Expression and localization of the mechanosensitive/osmosensitive ion channel TMEM63B in the mouse urinary tract.

The epithelial cells that line the kidneys and lower urinary tract are exposed to mechanical forces including shear stress and wall tension; however, the mechanosensors that detect and respond to these stimuli remain obscure. Candidates include the OSCA/TMEM63 family of ion channels, which can function as mechanosensors and osmosensors. Using Tmem63bHA-fl/HA-fl reporter mice, we assessed the localization of HA-tagged-TMEM63B within the urinary tract by immunofluorescence coupled with confocal microscopy. In the kidneys, HA-TMEM63B was expressed by proximal tubule epithelial cells, by the intercalated cells of the collecting duct, and by the epithelial cells lining the thick ascending limb of the medulla. In the urinary tract, HA-TMEM63B was expressed by the urothelium lining the renal pelvis, ureters, bladder, and urethra. HA-TMEM63B was also expressed in closely allied organs including the epithelial cells lining the seminal vesicles, vas deferens, and lateral prostate glands of male mice and the vaginal epithelium of female mice. Our studies reveal that TMEM63B is expressed by subsets of kidney and lower urinary tract epithelial cells, which we hypothesize are sites of TMEM63B mechanosensation or osmosensation, or both.

Long Non-coding RNA PCED1B Antisense RNA 1 Promotes Cell Proliferation and Invasion in Hepatocellular Carcinoma by Regulating the MicroRNA-34a/CD44 Axis.

OBJECTIVE: This study aimed to examine the role of long non-coding RNA PCED1B antisense RNA 1 (PCED1B-AS1) in the development of hepatocellular carcinoma (HCC). METHODS: A total of 62 pairs of HCC tissues and adjacent non-tumor tissues were obtained from 62 HCC patients. The interactions of PCED1B-AS1 and microRNA-34a (miR-34a) were detected by dual luciferase activity assay and RNA pull-down assay. The RNA expression levels of PCED1B-AS1, miR-34a and CD44 were detected by RT-qPCR, and the protein expression level of CD44 was determined by Western blotting. The cell proliferation was detected by cell proliferation assay, and the cell invasion and migration by transwell invasion assay. The HCC tumor growth after PCED1B-AS1 was downregulated was determined by in vivo animal study. RESULTS: PCED1B-AS1 was highly expressed in HCC tissues, which was associated with poor survival of HCC patients. Furthermore, PCED1B-AS1 interacted with miR-34a in HCC cells, but they did not regulate the expression of each other. Additionally, PCED1B-AS1 increased the expression level of CD44, which was targeted by miR-34a. The cell proliferation and invasion assay revealed that miR-34a inhibited the proliferation and invasion of HCC in vitro, while CD44 exhibited the opposite effects. Furthermore, PCED1B-AS1 suppressed the role of miR-34a. Moreover, the knockdown of PCED1B-AS1 repressed the HCC tumor growth in nude mice in vivo. CONCLUSION: PCED1B-AS1 may play an oncogenic role by regulating the miR-34a/CD44 axis in HCC.

Clinical Effects of Ultrasound-Guided Acupotomy in Knee Osteoarthritis Treatment.

The protocol presented here demonstrates the operation method of ultrasound-guided acupotomy for knee osteoarthritis (KOA), including patient recruitment, preoperative preparation, manual operation, and postoperative care. The purpose of this protocol is to relieve pain and improve knee function in patients with KOA. A total of 60 patients with KOA admitted between June 2022 and June 2023 were treated with ultrasound-guided acupotomy. Pathological changes and knee function scores were compared before and after the treatment. After 1 week of treatment, the synovial thickness of the suprapatellar bursae was significantly lesser than before treatment (p < 0.05), the Hospital for Special Surgery Knee Score (HSS) was significantly higher than before treatment (p < 0.05), the Visual analogue scale (VAS) was significantly lower than those of the control group (p < 0.05) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were significantly lower than those of the control group (p < 0.05). Therefore, ultrasound-guided acupotomy for the treatment of KOA can reduce synovial thickness, relieve pain, improve knee joint function, and have a remarkable curative effect.

