Yinyang Gongji Pills have the effects of strengthening the body resistance to eliminate pathogenic factors, removing stasis, and reducing swelling, which is a commonly used traditional Chinese medicine(TCM) formula for treating intestinal accumulation. A real-world, registered, and single-arm clinical trial was conducted to observe the clinical efficacy and safety of Yinyang Gongji Pills combined with capecitabine in the treatment of advanced colorectal cancer and analyze the clinical characteristics of the patients. A total of 60 patients with advanced colorectal cancer who refused or could not tolerate standard treatment of western medicine were included in the study. They were treated with Yinyang Gongji Pills combined with capecitabine until disease progression or intolerable adverse events occurred. The main observation indicators were progression-free survival(PFS) and safety. The treatment effects of the patients under different baseline characteristics were analyzed. The clinical trial has found that the median PFS of all enrolled patients was 7.3 months, with 30.1% of patients having a PFS exceeding 12.0 months. Layered analysis showed that the median PFS of patients with the onset site being the colon and rectum were respectively 8.4 and 4.7 months. The median PFS of patients with high, medium, and low tumor burden were respectively 7.0, 4.7, and 10.8 months. The median PFS of patients with wild-type and mutant-type RAS/BRAF were respectively 7.9 and 6.9 months. The median PFS of patients with KPS scores ≥80 and ≤70 were respectively 7.9 and 6.5 months. The median PFS of patients treated with Yinyang Gongji Pills for ≥6, 3-6, and ≤3 months were respectively 8.0, 5.2, and 4.2 months. The median PFS of patients with spleen, kidney, liver, and lung syndrome differentiation in TCM were respectively 8.3, 6.7, 7.3, and 5.6 months. The median PFS of patients with TCM pathological factors including phlegm, dampness, and blood stasis were respectively 7.0, 7.3, and 6.5 months. Common adverse reactions include anemia, decreased white blood cells, decreased appetite, fatigue, and hand foot syndrome, with incidence rates being respectively 44.2%, 34.6%, 42.3%, 32.7%, and 17.3%. The results showed that the combination of Yinyang Gongji Pills and capecitabine demonstrated potential clinical efficacy and good safety in this study. The patients have clinical characteristics such as low tumor burden, onset site at the colon, KPS scores ≥ 80, long duration of oral TCM, and TCM syndrome differentiation including spleen or liver.
Humans ; Capecitabine/adverse effects* ; Colorectal Neoplasms/mortality* ; Drugs, Chinese Herbal/adverse effects* ; Male ; Middle Aged ; Female ; Aged ; Adult ; Treatment Outcome

This study aims to explore the intervention effects of isorhamnetin(Isor) on acute lung injury(ALI) and its regulatory effects on pyroptosis mediated by the NOD-like receptor family pyrin domain containing 3(NLRP3)/apoptosis-associated speck-like protein containing a CARD(ASC)/cysteine aspartate-specific protease-1(caspase-1) axis. In the in vivo experiments, 60 BALB/c mice were divided into five groups. Except for the control group, the other groups were administered Isor by gavage 1 hour before intratracheal instillation of LPS to induce ALI, and tissues were collected after 12 hours. In the in vitro experiments, RAW264.7 cells were divided into five groups. Except for the control group, the other groups were pretreated with Isor for 2 hours before LPS stimulation and subsequent assessments. Hematoxylin-eosin(HE) staining was used to observe pathological changes in lung tissue, while lung swelling, protein levels in bronchoalveolar lavage fluid(BALF), and myeloperoxidase(MPO) levels in lung tissue were measured. Cell proliferation toxicity and viability were assessed using the cell counting kit-8(CCK-8) method. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of interleukin-1β(IL-1β), IL-6, IL-18, and tumor necrosis factor-α(TNF-α). Protein levels of NLRP3, ASC, cleaved caspase-1, and the N-terminal fragment of gasdermin D(GSDMD-N) were evaluated using immunohistochemistry, immunofluorescence, and Western blot. The results showed that in the in vivo experiments, Isor significantly improved pathological damage in lung tissue, reduced lung swelling, protein levels in BALF, MPO levels in lung tissue, and levels of inflammatory cytokines such as IL-1β, IL-6, IL-18, and TNF-α, and inhibited the high expression of the NLRP3/ASC/caspase-1 axis and the pyroptosis core gene GSDMD-N. In the in vitro experiments, the safe dose of Isor was determined through cell proliferation toxicity assays. Isor reduced cell death and inhibited the expression levels of the NLRP3/ASC/caspase-1 axis, GSDMD-N, and inflammatory cytokines. In conclusion, Isor may alleviate ALI by modulating pyroptosis mediated by the NLRP3/ASC/caspase-1 axis.
Animals ; Pyroptosis/drug effects* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Acute Lung Injury/physiopathology* ; Mice ; Mice, Inbred BALB C ; Quercetin/pharmacology* ; Caspase 1/genetics* ; CARD Signaling Adaptor Proteins/genetics* ; Male ; RAW 264.7 Cells ; Humans ; Lung/metabolism*

