Discovery of cinnamylaldehyde-derived mono-carbonyl curcumin analogs as anti-gastric cancer agents via suppression of STAT3 and AKT pathway.

The structural modification of curcumin has always been a hotspot in drug development. In this paper, a class of cinnamylaldehyde-derived mono-carbonyl curcumin analogs (MCAs) with 7-carbon-links were designed and synthesized and their anticancer properties were evaluated. Through screening anti-gastric cancer activity of these compounds, H1 exhibited the strongest cytotoxic activity by inhibiting cell viability and colony formation, inducing cell cycle G2/M phase arrest in vitro (SGC-7901 and AGS gastric cancer cells). Moreover, the SGC-7901 subcutaneous tumor-bearing mice studies revealed that H1 significantly inhibited the tumor growth of gastric cancer. We explored the possible potential targets of H1 through network pharmacology. Mechanistically, our results demonstrated that H1 showed potential anti-gastric cancer activity through suppression of the STAT3 and AKT signaling pathway in vitro and in vivo, which was validated by molecular docking. Overall, our results indicate the potential of H1 as a potent chemotherapeutic drug against gastric cancer.

The workload change and depression among emergency medical staff after the open policy during COVID-19: a cross-sectional survey in Shandong, China.

Introduction: In the middle of December 2022, the Chinese government adjusted the lockdown policy on coronavirus disease 2019 (COVID-19), a large number of infected patients flooded into the emergency department. The emergency medical staff encountered significant working and mental stress while fighting the COVID-19 pandemic. We aimed to investigate the workload change, and the prevalence and associated factors for depression symptoms among emergency medical staff after the policy adjustment. Methods: We conducted a cross-sectional online survey of emergency medical staff who fought against COVID-19 in Shandong Province during January 16 to 31, 2023. The respondents' sociodemographic and work information were collected, and they were asked to complete the 9-item Patient Health Questionnaire (PHQ-9) then. Univariate and multivariate logistic regression analyses were applied to identify the potential associated factors for major depression. Results: Nine hundred and sixteen emergency medical personnel from 108 hospitals responded to this survey. The respondents' weekly working hours (53.65 ± 17.36 vs 49.68 ± 14.84) and monthly night shifts (7.25 ± 3.85 vs 6.80 ± 3.77) increased after the open policy. About 54.3% of the respondents scored more than 10 points on the PHQ-9 standardized test, which is associated with depressive symptoms. In univariate analysis, being doctors, living with family members aged ≤16 or ≥ 65 years old, COVID-19 infection and increased weekly working hours after the open policy were significantly associated with a PHQ-9 score ≥ 10 points. In the multivariate analysis, only increased weekly working hours showed significant association with scoring ≥10 points. Conclusion: Emergency medical staff' workload had increased after the open policy announcement, which was strongly associated with a higher PHQ-9 scores, indicating a very high risk for major depression. Emergency medical staff working as doctors or with an intermediate title from grade-A tertiary hospitals had higher PHQ-9 scores, while COVID-19 infection and weekly working hours of 60 or more after the open policy were associated with higher PHQ-9 scores for those from grade-B tertiary hospitals. Hospital administrators should reinforce the importance of targeted emergency medical staff support during future outbreaks.

Association between anemia and sarcopenia among Chinese elderly: A cross-sectional study based on the China health and retirement longitudinal study.

BACKGROUND: Evidence regarding the association between anemia and sarcopenia in the elderly population is limited and controversial. The purpose of this study was to investigate the association between anemia and sarcopenia in Chinese elderly. METHODS: The cross-sectional study used the third wave of data from the China Longitudinal Study of Health and Retirement (CHARLS). Participants were classified as sarcopenic versus non-sarcopenic according to the guidelines developed by the Asian Working Group for Sarcopenia (AWGS) 2019. Meanwhile, participants were defined for anemia using World Health Organization criteria. Logistic regression models were conducted to assess the association between anemia and sarcopenia. Odds ratios (OR) were reported to indicate the strength of the association. RESULTS: A total of 5016 participants were included in the cross-sectional analysis. The overall prevalence of sarcopenia in this population was 18.3 %. After adjusting for all potential risk factors, anemia and sarcopenia were independently associated (OR = 1.43, 95 % CI 1.15-1.77, P = 0.001). In terms of subgroups, the association of anemia with sarcopenia was also significant in people over 71 years of age (OR = 1.93, 95 % CI 1.40-2.66, P < 0.001), women (OR = 1.48, 95 % CI 1.09-2,02, P = 0.012), rural residents (OR = 1.56, 95 % CI 1.24-1.97, P < 0.001), as well as in people with low education (OR = 1.50, 95 % CI 1.20-1.89, P < 0.001). CONCLUSION: Anemia is an independent risk factor for sarcopenia among elderly Chinese population.

Internal hernia caused by the appendix adhering to the right ovary: a case report.

Internal hernias are a rare condition and sometimes life-threatening, and they need an emergency exploratory laparotomy. Appendicectomy for chronic appendicitis is controversial. Without timely treatment, chronic appendicitis may develop into a ruptured appendix and an infection that spreads to other parts of the body, and other serious complications. Here we report the case of 48-year-old female who had intestinal ischemia secondary to internal hernia caused by the appendix adhering to the right ovary. Her medical history indicated a chronic, right lower abdominal pain for three years.

Gut Microbiota Dysbiosis Drives the Development of Colorectal Cancer.

BACKGROUND: The gut microbiota is a diverse community of microbes that maintain the stability of the intestinal environment. Dysbiosis of the gut microbiota has been linked to gastrointestinal diseases, such as colorectal cancer (CRC) - a leading cause of death for cancer patients. SUMMARY: Candidate pathogens have been identified using bacterial culture and high-throughput sequencing techniques. Currently, there is evidence to show that specific intestinal microbes drive CRC development and progression, yet their pathogenic mechanisms are still unclear. Key Messages: In this review, we describe the known healthy gut microbiota and its changes in CRC. We especially focus on exploring the pathogenic mechanisms of gut microbiota dysbiosis in CRC. This is crucial for explaining how gut microbiota dysbiosis drives the process of colorectal carcinogenesis and tumor progression. Evaluation of changes in the gut microbiota during CRC development and progression offers a new strategy for the diagnosis and treatment of this disease.

Prognostic factors in stage I gastric cancer: A retrospective analysis.

PURPOSE: The purpose of this research is to investigate the prognostic factors of patients with stage I gastric cancer (GC) and to determine whether adjuvant chemotherapy improves the prognosis for high-risk patients. METHODS: We performed a retrospective analysis at Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, and HwaMei Hospital, University of Chinese Academy of Sciences from January 2001 to December 2015. Cox regression and Kaplan-Meier were used to evaluate the relationship between the patients' clinicopathologic characteristics and prognosis. RESULTS: A total of 1,550 patients were eligible for the study. The 5-year disease-free survival (DFS) rate of all enrolled patients was 96.5%. The pT and pN stages were significantly associated with the prognosis. The 5-year DFS rates of the three subgroups (T1N0, T2N0, and T1N1) were 97.8%, 95.7%, and 90.5%, respectively (p < 0.001). In the T1N1 subgroup, patients not undergoing chemotherapy showed a lower 5-year DFS rate compared to those undergoing chemotherapy, although the difference was not statistically significant. CONCLUSIONS: Both the pT and pN stages were closely associated with the prognosis of patients with stage I GC. We also found that the danger coefficient of the pN stage was higher than that of the pT stage, and that postoperative adjuvant chemotherapy might be a reasonable approach to improve outcomes of high-risk patients, particularly in the T1N1 group.

Role of homocysteine in the development and progression of Parkinson's disease.

Homocysteine is an essential intermediate product of biochemical reactions that is present in various tissues of the human body. Homocysteine may be associated with the development and progression of Parkinson's disease. Plasma homocysteine levels in patients with Parkinson's disease are elevated compared to those of healthy individuals. High homocysteine drives PD development and progression while aggregating the clinical symptoms of PD patients. The relationship between PD and homocysteine involves multiple pathways, including nerve cell apoptosis, oxidative stress, and DNA damage. This is crucial for explaining how high homocysteine drives the PD procession. Elevated homocysteine level during PD development and progression offers a new strategy for the diagnosis and treatment of this disease.

Lipid storage droplet protein 5 reduces sodium palmitate­induced lipotoxicity in human normal liver cells by regulating lipid metabolism­related factors.

Lipid storage droplet protein 5 (LSDP5) is specifically expressed in tissues with high oxidative metabolism such as liver and heart. The present study aimed to explored the role of LSDP5 in sodium palmitate­induced lipotoxicity in LO2 normal human liver cells. LO2 cells were treated with various concentrations of sodium palmitate (25, 50, 75, 100, 125 and 150 µmol/l) for 12, 24 and 48 h, and cell viability was determined by Cell Counting Kit­8. Subsequently, LO2 cells were exposed to 100 µmol/l sodium palmitate for 48 h to induce lipotoxicity (Model). Lipotoxicity Model LO2 cells were also transfected with pCMV5­LSDP5 overexpression vector, and reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP) and apoptotic rates were measured. The contents of non­esterified fatty acid (NEFA), malondialdehyde (MDA) and superoxide dismutase (SOD) were also measured. The expression levels of LSDP5, and apoptosis­, mitochondrial­, lipid metabolism­related factors were detected using reverse transcription­quantitative polymerase chain reaction and western blot assays. The results indicated that sodium palmitate exposure inhibited cell viability and induced lipotoxicity in LO2 cells. LSDP5 overexpression decreased ROS and apoptotic rates, and reduced NEFA and MDA content. LSDP5 transfection rescued the loss of MMP and elevated SOD content in lipotoxicity Model LO2 cells. In addition, LSDP5 upregulated the expression levels of B­cell lymphoma­2, acetyl­CoA carboxylase1/2 and fatty acid synthase (Fas), whereas the expression levels of activated­caspase­3, Bcl­2­associated X protein, cytochrome c, cytochrome c oxidase subunits IV, carnitine palmitoyltransferase 1a and peroxisome proliferator­activated receptors α levels were downregulated. LSDP5 may produce a protective effect on sodium palmitate­induced lipotoxicity in LO2 cells by regulating lipid metabolism­related factors.

A Risk-Scoring Model for Predicting Lymph Node Metastasis in Early Gastric Cancer Patients: a Retrospective Study and External Validation.

BACKGROUND: The possibility of lymph node metastasis (LNM) is critical to the assessment of the indication for endoscopic submucosal dissection. Thus, the aim of this study is to identify the risk factors for LNM and construct a risk-scoring model for patients with early gastric cancer to guide treatment. METHODS: A retrospective examination of reports and studies carried out January 2000 and December 2014 was conducted. A risk-scoring model for predicting LNM was developed based on the data thus collected. In addition, the model is subject to verification and validation by three institutions. RESULTS: Of the 1029 patients, 228 patients (22%) had LNM. Multivariate analysis showed that female, depressed type, undifferentiated type, submucosa, tumor size, and lymphovascular invasion were significantly associated with LNM. An 11-point risk-scoring model was used to predict LNM risk. An area under the receiver operating characteristic (AUROC) of the risk-scoring model was plotted using the development set and the AUROC of the model [0.76 (95% CI 0.73-0.80)] to predict LNM risk. After internal and external validation, the AUROC curve for predicting LNM was 0.77 (95% CI 0.68-0.86), 0.82 (95% CI 0.72-0.91), and 0.82 (95% CI 0.70-0.94), respectively. CONCLUSIONS: A risk-scoring model for predicting LNM was developed and validated. It could help with personalized care for patients with EGC.

Soluble oligomers and fibrillar species of amyloid ß-peptide differentially affect cognitive functions and hippocampal inflammatory response.

Two major active species of ß-amyloid protein (Aß), fibrillar Aß1-42 (FAß) and soluble Aß1-42 oligomers (AßO), are known to play important roles in the pathogenesis of Alzheimer's disease. However, the differences between them are largely unknown. In this study, we explored the effects of FAß and AßO on cognitive functions and hippocampal inflammatory response through a 30-days infusion of FAß or AßO (144pmol/d) into the left lateral ventricles of the rat brain. Morris water maze showed that the impairment of learning and memory functions was much more significant in the AßO-infused rats, compared to the FAß-infused rats. AßO-induced neurodegeneration and ultrastructure damage in CA1 neurons were more remarkable than those induced by FAß. Compared to FAß, AßO exerted more potent effects on the expressions of inflammatory factors toll-like receptor 4 and TNF-α and activation of NF-κB signaling. Taken together, our results from in vivo model demonstrate that AßO is more neurotoxic than FAß, and this neurotoxicity may be related to NF-κB-medicated inflammatory response.

Alginic acid sodium hydrogel co-transplantation with Schwann cells for rat spinal cord repair.

INTRODUCTION: The aim of the study was investigating the influence of Schwann cells-alginic acid sodium hydrogel co-transplantation on a rat model of spinal cord injury. MATERIAL AND METHODS: Sprague-Dawley (SD) rats were randomly assigned to 4 groups: control, injury, injury with Schwann cell transplantation, and injury with Schwann cells-alginic acid sodium hydrogel co-transplantation. Gelatin sponge blocks containing a Schwann cell suspension were transplanted into the injury site in the Schwann cell group; Schwann cells seeded in alginic acid sodium hydrogel were transplanted into the injury site in the Schwann cells-alginic acid sodium hydrogel group. At 12 h, 1, 3, 7, and 21 days after surgery, animals were assessed on the Basso, Beattie and Bresnahan (BBB) locomotor rating scale and then were sacrificed. RESULTS: In the injury group, Bcl-2 immunoreactive cells peaked at 3 days after surgery, and the expression level returned to normal level at 14 days. In the co-transplantation group, Bcl-2 immunoreactive cells in the spinal cord-transected segments were significantly increased until 7 days (p < 0.05) and remained at this level for more than 14 days. In the injury group, the number of apoptotic cells was the highest, as compared with the other 3 groups, and peaked at 1 and 7 days following spinal cord injury, and they were mostly distributed in the white matter. The BBB scores were significantly higher in the Schwann cells-alginic acid sodium hydrogel transplantation group than in the simple injury and Schwann cell groups (p < 0.05). CONCLUSIONS: Schwann cells-alginic acid sodium hydrogel co-transplantation could inhibit cellular apoptosis and enhance Bcl-2 expression in the spinal cord-transected segments, and thereby promote the recovery of locomotor function after spinal cord injury, although it did not reach full rehabilitation.