An accurate haplotyping method using multiplex pyrosequencing with AS-PCR to detect ABCB1 haplotypes associated with rivaroxaban-derived hemorrhagic events.

In clinical practice, owing to the comprehensive genetic insights they offer, haplotypes have attracted greater attention than individual single nucleotide polymorphisms (SNPs). Due to the long distances across SNP locations, detecting the haplotype using genomic DNA is challenging. Current haplotyping methods are either expensive and labor-intensive (high-throughput DNA sequencing), or haplotyping a single clinical sample (computational approach) is impossible. Herein, we propose using mRNA as a haplotyping target to minimize the distance among SNPs and employing allele-specific PCR (AS-PCR) to pick up a desired haplotype, followed by multiplex pyrosequencing to type the alleles at the SNP location of interest. AS-PCR was improved by combining an additional 3'-phosphorylated modified probe to achieve the specific separation of two closely similar templates. Only the sample with more than two heterozygotes needs to be haplotyped; therefore, we propose a stratification strategy to screen the samples for further haplotyping. This method was evaluated by associating ABCB1 haplotypes with the rivaroxaban-derived side effect in a cohort of 505 patients with nephrotic syndrome, focusing on the SNPs of ABCB1: rs1236C > T, rs2677G > T/A, and rs3435C > T. We successfully identified five bleeding-related haplotypes: rs1236T-rs2677T-rs3435T, rs1236C-rs2677G-rs3435T, rs1236T-rs2677G-rs3435C, rs1236C-rs2677G-rs3435C, and rs1236T-rs2677T-rs3435C. We compared the results with those from the conventional computational algorithm PHASE and observed that PHASE results dismissed the impact of rs1236C-rs2677G-rs3435C and rs1236C-rs2677G-rs3435T on bleeding risk and erroneously suggested a false positive association of rs1236C-rs2677A-rs3435T with increased bleeding risk.

The triglyceride-glucose index is associated with no-reflow phenomenon in STEMI patients with type 2 diabetes after percutaneous coronary intervention.

Background: The relationship between the triglyceride-glucose (TyG) index and no-reflow phenomenon after percutaneous coronary intervention (PCI) in patients with type 2 diabetes mellitus (T2DM) and acute ST-segment elevation myocardial infarction (STEMI) remains unclear. This study aimed to investigate the relationship between baseline TyG index and no-reflow phenomenon in STEMI patients with T2DM after PCI. Methods: This study enrolled 695 patients with T2DM and STEMI from the General Hospital of Ningxia Medical University (2014-2019). Patients were divided into tertiles according to the TyG index levels. The incidence of no-reflow phenomenon was recorded. A multivariate regression model was developed to analyze the association between the baseline TyG index and no-reflow phenomenon. The linear association between the baseline TyG index and no-reflow phenomenon was explored using smooth curve fitting with parallel subgroup analyses. Receiver operating characteristic (ROC) curves were generated to determine the predictive power of the TyG index. Results: A multivariate logistic regression model revealed that the TyG index was an independent risk factor of no-reflow phenomenon [OR = 3.23, 95%CI: 2.15-4.86, P < 0.001], and the occurrence of no-reflow phenomenon increased gradually with the increase of TyG index tertile interval (P < 0.001). Smooth curve fitting showed that the TyG index was linearly related to the risk of no-reflow. Subgroup analysis showed that they participated in this positive correlation. The area under the ROC curve (AUC) of the TyG index for evaluating the occurrence of no-reflow was 0.710 (95% CI: 0.640-0.780; P < 0.01). Conclusions: The TyG index is independently associated with no-reflow phenomenon, suggesting that the simple index of the TyG index can be used for risk assessment of no-reflow phenomenon after PCI in STEMI patients with T2DM.

Antimicrobial properties of essential oil extracted from Schizonepeta annua against methicillin-resistant Staphylococcus aureus via membrane disruption.

