This study explores the effect and mechanism of Banxia Xiexin Decoction(BXD) in inhibiting colon cancer progression by reshaping tryptophan metabolism. Balb/c mice were assigned into control, model, low-dose BXD(BXD-L), and high-dose BXD(BXD-H) groups. Except the control group, the other groups were subcutaneously injected with CT26-Luc cells for the modeling of colon cancer, which was followed by the intervention with BXD. Small animal live imaging was employed to monitor tumor growth, and the tumor volume and weight were measured. Hematoxylin-eosin(HE) staining was used to observe the pathological changes in mouse tumors. Immunohistochemistry was used to detect Ki67 expression in tumors. Immunofluorescence and flow cytometry were used to detect the infiltration and number changes of CD3~+/CD8~+ T cells in the tumor tissue. Enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of interferon-gamma(IFN-γ) and interleukin-2(IL-2) in tumors. Targeted metabolomics was employed to measure the level of tryptophan(Trp) in the serum, and the Trp content in the tumor tissue was measured. Western blot and RT-qPCR were employed to determine the protein and mRNA levels, respectively, of indoleamine 2,3-dioxygenase 1(IDO1), MYC proto-oncogene, and solute carrier family 7 member 5(SLC7A5) in the tumor tissue. Additionally, a co-culture model with CT26 cells and CD8~+ T cells was established in vitro and treated with the BXD-containing serum. The cell counting kit-8(CCK-8) assay was used to examine the viability of CT26 cells. The content of Trp in CT26 cells and CD8~+ T cells, as well as the secretion of IFN-γ and IL-2 by CD8~+ T cells, was measured. RT-qPCR was used to determine the mRNA levels of MYC and SLC7A5 in CT26 cells. The results showed that BXD significantly inhibited the tumor growth, reduced the tumor weight, and decreased the tumor volume in the model mice. In addition, the model mice showed sparse arrangement of tumor cells, varying degrees of patchy necrosis, and downregulated expression of Ki67 in the tumor tissue. BXD elevated the levels of IFN-γ and IL-2 in the tumor tissue, while upregulating the ratio of CD3~+/CD8~+ T cells and lowering the levels of Trp, IDO1, MYC, and SLC7A5. The co-culture experiment showed that BXD-containing serum reduced Trp uptake by CT26 cells, increased Trp content in CD8~+T cells, enhanced IL-2 and IFN-γ secretion of CD8~+T cells, and down-regulated the mRNA levels of MYC and SLC7A5 in CT26 cells. In summary, BXD can inhibit the MYC/SLC7A5 pathway to reshape Trp metabolism and adjust Trp uptake by CD8~+ T cells to enhance the cytotoxicity, thereby inhibiting the development of colon cancer.
Animals ; Tryptophan/metabolism* ; Colonic Neoplasms/pathology* ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Mice, Inbred BALB C ; Humans ; Cell Line, Tumor ; Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism* ; Female ; Disease Progression ; Cell Proliferation/drug effects* ; Proto-Oncogene Mas ; Male

PURPOSE: The study aimed to examine the pattern of motorization and the mortality rate related to road traffic crashes in Zunyi (a city in northern Guizhou province of China) from 2013 to 2022, and to identify the epidemiological characteristics of these crashes with to provide insights that could help improve road safety. METHODS: Data were obtained from the Zunyi traffic management data platform, and the mortality rates were calculated. We deployed various analytical methods, including descriptive analysis, Chi-square test or Fisher's exact test for categorical variables, circular distribution map analysis, and Rayleigh test to characterize the traits of road traffic crashes in the region. RESULTS: During the 10-year study period, 7488 people died due to road traffic accidents, with males accounting for 70.4% and females 29.6% (χ² = 101.97, p < 0.001). The mortality rate increased from 7.80 deaths per 100,000 people in 2013 to 10.70 deaths per 100,000 people in 2016, but then decreased to 9.54 deaths per 100,000 people in 2019. A notable finding was that the death rate per 10,000 vehicles declined from 16.09 deaths per 10,000 vehicles in 2013 to 5.48 deaths per 10,000 vehicles in 2022. The study also found that vulnerable road users represented nearly half (48.76%) of all accident fatalities, and unlicensed or inexperienced driving contributed significantly to the occurrence of road traffic accidents. CONCLUSION Although the number of road traffic accidents in Zunyi has decreased, there are still some critical issues that need to be addressed, particularly for vulnerable road users and unlicensed drivers. Our results highlight the need for targeted interventions to address the specific risk factors of road traffic crashes, particularly those affecting vulnerable road users and drivers without sufficient experience or license.
Humans ; Accidents, Traffic/statistics & numerical data* ; China/epidemiology* ; Male ; Female ; Adult ; Middle Aged ; Aged ; Adolescent ; Young Adult ; Child

