BACKGROUND:Rev-erbα is involved in the regulation of inflammation,but pharmacological activation of Rev-erbα increases the risk for cardiovascular diseases.To reduce the relevant risk,an exploration on SR9009,a Rev-erbα agonist,combined with other drugs to relieve inflammation in skeletal myoblasts was conducted,laying the theoretical foundation for the treatment of inflammation-associated skeletal muscle atrophy. OBJECTIVE:To investigate the relationship of SR9009,indolepropionic acid and nuclear factor-κB signaling pathways in lipopolysaccharide-induced C2C12 myoblasts. METHODS:(1)C2C12 myoblasts were induced to differentiate in the presence of lipopolysaccharide(1 μg/mL).RNA-seq and KEGG pathway analysis were used to study signaling pathways.(2)C2C12 myoblast viability was assessed using the cell counting kit-8 assay to determine optimal concentrations of indolepropionic acid.Subsequently,cells were categorized into control group,lipopolysaccharide(1 μg/mL)group,SR9009(10 μmol/L)+lipopolysaccharide group,indolepropionic acid(80μmol/L)+lipopolysaccharide group,and SR9009+indolepropionic acid+lipopolysaccharide group.ELISA was employed to measure protein expression levels of interleukin-6 in the cultured supernatant.Real-time quantitative PCR were employed to measure mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Western blot assay were employed to measure protein expression levels of NF-κB p65 and p-NF-κB p65.(3)After Rev-erbα was knocked down by siRNA,knockdown efficiency was assessed by RT-qPCR.And mRNA levels of interleukin-6 and tumor necrosis factor α were also measured. RESULTS AND CONCLUSION:Compared with the blank control group,lipopolysaccharide time-dependently inhibited myofibroblast fusion to form myotubes,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were elevated,and the level of interleukin-6 in the cell supernatant was significantly increased.The results of KEGG pathway showed that the nuclear factor-κB signaling pathway was activated by lipopolysaccharide.Indolepropionic acid exhibited significant suppression of C2C12 myoblasts viability when its concentration exceeded 80 μmol/L.Indolepropionic acid and SR9009 inhibited the activation of NF-κB signaling pathway,thereby played an anti-inflammatory role,and suppressed the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Compared with the lipopolysaccharide group,the ratio of p-NF-κB p65/NF-κB p65 protein expression were downregulated.SR9009 combined with indolepropionic acid notably reduced lipopolysaccharide-induced inflammation,further downregulated the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.The ratio of p-NF-κB p65/NF-κB p65 protein expression was significantly lower than that in the SR9009+lipopolysaccharide group or indolepropionic acid+lipopolysaccharide group.Rev-erbα increases time-dependently with lipopolysaccharide induction.The knockdown efficiency of Rev-erbα by siRNA reached over 58%,and lipopolysaccharide was added after Rev-erbα was successfully knocked down.Compared with the lipopolysaccharide group,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were significantly up-regulated.These results conclude that Rev-erbα may act as a promising pharmacological target to reduce inflammation.SR9009 targeted activation of Rev-erbα combined with indolepropionic acid significantly inhibits the nuclear factor-κB signaling pathway and attenuates the inflammatory response of C2C12 myofibroblasts.Moreover,the combined anti-inflammatory effect is superior to that of the intervention alone.

BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

Posterior capsule opacification(PCO)is a common postoperative complication of cataract surgery, primarily caused by the proliferation and migration of residual lens epithelial cells(LECs). Although neodymium-doped yttrium aluminum garnet(Nd:YAG)laser posterior capsulotomy effectively treats PCO, it carries risks of complications such as cystoid macular edema(CME). Thus, preventing PCO formation is of critical clinical importance. Despite advancements in intraocular lens(IOL)materials and designs, achieving complete PCO eradication remains challenging. This review systematically examines recent advancements in surface-modified IOLs, including anti-biofouling IOL(reducing LECs adhesion), capsular adhesion-enhanced IOL(promoting capsular bag integration), micro-patterned IOL(physically inhibiting migration), photothermal/photodynamic IOL(inducing light-activated LECs apoptosis), and drug-eluting IOL(sustained drug release). These surface modification strategies demonstrate synergistic effects through complementary mechanisms(including physical barrier formation, chemical intervention, and bioactive regulation), effectively suppressing LECs proliferation while significantly reducing PCO incidence. Importantly, these approaches eliminate the risks associated with conventional Nd:YAG laser treatment, offering substantial advantages. By providing a comprehensive evaluation of these cutting-edge technologies, this review serves as a valuable reference for IOL design optimization. It represents a paradigm shift in cataract management strategies, transitioning from reactive therapeutic interventions to proactive preventive measures, and ultimately leads to improving long-term visual outcomes for patients.

