Sustained inflammatory responses are closely related to various severe diseases, and inhibiting the excessive activation of inflammasomes and pyroptosis has significant implications for clinical treatment. Natural products have garnered considerable concern for the treatment of inflammation. Huanglian-Wumei decoction (HLWMD) is a classic prescription used for treating inflammatory diseases, but the necessity of their combination and the exact underlying anti-inflammatory mechanism have not yet been elucidated. Inspired by the supramolecular self-assembly strategy and natural drug compatibility theory, we successfully obtained berberine (BBR)-chlorogenic acid (CGA) supramolecular (BCS), which is an herbal pair from HLWMD. Using a series of characterization methods, we confirmed the self-assembly mechanism of BCS. BBR and CGA were self-assembled and stacked into amphiphilic spherical supramolecules in a 2:1 molar ratio, driven by electrostatic interactions, hydrophobic interactions, and π-π stacking; the hydrophilic fragments of CGA were outside, and the hydrophobic fragments of BBR were inside. This stacking pattern significantly improved the anti-inflammatory performance of BCS compared with that of single free molecules. Compared with free molecules, BCS significantly attenuated the release of multiple inflammatory mediators and lipopolysaccharide (LPS)-induced pyroptosis. Its anti-inflammatory mechanism is closely related to the inhibition of intracellular nuclear factor-kappaB (NF-κB) p65 phosphorylation and the noncanonical pyroptosis signalling pathway mediated by caspase-11.

Objective:To investigate the correlation between triglyceride-glucose (TyG) index on admission and unfavorable outcomes of patients with moderate-to-severe traumatic brain injury (msTBI) at 6 months postinjury.Methods:A retrospective cohort study was conducted to analyze the clinical data of 277 patients with msTBI admitted to Affiliated Jiangyin Hospital of Nantong University from January 2019 to December 2022, including 208 males and 69 females, aged 18-88 years [(57.0±15.1)years]. Glasgow Coma Scale (GCS) scores on admission were 3-8 points in 168 patients and 9-12 points in 109. According to the Glasgow Outcome Scale-Extended (GOSE) assessment at 6 months after injury, there were 121 patients with unfavorable outcomes (GOSE≤4 points) and 156 with favorable outcomes (GOSE≥5 points). The following indicators of the patients were recorded, including gender, age, history of diabetes, cause of injury, admission GCS, GCS motor score (GCSM), pupillary light reflex, worst Marshall CT classification within the first 24 hours after admission, admission TyG index, Mean Amplitude of Glycemic Excursions (MAGE) within 24 hours after admission, GCSM decline≥2 points within 72 hours after admission, craniotomy or not after admission, and prognosis, etc. TyG index served as the exposure variable focused in this study, which was calculated with fasting triglycerides and fasting blood glucose within 24 hours after admission. The 6-month prognosis of the patients was designated as the outcome variable of the study. After the patients were divided into different groups according to the three quantiles of the TyG index and unfavorable or favorable outcomes, the univariate analysis was conducted on watch variables, and variables with statistically significant differences were included in directed acyclic graphs (DAGs) for further identification of confounding variables. Factors which were found with no statistical significance in the univariate analysis but might affect insulin resistance after injury according to the authors′ previous researches were also included in the DAGs analysis. Three Logistic regression models were designed (Model 1 without correction, Model 2 with core variables of International Mission for Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (IMPACT) corrected, and Model 3 with confounding variables screened by DAGs corrected) to analyze whether the TyG index was an independent risk factor for the prognosis of msTBI patients. The optimal Logistic regression model was selected and then restricted cubic spline (RCS) was employed to investigate the relationship between the TyG index and the unfavorable outcomes.Results:The univariate analysis suggested that there were significant differences in gender, history of diabetes, MAGE, GCSM decline, and prognosis among the three quantiles of the TyG index ( P<0.05 or 0.01). Significant differences in age, history of diabetes, GCSM, pupillary light reflex, Marshall CT classification, TyG index, MAGE and GCSM decline were observed between unfavorable and favorable outcome groups ( P<0.05 or 0.01). The results of Logistic regression analysis that identified the confounding variables that influenced the correlation between the TyG index and unfavorable prognosis with DAGs suggested that a high TyG index level was significantly correlated with unfavorable outcomes in msTBI patients. Moreover, Model 3 that was corrected with confounding variables screened by DAGs had an optimal goodness-of-fit and adaptability. Model 3-based further RCS analysis indicated that the risk of unfavorable outcomes following msTBI may increase approximately linearly with the increase in TyG index within a certain range (TyG index<9.79). Conclusions:A high TyG index level on admission is the identified as an independent risk factor for unfavorable outcomes of patients with msTBI at 6 months postinjury. As the TyG index level increases, the risk of unfavorable outcomes also rises and may show a linear increasing trend within a certain range (TyG index<9.79).