Type 2 diabetes (T2D) is an independent risk factor for cognitive impairment. The dysregulation of hypoxia inducible factor (HIF) signaling in T2D patients results in impaired adaptive responses to hypoxia, thereby accelerating the progression of complications. However, limited knowledge is available regarding its precise function in diabetes-associated cognitive impairment (DACI). Here, elevated HIF-1α levels were observed in brain endothelial cells (ECs) of db/db mice. Functionally, brain ECs-specific knockdown of H if1 a significantly ameliorated T2D-induced memory loss and neuronal damage. Glycolysis in brain ECs was inhibited in this process, as indicated by RNA-seq, leading to decreased hippocampal lactate production through reduced LDHA expression. Notably, T2D patients showed increased cerebrospinal fluid lactate levels, which were strongly associated with their cognitive dysfunction. Intrahippocampal injection of lactate accelerated cognitive dysfunction and impaired adult hippocampal neurogenesis (AHN) in db/db mice. Conversely, reducing hippocampal lactate levels through the intrahippocampal injection of oxamate delayed the onset of memory deficits. Furthermore, asiatic acid was discovered to protect db/db mice from cognitive impairment by decreasing brain endothelial HIF-1α expression and subsequently reducing hippocampal lactate-induced AHN damage. Overall, this study elucidates the inhibiting role played by endothelial HIF-1α-driven lactate in AHN and highlights a potential tactic of targeting HIF-1α in brain ECs for treating cognitive impairment.

OBJECTIVE: To systematically search and integrate the best evidence for early rehabilitation of ICU-acquired swallowing dysfunction (ICU-ASD) using evidence-based medicine methods, providing high-quality evidence-based support for intensive care unit (ICU) healthcare professionals in implementing early rehabilitation assessment and intervention strategies for ICU-ASD. METHODS: The systematic search was conducted according to the "6S" pyramid evidence model. Multiple authoritative databases and resources were comprehensively searched, including: National Guideline Clearinghouse (NGC), National Institute for Health and Care Excellence (NICE), Canadian Medical Association Clinical Practice Guidelines Library (CMACPGL), New Zealand Guidelines Group (NZGG), Guidelines International Network (GIN), Registered Nurses' Association of Ontario (RNAO), Scottish Intercollegiate Guidelines Network (SIGN), PubMed/Medline, Cochrane Library, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science, JBI Evidence-Based Health Care Database, Physiotherapy Evidence Database (PEDro), Chinese Medical Pulse Guidelines Website, SinoMed, CNKI, Wanfang Data, UpToDate, BMJ Best Practice, and professional association websites. The search encompassed guidelines, expert consensus statements, original studies [including cohort studies, quasi-experimental studies, and randomized controlled trials (RCT)], systematic reviews, and evidence summaries related to the prevention and management of ICU-ASD. The search period was limited from the inception of each database to November 30, 2024. The best evidence for early rehabilitation of ICU-ASD was summarized. The quality assessment of the literature and the extraction and synthesis of evidence were independently performed by two researchers with expertise in evidence-based medicine methodology. RESULTS: A total of 16 articles were included, consisting of 1 clinical decision-making study, 1 cohort study, 2 guidelines, 2 RCTs, 6 systematic reviews, 1 evidence summary, 2 expert consensuses, and 1 expert opinion. Following quality assessment, all 16 articles were incorporated into the analysis. For the early rehabilitation of ICU-ASD, five major themes were ultimately identified and 25 best evidence items were summarized, focusing on: multidisciplinary collaboration, swallowing screening and assessment, rehabilitation interventions, dietary and nutritional management, and oral hygiene. CONCLUSIONS The evidence summary provides individualized rehabilitation strategies for ICU-ASD patients, but their implementation still needs to be adapted to China's clinical practice context and patient preferences.
Humans ; Deglutition Disorders/etiology* ; Intensive Care Units ; Evidence-Based Medicine

Objective To analyze the efficacy and safety of ustekinumab(UST)in patients with moderate-to-severe Crohn's disease(CD),and to identify factors influencing clinical outcomes.Methods Data were retrospectively collected from patients with moderate-to-severe CD treated with UST in the First Affiliated Hospital of Zhejiang Chinese Medical University and Hangzhou Hospital of Traditional Chinese Medicine between November 2020 and May 2023.Patients were categorized into first-line(not treated with biologic agents,n=68)and second-line(treated with biologic agents,n=66)treatment groups based on prior use of biologic agents.Baseline characteristics,including age,sex,smoking status,disease duration,age at diagnosis,lesion site,disease behavior,perianal disease,history of intestinal surgery,and CD-related drug use,were compared between the two groups.Crohn's disease activity indices(CDAI)were recorded at baseline,week 14,and week 52 to assess the clinical efficacy at weeks 14 and 52.Endoscopic evaluations were performed at baseline and week 52 to evaluate endoscopic efficacy at week 52.The 52-week drug persistence rate and safety profile were also analyzed.Influencing factors related to clinical outcomes were evaluated using univariate and multivariate logistic regression.Results A total of 134 patients with moderate-to-severe CD treated with UST were included.At week 14,clinical response and remission rates were 75.4%(101/134)and 33.6%(45/134),respectively,with no significant difference in clinical efficacy between first-line and second-line groups(clinical response rate:77.9%vs.72.7%,P=0.484;clinical remission rate:38.2%vs.28.8%,P=0.247).At week 52,clinical response and remission rates were 79.9%(107/134)and 56.0%(75/134),respectively.The rates of endoscopic response and remission were 70.9%(95/134)and 38.8%(52/134),respectively.There were no significant differences in clinical efficacy(clinical response rate:80.9%vs.78.8%,P=0.763;clinical remission rate:60.3%vs.51.5%,P=0.306)and endoscopic efficacy(endoscopic response rate:76.5%vs.65.2%,P=0.149;endoscopic remission rate:42.6%vs.34.8%,P=0.354)between the two groups.The 52-week drug persistence rate was 85.8%(115/134),and the adverse reaction rate was 4.5%(6/134).Compared with first-line treatment group,biologic-experienced patients had a significantly higher proportion of dose-optimized therapy in second-line treatment group(45.5%vs.22.1%,P=0.004).Multivariate logistic regression showed that the 14-week clinical response was a significant predictor of 52-week clinical remission,while perianal disease and intestinal surgery history were significant factors associated with treatment failure(P<0.05).Conclusions UST demonstrates significant efficacy in improving clinical and endoscopic outcomes for moderate-to-severe CD patients,with a favorable safety profile.Clinical response at 14 weeks is strongly predictive of clinical remission at 52 weeks.Patients with perianal disease or a history of intestinal surgery were at higher risk of treatment failure.

Objective To explore the protective effect in a model of nicotinamide riboside(NR)against carbonyl cyanide m-chlorophenylhydrazone(CCCP)-induced oxidative stress in R28 cells.Methods 4 μmol/L CCCP was used to induce oxidative stress in R28 cells,and 400 nmol/L NR was used to intervene.The cell viability was quantified by CCK-8 assay.The apoptosis was detected by Annexin-V/PI double staining and flow cytometry.Western blotting was used to examine the levels of Cytochrome C,Caspase-3,and Caspase-9 to evaluate the apoptosis.Tetramethylrhodamine ethyl ester was used to detect the mitochondrial membrane potential(MMP),MitoSOX was used to detect the mitochondrial reactive oxygen species(mtROS)levels,and adenosine triphosphate(ATP)assay kit was used to assess ATP generation ability to evaluate mitochondrial function.Results After CCCP treatment of R28 cells,the cell viability decreased,the apoptotic protein levels and apoptosis rates increased,the MMP decreased,and the mtROS generation increased(P＜0.05).After NR pretreatment,the cell viability increased,the apoptotic protein levels and apoptosis rates decreased,the MMP increased,and the mtROS generation decreased(P＜0.05).Conclusion:NR enhances the cell viability,reduces the expression of apoptotic proteins,and ultimately reduces the apoptosis of retinal ganglion cell by inhibiting oxidative stress response and protecting mitochondrial function.

Objective:To investigate the establishment method, coordination points and safe transport management strategy of vena-arterial extracorporeal membrane oxygenation (VA-ECMO) in patients with downtime difficulties during cardiopulmonary bypass (CPB).Methods:A observation study was conducted. The patients admitted to the department of critical care medicine of the First Affiliated Hospital of Wannan Medical College (Yijishan Hospital) from January 2020 to October 2022 were enrolled. These patients could not be separated from CPB and received VA-ECMO-assisted CPB surgery. The clinical data of the patients were recorded, including the basic information of the patients, the data of VA-ECMO establishment and transport process, the clinical indicators before and after VA-ECMO installation, the operation data of VA-ECMO and clinical outcomes. The experience was summarized from the aspects of extracorporeal membrane oxygenation (ECMO) establishment, transport process, team cooperation, and adverse events during transport. The clinical indicators before and after ECMO operation were compared. According to whether ECMO was successfully weaned, the patients were divided into a successful weaning group and a failure weaning group, and the clinical data between the two groups were compared.Results:Eighteen patients who underwent VA-ECMO-assisted CPB were enrolled, including 10 males and 8 females. The average age was (56.7±12.3) years old. Preoperative left ventricular ejection fraction (LVEF) was 0.46±0.10, and the main reasons for switching to VA-ECMO assistance included right ventricular systolic weakness in 6 cases, total cardiac systolic weakness in 5 cases, left ventricular systolic weakness in 4 cases, high pulmonary arterial pressure in 2 cases, and intractable ventricular fibrillation in 1 case. Among the 18 patients transferred from CPB to VA-ECMO, 10 cases were successfully weaned and 8 cases failed. In ICU, 8 cases survived, 5 cases died, and 5 cases gave up treatment and discharged. The average time for successful CPB to VA-ECMO establishment was (24.6±7.4) minutes, initial blood flow was (3.3±0.4) L/min, and transit time was (8.4±1.5) minutes. ECMO-assisted duration averaged (82.0±69.3) hours. Adverse events occurred in 9 patients during ECMO establishment and transfer. Post-ECMO onboarding for 4 hours, significant improvements were noted in blood lactic acid (Lac), pH value, mean arterial pressure (MAP), central venous oxygen saturation (ScvO 2) as compared with pre-ECMO onboarding [Lac (mmol/L): 10.5±7.0 vs. 15.2±6.8, pH value: 7.38±0.92 vs. 7.26±0.87, MAP (mmHg, 1 mmHg≈0.133 kPa): 74.9±13.7 vs. 58.4±17.0, ScvO 2: 0.678±0.065 vs. 0.611±0.061, all P < 0.01], and vasoactive-inotropic score (VIS) was also decreased (39.8±29.8 vs. 68.9±64.4, P < 0.01). Compared with successful weaning group, the patients in the failed weaning group exhibited higher pre-machine Lac (mmol/L: 18.8±7.8 vs. 12.3±4.3, P < 0.05), longer CPB time [minutes: 238.0 (208.8, 351.2) vs. 200.0 (185.8, 217.0), P < 0.05], and shorter ECMO-assisted time [hours: 19.5 (11.0, 58.8) vs. 94.5 (65.8, 179.8), P < 0.01]. However, there was no statistically significant difference in pre-machine pH value, ScvO 2, MAP, VIS score, and initial blood flow and establishment time of ECMO between the two groups. Conclusions:VA-ECMO is an effective circulatory aid for CPB surgery that cannot be weaned after CPB. The establishment and transfer of CPB "bridge" to ECMO aid depends on multi-disciplinary treatment (MDT) cooperation. The success rate of ECMO weaning is related to the Lac and CPB duration. If it is not possible to detach from the CPB successfully, VA-ECMO should be initiated as early as possible.

Objective:To integrate the best evidence for early rehabilitation of mechanically ventilated ICU-acquired weakness (ICU-AW) patients using evidence-based methods, providing evidence-based basis for standardized evaluation and intervention of early exercise therapy for mechanically ventilated ICU-AW patients.Methods:A systematic search was conducted on the American Thoracic Society (ATS) Clinical Practice Guidelines, Registered Nurses' Association of Ontario (RNAO), Guidelines International Network (GIN), Canadian Medical Association Clinical Practice Guideline Library (CMACPGL), BMJ Clinical Evidence, UpToDate, Scottish Intercollegiate Guidelines Network (SIGN), PubMed, Cochrane Library, National Guideline Clearinghouse (NGC), Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), UM-library, Physiotherapy Evidence Database (PEDro), National Institute for Health and Care Excellence (NICE), New Zealand Guidelines Group (NZGG), Chinese Medical Pulse Guidelines Website, CNKI and Wanfang data and other Chinese and English databases, professional team websites, and guideline websites for expert consensus, guidelines, randomized collected trial (RCT), systematic reviews and other evidence on early exercise rehabilitation for mechanically ventilated ICU-AW patients. The search time limit was from the establishment of the database to December 31, 2023. Literature search, screening, evaluation, information extraction was independently conducted by two evaluators with cross checking, and quality evaluation of the included literature was conducted.Results:A total of 21 literatures were enrolled, including 5 guidelines, 5 systematic reviews, 4 expert consensuses, and 7 RCT, all of which with high evidence level and all were enrolled. They were summarized into seven aspects with assessment screening, exercise safety standards, precautions, setting of exercise time, exercise intensity, exercise sequence, and recommended exercise content as the core, and 32 best evidences.Conclusions:The evidence summarized can provide evidence-based basis for standardized assessment and intervention of early exercise rehabilitation in mechanically ventilated ICU-AW patients. ICU medical practitioners need to combine the actual clinical environment, individual differences and rehabilitation goals of patients, to provide targeted health guidance and intervention for the prevention of ICU-AW in mechanically ventilated patients.

Objective:To explore the application effect of ICU nursing sub-specialty management model in the clinical treatment of ICU patients.Methods:Based on the actual needs of ICU patients,a precise and systematic management plan including organizational structure,workflow,linkage mechanism,quality control system,dynamic follow-up,and scientific research transformation was formulated,to construct a working model of multi-linkage,multi-direction supplement and coordinated development of two-way feedback mechanism in sub-specialty nursing.The control group was set before the implementation of ICU nursing sub-specialty management mode(Jan 1 to Dec 31,2021),and the intervention group was set after the implementation of ICU nursing sub-specialty management model(Jan 1 to Dec 31,2022).The core competence,specialty,sensitive indicators,satisfaction,and impact on patients were compared before and after implementation.Results:After the implementation of the ICU nursing sub-specialty management model,the core competence of nurses was improved,and the hospitalization time and mechanical ventilation time of patients were reduced,the incidence of re-entry ICU,acquired weakness,acquired dysphagia and incontinence dermatitis was decreased,the proportion of unplanned extubation was decreased,and the satisfaction of patients,nurses,doctors and students was improved(P＜0.05).Conclusion:The construction of ICU nursing sub-specialty management model can effectively promote the construction of ICU nursing sub-specialty,improve the core competence of nurses,reshape the connotation of nursing,improve the prognosis of patients,and ultimately promote the benign and sustainable development of hospital nursing.

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens