Chemotherapy remains a primary treatment option for hepatocellular carcinoma (HCC), yet its clinical benefits are often unsatisfactory. Utilizing arsenic trioxide (ATO) as a model, this study elucidates the role of autophagy inhibition in modulating the cellular response to chemotherapy, shifting cell death from apoptosis to pyroptosis via the caspase-3-GSDME pathway, thereby augmenting the anti-tumor efficacy. Building upon these findings, an ATO nanomedicine delivery system capable of autophagy inhibition to promote pyroptosis for enhanced tumor treatment was developed. Folic acid-modified albumin served as the stabilizer for nano self-assemblies formed through ion pairing between Mn²⁺ and ATO, encapsulating DNAzyme (Dz) targeting Beclin 1, a key autophagy regulator. Characterization studies confirmed efficient encapsulation of ATO and Dz within nanoparticles, designed to disintegrate in the intracellular microenvironment, releasing the all-active components, i.e., ATO, Mn²⁺, and Dz. Mn²⁺ acted as a metal cofactor to activate Dz for Beclin 1 mRNA cleavage, inhibiting autophagy and augmenting ATO-induced cell pyroptosis. Elevated cell pyroptosis levels not only enhance ATO's direct tumor cell killing capacity but also trigger anti-tumor immune responses, synergistically enhancing efficacy. Upon intravenous injection, the nanomedicine accumulated in tumor tissue and targeted liver cancer cells. Compared to free ATO, the nanomedicine exhibited significantly improved in vivo anti-tumor effects, achieving a 100% 45-day survival rate in mice with favorable biosafety profiles. This study offers novel insights into tumor chemotherapy sensitization and presents a promising strategy for ATO nanoformulation development.

Objective:To investigate the activation of ubiquitin proteasome system (UPS) and autophagy in brain tissues of rats after severe traumatic brain injury (sTBI) and the role of autophagy in secondary traumatic brain injury.Methods:(1) Twenty-five SD rats were randomly divided into sham-operated group, group of 3 h after sTBI, group of 1 d after sTBI, group of 3 d after sTBI and group of 7 d after sTBI ( n=5). Only bone window was opened in sham-operated group, and controlled cortical impact (CCI)-induced sTBI models were established in the other 4 groups. Western blotting was used to detect the expressions of free ubiquitin, ubiquitinated protein, vacuolar protein sorting 34 (VPS34), P62, microtubule-associated protein-light chain 3-II, and Mature-cathepsin D (CTSD). (2) One hundred SD rats were randomly divided into normal control group, sTBI group, lactacystin group and SAR405 group ( n=25). Ten μL lactacystin or SAR405 were stereotactically injected into the lateral ventricle of lactacystin group and SAR405 group, respectively; 30 min after that, CCI-induced sTBI models were established in the sTBI group, lactacystin group and SAR405 group. Three d after modeling, the expressions of ubiquitinated protein, LC3-II, P62, and Caspase-3 were detected by Western blotting; percentage of brain water content was determined by dry/wet weight ratio; neurological functions were assessed by modified neurological deficit scale (mNSS); degrees of brain tissue damage were detected by HE staining; and cerebral blood perfusion was detected by laser scattering hemodynamic imaging system. Results:(1) Compared with sham-operated group, group of 3 h after sTBI, group of 1 d after sTBI, group of 3 d after sTBI and group of 7 d after sTBI had significantly decreased free ubiquitin, and group of 1 d after sTBI, group of 3 d after sTBI and group of 7 d after sTBI had significantly increased ubiquitinated protein in the brain tissues surrounding the injury lesions ( P<0.05). Compared with sham-operated group, group of 3 d after sTBI and group of 7 d after sTBI had statistically increased VPS34 and Mature-CTSD and significantly decreased P62 and group of 1 d after sTBI, group of 3 d after sTBI and group of 7 d after sTBI had significantly increased LC3-II in the brain tissues surrounding the injury lesions ( P<0.05). (2) The ubiquitinated protein relative expressions in the brain tissues surrounding the injury lesions of normal control group, sTBI group, lactacystin group and SAR405 group were 4.78±2.63, 10.62±0.73, 13.45±1.22 and 8.50±0.83, respectively, with significant differences ( P<0.05). Compared with the normal control group, the sTBI group, lactacystin group and SAR405 group had significantly higher LC3-II, ubiquitinated protein and cleaved caspase-3/pro-caspase-3, and significantly lower P62 in the brain tissues surrounding the injury lesions ( P<0.05); compared with the the sTBI group, the lactacystin group had significantly higher LC3-II, ubiquitinated protein, and cleaved caspase-3/pro-caspase-3, and significantly lower P62 in the brain tissues surrounding the injury lesions ( P<0.05); compared with the the sTBI group, the SAR405 group had significantly lower LC3-II, ubiquitinated protein and cleaved caspase-3/pro-caspase-3, and significantly higher P62 in the brain tissues surrounding the injury lesions ( P<0.05). Compared with the normal control group([67.60±2.51]%、[0±0] scores、[333.41±46.86] PU), the sTBI group, lactacystin group and SAR405 group had statistically higher percentage of brain water content and mNSS scores ([80.2±1.30]%, [87.0±1.58]% and [71.60±1.81]%; 13.8±1.10, 16.4±0.55 and 10.40±1.14) and signficantly lower cerebral blood perfusion volume ([53.98±5.99] PU, [21.71±2.62] PU and [87.97±6.75] PU, P<0.05); compared with the sTBI group, the lactacystin group had significantly higher brain water content and mNSS scores, and significantly lower cerebral blood perfusion volume ( P<0.05); compared with the sTBI group, the SAR405 group had significantly lower brain water content and mNSS scores, and significantly higher cerebral blood perfusion volume ( P<0.05). HE staining showed that the cortical tissues were most severely damaged in the lactacystin group, followed by the sTBI group; the least damage was noted in the SAR405 group, and no significant damage in the normal control group was noted. Conclusion:After sTBI, UPS activation is earlier than autophagy; autophagy inhibition helps to alleviate UPS dysfunction, reduce Caspase-3-induced apoptosis, and is beneficial to the recovery of neurological function.