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Aim To explore the potential genes and mechanism of alisol B in the treatment of non-small cell lung cancer(NSCLC).Methods The proliferation and migration of NSCLC cells were detected by CCK-8 and Transwell.Genes of NSCLC and alisol B were col-lected through TCGA and compound gene prediction database,and their intersection genes were obtained.The network of protein-protein interaction(PPI)was constructed by using String database,and the top 20 key nodes were screened out,and the prognosis-related proteins related to the prognosis of NSCLC were screened out by using R language,and the intersection of them was obtained.The potential mechanism of ali-sol B on NSCLC was explored by KEGG and GO en-richment analysis and the relationship between related genes and immune cells,which was verified by cell-lev-el experiments.Results Alisol B inhibited the cell activity and migration ability of NSCLC cells.Five im-portant genes were identified by network pharmacologi-cal analysis:CCNE1,CDK1,COL1A1,COL1A2 and COL3A1.The results of cell experiment showed that al-isol B down-regulated the expression of Cyclin E1,CDK1 and COL1A2 in NSCLC cells.In addition,alisol B could inhibit the expression of COL1A2 and M2 macrophage marker CD206 in macrophages.Conclu-sions Alisol B may inhibit the proliferation of tumor cells by down-regulating CDK1 and Cyclin E1,and may affect the function of macrophages by inhibiting COL1A2,thus regulating the tumor immune microenvi-ronment and inhibiting NSCLC.

Combined radiation and burn injury (CRBI) is a severe syndrome, which is induced by the simultaneous or successive radiation and burn; but no appropriate clinical therapies are available. Loong oil (LO) is a traditional Chinese medicine oil composed of the oil extracts of cuttlebone, safflower, walnut oil, and rapeseed oil, which has been demonstrated to own anti-radiation and tissue healing functions. In this study, glyceryl monostearate (GMO) was used for the preparation of lyotropic liquid crystals that loaded LO to obtain Loong oil-lyotropic liquid crystals (LOL) for the treatment of skin CRBI. The hexagonal phase structure of LOL was proved by small X-ray scattering (SAXS) analysis with an approximate 7:9:11 ratio of peaks and under the polarizing microscope with the birefringence phenomenon. LOL had a high LO loading capacity (4%) and good bio-adhesive force, favoring skin administration. Animal experiments were approved by the Ethics Committee of the Beijing Institute of Radiation Medicine, Academy of Military Medical Sciences and the experiments were conducted in accordance with relevant guidelines and regulations (approval number: IACUC-DWZX-2022-834). Compared to triethanolamine creams, LOL had higher skin permeability with total skin penetration within 1 h, benefiting the treatment of deep CRBI. A deep II degree burn CRBI mouse model was established after whole-body irradiation with 5 Gy ⁶⁰Co γ-ray and the next 6-second 100 ℃ burn injury. LOL promoted LO skin penetration, improved epithermal cell proliferation and the formation of hair follicles, accelerated wound healing, and inhibited scarring, which benefitted the therapy of CRBI. In this study, LO application fields are expanded and LO is a promising medication for the treatment of CRBI.