Septic shock, a prevalent critical condition in intensive care units (ICU) and a major cause of patient mortality, is fundamentally attributed to microcirculatory dysfunction. Traditional macrocirculatory parameters are often insufficiently sensitive to reflect microcirculatory status. Consequently monitoring peripheral microcirculatory function holds crucial significance for assessing disease progression and evaluating therapeutic efficacy in septic shock. The peripheral perfusion index (PPI), obtained from a standard pulse oximeter, is based on photoplethysmography (PPG). It calculates the differential absorption of red and infrared light emitted by the sensor between pulsatile arterial blood and non-pulsatile tissue, enabling real-time reflection of peripheral perfusion and thus providing non-invasive, continuous monitoring of microcirculatory function. Although often overlooked compared to other ICU monitoring parameters, PPI has demonstrated notable clinical advances in septic shock management. Specifically, in early identification, PPI combined with sequential organ failure assessment (SOFA) predicts disease progression, with its dynamic changes further aiding prognosis assessment. During fluid resuscitation, it guides fluid responsiveness evaluation and serves as a therapeutic target to optimize strategies. In circulatory support, it assists in determining vasoactive drug initiation timing and dosage titration. Additionally, PPI aids mechanical ventilation weaning and organ dysfunction evaluation. This article reviews the principles, influencing factors, and clinical application advances of PPI in septic shock, aiming to provide clinicians with a basis for individualized intervention, improved patient outcomes, and the advancement of precision medicine in septic shock management.
Humans ; Shock, Septic/therapy* ; Microcirculation ; Perfusion Index ; Prognosis ; Photoplethysmography

  Objective  This study aimed to investigate Chinese anesthesiologists' comprehension of palliative care and their experiences with palliative sedation for patients in the end-stage of life.  Methods  From October to December 2021, a national cross-sectional survey was conducted among anesthesiologists in China distributed by the Chinese Society of Anesthesiology, Chinese Medical Association with convenient sampling. The survey questionnaire encompassed general information, professional experience, familiarity with palliative care, emotional responses to end-stage cases, experience with sedation for critically ill or end-stage patients, and preferences for sedation medication.  Results  A total of 2536 anesthesiologists from 29 provinces in China completed valid questionnaires. Among them, 572 anesthesiologists(22.6%, 572/2536) reported familiarity with palliative medicine. Male anesthesiologists, as well as those with prior experience in caring for critically ill or end-stage patients, involved in pain management and practicing in hospitals with established institutional palliative care teams, demonstrated greater familiarity with palliative care concepts(all P<0.05). Over 40% of respondents felt powerless, helpless, and indecisive when confronted with end-stage patients. Anesthesiologists knowledgeable about palliative care exhibited greater confidence in managing critically ill or end-stage patients(9.8% vs. 4.4%, P=0.001). Among the anesthesiologists surveyed, 734 had administered sedation to end-stage patients, with 151 of them(20.6%, 151/734) inappropriately relying solely on opioids for sedation.  Conclusions  The understanding of palliative care and palliative sedation medication choice among anesthesiologists in China is still very limited. The establishment of palliative care teams, provision of education and training in palliative care, and enhancement of familiarity with palliative principles may bolster anesthesiologists' confidence when encountering critically ill or end-stage patients and subsequently enhance the quality of care for patients in the terminal stages of life.

Although significant progress has been made in the development of novel targeted drugs for the treatment of acute myeloid leukemia(AML)in recent years,chemotherapy still remains the mainstay of treatment and the overall survival is poor in most patients.Here,we demonstrated the antileukemia activity of a novel small molecular compound NL101,which is formed through the modification on bendamustine with a suberanilohydroxamic acid(SAHA)radical.NL101 suppresses the proliferation of myeloid malignancy cells and primary AML cells.It induces DNA damage and caspase 3-mediated apoptosis.A genome-wide clustered regularly interspaced short palindromic repeats(CRISPR)library screen revealed that phosphatase and tensin homologous(PTEN)gene is critical for the regulation of cell survival upon NL101 treatment.The knockout or inhibition of PTEN significantly reduced NL101-induced apoptosis in AML and myelodysplastic syndrome(MDS)cells,accompanied by the activation of protein kinase B(AKT)signaling pathway.The inhibition of mammalian target of rapamycin(mTOR)by rapamycin enhanced the sensitivity of AML cells to NL101-induced cell death.These findings uncover PTEN protein expression as a major determinant of chemosensitivity to NL101 and provide a novel strategy to treat AML with the combination of NL101 and rapamycin.

Objective:To investigate the association between body composition and coronary artery calcification in patients with chronic kidney disease (CKD).Methods:This cross-sectional study enrolled patients with CKD hospitalized from May 2019 to April 2022 at Sun Yat-sen Memorial Hospital, Guangzhou, China. Skeletal muscle mass index and visceral fat area were measured by bioelectrical impedance analysis. Coronary artery calcification was assessed by computed tomography. Patients were divided into coronary artery calcification group and non-coronary artery calcification group according to the incidence of coronary artery calcification. Patients were categorized into tertile groups according to their skeletal muscle mass index and visceral fat area levels ranging from the lowest to the highest levels (T1 to T3). We defined skeletal muscle mass index≤30.4% as low muscle mass and visceral fat area≥80.6 cm 2 as high visceral fat based on the results of the restricted cubic spline graph. All individuals were divided into 4 phenotypes: normal body composition, low muscle mass, high visceral fat, and low muscle mass with high visceral fat. Spearman correlation analysis and logistic regression analysis were used to assess the association between skeletal muscle mass index, visceral fat area and coronary artery calcification. Results:A total of 107 patients with CKD were enrolled, with an age of (60.0±14.1) years, including 41 female patients (38.3%). Patients of coronary artery calcification group had lower skeletal muscle mass index ((32.0±4.8) vs. (34.3±4.8), P=0.016) and higher visceral fat area ((70.8±32.6) cm 2 vs. (47.9±23.8) cm 2, P<0.001) than those of non-coronary artery calcification group. Patients in the T3 group of skeletal muscle mass index had a lower prevalence of coronary artery calcification (17 (48.6%) vs. 28 (77.8%)) and a lower coronary artery calcification score (0.5 (0, 124.0) vs. 12.0 (0.3, 131.0)) than those in the T1 group ( P<0.05). Similarly, patients in the T1 group of visceral fat area had a lower prevalence of coronary artery calcification (14 (40.0%) vs. 29 (80.6%)) and a lower coronary artery calcification score (0 (0, 3.0) vs. 37.0 (2.0, 131.0)) than those in the T3 group ( P<0.05). Likewise, patients with both low muscle mass and low muscle mass with high visceral fat had a higher prevalence of coronary artery calcification (11(78.6%) vs. 33 (47.8%); 15 (83.3%) vs. 33 (47.8%)) and a higher coronary artery calcification score (31.1 (0.8, 175.8) vs. 0 (0, 16.4); 27.6 (6.4, 211.4) vs. 0 (0, 16.4)) than those with normal body composition ( P<0.05). Spearman correlation analysis showed that skeletal muscle mass index was inversely correlated with coronary artery calcification score ( r=-0.212, P=0.028), and visceral fat area was positively correlated with coronary artery calcification score ( r=0.408, P<0.001). Multivariate logistic regression analysis showed that increased skeletal muscle mass index was inversely associated with coronary artery calcification prevalence (T2: OR=0.208, 95% CI: 0.056-0.770, P=0.019; T3: OR=0.195, 95% CI: 0.043-0.887, P=0.034), and reduced visceral fat area was inversely associated with coronary artery calcification prevalence (T1: OR=0.256, 95% CI: 0.071-0.923, P=0.037; T2: OR=0.263, 95% CI: 0.078-0.888, P=0.031). Consistently, both low muscle mass and low muscle mass with high visceral fat were associated with coronary artery calcification prevalence ( OR=6.616, 95% CI: 1.383-31.656, P=0.018; OR=5.548, 95% CI: 1.062-28.973, P=0.042). Conclusion:Reduced skeletal muscle mass index and increased visceral fat area are significantly associated with both the prevalence and severity of coronary artery calcification in patients with CKD.

Objective:To observe the efficacy of cosmetic suturing techniques combined with topical recombinant human basic fibroblast growth factor (rh-bFGF) in repairing facial trauma.Methods:A prospective study was conducted on 140 patients with facial trauma admitted to the Department of Burn and Plastic Surgery, Northern Jiangsu People＇s Hospital from January to December 2022. Patients were divided into two groups based on different treatment methods using a random number table method: treatment group (70 cases), including 38 males and 32 females aged 3 to 54 (23.1±8.2) years, received cosmetic suturing techniques combined with topical rh-bFGF for wound repair; control group (70 cases), including 36 males and 34 females aged 2 to 49 (22.3±7.5) years, only received cosmetic suturing techniques for wound repair. Patients were followed up 2 weeks post-surgery to evaluate wound healing quality. Patient satisfaction was assessed using the visual analogue scale (VAS). Six months post-surgery, scar conditions were evaluated using the Vancouver scar scale (VSS).Results:In the treatment group, 65 cases were directly sutured, and 5 cases were repaired with skin flaps, with a first-class healing rate of 100% (70/70). In the control group, 66 cases were directly sutured, and 4 cases were repaired with skin flaps, with a first-class healing rate of 91.4% (64/70). The first-class healing rate in the treatment group was higher than that in the control group, with a statistically significant difference ( P=0.037). Two weeks post-surgery, the VAS score for surgical satisfaction in the treatment group was (1.13±0.52) scores, which was lower than that in the control group (2.56±1.32) scores, with a statistically significant difference ( P<0.001). Six months post-surgery, the VSS score for the treatment group was (2.49±1.27) scores, which was lower than that in the control group (4.67±1.93) scores, with a statistically significant difference ( P<0.001). Conclusions:In repairing facial trauma, the combination of cosmetic suturing techniques and topical rh-bFGF can improve wound healing quality, reduce wound scarring, and enhance patient satisfaction with surgery.

Objective To explore the clinical efficacy of Fuling Zexie Decoction combined with lifestyle intervention in patients with metabolic syndrome (MetS) of dampness syndrome. Methods A total of 40 patients with MetS of dampness syndrome were randomly divided into experimental group (n=20) and control group (n=20) according to a randomized double-blind placebo-controlled design. The experimental group was given oral administration of Fuling Zexie Decoction,the control group was given placebo,150 mL each time,twice a day. Both groups were given healthy lifestyle(healthy eating habits and exercise mode) education. The intervention period was 16 weeks. Traditional Chinese medicine dampness syndrome scale score and the diagnostic indexes of MetS,including waist circumference (WC),systolic blood pressure (SBP),diastolic blood pressure (DBP),triglyceride (TG),high density lipoprotein cholesterol (HDL-C) and fasting blood glucose (FBG),were evaluated before and after treatment. Other metabolic indexes such as body mass index(BMI),total cholesterol(TC),low density lipoprotein cholesterol(LDL-C),homeostasis model assessment of insulin resistance(HOMA-IR),uric acid(UC),as well as inflammation related indexes including C-reactive protein (CRP),interleukin-6 (IL-6) and tumor necrosis factor(TNF-α) were also evaluated. Results A total of 33 people completed the trial,including 17 people in the experimental group and 16 people in the control group. Compared to the baseline period,FBG,BMI,LDL-C and dampness syndrome scale score in the experimental group were significantly decreased at the 8th and 16th week of intervention(P<0.05). WC was significantly decreased at the 8th week of intervention(P<0.05). CRP showed a downward trend at the 16th week of intervention(P<0.05). Moreover,SBP and IL-6 in control group decreased significantly at the 8th and 16th week of intervention(P<0.05). WC,DBP and HOMA-IR decreased significantly at the 8th week of intervention (P<0.05). There was no significant difference in other outcome indexes between the two groups at the 8th and 16th week of intervention (P>0.05). The safety indexes of all patients before and after intervention were not significantly abnormal,and no serious adverse events occurred. Conclusion This study initially shows the positive regulatory effect of Fuling Zexie Decoction combined with lifestyle on metabolism and inflammation-related indexes in people with MetS of dampness syndrome,which helps to improve the level of dampness syndrome and provides a basis for further research.