Objective:To analyze the relationship among self-efficacy, family support and diabetes self-management behavior in rural patients with type 2 diabetes mellitus, and to explore the mediating role of self-efficacy between self-management behavior and family support in rural patients with type 2 diabetes mellitus.Methods:From June to July 2023, Jingde county in southern Anhui, Jinzhai county in central Anhui, and Mengcheng county in northern Anhui were selected by multistage stratified cluster random sampling method as investigation sites. A total of 258 patients with type 2 diabetes mellitus were investigated by face-to-face survey. The questionnaire included general situation survey from, the summary of diabetes self-care activities measure, the self-efficacy for diabetes and diabetes family behavior checklist. SPSS 25.0 and AMOS 26.0 softwares were used for descriptive analysis, correlation analysis, common method bias test and mediation analysis.Results:The self-management behavior score of rural patients with type 2 diabetes mellitus was(2.15±0.96).The self-efficacy score was(28.50±7.02).The family support score was(29.37±9.45).Self-efficacy and family support were positively correlated with self-management behavior( r=0.390, 0.333, both P<0.01), and family support was positively correlated with self-efficacy( r=0.511, P<0.01). Self-efficacy played a partial mediating role between self-management behavior and family support in rural patients with type 2 diabetes, and the mediating effect accounted for 45.2%(0.147/0.325) of the total effect. Conclusion:Family support not only has direct influence on self-management behavior of rural patients with diabetes mellitus, but also has indirect influence on self-management behavior by improving self-efficacy.

Objective:To analyze the relationship among self-efficacy, family support and diabetes self-management behavior in rural patients with type 2 diabetes mellitus, and to explore the mediating role of self-efficacy between self-management behavior and family support in rural patients with type 2 diabetes mellitus.Methods:From June to July 2023, Jingde county in southern Anhui, Jinzhai county in central Anhui, and Mengcheng county in northern Anhui were selected by multistage stratified cluster random sampling method as investigation sites. A total of 258 patients with type 2 diabetes mellitus were investigated by face-to-face survey. The questionnaire included general situation survey from, the summary of diabetes self-care activities measure, the self-efficacy for diabetes and diabetes family behavior checklist. SPSS 25.0 and AMOS 26.0 softwares were used for descriptive analysis, correlation analysis, common method bias test and mediation analysis.Results:The self-management behavior score of rural patients with type 2 diabetes mellitus was(2.15±0.96).The self-efficacy score was(28.50±7.02).The family support score was(29.37±9.45).Self-efficacy and family support were positively correlated with self-management behavior( r=0.390, 0.333, both P<0.01), and family support was positively correlated with self-efficacy( r=0.511, P<0.01). Self-efficacy played a partial mediating role between self-management behavior and family support in rural patients with type 2 diabetes, and the mediating effect accounted for 45.2%(0.147/0.325) of the total effect. Conclusion:Family support not only has direct influence on self-management behavior of rural patients with diabetes mellitus, but also has indirect influence on self-management behavior by improving self-efficacy.