Objective To establish a mouse model of type Ⅰ tricho-hepato-enteric syndrome(THES)induced by Ttc37 deficiency.Methods Ttc37 flox strain was established by site-specifically inserted loxP sites into Ttc37 gene via CRISPR/CAS9 technology.Ubiquitously expressed CAG-Cre was introduced for all-tissue removal of Ttc37 in Ttc37flox/flox;CAG-Cre mice.The knock-out effect was confirmed by fluorescence quantitative PCR and Western blot.Phenotypic evaluations were conducted in 8-week-old mice including hematoxylin-eosin staining of skin,spleen,liver,bladder,and gastrointestinal tract(GI),serum enzyme activity assay of aspartate aminotransferase(AST)and alanine aminotransferase(ALT),measurement of serum hemoglobin level,and ELISA for IgG and IgM level upon antigen immunization.Results Similar to type Ⅰ THES patients,Ttc37flox/flox;CAG-Cre mice exhibited impaired development of hair shaft,epidermis,B cell and eyes,while liver,GI,bladder and serum hemoglobin level seemed normal under unstressed condition.Conclusion A novel mouse model of typeⅠ THES was constructed successfully,which was applicable for pathological study.

As artificial intelligence technology rapidly advances, its deployment within the medical sector presents substantial ethical challenges. Consequently, it becomes crucial to create a standardized, transparent, and secure framework for processing medical data. This includes setting the ethical boundaries for medical artificial intelligence and safeguarding both patient rights and data integrity. This consensus governs every facet of medical data handling through artificial intelligence, encompassing data gathering, processing, storage, transmission, utilization, and sharing. Its purpose is to ensure the management of medical data adheres to ethical standards and legal requirements, while safeguarding patient privacy and data security. Concurrently, the principles of compliance with the law, patient privacy respect, patient interest protection, and safety and reliability are underscored. Key issues such as informed consent, data usage, intellectual property protection, conflict of interest, and benefit sharing are examined in depth. The enactment of this expert consensus is intended to foster the profound integration and sustainable advancement of artificial intelligence within the medical domain, while simultaneously ensuring that artificial intelligence adheres strictly to the relevant ethical norms and legal frameworks during the processing of medical data.
Artificial Intelligence/legislation & jurisprudence* ; Humans ; Consensus ; Computer Security/standards* ; Confidentiality/ethics* ; Informed Consent/ethics*

The neurovascular unit (NVU) is highly responsible for cerebral homeostasis and its dysfunction emerges as a critical contributor to Alzheimer's disease (AD) pathology. Hence, rescuing NVU dysfunction might be a viable approach to AD treatments. Here, we fabricated a self-regulated muti-functional nano-modulator (siR/PIO@RP) that can intelligently navigate to damaged blood-brain barrier and release therapeutical cargoes for synergetic AD therapy. The resulting siR/PIO@RP enables self-regulation of its distribution in accordance with the physio/pathological state (low/high RAGE expression) of the target site via a feedback loop. siR/PIO@RP is capable of performing intricate tasks and goes beyond the capabilities of single-target therapeutic agents utilized in AD therapy, such as reducing cerebral Aβ load, relieving neuroinflammation, and alleviating the dysfunction of NVU. Overall, the current study provides proof of concept that normalizing NVU holds promise as a means of alleviating AD symptoms.

Humans ; Nutrition Surveys ; Diabetes Mellitus, Type 2/chemically induced* ; Environmental Exposure/analysis* ; Environmental Monitoring ; Phthalic Acids/toxicity* ; Environmental Pollutants/toxicity*

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis