BackgroundPatients with depressive episode and schizophrenia have a high risk of suicide. The sleep electroencephalogram power spectral density characteristics of patients with depressive episode accompanied by suicidal behavior and those with schizophrenia may be different， but there is currently a lack of direct comparative studies on these two groups of patients. ObjectiveTo compare the sleep electroencephalogram power spectral density between depressive episode and schizophrenic patients with suicidal behavior， in order to provide references for exploring predictive indicators of suicidal behavior. MethodsFrom June 2018 to December 2020， 20 patients with depressive episode and 20 patients with schizophrenia who had committed suicide within the past month and were treated at the outpatient department of Shenzhen Kangning Hospital were selected. All of them met the diagnostic criteria for depressive episode or schizophrenia as defined in the International Classification of Diseases， tenth edition （ICD-10）. Using a random sampling method， 20 volunteers with matching gender and age to the patient groups were selected from the Cuiping community in Shenzhen as the control group. The subjective sleep of the patients was evaluated using the Insomnia Severity Index （ISI）， the Dysfunctional Belief and Attitude about Sleep （DBAS）， the Disturbing Dreams and Nightmare Severity Index （DDNSI）， and the Epworth Somnolence Scale （ESS）. The objective sleep of the patients was assessed using polysomnography. The sleep electroencephalogram was filtered and the power spectral density of the brain wave was analyzed and processed for all the subjects. The subjective and objective sleep conditions of the two patient groups were compared， and the sleep electroencephalogram power spectral density of the patient groups and the control group were also compared. ResultsA comparison of subjective and objective sleep conditions between patients with depressive episode accompanied by suicidal behavior and patients with schizophrenia accompanied by suicidal behavior showed no statistically significant differences （P>0.05）. Comparisons of sleep electroencephalogram power spectral density in the W stage （average power of α wave， total power of δ wave， average power of δ wave， average power of θ wave）， N1 stage （average power of β wave， total power of α wave， total power of δ wave）， N2 stage （total power of α wave， average power of α wave， total power of δ wave， average power of δ wave）， N3 stage （average power of α wave， average power of δ wave）， and R stage （total power of α wave， average power of α wave， total power of δ wave， average power of δ wave） between patients with depressive episode accompanied by suicidal behavior， patients with schizophrenia accompanied by suicidal behavior， and the control group showed statistically significant differences （P<0.05 or 0.01）. The total power of δ wave in the W stage and the average power of β wave and δ wave in the N1 stage were higher in two patient groups were higher than those of the control group. The total power of α wave and the average power of α wave in the N2 stage were lower than those of the control group， while the average power of δ wave was higher than that of the control group. The average power of α wave in the N3 stage of both patient groups were lower than that of the control group， while the average power of δ wave was higher than that of the control group. The total power and average power of α wave in the R stage were lower than those of the control group， while the total power and average power of δ wave were higher than those of the control group. All the differences were statistically significant. Patients with depressive episode accompanied by suicidal behavior had higher average powers of α wave， δ wave， and θ wave in the W stage compared with the control group， while the total power of α wave in the N1 stage was lower in the former group. All these differences were statistically significant （P<0.05）. ConclusionThe depressive episode patients accompanied by suicidal behavior have highly overlapping sleep electroencephalogram abnormal patterns with those of schizophrenia patients， mainly manifested as a general decrease in α wave power （N2， N3， R stage） and a general increase in δ wave power （W， N1， N2， N3， R stage） as well as β wave power in N1 stage. At the same time， patients with depressive episode accompanied by suicidal behavior also show specific changes， including an increase in the average power of α and θ waves during the wakefulness period （W stage）， and a decrease in the total power of α wave in N1 stage. ［Funded by Guangdong Province High-level Clinical Key Specialty （with supporting funds from Shenzhen City） （number， SZGSP013）； Shenzhen Key Medical Discipline （number， SZXK041）； Shenzhen Clinical Medicine Research Center Project （number， 20210617155253001）］

Objective To elucidate the molecular mechanism of sirtuin-3 (SIRT3) in regulating mitochondrial biogenesis in human renal tubular epithelial cells. Methods Cells were stimulated with different concentrations of H₂O₂ and divided into four groups: control (NC), 50 μmol/L H₂O₂, 110 μmol/L H₂O₂ and 150 μmol/L H₂O₂. SIRT3 protein expression was then measured. SIRT3 was knocked down with siRNA, and cells were further assigned to five groups: control (NC), negative-control siRNA (NCsi), SIRT3-siRNA (siSIRT3), NCsi+H₂O₂, and siSIRT3+H₂O₂. After 24 h, cellular adenosine triphosphate (ATP) and mitochondrial superoxide anion (O₂•⁻) levels were determined, together with mitochondrial expression of SIRT3, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), nuclear respiratory factor 1 (NRF1), mitochondrial transcription factor A (TFAM), superoxide dismutase 2 (SOD2), acetylated-SOD2 and adenosine monophosphate activated protein kinase α1 (AMPKα1). Results The 110 and 150 μmol/L H₂O₂ decreased SIRT3 protein (both P<0.05). ATP and mitochondrial O₂•⁻ did not differ between NC and NCsi groups (both P>0.05). Compared to the NCsi group, the siSIRT3 group exhibited elevated O₂•⁻ level, decreased SIRT3 protein and increased expression levels of SOD2 and acetylated SOD2 protein (all P<0.05). Compared to the NCsi group, the NCsi+H₂O₂ group exhibited decreased cellular ATP levels, elevated mitochondrial O₂•⁻ levels, and reduced protein expression levels of SIRT3, SOD2, TFAM, AMPKα1, PGC-1α and NRF1 (all P<0.05). Compared with the siSIRT3 group, the siSIRT3+H₂O₂ group showed a decrease in cellular ATP levels, an increase in mitochondrial O₂•⁻ levels, a decrease in SIRT3, SOD2, TFAM, AMPKα1, PGC-1α and NRF1 protein expression levels and a decrease in acetylated SOD2 protein expression levels (all P<0.05). Compared with the NCsi+H₂O₂ group, the siSIRT3+H₂O₂ group showed a decrease in cellular ATP levels, an increase in mitochondrial O₂•⁻ levels, a decrease in SIRT3, AMPKα1, PGC-1α and NRF1, TFAM protein expression levels, and an increase in SOD2 and acetylated SOD2 protein expression levels (all P<0.05). Conclusions SIRT3 promotes mitochondrial biogenesis in tubular epithelial cells via the AMPK/PGC-1α/NRF1/TFAM axis, representing a key mechanism through which SIRT3 ameliorates oxidative stress-induced mitochondrial dysfunction.

Background/Aims: Lenvatinib resistance remains a critical barrier in advanced hepatocellular carcinoma (HCC) therapy. However, the underlying mechanisms and strategies for reversing resistance remain incompletely understood. Methods: Integrated transcriptomics of lenvatinib-resistant patient tumors and an acquired-resistance murine model identified a novel macrophage subpopulation. Functional validation employed CRISPR-SAM screening, conditioned medium (CM) assays, subcutaneous/orthotopic xenografts, patient-derived organoids (PDOs), and patient-derived xenografts (PDXs). Mechanistic studies included ChIP-qPCR, co-immunoprecipitation, and pharmacologic targeting. Clinical relevance was assessed in a retrospective cohort. Results: Resistant HCC exhibited significant enrichment of a COLEC12high TAM subset , which correlated with poor survival and treatment response. These TAMs secreted neuregulin-1 (NRG1) , activating HER2/HER3-AKT signaling in tumor cells to drive cancer stemness and lenvatinib resistance. Mechanistically, in TAMs COLEC12 sequestered STAT1 in the cytoplasm, preventing its phosphorylation, and thereby derepressing STAT3-mediated NRG1 transcription. Depletion of NRG1 reversed the stemness phenotypes and resensitized tumors to lenvatinib both in vitro and in vivo. Clinically, high NRG1 expression predicted an inferior lenvatinib response and shorter survival. Crucially, the bispecific anti-HER2/HER3 antibody zenocutuzumab restored lenvatinib efficacy in PDOs, PDXs, and murine models. Conclusions Our work establishes the COLEC12high TAM/NRG1 axis as a master regulator of therapeutic resistance and identifies NRG1 as a predictive biomarker, providing a clinically actionable strategy to overcome lenvatinib resistance in HCC.