Neutrophil extracellular traps (NETs) are compounds composed of depolymerized DNA fibers and antimicrobial peptides released by neutrophils. NETs formation not only plays a role in pathological process of non-infectious diseases such as cystic fibrosis, systemic lupus erythematosus, diabetes and cancer, but also is closely related to many central nervous system diseases. In recent years, a large number of studies have found the presence of neutrophils and NETs in perivascular space of the infarcted lesions in patients with ischemic stroke (IS) and corresponding animal models. This article provides a review on NETs formation and clearance process, characteristics of NETs changes after IS, pathological processes involved in NETs after IS, and effects of NETs on neurons, to provide some references for IS.

This study aimed to explore key quality control factors that affected the prognosis of intensive care unit (ICU) patients in Chinese mainland over six years (2015-2020). The data for this study were from 31 provincial and municipal hospitals (3425 hospital ICUs) and included 2 110 685 ICU patients, for a total of 27 607 376 ICU hospitalization days. We found that 15 initially established quality control indicators were good predictors of patient prognosis, including percentage of ICU patients out of all inpatients (%), percentage of ICU bed occupancy of total inpatient bed occupancy (%), percentage of all ICU inpatients with an APACHE II score ⩾15 (%), three-hour (surviving sepsis campaign) SSC bundle compliance (%), six-hour SSC bundle compliance (%), rate of microbe detection before antibiotics (%), percentage of drug deep venous thrombosis (DVT) prophylaxis (%), percentage of unplanned endotracheal extubations (%), percentage of patients reintubated within 48 hours (%), unplanned transfers to the ICU (%), 48-h ICU readmission rate (%), ventilator associated pneumonia (VAP) (per 1000 ventilator days), catheter related blood stream infection (CRBSI) (per 1000 catheter days), catheter-associated urinary tract infections (CAUTI) (per 1000 catheter days), in-hospital mortality (%). When exploratory factor analysis was applied, the 15 indicators were divided into 6 core elements that varied in weight regarding quality evaluation: nosocomial infection management (21.35%), compliance with the Surviving Sepsis Campaign guidelines (17.97%), ICU resources (17.46%), airway management (15.53%), prevention of deep-vein thrombosis (14.07%), and severity of patient condition (13.61%). Based on the different weights of the core elements associated with the 15 indicators, we developed an integrated quality scoring system defined as F score=21.35%xnosocomial infection management + 17.97%xcompliance with SSC guidelines + 17.46%×ICU resources + 15.53%×airway management + 14.07%×DVT prevention + 13.61%×severity of patient condition. This evidence-based quality scoring system will help in assessing the key elements of quality management and establish a foundation for further optimization of the quality control indicator system.
Humans ; China/epidemiology* ; Cross Infection/epidemiology* ; Intensive Care Units/statistics & numerical data* ; Quality Control ; Quality Indicators, Health Care/statistics & numerical data* ; Sepsis/therapy* ; East Asian People/statistics & numerical data*

Chemotherapy is an important adjuvant treatment of glioma, while the efficacy is far from satisfactory, due not only to the biological barriers of blood‒brain barrier (BBB) and blood‒tumor barrier (BTB) but also to the intrinsic resistance of glioma cells via multiple survival mechanisms such as up-regulation of P-glycoprotein (P-gp). To address these limitations, we report a bacteria-based drug delivery strategy for BBB/BTB transportation, glioma targeting, and chemo-sensitization. Bacteria selectively colonized into hypoxic tumor region and modulated tumor microenvironment, including macrophages repolarization and neutrophils infiltration. Specifically, tumor migration of neutrophils was employed as hitchhiking delivery of doxorubicin (DOX)-loaded bacterial outer membrane vesicles (OMVs/DOX). By virtue of the surface pathogen-associated molecular patterns derived from native bacteria, OMVs/DOX could be selectively recognized by neutrophils, thus facilitating glioma targeted delivery of drug with significantly enhanced tumor accumulation by 18-fold as compared to the classical passive targeting effect. Moreover, the P-gp expression on tumor cells was silenced by bacteria type III secretion effector to sensitize the efficacy of DOX, resulting in complete tumor eradication with 100% survival of all treated mice. In addition, the colonized bacteria were finally cleared by anti-bacterial activity of DOX to minimize the potential infection risk, and cardiotoxicity of DOX was also avoided, achieving excellent compatibility. This work provides an efficient trans-BBB/BTB drug delivery strategy via cell hitchhiking for enhanced glioma therapy.

Sacral cyst usually occurs around the nerve root, which is the accumulation of cerebrospinal fluid between the intima and the perineurium at the junction of the posterior spinal nerve root and the dorsal root ganglion. Its typical clinical manifestations include low back pain, lower limb radiation pain, rectal/bladder dysfunction and so on. Complications of acute subdural hematoma with cerebral hernia after posterior midline cystectomy of sacral cyst are rare. A middle-aged female patient with sacral cyst was admitted to Gansu Provincial Hospital. After the operation, acute subdural hematoma occurred in the right frontoparietal temporal occipital region, and cerebral herniation was formed. After the operation, the patient was given rehabilitation exercise and discharged well. No neurological deficits were observed during follow-up.

Objective To explore the effect of hematoma aspiration device combined with low posterior osteotomy and small bone window craniotomy on neurological function and prognosis in patients with hypertensive intracerebral hemorrhage(HICH).Methods The clinical data of 132 patients with HICH in the Department of Neurosurgery,Gansu Provincial people's Hospital from February 2020 to February 2022 were collected and divided into small bone window group(n=52)and aspiration group(n=80).The levels of serum neuron specific enolase(NSE)and interleukin-6(IL-6)were detected by enzyme linked immunosorbent assay(ELISA).The intraoperative condition(duration of operation and intraoperative blood loss),intracranial pressure,complete clearance rate of intracranial hematoma and the incidence of postoperative complications were compared.The prognosis of the patients was evaluated by activity of daily living scale(ADL).Results There was no significant difference in the levels of serum NSE and IL-6 between the two groups before operation(P>0.05).The levels of NSE and IL-6 in serum after operation were significantly lower than those before operation,and the intracranial pressure was improved after treatment,the difference has statistic significance(P<0.05).The postoperative serum NSE and IL-6 levels,operation duration,postoperative intracranial pressure and the total incidence of complications in aspiration group were lower than those in small bone window group(P<0.05),but there was no significant difference in intraoperative blood loss and the total incidence of long-term complications between the two groups(P>0.05).During the 6-month follow-up after surgery,the good prognosis rate of aspiration group was higher than that of small bone window group,and the difference was statistically significant(P<0.05);There was no statistically significant difference in the complete clearance rate of intracranial hematoma between the two groups of patients(P>0.05).Conclusion Low posterior osteotomy combined with hematoma aspiration can effectively treat HICH,promote the recovery of neurological function in patients.

ObjectiveTo evaluate the clinical efficacy of TDP （specific electromagnetic wave） combined with Osteoking in the treatment of knee osteoarthritis of Qi stagnation and blood stasis type. MethodA total of 104 patients with knee osteoarthritis of Qi stagnation and blood stasis type， who received conservative therapy in The Third People's Hospital of Xinjiang Uygur Autonomous Region from July 2019 to December 2021， were randomized into the control group and study group with the random number table method， 52 cases in either group. The control group was treated with TDP， and the study group with TDP and Osteoking. The treatment lasted 1 week for both groups， with 1-month follow-up. Subjective indexes of visual analog scale （VAS） score and Western Ontario McMaster Universities Osteoarthritis Index （WOMAC） score， and objective indexes of visual tenderness index and visual knee range of motion were determined before and after treatment to evaluate the pain and functions of patients. Traditional Chinese medicine （TCM） syndrome score was calculated. The serum erythrocyte sedimentation rate （ESR） and high sensitivity C-reactive protein （hs-CRP） were detected before and after treatment， and the total clinical effective rate was calculated. ResultBefore treatment， the baseline information and all the scores of the two groups were comparable. After treatment， the VAS score， WOMAC score， tenderness index， knee range of motion， and TCM syndrome score were improved in both groups （P<0.01）. After the treatment， the VAS score and WOMAC score of the study group were lower than those of the control group （P<0.01） and the improvement of tenderness index in the study group was better than that in the control group （P<0.05）. The knee range of motion in the study group was better than that in the control group （P=0.061）. The TCM syndrome score of study group was lower than that of control group （P<0.01） after treatment. The post-treatment serum ESR and hs-CRP level in the two groups decreased significantly after treatment， and the study group were lower than those of the control group （P<0.01）. The total clinical effective rate of the study group was 90.4%（47/52）， as compared with the 53.8%（28/52） in the control group （P<0.05）. No obvious adverse events occurred during treatment in both groups. ConclusionThe clinical efficacy of TDP combined with Osteoking in the treatment of knee osteoarthritis of Qi stagnation and blood stasis type is remarkable， which can improve knee pain and functions， alleviate TCM syndrome， and reduce inflammatory indexes， with high safety.