Objective To analyze the risk factors for poor prognosis in young and middle-aged patients with acute myocardial infarction (AMI), and to construct a prediction model for poor prognosis based on risk factors. Methods A total of 326 young and middle-aged patients with AMI admitted to Chengdu Third People's Hospital were selected between March 2023 and June 2025, and were followed up for 6 months after discharge. Based on their prognosis status, these patients were divided into a poor prognosis group (n=40) and a good prognosis group (n=286). Clinical data were collected. Univariate and multivariate logistic regression analyses were conducted to identify risk factors for poor prognosis, and a prediction model was constructed. The predictive performance of the model was evaluated using the receiver operating characteristic (ROC) curve. Results Compared with the good prognosis group, the poor prognosis group exhibited a higher proportion of hypertension, higher Global Registry of Acute Coronary Events (GRACE) scores, elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, and higher neutrophil-to-lymphocyte ratios (NLR), whereas the left ventricular ejection fraction (LVEF) was lower (P<0.05). Logistic regression analysis indicated that a high GRACE score, elevated NT-proBNP and NLR levels, and low LVEF were risk factors for poor prognosis (P<0.05). Based on these risk factors, a model was constructed as logit(P)=-18.333 + 0.086 × GRACE score + 0.005 × NT-proBNP + 0.843 × NLR - 0.083 × LVEF. The ROC curve analysis found that the area under the curve of this model in predicting poor prognosis was 0.967, which was higher than that of any single indicator used alone for prediction (z=4.431, 3.712, 3.705, 5.329, P<0.05). Conclusion GRACE score, NT-proBNP level, NLR and LVEF are risk factors influencing poor prognosis in young and middle-aged patients with AMI. The prediction model based on these factors demonstrates good predictive performance.

Cancer-related fatigue(CRF)is an adverse symptom associated with cancer and its treatments,with a clinical inci-dence rate ranging from 60%to 90%,severely impacting patients'quality of life.The pathogenesis of CRF is complex,involving the interaction of multiple mechanisms such as inflammatory cytokine dysregulation,neuroendocrine disorders,and mitochondrial dysfunc-tion.Although existing clinical interventions like central nervous system stimulants and exercise interventions can partially alleviate symptoms,they are limited by side effects and applicability constraints.Traditional Chinese medicine(TCM)shows unique potential in the clinical treatment of CRF by exerting a variety of pharmacological effects.Therapeutic approaches including acupuncture,moxibus-tion,traditional Chinese herbal formulations,as well as Chinese herbal preparations and extracts,have been proven to significantly im-prove fatigue status in CRF patients.This article systematically reviews the internal relationship between the modern pathological mech-anism of CRF and the pathogenesis of"consumptive disease"of TCM,and conducts evidence-based evaluation of the existing TCM in-tervention programs,so as to provide a new theoretical basis and treatment strategy for the clinical prevention and treatment of CRF.

Dry eye disease (DED) is a prevalent and intractable ocular disease induced by a variety of causes. Elevated sphingomyelin (SM) levels and pro-inflammatory cytokines were detected on the ocular surface of DED patients, particularly in the meibomian glands. Sphingomyelin synthase 2 (SMS2), one of the proteins involved in SM synthesis, would light a novel way of developing a DED therapy strategy. Herein, we report the design and optimization of a series of novel thiophene carboxamide derivatives to afford 14l with an improved highly potent inhibitory activity on SM synthesis (IC_{50, SMS2} = 28 nmol/L). Moreover, 14l exhibited a notable protective effect of anti-inflammation and anti-apoptosis on human corneal epithelial cells (HCEC) under TNF-α-hyperosmotic stress conditions in vitro, with an acceptable ocular specific distribution (corneas and meibomian glands) and pharmacokinetics (PK) profiles (t _{1/2, cornea} = 1.11 h; t _{1/2, meibomian glands} = 4.32 h) in rats. Furthermore, 14l alleviated the dry eye symptoms including corneal fluorescein staining scores and tear secretion in a dose-dependent manner in mice. Mechanically, 14l reduced the mRNA expression of Tnf-α, Il-1β and Mmp-9 in corneas, as well as the proportion of very long chain SM in meibomian glands. Our findings provide a new strategy for DED therapy based on selective SMS2 inhibitors.