OBJECTIVE To evaluate the influence of pharmaceutical quality control on the efficiency and outcomes of standardized medication therapy management （MTM） services for patients with coronary heart disease by using Economic， Clinical and Humanistic Outcomes （ECHO） model. METHODS This study collected case data of coronary heart disease patients who received MTM services during January-March 2023 （pre-quality control implementation group， n＝96） and June-August 2023 （post-quality control implementation group， n＝164）. Using propensity score matching analysis， 80 patients were selected from each group. The study subsequently compared the economic， clinical， and humanistic outcome indicators of pharmaceutical services between the two matched groups. RESULTS There were no statistically significant differences in baseline data between the two groups after matching （P＞0.05）. Compared with pre-quality control implementation group， the daily treatment cost （16.26 yuan vs. 24.40 yuan， P＜0.001）， cost-effectiveness ratio [23.12 yuan/quality-adjusted life year （QALY） vs. 32.32 yuan/QALY， P＜0.001]， and the incidence of general adverse drug reactions （2.50% vs. 10.00%， P＝0.049） of post-quality control implementation group were decreased significantly； the utility value of the EuroQol Five-Dimensional Questionnaire （0.74± 0.06 vs. 0.71±0.07， P＝0.003）， the reduction in the number of medication related problems （1.0 vs. 0.5， P＜0.001）， the medication adherence score （[ 6.32±0.48） points vs. （6.10±0.37） points， P＝0.001]， and the satisfaction score （[ 92.56±1.52） points vs. （91.95±1.56） points， P＝0.013] all showed significant improvements. Neither group experienced serious adverse drug reactions. There was no statistically significant difference in the incidence of new adverse reactions between the two groups （1.25% vs. 3.75%， P＝0.310）. CONCLUSIONS Pharmaceutical quality control can improve the quality of pharmaceutical care， and the ECHO model can quantitatively evaluate the effect of MTM services， making pharmaceutical care better priced and more adaptable to social needs， thus being worthy of promotion.

Objective To investigate the predictive value of serum uric acid(UA),homocysteine(Hcy)and the product index of UA and Hcy in patients with stable coronary artery disease(SCAD).Methods A total of 783 patients with suspected coronary heart disease were collected,all of whom underwent coronary angiography.Patients were divided into coronary heart disease(CHD)group and non-coronary heart disease(NCHD)group.The CHD group was further divided into low score group(≤35 points)and high score group(>35 points)according to Gensini scores.Baseline data,blood lipids,Hcy,UA,left ventricular function ultrasound indicators,and comorbidities were collected.Logistic regression analysis was used to evaluate the risk factors associated with the onset of SCAD and severe coronary artery disease,while the Receiver Operating Characteristic(ROC)curve was conducted to assess the predictive efficacy of the product index of UA and Hcy,and related risk factors,for SCAD onset and severe coronary artery disease.Results 1.In CHD group,UA,Hcy and the product index of UA and Hcy were all higher than in the NCHD group(P<0.001);the high-score group had higher UA,Hcy and the product index of UA and Hcy than the low Gensini score group(P<0.001).2.Multivariate logistic regression analysis showed that female age,sex,body mass index(BMI),product index of UA and Hcy,high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C),left ventricular end-systolic volume(LVESV),left ventricular ejection fraction(LVEF),type 2 diabetes mellitus(T2DM)and hypertension(HTN)were independent risk factors for SCAD(P<0.05).BMI,the product index of UA and Hcy,HDL-C,LDL-C and LVEF were independent risk factors for severe coronary artery disease(P<0.05).3.There was a positive correlation between UA and Hcy product index and Gensini scores(r=0.433,P<0.05).4.Receiver operating characteristic curve analysis showed that the product index of UA and Hcy and combined detection of coronary heart disease risk factors had predictive value for the occurrence of SCAD(P<0.05),and the predictive value of combined detection was higher(area under the curve 0.808);both the product index of UA and Hcy and the combined detection of coronary heart disease risk factors had predictive value for severe coronary artery lesions(P<0.05),with a higher predictive value for combined detection(area under the curve 0.771).Conclusion As an independent predictor of the risk of SCAD and severe coronary stenosis,the product index of UA and Hcy has a high predictive efficacy regarding disease risk and the severity of coronary artery in patients with SCAD.

Objective To evaluate the predictive value of changes in serum homocysteine(Hcy),high-density lipoprotein cholesterol(HDL-C),and the homocysteine-to-HDL-C ratio(HHR)for the incidence and short-term prognosis of patients with premature coronary heart disease(PCHD).Methods Between January 2022 and December 2023,301 patients with the suspected coronary heart disease(males≤55 years,females≤65 years)were retrospectively selected from the Department of Cardiology at the Third People's Hospital of Yunnan Province.All patients who underwent coronary angiography(CAG)were divided into the premature coronary heart disease(PCHD)group(n=98)and the non-coronary heart disease(NCHD)group(n=203).Patients with PCHD were followed up six months after the discharge and were further classified into the good prognosis group(n=55)and the poor prognosis group(n=43)based on the presence of worsening clinical symptoms such as chest tightness,chest pain,arrhythmias,heart failure,or death.Data collected included general patient information,blood lipid levels,Hcy levels,left ventricular function ultrasound indicators,and the presence of hypertension and type 2 diabetes.Results Hcy and HHR levels were significantly higher in the PCHD group compared to the NCHD group,while HDL-C levels were lower(P<0.001).In the poor prognosis group,Hcy and HHR levels were elevated,and HDL-C levels were reduced compared to the good prognosis group(P<0.001).The Hcy and HHR levels in the severe coronary artery stenosis group were markedly higher than those in the normal coronary artery group and the mild to the moderate stenosis group,with HDL-C levels being lower(P<0.001).Multivariate logistic regression analysis identified that male sex,HHR,Hcy,low-density lipoprotein cholesterol(LDL-C),and left ventricular ejection fraction(LVEF)were independent factors influencing premature coronary heart disease(P<0.05).HHR was found to be an independent risk factor for the poor short-term prognosis in PCHD.The analysis of the operating characteristic curve of the subjects showed that serum Hcy and HHR had the predictive value for the occurrence of PCHD(P<0.05),with HHR showing higher predictive value(area under the curve[AUC]=0.713).HHR also had the substantial predictive value for the short-term prognosis of PCHD(AUC=0.715).Conclusion Elevated HHR levels are associated with the severe coronary artery disease in patients with PCHD.HHR serves as a significant predictor for both the occurrence and short-term prognosis of PCHD.

Objective:To investigate the differences in clinical characteristics and antibiotic resistance of neonatal sepsis（NS）caused by different Gram-staining pathogens.Methods:A retrospective study was conducted on confirmed NS cases admitted to the Neonatal Ward of the Pediatric Department at The First Affiliated Hospital of Dali University，from June 1，2014，to May 31，2024.Patients were divided into Gram-positive and Gram-negative groups based on blood or cerebrospinal fluid（CSF）culture results.Clinical characteristics，pathogen distribution，and antibiotic resistance were compared between the two groups.Results:A total of 98 cases were included，with 81 in the Gram-positive group and 17 in the Gram-negative group.Multivariate logistic regression analysis revealed that NS cases with a high neutrophil percentage（ OR=0.933，95% CI：0.899-0.969）or hemorrhagic symptoms/signs（ OR=0.059，95% CI：0.008-0.458）were less likely to have Gram-positive pathogens detected in blood or CSF cultures（ P<0.05）.Common Gram-positive pathogens included Staphylococcus epidermidis with 35 strains（33.65%）and Staphylococcus hominis with 22 strains（21.15%）.The predominant Gram-negative pathogen was Escherichia coli with 14 strains（13.46%）.Gram-positive pathogens exhibited high resistance to oxacillin（91.30%），erythromycin（90.91%），and penicillin G（90.00%），but low resistance to tigecycline（0），linezolid（0），and vancomycin（0）.Gram-negative pathogens showed high resistance to ampicillin（92.31%），cefazolin（90.00%），and ampicillin/sulbactam（75.00%），but low resistance to amikacin（6.25%），latamoxef（0），and ertapenem（0）.The incidence of concurrent purulent meningitis was lower in the Gram-positive group than in the Gram-negative group（9.88% vs.47.06%， χ2=11.628， P<0.05），and there was significant difference. Conclusion:NS cases with high neutrophil percentages or hemorrhagic symptoms/signs are less likely to be caused by Gram-positive pathogens.Staphylococcus epidermidis and Staphylococcus hominis are common Gram-positive pathogens，while Escherichia coli is the predominant Gram-negative pathogen in NS.Both Gram-positive and Gram-negative pathogens exhibit resistance to specific antibiotics.NS caused by Gram-positive pathogens is less likely to be complicated by purulent meningitis compared to those caused by Gram-negative pathogens.

Objective To explore the predictive value of early variability of levels of multiple inflammatory factors for the prognosis of children with Mycoplasma pneumoniae pneumonia(MPP).Methods A total of 253 MPP children admitted to the hospital from May 2022 to October 2024 were selected as the research sub-jects.Blood samples were collected from all patients at admission and up to 72 h[T0(0-6 h at admission),T1(24 h after admission),T2(48 h after admission),T3(72 h after admission)].Serum inflammatory fac-tors,including C-reactive protein(CRP),interleukin(IL)-2,IL-4,IL-5,IL-6,IL-8,IL-10,IL-17A,IL-1β,γ-in-terferon(IFN-γ),and tumor necrosis factor-α(TNF-α)were measured,and variability was calculated(T1=[(T1-T0)/T0]× 100％,△T2=[(T2-T0)/T0]× 100％,△T3=[(T3-T0)/T0]× 100％).MPP patients were divided into the good prognosis group and poor prognosis according to the prognosis condition.The ser-um inflammatory factor levels and their variability at different time points in the good prognosis group and the poor prognosis group were compared,multivariate Logistic regression was used to analyze the influencing fac-tors of MPP children's prognosis,and receiver operating characteristic(ROC)curve was used to analyze the predictive value of early variability of inflammatory factor levels for MPP children's prognosis.Results After 3 months of follow-up observation,a total of 7 cases were lost to follow-up,and a total of 246 cases were final-ly included for analysis.Among them,58 cases were in the poor prognosis group,and 188 cases were in the good prognosis group.The disease course of the poor prognosis group was longer than that of the good prog-nosis group(P＜0.05),the severity of the disease was more severe than that of the good prognosis group(P＜0.05),and the proportion of affected lung lobes≥2/3 was higher in the poor prognosis group than in the good prognosis group(P＜0.05).IL-6,IL-17A and IL-1β levels at T1-T3 were higher than those at T0(P＜0.0125).The level of IL-6 at T0-T3,IL-1 β level at T2-T3,and IL-17A at T3 in the poor prognosis group were higher than those in the good prognosis group(P＜0.05).IL-6(△T2),IL-17A(△T3),IL-1β(△T2),IL-1β(△T3)in the poor prognosis group were higher than those in the good prognosis group(P＜0.05).The results of the multivariate Logistic regression analysis showed that IL-6(T0),IL-6(T1),IL-6(△T2),IL-1β(△T3),IL-17A(△T3)were the factors influencing the prognosis of children with MPP(P＜0.05).The ROC curve showed that the area under the curve of IL-6(T0),IL-6(T1),IL-6(△T2),IL-1β(△T3),IL-17A(△T3)for predicting the prognosis of children with MPP was all above 0.7.Conclusion The prognosis of MPP patients is related to the phase sensitivity and dynamic remodeling of the inflammatory network.IL-6(T0),IL-6(T1),IL-6(△T2),IL-1β(△T3),IL-17A(△T3)are key prognostic indicators for MPP patients.Dy-namic monitoring of inflammatory factor levels can help intervene in immune imbalances and cytokine storms in a timely manner to improve the prognosis of pediatric patients.

Osteoarthritis(OA)is a common joint disease in clinical practice,and cartilage damage is a typical pathological change.The pathogenesis of OA is complex,and various adverse factors can lead to the occurrence of OA.Mitochondria are im-portant organelles within cells and play important roles in cellular physiological and pathological activ-ities.Mitochondrial quality control is an important regulatory mechanism in the body to maintain nor-mal mitochondrial structure and function,mainly including mitochondrial biogenesis,mitochondrial dynamics,mitochondrial autophagy,mitochondrial oxidative stress,and other forms.The imbalance of mitochondrial quality control in chondrocytes is closely related to the occurrence and development of osteoarthritis,and regulating the balance of mi-tochondrial quality control is a potential therapeu-tic point for osteoarthritis.The author reviewed rel-evant research literature in recent years to provide a review of the relationship between mitochondrial quality control and the occurrence and develop-ment of osteoarthritis,in order to provide new ideas and directions for the research and diagnosis and treatment strategies of osteoarthritis.

Among tumor microenvironment (TME), the entire metabolic characteristics of tumor-resident cells are reprogrammed to benefit the expansion of tumor cells, which count on glutamine in large part to fuel the tricarboxylic acid cycle for energy generation and anabolic metabolism support. Endothelial cells that are abducted by tumor cells to form a pathological tumor vascular network for constructing the hypoxic immunosuppressive TME, also rely on glutaminolysis as the "engine" of angiogenesis. Additionally, the glutamine metabolic preference benefits the polarization of TAMs towards pro-tumoral M2 phenotype as well. Herein, we developed a type of siRNA micelleplexes (MH@siGLS1) to reverse immunosuppressive TME by targeting glutaminolysis within tumor-resident cells for tumor vasculature normalization- and TAMs repolarization-enhanced photo-immunotherapy. Tumor cell starvation and antioxidant system destruction achieved by MH@siGLS1-mediated glutaminolysis inhibition could promote photodynamic therapy efficacy, which was available to trigger immunogenic cell death for adaptive antitumor immune responses. Meanwhile, glutaminolysis inhibition of tumor endothelial cells and TAMs could realize tumor vascular normalization and TAMs repolarization for antitumor immunity amplification. This study provides a unique perspective on cancer treatments by focusing on the interrelations of metabolic characteristics and the biofunctions of various cell types within TME.