With the improved understanding of driver mutations in non-small cell lung cancer (NSCLC), expanding the targeted therapeutic options improved the survival and safety. However, responses to these agents are commonly temporary and incomplete. Moreover, even patients with the same oncogenic driver gene can respond diversely to the same agent. Furthermore, the therapeutic role of immune-checkpoint inhibitors (ICIs) in oncogene-driven NSCLC remains unclear. Therefore, this review aimed to classify the management of NSCLC with driver mutations based on the gene subtype, concomitant mutation, and dynamic alternation. Then, we provide an overview of the resistant mechanism of target therapy occurring in targeted alternations ("target-dependent resistance") and in the parallel and downstream pathways ("target-independent resistance"). Thirdly, we discuss the effectiveness of ICIs for NSCLC with driver mutations and the combined therapeutic approaches that might reverse the immunosuppressive tumor immune microenvironment. Finally, we listed the emerging treatment strategies for the new oncogenic alternations, and proposed the perspective of NSCLC with driver mutations. This review will guide clinicians to design tailored treatments for NSCLC with driver mutations.
Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Mutation ; Tumor Microenvironment/genetics*

Humans ; Esophageal Squamous Cell Carcinoma/pathology* ; Esophageal Neoplasms/pathology* ; Carcinoma, Squamous Cell/pathology* ; Precancerous Conditions/pathology* ; Early Diagnosis

BACKGROUND: Family clustering of esophageal cancer (EC) has been found in high-risk areas of China. However, the relationships between cancer family history and esophageal cancer and precancerous lesions (ECPL) have not been comprehensively reported in recent years. This study aimed to provide evidence for identification of high-risk populations. METHODS: This study was conducted in five high-risk areas in China from 2017 to 2019, based on the National Cohort of Esophageal Cancer. The permanent residents aged 40 to 69 years were examined by endoscopy, and pathological examination was performed for suspicious lesions. Information on demographic characteristics, environmental factors, and cancer family history was collected. Unconditional logistic regression was applied to evaluate odds ratios between family history related factors and ECPL. RESULTS: Among 33,008 participants, 6143 (18.61%) reported positive family history of EC. The proportion of positive family history varied significantly among high-risk areas. After adjusting for risk factors, participants with a family history of positive cancer, gastric and esophageal cancer or EC had 1.49-fold (95% confidence interval [CI]: 1.36-1.62), 1.52-fold (95% CI: 1.38-1.67), or 1.66-fold (95% CI: 1.50-1.84) higher risks of ECPL, respectively. Participants with single or multiple first-degree relatives (FDR) of positive EC history had 1.65-fold (95% CI: 1.47-1.84) or 1.93-fold (95% CI: 1.46-2.54) higher risks of ECPL. Participants with FDRs who developed EC before 35, 45, and 50 years of age had 4.05-fold (95% CI: 1.30-12.65), 2.11-fold (95% CI: 1.37-3.25), and 1.91-fold (95% CI: 1.44-2.54) higher risks of ECPL, respectively. CONCLUSIONS: Participants with positive family history of EC had significantly higher risk of ECPL. This risk increased with the number of EC positive FDRs and EC family history of early onset. Distinctive genetic risk factors of the population in high-risk areas of China require further investigation. TRIAL REGISTRATION ChiCTR-EOC-17010553.
Case-Control Studies ; China/epidemiology* ; Esophageal Neoplasms/pathology* ; Humans ; Precancerous Conditions/pathology* ; Risk Factors ; Stomach Neoplasms

Background:It remains unclear about the association of muscle mass, strength, and quality with death in the general Chinese population of diverse economical and geographical backgrounds. The present study aimed to comprehensively examine such associations across different regions in China.Methods:Based on the China Kadoorie Biobank study, the present study included 23,290 participants who were aged 38 to 88 years and had no prevalent cardiovascular diseases or cancer. Muscle mass and grip strength were measured using calibrated instruments. Arm muscle quality was defined as the ratio of grip strength to arm muscle mass. Low muscle mass, grip strength, and arm muscle quality were defined as the sex-specific lowest quintiles of muscle mass index, grip strength, and arm muscle quality, respectively. Cox proportional hazards models yielded hazard ratios (HRs) and 95% confidence intervals (CIs) for risks of all-cause mortality in relation to muscle mass, strength, and quality.Results:During a median follow-up of 3.98 years, 739 participants died. The HR (95% CI) of all-cause mortality risk was 1.28 (1.08-1.51) for low appendicular muscle mass index, 1.38 (1.16-1.62) for low total muscle mass index, 1.68 (1.41-2.00) for low grip strength, and 1.41 (1.20-1.66) for low arm muscle quality in models adjusted for sociodemographic characteristics, lifestyle factors, and medical histories.Conclusion:Low muscle mass, grip strength, and arm muscle quality are all associated with short-term increased risks of mortality, indicating the importance of maintaining normal muscle mass, strength, and quality for general Chinese adults.

