Objective To examine the safety, efficacy and durability of totally endoscopic minimally invasive (TEMI) mitral valve repair in Barlow’s disease (BD). Methods A retrospective study was performed on patients who underwent mitral valve repair for BD from January 2010 to June 2021 in the Guangdong Provincial People’s Hospital. The patients were divided into a MS group and a TEMI group according to the surgery approaches. A comparison of the clinical data between the two groups was conducted. Results A total of 196 patients were enrolled, including 133 males and 63 females aged (43.8±14.9) years. There were 103 patients in the MS group and 93 patients in the TEMI group. No hospital death was observed. There was a higher percentage of artificial chordae implantation in the TEMI group compared to the MS group (P=0.020), but there was no statistical difference between the two groups in the other repair techniques (P>0.05). Although the total operation time between the two groups was not statistically different (P=0.265), the TEMI group had longer cardiopulmonary bypass time (P<0.001) and aortic clamp time (P<0.001), and shorter mechanical ventilation time (P<0.001) and postoperative hospitalization time (P<0.001). No statistical difference between the two groups in the adverse perioperative complications (P>0.05). The follow-up rate was 94.2% (180/191) with a mean time of 0.2-12.4 (4.0±2.4) years. Two patients in the MS group died with non-cardiac reasons during the follow-up period. The 3-year, 5-year and 10-year overall survival rates of all patients were 100.0%, 99.2%, 99.2%, respectively. Compared with the MS group, there was no statistical difference in the survival rate, recurrence rate of mitral regurgitation, reoperation rate of mitral valve or adverse cardiovascular and cerebrovascular events in the TEMI group (P＞0.05). Conclusion TEMI approach is a safe, feasible and effective approach for BD with a satisfying long-term efficacy.

OBJECTIVES: Managing patients with refractory head and neck cancer pain is one of the more challenging issues in clinical practice, and traditional intrathecal drug delivery also fails to provide adequate analgesia. There are currently no comprehensive and effective treatment methods. This study aims to observe the efficacy and safety of treating intractable head and neck cancer pain with morphine pump via lumbar approach to the prepontine cistern. METHODS: A total of 18 patients with intractable head and neck cancer pain treated with prepontine cistern morphine pumps were selected from the Department of Pain Management, Second Xiangya Hospital, Central South University between September 2019 and July 2023. Statistical analysis was performed on patients' preoperative and postoperative (1 week, 1 month, and 2 months after surgery), Numerical Rating Scale (NRS) scores, Self-Rating Depression Scale (SDS) scores, daily oral morphine consumption, the number of daily breakthrough pain episodes, and postoperative daily intrathecal morphine dosage. RESULTS: The NRS scores, SDS scores, daily oral morphine consumption, and the number of daily breakthrough pain episodes of patients at each time point after surgery were significantly lower than before surgery (all P<0.05). With the gradual increase in the dosage of intrathecal morphine, the daily oral morphine consumption of patients at each postoperative time point was significantly reduced compared to preoperative levels (all P<0.05). The complications related to the operation were mild, including nausea in 5 cases (31.3%), headache in 2 cases (12.5%); hypotension, urine retention, hypersomnia and constipation in 1 case (6.3% each), and no serious adverse events occurred. All improved and were discharged after symptomatic treatment. CONCLUSIONS The implantation of prepontine cistern morphine pump effectively controls intractable head and neck cancer pain, demonstrating characteristics of minimal invasiveness, mild side effects, and low medication dosage under the premise of standardized procedures.
Humans ; Morphine/administration & dosage* ; Male ; Female ; Middle Aged ; Head and Neck Neoplasms/surgery* ; Analgesics, Opioid/administration & dosage* ; Cancer Pain/drug therapy* ; Pain, Intractable/etiology* ; Aged ; Adult ; Infusion Pumps, Implantable ; Pain Management/methods*

[This corrects the article DOI: 10.1016/j.apsb.2024.03.030.].

Myocardial fibrosis is a serious cause of heart failure and even sudden cardiac death. However, the mechanisms underlying myocardial ischemia-induced cardiac fibrosis remain unclear. Here, we identified that the expression of sterile alpha and TIR motif containing 1 (SARM1), was increased significantly in the ischemic cardiomyopathy patients, dilated cardiomyopathy patients (GSE116250) and fibrotic heart tissues of mice. Additionally, inhibition or knockdown of SARM1 can improve myocardial fibrosis and cardiac function of myocardial infarction (MI) mice. Moreover, SARM1 fibroblasts-specific knock-in mice had increased deposition of extracellular matrix and impaired cardiac function. Mechanically, elevated expression of SARM1 promotes the deposition of extracellular matrix by directly modulating P4HA1. Notably, by using the Click-iT reaction, we identified that the increased expression of ZDHHC17 promotes the palmitoylation levels of SARM1, thereby accelerating the fibrosis process. Based on the fibrosis-promoting effect of SARM1, we screened several drugs with anti-myocardial fibrosis activity. In conclusion, we have unveiled that palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis. Inhibition of SARM1 is a potential strategy for the treatment of myocardial fibrosis. The sites where SARM1 interacts with P4HA1 and the palmitoylation modification sites of SARM1 may be the active targets for anti-fibrosis drugs.

OBJECTIVES: To compare the efficacy of toric implantable collamer lens (Toric-ICL) and femtosecond laser-assisted in situ keratomileusis (FS-LASIK) for myopia correction in patients with moderate to high myopia complicated with astigmatism. METHODS: We retrospectively collected data from 64 patients (aged 18-42 years) with moderate to high myopia complicated with astigmatism (128 eyes) undergoing either Toric-ICL (28 patients/56 eyes) or FS-LASIK (36 patients/72 eyes) at our department between January, 2019 and December, 2020. The changes of uncorrected distance visual acuity (UCVA), spherical equivalent (SE), mean astigmatism correction index (CI), corneal endothelial cell density (ECD) and intraocular pressure (IOP) following the procedures were compared between the two groups. RESULTS: In FS-LASIK group, all the eyes (72/72) achieved an UCVA≥1.0, similar to the rate in Toric-ICL group (55/56 eyes; P=0.2374). The postoperative SE was also comparable between FS-LASIK and Toric-ICL groups [0.43±0.06 D (range: -1.0 to 1.50 D) vs 0.38±0.05 D (range: -0.75 to 1.00 D); P=0.56]. The mean astigmatism CI was significantly higher in FS-LASIK group than in Toric-ICL group (0.8561 vs 0.7176; P<0.0001), and 88.89% of the eyes in FS-LASIK group and 69.64% in Toric-ICL group had postoperative astigmatism ≤0.50 D. No significant changes were observed in postoperative corneal ECD in FS-LASIK group, whereas ECD decreased significantly after the procedure in Toric-ICL group (P=0.0057). The patients undergoing Toric-ICL exhibited no significant changes of postoperative IOP, but the patients receiving FS-LASIK had significantly reduced IOP after the procedure (P<0.001). CONCLUSIONS Although the patients included in Toric-ICL group had higher myopia and astigmatism, Toric-ICL still showed better predictability and efficacy for astigmatic correction in Toric-ICL group. Toric-ICL is an effective and safe equivalent of FS-LASIK for correcting moderate myopia but can be more advantageous for correcting high myopia with astigmatism.
Humans ; Astigmatism/complications* ; Myopia/complications* ; Keratomileusis, Laser In Situ/methods* ; Retrospective Studies ; Adult ; Visual Acuity ; Adolescent ; Young Adult ; Treatment Outcome ; Male ; Lens Implantation, Intraocular/methods* ; Female ; Phakic Intraocular Lenses ; Intraocular Pressure

Objective:To analyze the drug resistance characteristics of Klebsiella pneumoniae in the nasopharynx of hospitalized patients in North China from 2022 to 2023. Methods:From November 2022 to July 2023, nasopharyngeal swabs were collected from 100 inpatients in Affiliated Hospital of North China University of Science and Technology, and Klebsiella pneumoniae was isolated and cultured. At the same time, the clinical data of the patients were collected, including gender, age, department, clinical diagnosis of disease type, etc. The minimum inhibitory concentration of strains was detected by an automatic bacterial drug sensitivity system. The drug resistance genes, ST types, capsule serotypes and population structure of the strains were analyzed by whole genome sequencing and data analysis. Results:Klebsiella pneumoniae was isolated from 55 nasopharyngeal swabs of 100 inpatients(55.00%). Among the 55 inpatients with Klebsiella pneumoniae in the nasopharynx, 70.91% (39/55) were male, with an age distribution concentrated between 61 and 80 years old (58.18%, 32/55), and 50.91% (28/55) were in intensive care units (ICU). The main underlying disease type was nervous system disease (49.09%, 27/55). The results of drug sensitivity showed that the non-susceptibility rates of 55 strains of Klebsiella pneumoniae to cephalosporins, quinolones, aztreonam and nitrofurantoin were all more than 80.00%. Twenty-eight carbapenem-resistant Klebsiella pneumoniae strains (50.91%), 47 extended-spectrum β-lactamase producing strains (85.45%), and 48 multi-drug-resistant strains (87.27%) were detected. A total of 11 antibiotic resistance genes were detected, including carbapenems (carrying rate 76.36%) and extended-spectrum β-lactamase (carrying rate 96.36%). The 55 strains could be divided into 17 ST types, and the most common type was ST11 (25.45%). The 55 strains were divided into 18 capsular serotypes, among which K102 was the most prevalent (23.64%). OXA-1_ST307_K102 (21.82%) and KPC-2_ST5492_K125 (18.18%) were the dominant clones, distributed in the Department of Neurosurgery and ICU. The result of whole genome sequence analysis showed that there were four clusters with high homology among the 55 strains. The strains from the ICU formed two independent clusters, and strains from the Neurology ICU and Neurosurgery department formed one cluster respectively. Conclusion:The carrying rate of Klebsiella pneumoniae in the nasopharynx of inpatients is high, and the drug resistance of the strains is serious. There are many types of drug-resistant genes.

Objective:To investigate the protective effect of quercetin against LasB-induced apoptosis, inflammation, and oxidative stress in THP-1 macrophages, providing valuable insights into the use of quercetin as a virulence inhibitor for Pseudomonas aeruginosa infection treatment. Methods:This was an experimental study. The experimental strain was the standard strain. The LasB protein was obtained utilizing protein recombination technology, while the enzyme activity of LasB was assessed through both the Elastin Congo red assay and fluorescently labelled elastin assay. The LasB-induced THP-1 macrophage infection model was established, and quercetin was utilized for intervention. Cell viability was evaluated via CCK-8 assay, while cell morphology was observed under an inverted microscope. Apoptosis detection involved employing both TUNEL and Annexin V/PI staining. The mRNA expression and protein levels of inflammatory cytokines and COX-2 were determined by RT-qPCR and ELISA respectively. Intracellular ROS levels were quantified using the DCFH-DA fluorescent probe. One-way ANOVA was used for statistical analysis, and Tukey test was used for multiple comparisons. Results:The pLasB with a molecular weight of 33 000 and acceptable enzymatic activity (purity>90%), was successfully obtained. THP-1 macrophages treated with pLasB at a concentration of 100 μg/ml presented significantly decreased viability and integrity rate when compared with the normal control group. Additionally, pLasB promoted apoptosis, up-regulated the levels of inflammatory cytokines IL-1α, IL-1β, IL-6, IL-10, IL-12, and TNF-α, increased intracellular ROS fluorescence intensity, and elevated COX-2 mRNA expression level. Furthermore, the viability of THP-1 macrophages was significantly enhanced under quercetin intervention at concentrations of 2.5 μmol/L, 5 μmol/L and 10 μmol/L. The apoptosis rate exhibited a significant reduction from 18.32%±0.17% to 13.17%±0.20%, 11.43%±0.06% and 7.74%±0.04%, respectively ( F=1 679, P<0.05). There was a notable down-regulation of pro-inflammatory cytokines IL-1α, IL-1β, IL-6, IL-12 and TNF-α while the anti-inflammatory cytokine IL-10 showed a significant up-regulation. Both intracellular ROS fluorescence intensity ( F=86.92, P<0.05) and COX-2 level ( F=24.62, P<0.05) demonstrated a substantial decrease. Conclusion:Quercetin demonstrates significant efficacy in inhibiting LasB-induced apoptosis, inflammation, and oxidative stress in THP-1 macrophages, which highlights immense potential as a potent virulence inhibitor of Pseudomonas aeruginosa.

To investigate the clinical assessment of dual-enhanced antiplatelet therapy after cerebrovascular intervention to reduce the risk of cerebral infarction recurrence, and to provide a reference for the prevention and treatment of cerebral infarction recurrence risk. 202 patients with cerebral infarction who underwent cerebrovascular intervention in Tianjin Fifth Central Hospital from January 2018 to October 2022 were selected as study subjects. The patients were divided into a treatment group ( n=104) based on randomized controlled single-blind method with 61 males and 43 females with a mean age of (62.33±2.57) years old and a control group ( n=98) with 56 males and 42 females with a mean age of (62.49±2.36) years old. The control group was given aspirin mono-antiplatelet therapy, and the treatment group was given clopidogrel doublet augmented antiplatelet therapy on the basis of the control group, and both groups continued the treatment for 2 months. Platelet counts, coagulation indexes and inflammatory factors were compared between the two groups before and after treatment, and the America National Institutes of Health Stroke Scale (NIHSS) score was used to assess the neurological functions of the two groups before and after treatment, and the recurrence of cerebral infarction in the two groups was counted within 6 months after treatment. In addition, the patients in the treatment group were divided into the cerebral infarction recurrence group and the cerebral infarction non-recurrence group according to whether they had cerebral infarction recurrence within 6 months after treatment, and the clinical data of the patients in the treatment group were collected to analyze the influencing factors of the dual-enhancement antiplatelet therapy for the recurrence of cerebral infarction in patients with cerebral infarction after cerebral vascular intervention by multifactorial logistic regression. The results showed that after treatment, patients in the treatment group had an international normalized ratio (INR) of (1.76±0.38), a platelet activation rate of (39.52±4.79)%, a platelet aggregation rate of (48.54±5.21)%, a tumor necrosis factor-alpha (TNF-alpha) of (28.37±4.47)ng/L, an interleukin 6 (IL-6) of (24.77±3.52)ng/L, a high-sensitivity C-reactive protein (hs-CRP) of (7.39±1.53)mg/L and an NIHSS score of (6.11±1.39) were lower than those of the control group (2.32±0.41), (44.81±6.37)%, (51.39±5.58)%, (39.66±4.51) ng/L, (29.25±4.04) ng/L, (9.03±1.78) mg/L and (9.93±1.46) points (all P<0.05). At 6-month follow-up of all patients, cerebral infarction recurred in 16 (15.38%) patients in the treatment group and in 33 (33.67%) patients in the control group ( χ2=9.185, P<0.05). Kaplan-Meier results showed a statistically significant difference in the rate of recurrence without cerebral infarction in the treatment group compared with the control group(LogRank χ2=4.595, P<0.05). Logistic regression analysis showed that smoking history, cervical vascular plaque, post-treatment NIHSS score, post-treatment stenosis score, post-treatment INR, post-treatment hs-CRP and CYP2C19 gene polymorphism were independent influences on the recurrence of cerebral infarction in cerebral infarction patients with cerebral vascular interventions followed by doublet augmentation of antiplatelet therapy (all P<0.05). In conclusion, dual-enhanced antiplatelet therapy may be an effective measure to reduce the risk of cerebral infarction recurrence after cerebrovascular intervention in patients with cerebral infarction, but it is still influenced by more factors.

Objective To predict the target and molecular mechanism of Huayu Xiaopi decoction in the intervention of Precancerous lesions of gastric cancer(PLGC)based on network pharmacology and molecular docking technology,and to conduct experimental verification.Methods A total of 60 SPF SD male rats were randomly selected as blank control,and the other rats were replicated in PLGC model.After successful modeling,the rats were randomly divided into model group,folic acid group(2 mg·kg-1·d-1),Huayu Xiaopi decoction high,medium and low dose groups(24.8,12.4,6.2 g·kg-1·d-1),which were continuously administered for 90 days.The body mass and food intake of rats at 3 h were recorded,and the gastric histopathology was observed by HE staining.Network pharmacology and molecular docking techniques were used to predict the potential targets of Huayu Xiaopi decoction in PLGC intervention,and the core targets were verified by Western blot technique.Results Compared with the blank group,the body mass and 3 h food intake of rats in the model group were significantly decreased(P<0.05),the gastric mucosa of rats was significantly thinner,the glands were significantly reduced and disordered,and the intestinal metaplasia goblet cells and a large number of inflammatory cells were visible in some areas.Compared with the model group,the body mass and 3 h food intake of rats in each administration group were improved to varying degrees.Huayu Xiaopi Decoction improved significantly in medium and high doses(P<0.05),the gastric mucosa was repaired in different degrees,the glandular arrangement tended to be orderly,and the inflammatory cells in the interstitial were gradually reduced.The results of network pharmacology and molecular docking showed that TP53,JUN and MAPK3/1(ERK1/2)were the core targets of Huayu Xiaopi decoction in the intervention of PLGC.Molecular biological detection results showed that compared with blank group,the protein phosphorylation levels of TP53,c-Jun and ERK1/2 in gastric tissue of model group were significantly increased(P<0.05).Compared with model group,the protein phosphorylation levels of TP53,c-Jun and ERK1/2 in gastric tissue of rats in all administration groups were decreased to different degrees,and significantly decreased in Huayu Xiaopi decoction high-dose and medium-dose groups(P<0.05).Conclusion Huayu Xiaopi Decoction can significantly improve the survival condition of PLGC rats and promote gastric mucosal repair,the specific mechanism of which may be related to the decrease of ERK1/2,c-Jun and TP53 protein phosphorylation levels in gastric tissue of PLGC rats,and then regulate the downstream signaling molecular response.

Cuproptosis is a type of independent cell death form, that differs from apoptosis, necroptosis and ferroptosis. It is mediated by Copper (Cu), and mainly affects the lipoylation of proteases in the mitochondrial tricarboxylic acid (TCA) cycle and exhibits cytotoxicity through oligomerization; however, its specific mechanism, signal transduction process and regulation mode are still not clear. Mitochondria affect the sensitivity of cells to copper toxicity and play a central role in the occurrence and development of copper-related death. In recent years, though hematological tumors have achieved better remission through targeted therapy and immunotherapy, they are associated with high recurrence rates and poor prognoses. It is therefore imperative to find better prognostic indicators and new treatment ideas. This paper summarizes the interaction between Cu and mitochondria in the development of tumors and provides ideas for further exploration of the mechanism of copper death and coping with hematological tumors.