics (age, ethnicity, region, area etc.), social economic status (education level and occupation), marriage, and the attitude towards potential child's gender. Multi-logistic regression was used to test potential predictors for conducting abortion stratified by consistency between gender preference and current infants' gender, and indicating adjusted estimation on selected models of risk factors for abortion. RESULTS: The mean age of participants was 27.96 ± 4.10 years (median 27 years). Among those women, the prevalence of induced abortion was 8.13 %. In the final model, females living in rural areas (OR = 1.21, 95 %CI: 1.04-1.39), individuals ages 18-25 (OR = 0.84, 95% CI: 0.72-0.99), individuals ages 30 or older (OR = 1.63, 95% CI: 1.42-1.86), and single individuals (OR = 1.72, 95% CI: 1.05-2.83) were more likely to experience induced abortion. Wife gender preference (OR = 0.66, 95 %CI: 0.53-0.83), husband gender preference (Boy: OR = 1.33, 95 %CI: 1.10-1.63; Girl: OR = 1.5, 95% CI: 1.22-1.86), and the area where the individuals were located were significantly associated with the reporting of induced abortion. CONCLUSION: The prevalence of induced abortion is high among married women with child in China. There are also socio-demographic characteristics associated with induced abortion in China.

Keratin-dependent regulation of Aire and gene expression in skin tumor keratinocytes.

Expression of the intermediate filament protein keratin 17 (K17) is robustly upregulated in inflammatory skin diseases and in many tumors originating in stratified and pseudostratified epithelia. We report that autoimmune regulator (Aire), a transcriptional regulator, is inducibly expressed in human and mouse tumor keratinocytes in a K17-dependent manner and is required for timely onset of Gli2-induced skin tumorigenesis in mice. The induction of Aire mRNA in keratinocytes depends on a functional interaction between K17 and the heterogeneous nuclear ribonucleoprotein hnRNP K. Further, K17 colocalizes with Aire protein in the nucleus of tumor-prone keratinocytes, and each factor is bound to a specific promoter region featuring an NF-κB consensus sequence in a relevant subset of K17- and Aire-dependent proinflammatory genes. These findings provide radically new insight into keratin intermediate filament and Aire function, along with a molecular basis for the K17-dependent amplification of inflammatory and immune responses in diseased epithelia.