As a low-load physiological monitoring technology, wearable devices can provide new methods for monitoring, evaluating and managing chronic diseases, which is a direction for the future development of monitoring technology. However, as a new type of monitoring technology, its clinical application mode and value are still unclear and need to be further explored. In this study, a central monitoring system based on wearable devices was built in the general ward (non-ICU ward) of PLA General Hospital, the value points of clinical application of wearable physiological monitoring technology were analyzed, and the system was combined with the treatment process and applied to clinical monitoring. The system is able to effectively collect data such as electrocardiogram, respiration, blood oxygen, pulse rate, and body position/movement to achieve real-time monitoring, prediction and early warning, and condition assessment. And since its operation from March 2018, 1 268 people (657 patients) have undergone wearable continuous physiological monitoring until January 2020, with data from a total of 1 198 people (632 cases) screened for signals through signal quality algorithms and manual interpretation were available for analysis, accounting for 94.48 % (96.19%) of the total. Through continuous physiological data analysis and manual correction, sleep apnea event, nocturnal hypoxemia, tachycardia, and ventricular premature beats were detected in 232 (36.65%), 58 (9.16%), 30 (4.74%), and 42 (6.64%) of the total patients, while the number of these abnormal events recorded in the archives was 4 (0.63%), 0 (0.00%), 24 (3.80%), and 15 (2.37%) cases. The statistical analysis of sleep apnea event outcomes revealed that patients with chronic diseases were more likely to have sleep apnea events than healthy individuals, and the incidence was higher in men (62.93%) than in women (37.07%). The results indicate that wearable physiological monitoring technology can provide a new monitoring mode for inpatients, capturing more abnormal events and provide richer information for clinical diagnosis and treatment through continuous physiological parameter analysis, and can be effectively integrated into existing medical processes. We will continue to explore the applicability of this new monitoring mode in different clinical scenarios to further enrich the clinical application of wearable technology and provide richer tools and methods for the monitoring, evaluation and management of chronic diseases.
Heart Rate ; Humans ; Monitoring, Physiologic ; Movement ; Sleep Apnea Syndromes ; Wearable Electronic Devices

Esophageal cancer is the main malignant cancer in China. In 2015, the incidence and mortality of esophageal cancer were 17.87 per 100 000 and 13.68 per 100 000, respectively, ranking 6th and 4th in the incidence and death. Esophageal squamous cell carcinoma (ESCC) is the main pathological type of esophageal cancer, accounting for 86.3% of new cases. ESCC′s pathogenesis is still not clear and its related risk factors remain to be explored. There are no detection biomarkers that can be widely applied in the whole country nowadays. In order to provide a scientific basis for exploring the pathogenesis of ESCC and improve screening technology, this paper summarizes the research status of various risk factors and potential biomarkers of ESCC.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease discovered in the 21 st century. This disease has been reported in several Asian countries, including China, Japan, South Korea, Vietnam, and Myanmar. Until 2019, SFTS cases have been reported in 25 provinces in China, and most of them were rural residents from mountains and hilly regions. Most SFTS cases were sporadic but geographically concentrated, mainly in Henan, Shandong, Anhui, Hubei, Liaoning, Zhejiang, and Jiangsu provinces. SFTSV infection was transmitted predominantly by a tick bite and potentially through close contact with the patient's blood or body fluids. Fever, gastrointestinal symptoms, thrombocytopenia, and leukopenia were common initial manifestations, and multiple organ failure or even death could occur in severe cases. The reported cases of SFTS have been gradually increasing, and the case fatality rate has remained at a high level, posing a severe threat to public health in China. This paper reviewed the epidemiological features, risk factors for disease transmission, and the clinical characteristics of SFTS to gain further knowledge of the disease, guide the prevention and management, and help reduce the case fatality rate.

Esophageal cancer is the main malignant cancer in China. In 2015, the incidence and mortality of esophageal cancer were 17.87 per 100 000 and 13.68 per 100 000, respectively, ranking 6th and 4th in the incidence and death. Esophageal squamous cell carcinoma (ESCC) is the main pathological type of esophageal cancer, accounting for 86.3% of new cases. ESCC′s pathogenesis is still not clear and its related risk factors remain to be explored. There are no detection biomarkers that can be widely applied in the whole country nowadays. In order to provide a scientific basis for exploring the pathogenesis of ESCC and improve screening technology, this paper summarizes the research status of various risk factors and potential biomarkers of ESCC.