Schizonepeta annua (Pall.) Schischk. has long been traditionally employed in China for its anti-inflammatory, antimicrobial, and soothing properties. This study evaluates the antibacterial properties of essential oil extracted from Schizonepeta annua (SEO) and oregano (OEO) against methicillin-resistant Staphylococcus aureus (MRSA). SEO and OEO demonstrated substantial antibacterial efficacy, with SEO exhibiting significantly enhanced antibacterial activity due to its complex composition. Mechanistic investigations revealed that both essential oils disrupt bacterial membrane integrity and biosynthetic pathways, leading to the extrusion of intracellular contents. Metabolomic analyses using GC-Q-TOF-MS highlighted SEO's selective targeting of bacterial membranes, while non-targeted metabolomics indicated significant effects on MRSA's amino acid metabolism and aminoacyl-tRNA biosynthesis. These findings suggest that SEO causes considerable damage to MRSA cell membranes and affects amino acid metabolism, supporting its traditional use and highlighting its potential in treating infections. Our results offer robust theoretical support for SEO's role as an antimicrobial agent and establish a solid foundation for its practical application in combating multidrug-resistant infections.

FGF7 and FGF10 Promote Fate Transition of Human Epidermal Cell-derived Organoids to an Eccrine Gland Phenotype.

Rationale: Reconstruction of hair follicles (HFs) and eccrine sweat glands (ESGs) is essential for functional skin regeneration. In skin reconstruction research, we found that foreskin-derived epidermal cells reconstructed HF organoids unidirectionally, but not ESG organoids. Methods: To investigate key genes and pathways influencing the fate of ESG and HF, a transcriptome profiling of ESG placode-containing skin and HF placode-containing skin was employed, and key DEGs were identified and validated by RT-qPCR and immunofluorescence staining in mice and rats. Subsequently, adult human epidermal cell-derived organoids were reconstructed to probe functional roles and mechanisms of FGF7 and FGF10 by series of approaches integrating RT-qPCR, immunofluorescence-staining, WB, apoptosis assay, and pathway interference assay. Results: All members of FGF7 subfamily were among the key DEGs screened, the differential expression of FGF7 and FGF10 and their receptors FGFR1/FGFR2 was verified between ESG placode-containing skin and HF placode-containing skin. In vivo and in vitro Matrigel plug models showed that both FGF7 and FGF10 promoted fate transition of human epidermal cell-derived organoids to ESG phenotype organoids, FGF7 and FGF10 had a synergistic effect, and mainly function through the FGFR1/2-MEK1/2-ERK1/2 pathway. Conclusions: Adult epidermal cells can be manipulated to reconstruct personalized HF and ESG to meet different needs.

Timing of percutaneous coronary intervention and risk of new-onset acute ischemic stroke in non-ST elevation myocardial infarction: A retrospective cohort study insight into the National Inpatient Sample Database (2016-2019).

Background and Aims: For patients with high-risk non-ST elevation myocardial infarction (NSTEMI), current guidelines recommend an early invasive strategy within 24 h. New-onset acute ischemic stroke (NAIS) is a rare but fatal complication of percutaneous coronary intervention (PCI). However, the effect of the timing of PCI and the risk of NAIS in NSTEMI is poorly defined. Methods: Patients with NSTEMI who underwent PCI were queried from the National Inpatient Sample Database (2016-2019) and stratified into three groups: early (<24 h), medium (24-72 h), and late (>72 h) PCI. Multivariate logistic regression models were used to determine the association between timing of PCI and NAIS. Results: Among 633,115 weighted hospitalizations, patients in the late PCI group had a higher incidence of NAIS (1.3%) than those in the early (0.67%) and medium (0.71%) PCI groups. Patients undergoing late PCI were older, more likely to be female, and had a greater incidence of comorbidities (e.g., diabetes mellitus, chronic pulmonary and renal illness, and atrial fibrillation) than those undergoing early or medium PCI. After adjustment, only late PCI was significantly associated with a 54% increased NAIS risk (adjusted odds ratio: 1.54 [95% confidence interval: 1.29-1.84]). Additionally, there was heterogeneity in the magnitude of risk by age and sex. Younger people (<65 years) (p for interaction <0.001) and men (interaction-value p = 0.040) were more likely to encounter NAIS. Conclusion: Late PCI was associated with a higher risk of NAIS than early PCI, particularly among men and those aged <65 years.

Primary exophytic urothelial carcinoma of the bladder: A case report.

RATIONALE: Bladder urothelial carcinoma (UC) is a common urinary system tumor that is generally diagnosed by cystoscopy combined with pathological biopsy. However, complete exophytic UC of the bladder is very rare and difficult to diagnose. Early diagnosis and accurate identification of such tumors, followed by aggressive surgical treatment, is essential for the management of these patients. PATIENT CONCERNS: An 84-year-old man was admitted to the hospital with dysuria, a poor diet, and significant weight loss. DIAGNOSIS: Pelvic computed tomography and magnetic resonance imaging revealed an exteriophytic round mass on the right lateral wall of the bladder. Cystoscopy revealed a necrotic mass on the right lateral wall of the bladder cavity, and no tumor cells were found following the biopsy. The tumor was removed via partial cystectomy, and the pathological result indicated high-grade muscle-invasive UC. INTERVENTIONS: The patient refused radical cystectomy and underwent laparoscopic partial cystectomy plus pelvic lymph node dissection followed by cisplatin plus gemcitabine chemotherapy. OUTCOMES: The patient's mental state and appetite were significantly improved after the urinary tube was removed 1 week after surgery. His general state was significantly improved after 1 month of follow-up but died of acute cerebral infarction 3 months after surgery. LESSONS: UC of the bladder may grow completely out of the bladder without symptoms such as gross hematuria; thus, early diagnosis is difficult. For high-risk individuals, regular imaging tests may help to detect tumors early. Partial cystectomy is a reliable surgical modality for bladder preservation in such patients.

The effect of biofeedback on nonneurological dysfunctional voiding in children: A meta-analysis and systematic review.

OBJECTIVE: This study was conducted to investigate the effect of biofeedback (BF) on the rehabilitation of children with nonneurological dysfunctional voiding (NDV). METHODS: RCTs were retrieved from various databases (published from inception to February 29, 2024). The effects of the BF and non-BF treatments were compared. A random-effects model was used to evaluate the combined data. RESULTS: Meta-analysis revealed that BF increased the maximum urinary flow rate (SMD = 3.78, 95% CI 1.33∼6.22), improved urination time (SMD = 5.88, 95% CI 3.75∼8.01), and reduced the postvoid residual (SMD = -19.18, 95% CI -27.03∼-11.33) and urinary tract infection incidence (RR = 0.43, 95% CI 0.21∼0.87). Electromyogram activity (RR = 0.46, 95% CI 0.25∼0.84) and abnormal urination patterns (RR = 0.51, 95% CI 0.35∼0.74) improved, with effects persisting for more than 1 year. However, the effect of BF on the mean urinary flow rate in children with NDV was significant only after 1 year of follow-up (SMD = 1.90, 95% CI 0.87∼2.92). CONCLUSION: Existing evidence indicates that BF can enhance urinary parameters and patterns in children with NDV. However, its effectiveness in addressing constipation, daytime urinary incontinence, and nocturnal urinary incontinence is not substantial. High-quality randomized controlled trials can offer additional insights.

Molecular epidemiology of Brucella abortus isolated from the environment in Ningxia Hui autonomous region, China.

Brucellosis is among the key zoonotic infectious diseases in China, and The Ningxia Hui Autonomous Region represents a major endemic area, and it is one of the main causes of poverty in the region due to illness. In Ningxia, there is substantial research on Brucella melitensis, studies on the molecular epidemiology of Brucella abortus are notably scarce. Consequently, this study aims to undertake pathogenic isolation and molecular epidemiological research on Brucella abortus isolated from the environment in Ningxia, providing insights and evidence to advance the prevention and control measures for brucellosis in the region. Building on traditional pathogenic detection methods, this research employs whole-genome sequencing(WGS) techniques and bioinformatics software to conduct a phylogenetic comparison of Ningxia strains and strains of Brucella abortus from various geographical origins. The results indicate that four Brucella abortus strains are classified as biovar 3 and MLST type ST2. It is shown that the local strains were closer phylogenetic relationships with strains from Asian and European countries. The presence of Brucella abortus in certain environmental sectors of Ningxia indicates a risk of transmission from the environment to animals and subsequently to humans. In conclusion, the Brucella abortus exists in some farming environments in Ningxia, and exists for a long time. Therefore, it is necessary to strengthen the monitoring of the disinfection effect of the farming environment to provide a basis for the forward movement of the gate of brucellosis prevention and control.

The prevalence of hepatitis B virus infection among HIV-infected patients in the Ningxia Hui Autonomous Region, China, November 2002 to July 2023.

We tested HIV-infected people with HBV serological markers of Ningxia. Of 1008 HIV-positive individuals, 70 (6.9 %) tested positive for HBsAg, 570 (56.5 %) tested positive for anti-HBs, and 483 (47.9 %) tested positive for anti-HBc. Of 70 HBV-positive individuals, 13 (18.5 %) tested positive for HBeAg, 31 (44.3 %) tested positive for anti-HBe, 3 (4.2 %) exhibited acute infection.

Profiling the volatile compounds of Peganum harmala L. Based on multiple sample preparation coupled with gas chromatography-mass spectrometry analysis and explored its antidepressants-like activity.

Peganum harmala L., a traditional medicinal plant in China, is renowned for its significant alkaloid content in seeds and roots exhibiting a wide range of pharmacological activities, including antidepressant, antiseptic, and antiviral. However, the volatile composition of the herb remained unclear. Apart from that, the extraction of volatile compounds through essential oil presents challenges due to the low yield and the degradation of volatile active compounds at high temperatures. This study used multiple sample preparation methods including headspace (HS), needle trap device (NTD), and liquid-liquid extraction (LLE) coupled with gas chromatography-mass spectrometry (GC-MS) to analyze the volatile compounds from the areal part of P. harmala L.. A total of 93 compounds were identified with NTD facilitating the first detection of harmine among the volatile organic compounds. Through network pharmacology and protein interaction analysis, the compounds' potential therapeutic targets of the compounds were explored, and 23 key targets were obtained (AKT1, ALB, PTGS2, MAOA, etc). KEGG pathway enrichment analysis indicated significant involvement in neuroactive ligand-receptor interactions and serotonergic synapses. The results enhanced the understanding of P. harmala's pharmacological mechanisms and supported its ethnopharmacological use.

Association between homocysteine and blood pressure in the NHANES 2003-2006: the mediating role of Vitamin C.

Background: The yearly escalation in hypertension prevalence signifies a noteworthy public health challenge. Adhering to a nutritious diet is crucial for enhancing the quality of life among individuals managing hypertension. However, the relationship between vitamin C and hypertension, as well as homocysteine, remains unclear. Objective: The primary aim of this investigation was to scrutinize the potential mediating role of Vitamin C in the association between homocysteine levels and blood pressure, utilizing data extracted from the National Health and Nutrition Examination Survey (NHANES) database. Methods: A total of 7,327 participants from the NHANES 2003-2006 were enrolled in this cross-sectional survey. The main information was obtained using homocysteine, Vitamin C, systolic blood pressure (SBP) and diastolic blood pressure (DBP). Correlation analysis was used to assess the correlation between homocysteine, SBP, DBP and vitamin C. Linear regression analysis was utilized to determine the ß value (ß) along with its 95% confidence intervals (CIs). Mediation analysis was performed to investigate whether the relationship between homocysteine and blood pressure was mediated by Vitamin C, and to quantify the extent to which Vitamin C contributed to this association. Results: The results manifested that the homocysteine was positively associated with SBP (r = 0.24, p < 0.001) and DBP (r = 0.03, p < 0.05), while negatively correlated with Vitamin C (r = -0.008, p < 0.001). Vitamin C was found to be negatively associated with SBP (r = -0.03, p < 0.05) and DBP (r = 0.11, p < 0.001). Mediation effect analysis revealed that a partial mediation (indirect effect: 0.0247[0.0108-0.0455], p < 0.001) role accounting for 11.5% of total effect, among homocysteine and SBP. However, the mediating effect of Vitamin C between homocysteine and DBP was not statistically significant. Conclusion: Hypertension patients should pay attention to homocysteine and Vitamin C level. What is more, hypertension patients ought to formulate interventions for Vitamin C supplementation as well as homocysteine reduce strategies to lower blood pressure.

Obesity is associated with acute kidney injury in ST-segment-elevation myocardial infarction undergoing percutaneous coronary intervention: A national representative cohort study.

BACKGROUND: Acute kidney injury (AKI) is a frequent and potentially life-threatening complication after percutaneous coronary intervention (PCI) in patients with ST-segment-elevation myocardial infarction (STEMI). However, the relationship between obesity and the risk of AKI in this specific patient population has not been previously examined. METHODS: We queried the National Inpatient Sample (2016-2019) using ICD-10 codes to obtain a sample of adults with STEMI undergoing PCI. All patients were further subcategorized into obese and nonobese cohorts. The primary outcome was the incidence of AKI. Multivariate regression analysis was performed to assess the impact of obesity on AKI. The consistency of this correlation between subgroups was investigated using subgroup analysis and interaction testing. RESULTS: A total of 62,599 (weighted national estimate of 529,016) patients were identified, of which 9.80% (n = 6137) had AKI. Obesity comprised 19.78% (n = 1214) of the AKI cohort. Obese patients were on average younger, male, white, and had more comorbidities. Additionally, there was a significant positive association between obesity and AKI incidence (adjusted odds ratio [aOR]: 1.24, 95% confidence interval [CI]: 1.15-1.34), which was more pronounced in female patients (aOR: 1.56, 95% CI: 1.33-1.82, p < 0.001, p-interaction = 0.008). The AKI incidence in these patients increased steadily during the 4-year study period, and it was consistently higher in obese patients than in nonobese patients (p-trend < 0.001 for all). CONCLUSIONS: Obesity was independently associated with a greater risk of AKI among adults with STEMI undergoing PCI, particularly in female patients.

Symptomatic HIV infection and in-hospital outcomes for patients with acute myocardial infarction undergoing percutaneous coronary intervention from national inpatient sample.

Human immunodeficiency virus (HIV) infection increases the risk of acute myocardial infarction (AMI). However, little is known about its association with in-hospital outcomes and temporal trends in patients with AMI undergoing percutaneous coronary intervention (PCI). We queried patients with AMI who underwent PCI from the National Inpatient Sample Database (2003-2015) and stratified them into three groups: symptomatic, asymptomatic, and HIV-negative. After 1:2 case-control matching (CCM), logistic regression analysis was conducted to determine how HIV infection affected in-hospital outcomes. We also evaluated their recent trends from 2003 to 2015. The total weighted national estimate of 2,191,129 AMI cases included 2,178,995 HIV/AIDS-negative, 4994 asymptomatic, and 7140 symptomatic HIV cases. Symptomatic but not asymptomatic patients with HIV suffered more than triple the in-hospital mortality (adjusted odds ratio (aOR) 3.6, 95% confidence interval (CI) 2.5-5.2), over one-fold incidence of acute kidney injury (aOR 2.6 95% CI 1.9-3.4) and cardiogenic shock risk (aOR 1.9, 95% CI 1.3-2.7), a longer length of hospital stay (beta 1.2, 95% CI 1.0-1.5), and had more procedures (beta 1.3, 95% CI 1.2-1.5). These disparities relating to symptomatic HIV infection persisted from 2003 to 2015. In patients with AMI who underwent PCI, symptomatic HIV infection was associated with higher in-hospital mortality and more severe outcomes.

FEN1-assisted DNA logic amplifier circuit for fast and compact DNA computing.

This work developed DNA amplifier logic gates (AND-OR, OR-AND, FAN-IN, FAN-OUT, and 4-bit square-root circuits) using a flap endonuclease 1 (FEN1)-catalyzed signal amplification reaction, for the fastest and compact DNA computing. Moreover, the logic circuit can use input strands with concentrations of less than 1 nM, which is more than 100 times lower than the input concentration of other DNA logic circuits, providing a promising methodology for constructing fast and compact DNA computations.

Predictive effect of triglyceride-glucose index on No-Reflow Phenomenon in patients with type 2 diabetes mellitus and acute myocardial infarction undergoing primary percutaneous coronary intervention.

OBJECTIVE: Triglyceride glucose (TyG) index is considered as a new alternative marker of insulin resistance and a clinical predictor of type 2 diabetes mellitus (T2DM) combined with coronary artery disease. However, the prognostic value of TyG index on No-Reflow (NR) Phenomenon in T2DM patients with acute myocardial infarction (AMI) remains unclear. METHODS: In this retrospective study, 1683 patients with T2DM and AMI underwent primary percutaneous coronary intervention (PCI) were consecutively included between January 2014 and December 2019. The study population was divided into two groups as follows: Reflow (n = 1277) and No-reflow (n = 406) group. The TyG index was calculated as the ln [fasting triglycerides (mg/dL)×fasting plasma glucose (mg/dL)/2].Multivariable logistic regression models and receiver-operating characteristic curve analysis were conducted to predict the possible risk of no-reflow. Net Reclassification Improvement (NRI) and Integrated Discrimination Improvement (IDI) were calculated to determine the ability of the TyG index to contribute to the baseline risk model. RESULTS: Multivariable logistic regression models revealed that the TyG index was positively associated with NR[OR,95%CI:5.03,(2.72,9.28),p<0.001] in patients with T2DM and AMI. The area under the curve (AUC) of the TyG index predicting the occurrence of NR was 0.645 (95% CI 0.615-0.673; p < 0.001)], with the cut-off value of 8.98. The addition of TyG index to a baseline risk model had an incremental effect on the predictive value for NR [net reclassification improvement (NRI): 0.077(0.043to 0.111), integrated discrimination improvement (IDI): 0.070 (0.031to 0.108), all p < 0.001]. CONCLUSIONS: High TyG index was associated with an increased risk of no-reflow after PCI in AMI patients with T2DM. The TyG index may be a valid predictor of NR phenomenon of patients with T2DM and AMI. Early recognition of NR is critical to improve outcomes with AMI and T2DM patients.

Chinese Society of Cardiology guidelines on the diagnosis and treatment of adult fulminant myocarditis.

Fulminant myocarditis is an acute diffuse inflammatory disease of myocardium. It is characterized by acute onset, rapid progress and high risk of death. Its pathogenesis involves excessive immune activation of the innate immune system and formation of inflammatory storm. According to China's practical experience, the adoption of the "life support-based comprehensive treatment regimen" (with mechanical circulation support and immunomodulation therapy as the core) can significantly improve the survival rate and long-term prognosis. Special emphasis is placed on very early identification,very early diagnosis,very early prediction and very early treatment.

Epidemiological changes and molecular characteristics of Brucella strains in Ningxia, China.

Objective: Human brucellosis causes serious public health concerns in Ningxia, China. Methods: This study employed epidemiological, bacteriological, and multiple-locus variable-number tandem repeat analysis (MLVA) methods to conduct an epidemiological investigation, which is necessary for devising tailored control strategies. Results: Between 1958 and 2022, 29,892 cases were reported, with an average annual number of cases and incidence of 467 and 7.1/100,000, respectively. The epidemic situation gradually worsened, with cases escalating from 26 cases in 2005 to 6,292 in 2022, with the incidence rate rising from 0.441 in 2005 to 86.83 in 2022. Geographically, the disease spread from a single affected county in 2004 to encompass all 22 counties in 2022. Yanchi County had the highest incidence, followed by the Hongsibao and Tongxin counties. These data suggest that Brucella infection has become a rampant regional concern in human brucellosis. Between 1958 and 2019, a total of 230 Brucella strains were identified across four studied hosts. These strains comprised four species with 12 biovars, including B. melitensis bv. 1, bv. 2, bv. 3, B. abortus bv. 1, bv. 3, bv. 4, bv. 5, bv. 6, bv. 7, B. suis bv. 1 and bv. 3, and B. canis. These data highlight the high species/biovars and host diversity of the Brucella population, posing a substantial challenge to brucellosis surveillance. There was an apparent transition from multiple species/biovars historically to the current dominance of a single species, B. melitensis, emphasizing the requirement for strengthening surveillance of B. melitensis. Genotypes 42 and 116, constituting 96.2% of the total number of genotypes, predominated in panel 1 and MLVA-11, indicating that all strains belong to the East Mediterranean lineage. MLVA cluster analysis revealed persistent transmission of dominant circulating genotypes, presenting an epidemic pattern characterized primarily by epidemiologically related cases with a few sporadic cases. Strains in this study exhibited high genetic homogeneity with strains from the Northwest, and those from Kazakhstan and Mongolia. Conclusion: The epidemic situation of human brucellosis has gradually worsened; the rampant epidemic of the disease has become a regional concern. The present study highlights that implementing the of targeted surveillance and intervention strategies is urge.

Comparative efficacy of various pharmacologic treatments for alcohol withdrawal syndrome: a systematic review and network meta-analysis.

This study was to compare multiple classes of medications and medication combinations to find alternatives or additives for patients not applicable to benzodiazepines (BZDs). We performed a network meta-analysis to assess the comparative effect of 11 pharmacologic treatments in patients with alcohol withdrawal syndrome. Forty-one studies were included, comprising a total sample size of 4187 participants. The pooled results from the randomized controlled trials showed that there was no significant difference in the Clinical Institute Withdrawal Assessment-Alcohol, revised (CIWA-Ar) reduction with other medications or medication combinations compared to BZDs. Compared to BZDs, the mean difference in ICU length of stay of anticonvulsants + BZDs was -1.71 days (95% CI = -2.82, -0.59). Efficacy rankings from cohort studies showed that anticonvulsant + BZDs were superior to other treatments in reducing CIWA-Ar scores and reducing the length of stay in the ICU. Synthesis results from randomized controlled trials indicate that there are currently no data suggesting that other medications or medication combinations can fully replace BZDs. However, synthetic results from observational studies have shown that BZDs are effective in the context of adjuvant anticonvulsant therapy, particularly with early use of gabapentin in combination with BZDs in the treatment of alcohol withdrawal syndrome, which represents a promising treatment option.

Risk Factors of Acute Pain in Elderly Patients After Laparoscopic Radical Resection of Colorectal Cancer.