Acupuncture versus tricyclic antidepressants in the prophylactic treatment of tension-type headaches: an indirect treatment comparison meta-analysis.

BACKGROUND: Acupuncture showed better improvement than sham acupuncture in reducing attack frequency of tension-type headache (TTH), but its effectiveness relative to first-line drugs for TTH is unknown, which impedes the recommendation of acupuncture for patients who are intolerant to drugs for TTH. We aimed to estimate the relative effectiveness between acupuncture and tricyclic antidepressants (TCAs) through indirect treatment comparison (ITC) meta-analysis. METHODS: We searched Ovid Medline, Embase, and Cochrane Library from database inception until April 13, 2023. Randomized controlled trials of TCAs or acupuncture in the prevention of TTH in adults were included. The primary outcome was headache frequency. The secondary outcomes were headache intensity, responder rate, and adverse event rate. Bayesian random-effect models were used to perform ITC meta-analysis, and confidence of evidence was evaluated by using the GRADE approach. RESULTS: A total of 34 trials involving 4426 participants were included. Acupuncture had similar effect with TCAs in decreasing TTH frequency (amitriptyline: mean difference [MD] -1.29, 95% CI -5.28 to 3.02; amitriptylinoxide: MD -0.05, 95% CI -6.86 to 7.06) and reducing TTH intensity (amitriptyline: MD 2.35, 95% CI -1.20 to 5.78; clomipramine: MD 1.83, 95% CI -4.23 to 8.20). Amitriptyline had a higher rate of adverse events than acupuncture (OR 4.73, 95% CI 1.42 to 14.23). CONCLUSION: Acupuncture had similar effect as TCAs in reducing headache frequency of TTH, and acupuncture had a lower adverse events rate than amitriptyline, as shown by very low certainty of evidence.

Progressive reduction of nuclear receptor Nr4a1 mediates age-dependent cognitive decline.

INTRODUCTION: Cognitive decline progresses with age, and Nr4a1 has been shown to participate in memory functions. However, the relationship between age-related Nr4a1 reduction and cognitive decline is undefined. METHODS: Nr4a1 expressions were evaluated by quantitative PCR and immunochemical approaches. The cognition of mice was examined by multiple behavioral tests. Patch-clamp experiments were conducted to investigate the synaptic function. RESULTS: NR4A1 in peripheral blood mononuclear cells decreased with age in humans. In the mouse brain, age-dependent Nr4a1 reduction occurred in the hippocampal CA1. Deleting Nr4a1 in CA1 pyramidal neurons (PyrNs) led to the impairment of cognition and excitatory synaptic function. Mechanistically, Nr4a1 enhanced TrkB expression via binding to its promoter. Blocking TrkB compromised the cognitive amelioration with Nr4a1-overexpression in CA1 PyrNs. DISCUSSION: Our results elucidate the mechanism of Nr4a1-dependent TrkB regulation in cognition and synaptic function, indicating that Nr4a1 is a target for the treatment of cognitive decline. HIGHLIGHTS: Nr4a1 is reduced in PBMCs and CA1 PyrNs with aging. Nr4a1 ablation in CA1 PyrNs impaired cognition and excitatory synaptic function. Nr4a1 overexpression in CA1 PyrNs ameliorated cognitive impairment of aged mice. Nr4a1 bound to TrkB promoter to enhance transcription. Blocking TrkB function compromised Nr4a1-induced cognitive improvement.

Fire acupuncture for plaque psoriasis case series.

OBJECTIVE: To investigate the clinical efficacy of fire acupuncture (FA) on plaque psoriasis (PP), exploring its suitable syndrome types, in order to achieve better therapeutic effects, accelerate the possibility of psoriasis skin lesion recovery, and provide assistance for clinical treatment. METHODS: A total of 8 patients with PP aged between 18 and 60 years were recruited and treated with FA once a week, and the lesion area and severity index (PASI), visual analog scale and pruritus were measured before, 2, 4 and 8 weeks after treatment and at the follow-up period (week 12), respectively. Visual analog scale, and dermoscopy were used for assessment. RESULTS: All patients showed improvement in pruritus after 1 FA treatment, and lesions were reduced to varying degrees after 2 weeks. Except for patients 5 and 8, who only achieved effective results due to severe disease, all other patients with psoriasis achieved significant results at 8 weeks after treatment. CONCLUSION: FA can significantly control the development of lesions, reduce the symptoms of PP lesions and pruritus, and help prevent psoriasis recurrence.

Comprehensive quantitative determination of aquifer confinement based on tidal response of well water level and its application in North China.

Aquifer confinement represents a pivotal property that significantly influences the vulnerability and contamination risk of groundwater resources. Several methods have been proposed for determining aquifer confinement by analyzing the response of well water level to Earth tides and atmospheric tides. In this study, we evaluated the performance of the existing single methods and put forward an optimized comprehensive approach. We compared the determination results of the three single methods with those of a comprehensive method using water-level data from 39 earthquake precursor monitoring wells in North China. The results demonstrate that the comprehensive method effectively determined aquifer confinement, significantly reducing the uncertainty associated with the three single methods. The application of the comprehensive method in North China reveals that aquifer confinement may undergo temporal variations during long-term continuous observation, especially in areas where the confining properties of aquifers may vary due to human activities and earthquakes. In such areas, the comprehensive method facilitates accurate assessment of groundwater vulnerability, as well as the potential dispersion of underground pollutants.

Amino acid transporter SLC7A5 regulates cell proliferation and secretary cell differentiation and distribution in the mouse intestine.

The intestine is critical for not only processing nutrients but also protecting the organism from the environment. These functions are mainly carried out by the epithelium, which is constantly being self-renewed. Many genes and pathways can influence intestinal epithelial cell proliferation. Among them is mTORC1, whose activation increases cell proliferation. Here, we report the first intestinal epithelial cell (IEC)-specific knockout (ΔIEC) of an amino acid transporter capable of activating mTORC1. We show that the transporter, SLC7A5, is highly expressed in mouse intestinal crypt and Slc7a5ΔIEC reduces mTORC1 signaling. Surprisingly, adult Slc7a5ΔIEC intestinal crypts have increased cell proliferation but reduced mature Paneth cells. Goblet cells, the other major secretory cell type in the small intestine, are increased in the crypts but reduced in the villi. Analyses with scRNA-seq and electron microscopy have revealed dedifferentiation of Paneth cells in Slc7a5ΔIEC mice, leading to markedly reduced secretory granules with little effect on Paneth cell number. Thus, SLC7A5 likely regulates secretory cell differentiation to affect stem cell niche and indirectly regulate cell proliferation.

A novel member of drug/metabolite transporter (DMT) family efflux pump, SA00565, contributes to tetracycline antibiotics resistance in Staphylococcus aureus USA300.

Drug efflux systems have recently been recognized as a significant mechanism responsible for multidrug resistance in bacteria. In this study, we described the identification and characterization of a new chromosomally encoded efflux pump (SA00565) in Staphylococcus aureus. SA00565, which belongs to the drug/metabolite transporter (DMT) superfamily, was predicted to be a 10-transmembrane segment transporter. To evaluate the role of sa00565 in resistance, we generated sa00565 gene deletion mutant (Δsa00565) and assessed its susceptibility to 35 different antibiotic treatments. Our results demonstrated that the Δsa00565 mutant exhibited reduced resistance to tetracycline and doxycycline, with 64-fold and 12-fold decreased MICs, respectively. The mechanism of SA00565-mediated tetracycline resistance was demonstrated that SA00565 possesses the capability to efficiently extrud intracellular tetracycline into the environment. The efflux activity of SA00565 was further validated using EtBr accumulation and efflux assays. In summary, our study uncovered a previously unknown function of a DMT family transporter, which serves as a tetracycline efflux pump, thereby contributing to tetracycline resistance in S. aureus.IMPORTANCEIn this study, we addressed the significance of drug efflux systems in multidrug resistance of Staphylococcus aureus, focusing on the unexplored efflux pump SA00565 in the drug/metabolite transporter (DMT) superfamily. Through phylogenetic analysis, gene knockout, and overexpression experiments, we identified the role of SA00565 in antibiotic resistance. The Δsa00565 mutant showed increased susceptibility to tetracycline and doxycycline in disk diffusion assays, with significantly lower MICs compared to the WT. Remarkably, intracellular tetracycline concentration in the mutant was two- to threefold higher, indicating SA00565 actively eliminates intracellular tetracycline. Our findings emphasize the pivotal contribution of SA00565 to tetracycline antibiotic resistance in S. aureus, shedding light on its functional attributes within the DMT superfamily and providing valuable insights for combating multidrug resistance.

Aspirin/amoxicillin loaded chitosan microparticles and polydopamine modified titanium implants to combat infections and promote osteogenesis.

It is known that titanium (Ti) implant surfaces exhibit poor antibacterial properties and osteogenesis. In this study, chitosan particles loaded with aspirin, amoxicillin or aspirin + amoxicillin were synthesized and coated onto implant surfaces. In addition to analysing the surface characteristics of the modified Ti surfaces, the effects of the modified Ti surfaces on the adhesion and viability of rat bone marrow-derived stem cells (rBMSCs) were evaluated. The metabolic activities of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) biofilms on the modified Ti surfaces were also measured in vitro. Moreover, S. aureus was tested for its antibacterial effect by coating it in vivo. Using water as the droplet medium, the contact angles of the modified Ti surfaces increased from 44.12 ± 1.75° to 58.37 ± 4.15°. In comparison to those of the other groups tested, significant increases in rBMSC adhesion and proliferation were observed in the presence of aspirin + amoxicillin-loaded microspheres, whereas a significant reduction in the metabolic level of biofilms was observed in the presence of aspirin + amoxicillin-loaded microspheres both in vitro and in vivo. Aspirin and amoxicillin could be used in combination to coat implant surfaces to mitigate bacterial activities and promote osteogenesis.

A Pilot Study on a Possible Mechanism behind Olfactory Dysfunction in Parkinson's Disease: The Association of TAAR1 Downregulation with Neuronal Loss and Inflammation along Olfactory Pathway.

Parkinson's disease (PD) is characterized not only by motor symptoms but also by non-motor dysfunctions, such as olfactory impairment; the cause is not fully understood. Our study suggests that neuronal loss and inflammation in brain regions along the olfactory pathway, such as the olfactory bulb (OB) and the piriform cortex (PC), may contribute to olfactory dysfunction in PD mice, which might be related to the downregulation of the trace amine-associated receptor 1 (TAAR1) in these areas. In the striatum, although only a decrease in mRNA level, but not in protein level, of TAAR1 was detected, bioinformatic analyses substantiated its correlation with PD. Moreover, we discovered that neuronal death and inflammation in the OB and the PC in PD mice might be regulated by TAAR through the Bcl-2/caspase3 pathway. This manifested as a decrease of anti-apoptotic protein Bcl-2 and an increase of the pro-apoptotic protein cleaved caspase3, or through regulating astrocytes activity, manifested as the increase of TAAR1 in astrocytes, which might lead to the decreased clearance of glutamate and consequent neurotoxicity. In summary, we have identified a possible mechanism to elucidate the olfactory dysfunction in PD, positing neuronal damage and inflammation due to apoptosis and astrocyte activity along the olfactory pathway in conjunction with the downregulation of TAAR1.

The Prevalence of Difficult Airway and Associated Risk Factors in Pediatric Patients: A Cross-sessional Observational Study.

BACKGROUND: Difficult airway remains a great challenge in pediatric anesthesia practice. Previously published data show the prevalence of difficult airways in pediatric population varies in a wide range. However, there is a lack of studies in the Asian region. METHODS: This cross-sectional single-center study was conducted in a tertiary pediatric hospital in China from October 2022 to October 2023. The patients who underwent elective surgery under general anesthesia with tracheal intubation were recruited consecutively. Data on patient characteristics, airway assessment, and airway management information were collected. Multivariable logistic regression analysis was performed to detect the independent variables of difficult airway in pediatric patients. RESULTS: A total of 18,491 pediatric patients were included in this study. The overall incidence of difficult airways was 0.22%, 39% of whom were unanticipated. Very few previous airway management information was available in the patients presented with a known difficult airway. Patients with younger age, higher American Society of Anesthesiologists (ASA) physical status classification grade, and presented for craniofacial and thoracic surgery were associated with higher incidence of difficult airway. Further multivariable logistic regression analysis revealed that age ≤28 days (OR=50.48), age between 28days and 1 year (OR=6.053), craniofacial surgery (OR=1.81), and thoracic surgery (OR=0.2465) were independent risk factors of increased incidence of difficult airway. CONCLUSIONS: Our study showed the prevalence of difficult airways in pediatric surgical patients. Patient characteristics, age, and type of surgery were identified as the independent factors associated with increased occurrence of difficult airways. Unanticipated difficult airway was not unusual in our study population, even for the patients with previous surgical history.

Pedigree Analysis of Nonclassical Cholesteryl Ester Storage Disease with Dominant Inheritance in a LIPA I378T Heterozygous Carrier.

BACKGROUND: Cholesterol ester storage disorder (CESD; OMIM: 278,000) was formerly assumed to be an autosomal recessive allelic genetic condition connected to diminished lysosomal acid lipase (LAL) activity due to LIPA gene abnormalities. CESD is characterized by abnormal liver function and lipid metabolism, and in severe cases, liver failure can occur leading to death. In this study, one Chinese nonclassical CESD pedigree with dominant inheritance was phenotyped and analyzed for the corresponding gene alterations. METHODS: Seven males and eight females from nonclassical CESD pedigree were recruited. Clinical features and LAL activities were documented. Whole genome Next-generation sequencing (NGS) was used to screen candidate genes and mutations, Sanger sequencing confirmed predicted mutations, and qPCR detected LIPA mRNA expression. RESULTS: Eight individuals of the pedigree were speculatively thought to have CESD. LAL activity was discovered to be lowered in four living members of the pedigree, but undetectable in the other four deceased members who died of probable hepatic failure. Three of the four living relatives had abnormal lipid metabolism and all four had liver dysfunctions. By liver biopsy, the proband exhibited diffuse vesicular fatty changes in noticeably enlarged hepatocytes and Kupffer cell hyperplasia. Surprisingly, only a newly discovered heterozygous mutation, c.1133T>C (p. Ile378Thr) on LIPA, was found by gene sequencing in the proband. All living family members who carried the p.I378T variant displayed reduced LAL activity. CONCLUSIONS: Phenotypic analyses indicate that this may be an autosomal dominant nonclassical CESD pedigree with a LIPA gene mutation.

Tumor necrosis factor α1 decreases mucosal immune and antioxidant response in the midgut of hybrid fish (white crucian carp ♀ × red crucian carp ♂).

Tumor necrosis factor α1 (TNFα) is a pleiotropic cytokine involved in immune regulation and cellular homeostasis, but the crucial role of TNFα in fish gut remained unclear. The current study aimed to evaluate the immunoregulatory function of TNFα1 on gut barrier in a novel hybrid fish (WR), which was produced by crossing white crucian carp (Carassius cuvieri, ♀) with red crucian carp (Carassius auratus red var, ♂). In this study, WR-tnfα1 sequence was identified, and a high-level expression was detected in the intestine. Elevated levels of WR-tnfα1 expressions were detected in immune-related tissues and cultured fish cells on stimulation. The appearance of vacuolization and submucosal rupture was observed in TNFα1-treated midgut of WR, along with elevated levels of goblet cell atrophy, whereas no significant changes were detected in most expressions of tight-junction genes and mucin genes. In contrast, WR receiving gut perfusion with WR-TNFα1 showed a remarkable decrease in antioxidant status in midgut, whereas the expression levels of apoptotic genes and redox responsive genes increased sharply. These results suggested that TNFα1 could exhibit a detrimental effect on antioxidant defense and immune regulation in the midgut of WR.

Preliminary establishment and validation of the inversion method for growth and remodeling parameters of patient-specific abdominal aortic aneurysm.

Traditional medical imaging and biomechanical studies have challenges in analyzing the long-term evolution process of abdominal aortic aneurysm (AAA). The homogenized constrained mixture theory (HCMT) allows for quantitative analysis of the changes in the multidimensional morphology and composition of AAA. However, the accuracy of HCMT still requires further clinical verification. This study aims to establish a patient-specific AAA growth model based on HCMT, simulate the long-term growth and remodeling (G&R) process of AAA, and validate the feasibility and accuracy of the method using two additional AAA cases with five follow-up datasets. The media and adventitia layers of AAA were modeled as mixtures composed of elastin, collagen fibers, and smooth muscle cells (SMCs). The strain energy function was used to describe the continuous deposition and degradation effect of the mixture during the AAA evolution. Multiple sets of growth parameters were applied to finite element simulations, and the simulation results were compared with the follow-up data for gradually selecting the optimal growth parameters. Two additional AAA patients with different growth rates were used for validating this method, the optimal growth parameters were obtained using the first two follow-up imaging data, and the growth model was applied to simulate the subsequent four time points. The differences between the simulated diameters and the follow-up diameters of AAA were compared to validate the accuracy of the mechanistic model. The growth parameters, especially the stress-mediated substance deposition gain factor, are highly related to the AAA G&R process. When setting the optimal growth parameters to simulate AAA growth, the proportion of simulation results within the distance of less than 0.5 mm from the baseline models is above 80%. For the validating cases, the mean difference rates between the simulated diameter and the real-world diameter are within 2.5%, which basically meets the clinical demand for quantitatively predicting the AAA growth in maximum diameters. This study simulated the growth process of AAA, and validated the accuracy of this mechanistic model. This method was proved to be used to predict the G&R process of AAA caused by dynamic changes in the mixtures of the AAA vessel wall during long-term, assisting accurately and quantitatively predicting the multidimensional morphological development and mixtures evolution process of AAA in the clinic.

Enhanced predictive validity of integrative models for refractory hyperthyroidism considering baseline and early therapy characteristics: a prospective cohort study.

BACKGROUND: A subset of Graves' disease (GD) patients develops refractory hyperthyroidism, posing challenges in treatment decisions. The predictive value of baseline characteristics and early therapy indicators in identifying high risk individuals is an area worth exploration. METHODS: A prospective cohort study (2018-2022) involved 597 newly diagnosed adult GD patients undergoing methimazole (MMI) treatment. Baseline characteristics and 3-month therapy parameters were utilized to develop predictive models for refractory GD, considering antithyroid drug (ATD) dosage regimens. RESULTS: Among 346 patients analyzed, 49.7% developed ATD-refractory GD, marked by recurrence and sustained Thyrotropin Receptor Antibody (TRAb) positivity. Key baseline factors, including younger age, Graves' ophthalmopathy (GO), larger goiter size, and higher initial free triiodothyronine (fT3), free thyroxine (fT4), and TRAb levels, were all significantly associated with an increased risk of refractory GD, forming the baseline predictive model (Model A). Subsequent analysis based on MMI cumulative dosage at 3 months resulted in two subgroups: a high cumulative dosage group (average ≥ 20 mg/day) and a medium-low cumulative dosage group (average < 20 mg/day). Absolute values, percentage changes, and cumulative values of thyroid function and autoantibodies at 3 months were analyzed. Two combined predictive models, Model B (high cumulative dosage) and Model C (medium-low cumulative dosage), were developed based on stepwise regression and multivariate analysis, incorporating additional 3-month parameters beyond the baseline. In both groups, these combined models outperformed the baseline model in terms of discriminative ability (measured by AUC), concordance with actual outcomes (66.2% comprehensive improvement), and risk classification accuracy (especially for Class I and II patients with baseline predictive risk < 71%). The reliability of the above models was confirmed through additional analysis using random forests. This study also explored ATD dosage regimens, revealing differences in refractory outcomes between predicted risk groups. However, adjusting MMI dosage after early risk assessment did not conclusively improve the prognosis of refractory GD. CONCLUSION: Integrating baseline and early therapy characteristics enhances the predictive capability for refractory GD outcomes. The study provides valuable insights into refining risk assessment and guiding personalized treatment decisions for GD patients.

Efficacy and safety of Tongxin formula after stent implantation for acute coronary syndrome: A multicenter, double-blind, placebo-controlled randomized trial.

OBJECTIVE: The aim of this study is to comprehensively evaluate both the efficacy and safety profile of integrating the Tongxin formula with optimal medical therapy (OMT) for patients experiencing acute coronary syndromes subsequent to coronary stenting, over the course of one year. METHODS: We enrolled 150 patients diagnosed with acute coronary syndromes who had received stent placement within one month and exhibited a TCM syndrome characterized by Qi deficiency and blood stasis. This group comprised patients with unstable angina, non-ST-segment elevation myocardial infarction, and ST-segment elevation myocardial infarction. The participants were divided equally, allocating 75 to the Tongxin formula group and 75 to a placebo-controlled group. After undergoing percutaneous coronary intervention (PCI) surgery, both groups received conventional Western medical care, including dual antiplatelet therapy and lipid-lowering medications. The placebo-controlled group received a placebo, while the Tongxin formula group were administered Tongxin formula granules orally. Both study cohorts were monitored for a duration of 6 months. The primary endpoints included the occurrence of major adverse cardiovascular events and the rate of lumen diameter reduction post-treatment in both groups, with the Seattle Angina Scale serving as a secondary assessment tool. Safety evaluations encompassed the measurement of liver and kidney function, coagulation parameters, and other relevant indicators. RESULTS: The rate of adverse cardiovascular events in the placebo-controlled group was 42.46 % within a year of surgery, whereas it was 16.90 % in the Tongxin formula group (P < 0.05). Comparing the Tongxin formula group to the placebo-controlled group, there was a decrease in the frequency of unstable angina and readmission due to cardiovascular events (P < 0.05). Coronary angiography performed 6 months after surgery revealed that the Tongxin formula group had considerably less lumen loss than the placebo-controlled group in a number of segments, including the entire segment, within the stent, at the proximal end, and at the distal end (P < 0.05). Six months after surgery, the Seattle angina score was higher in the Tongxin formula group than in the placebo-controlled group (P < 0.05). There were no significant changes in indicators such as liver and renal function as well as coagulation indexes in both groups within the first 12 months after surgery (P > 0.05). CONCLUSION: Tongxin formula has been shown to lower the occurrence of major adverse cardiovascular events, minimize narrowing of blood vessel lumen, enhance clinical symptoms, and enhance the quality of life of patients following PCI surgery, all while maintaining a good safety profile.

Classification of recurrent major depressive disorder using a residual denoising autoencoder framework: Insights from large-scale multisite fMRI data.

BACKGROUND AND OBJECTIVE: Recurrent major depressive disorder (rMDD) has a high recurrence rate, and symptoms often worsen with each episode. Classifying rMDD using functional magnetic resonance imaging (fMRI) can enhance understanding of brain activity and aid diagnosis and treatment of this disorder. METHODS: We developed a Residual Denoising Autoencoder (Res-DAE) framework for the classification of rMDD. The functional connectivity (FC) was extracted from fMRI data as features. The framework addresses site heterogeneity by employing the Combat method to harmonize feature distribution differences. A feature selection method based on Fisher scores was used to reduce redundant information in the features. A data augmentation strategy using a Synthetic Minority Over-sampling Technique algorithm based on Extended Frobenius Norm measure was incorporated to increase the sample size. Furthermore, a residual module was integrated into the autoencoder network to preserve important features and improve the classification accuracy. RESULTS: We tested our framework on a large-scale, multisite fMRI dataset, which includes 189 rMDD patients and 427 healthy controls. The Res-DAE achieved an average accuracy of 75.1 % (sensitivity = 69 %, specificity = 77.8 %) in cross-validation, thereby outperforming comparison methods. In a larger dataset that also includes first-episode depression (comprising 832 MDD patients and 779 healthy controls), the accuracy reached 70 %. CONCLUSIONS: We proposed a deep learning framework that can effectively classify rMDD and 33 identify the altered FC associated with rMDD. Our study may reveal changes in brain function 34 associated with rMDD and provide assistance for the diagnosis and treatment of rMDD.

Outcomes of Excimer Laser Ablation Combined with Drug-coated Balloon in Atherosclerotic Lesions of the Popliteal Artery.

BACKGROUND: The treatment of atherosclerotic lesions in the popliteal artery is challenging. This study aims to investigate the efficacy and safety of excimer laser ablation (ELA) combined with drug-coated balloon (DCB) for these lesions. METHODS: From June 2019 to December 2021, data of patients who underwent ELA combined with DCB in the popliteal artery were retrospectively reviewed. Demographics, lesion characteristics, periprocedural complications, and follow-up information were analyzed. The primary endpoint was primary patency. Secondary endpoints included major amputation-free survival rate, technical success, bailout stenting, clinically-driven target lesion reintervention, improvement of ankle-brachial index (ABI), and Rutherford class. RESULTS: A total of 61 patients were enrolled. The mean age was 73.4 ± 11.7 years. 20 (32.8%) patients had stenotic lesions, while 41 (67.2%) patients had chronic total occlusions. The mean length of these lesions was 7.3 ± 2.8 cm. Procedure technical success rate was 95.1%. Bailout stent was performed in 3 (4.9%) patients. Intraprocedural distal embolization occurred in 3 (4.9%) patients, while flow limiting dissections occurred in 3 (4.9%) patients. The mean ABI was significantly improved from 0.45 ± 0.13 at baseline to 0.90 ± 0.12 after ELA, 0.88 ± 0.11 at 6 months and 0.85 ± 0.12 at 12 months during the follow-up period. The median follow-up time was 28.2 ± 6.1 months. Reintervention was performed in 5 (8.2%) patients. The 2-year primary patency was 83.5%. CONCLUSIONS: ELA combined with DCB is a safe and effective strategy in the treatment of popliteal artery atherosclerotic lesions with low rates of bail-out stenting and high primary patency.

ROCK1 inhibition improves wound healing in diabetes via RIPK4/AMPK pathway.

Refractory wounds are a severe complication of diabetes mellitus that often leads to amputation because of the lack of effective treatments and therapeutic targets. The pathogenesis of refractory wounds is complex, involving many types of cells. Rho-associated protein kinase-1 (ROCK1) phosphorylates a series of substrates that trigger downstream signaling pathways, affecting multiple cellular processes, including cell migration, communication, and proliferation. The present study investigated the role of ROCK1 in diabetic wound healing and molecular mechanisms. Our results showed that ROCK1 expression significantly increased in wound granulation tissues in diabetic patients, streptozotocin (STZ)-induced diabetic mice, and db/db diabetic mice. Wound healing and blood perfusion were dose-dependently improved by the ROCK1 inhibitor fasudil in diabetic mice. In endothelial cells, fasudil and ROCK1 siRNA significantly elevated the phosphorylation of adenosine monophosphate-activated protein kinase at Thr172 (pThr172-AMPKα), the activity of endothelial nitric oxide synthase (eNOS), and suppressed the levels of mitochondrial reactive oxygen species (mtROS) and nitrotyrosine formation. Experiments using integrated bioinformatics analysis and coimmunoprecipitation established that ROCK1 inhibited pThr172-AMPKα by binding to receptor-interacting serine/threonine kinase 4 (RIPK4). These results suggest that fasudil accelerated wound repair and improved angiogenesis at least partially through the ROCK1/RIPK4/AMPK pathway. Fasudil may be a potential treatment for refractory wounds in diabetic patients.