OBJECTIVE: To investigate the risk factors of acute pain after laparoscopic radical resection of colorectal cancer (CRC) in elderly patients. METHODS: Totally, 143 elderly patients (≥ 60 y old) who received laparoscopic radical resection of CRC in the People's Hospital of Xinjiang Uygur Autonomous Region from March 2021 to August 2022 were retrospectively analyzed. The patients were divided into 2 groups according to visual analog scale (VAS) scores 24 h after surgery: mild pain group (VAS score ≤ 3, n=108) and moderate to severe pain group (VAS score >3, n=35). The data of the patients, including sex, age, height, body mass, intraoperative blood loss, intraoperative urine volume, intraoperative opioid dosage, operation duration, preoperative Hospital Anxiety and Depression Scale (HADS) scores, preoperative Mini-Mental State Examination scores, VAS scores, postoperative nausea and vomiting scores were recorded. Multivariate logistic regression analysis was used to screen the risk factors of postoperative acute pain in elderly patients undergoing laparoscopic radical resection of CRC. RESULTS: The preoperative HADS score of the moderate to severe pain group was significantly increased compared with that of the mild pain group (10.8±2.4 vs. 6.2±1.9), as well as the operation duration (226.4±18.3 vs. 186.1±12.7), the intraoperative dosage of remifentanil (3.7±0.2 vs. 3.2±0.4), the preoperative VAS score [4(2, 7) vs. 2 (0, 4)] and postoperative VAS score [5 (4, 6) vs. 3 (2, 3)] ( P <0.05). Multivariate logistic regression analysis showed that high preoperative HADS score, long operation duration, and high preoperative VAS score ( P <0.05) were independent risk factors for acute pain after laparoscopic radical resection of CRC in elderly patients. CONCLUSION: Preoperative anxiety and depression, preoperative pain, and long operation duration are risk factors for acute pain in elderly patients after laparoscopic radical resection of CRC.

Sodium Selenite Ameliorates Silver Nanoparticles Induced Vascular Endothelial Cytotoxic Injury by Antioxidative Properties and Suppressing Inflammation Through Activating the Nrf2 Signaling Pathway.

Silver nanoparticles (AgNP) are the dominant nanomaterials in commercial products and the medical field, but the widespread occurrence of AgNP has become a global threat to human health. Growing studies indicate that AgNP exposure can induce vascular endothelial toxicity by excessive oxidative stress and inflammation, which is closely related to cardiovascular disease (CVD), but the potential intrinsic mechanism remains poorly elucidated. Thus, it has been crucial to control the toxicological effects of AgNP in order to improve their safety and increase the outcome of their applications.Multiple researches have demonstrated that sodium selenite (Se) possesses the capability to counteract the toxicity of AgNP, but the functional role of Se in AgNP-induced CVD is largely unexplored. The aim of this study was to explore the potential protective effect of Se on AgNP-induced vascular endothelial lesion and elucidate the underlying mechanisms. An in vivo model of toxicity in animals was established by the instillation of 200 µL of AgNP into the trachea of rats both with (0.2 mg/kg/day) and without Se treated. In vitro experiments, human umbilical vein endothelial cells (HUVECs) were incubated with AgNP (0.3 µg/mL ) and Se for a duration of 24 h. Utilizing transmission electron microscopy, we observed that the internalization of AgNP-induced endothelial cells was desquamated from the internal elastic lamina, the endoplasmic reticulum was dilated, and the medullary vesicle formed. Se treatment reduced the levels of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), inhibited the release of pro-inflammatory cytokines (specifically tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and IL-6), improved endothelial cell permeability, integrity, and dysfunction, and prevented damage to the aortic endothelium caused by AgNP. Importantly, we found that Se showed the capacity against AgNP with biological functions in guiding the intracellular reactive oxygen species (ROS) scavenging and meanwhile exhibiting anti-inflammation effects. Se supplementation decreased the intracellular ROS release and suppressed NOD-like receptor protein 3 (NLRP3) and nuclear factor kappa-B (NF-κB) mediated inflammation within AgNP-intoxicated rats and HUVECs. The anti-oxidant stress and anti-inflammatory effects of Se were at least partly dependent on nuclear factor erythroid 2-related factor 2 (Nrf2). Overall, our results indicated that the protectiveness of Se against AgNP-induced vascular endothelial toxicity injury was at least attributed to the inhibition of oxidative ROS and pro-inflammatory NF-κB/NLRP3 inflammasome by activating the Nrf2 and antioxidant enzyme (HO-1) signal pathway.