Cancer-related fatigue(CRF)is an adverse symptom associated with cancer and its treatments,with a clinical inci-dence rate ranging from 60%to 90%,severely impacting patients'quality of life.The pathogenesis of CRF is complex,involving the interaction of multiple mechanisms such as inflammatory cytokine dysregulation,neuroendocrine disorders,and mitochondrial dysfunc-tion.Although existing clinical interventions like central nervous system stimulants and exercise interventions can partially alleviate symptoms,they are limited by side effects and applicability constraints.Traditional Chinese medicine(TCM)shows unique potential in the clinical treatment of CRF by exerting a variety of pharmacological effects.Therapeutic approaches including acupuncture,moxibus-tion,traditional Chinese herbal formulations,as well as Chinese herbal preparations and extracts,have been proven to significantly im-prove fatigue status in CRF patients.This article systematically reviews the internal relationship between the modern pathological mech-anism of CRF and the pathogenesis of"consumptive disease"of TCM,and conducts evidence-based evaluation of the existing TCM in-tervention programs,so as to provide a new theoretical basis and treatment strategy for the clinical prevention and treatment of CRF.

Objective To investigate the effect and mechanism of Nuanxinkang on plaque formation in obstructive sleep apnea-hypopnea syndrome(OSAHS)comorbid with atherosclerosis(AS)mice by inhibiting endothelial-to-mesenchymal transition(EndMT).Methods Male ApoE-/-mice were randomly divided into six groups:control group,model group,atorvastatin group(2.6 mg·kg-1)and Nuanxinkang low-,medium-and high-dose groups(crude drug 3.5,7.0,14.0 g·kg-1),with eight mice in each group.The mice were exposed to chronic intermittent hypoxia(CIH)environment during sleep for a long time,and fed with high-fat diet to replicate OSAHS comorbid with AS mouse model.Oil red O staining was used to observe the formation of plaque on aortic intima in mice.Masson trichrome staining was used to evaluate the collagen content of atherosclerotic plaques in the aortic root of mice.The expressions of endothelial cell marker CD31 and EndMT marker Vimentin in aortic plaque were detected by immunofluorescence.Blood lipid levels were determined by ELISA;the mRNA expression levels of EndMT markers α-SMA and Cdh2 in aortic tissue were detected by qPCR.Results Compared with the control group,the area of aortic atherosclerotic plaque in the model group was significantly increased(P＜0.01),and the area of collagen deposition in the aortic root plaque was significantly increased(P＜0.01).The number of CD31 positive cells in the plaque were significantly decreased(P＜0.01),and the number of Vimentin positive cells were significantly increased(P＜0.01).Serum TG,T-CHO and LDL-C levels were significantly increased(P＜0.01),and HDL-C level was significantly decreased(P＜0.01).The mRNA expression levels of α-SMA and Cdh2 in aortic tissue were significantly increased(P＜0.01).Compared with the model group,the area of aortic atherosclerotic plaque in Nuanxinkang groups were significantly reduced(P＜0.05,P＜0.01),and the collagen deposition area of aortic root atherosclerotic plaque were significantly reduced(P＜0.05,P＜0.01).The number of CD31 positive expression cells in the plaque of Nuanxinkang high-dose group were significantly increased(P＜0.05),and the number of Vimentin positive expression cells in the plaque of Nuanxinkang medium-and high-dose groups were significantly decreased(P＜0.05,P＜0.01).The serum TG level of mice in the high-dose group of Nuanxinkang was significantly decreased(P＜0.01).The serum T-CHO and LDL-C levels of mice in each Nuanxinkang administration group were significantly decreased(P＜0.05,P＜0.01).The serum HDL-C levels of mice in the medium-and high-dose groups of Nuanxinkang were significantly increased(P＜0.01).The mRNA expression levels of α-SMA and Cdh2 in aortic tissue of mice in each treatment group were significantly decreased(P＜0.01).Conclusion Nuanxinkang can effectively reduce the plaque formation in OSAHS comorbid with atherosclerosis mice,which may be related to its inhibition of EndMT and reduction of collagen fiber formation.

Objective:pH low insertion peptide (pHLIP)-variant 7 (var7)-fluorescein isothiocyanate (FITC) was used to explore an accurate imaging tool that targeted burn wounds to better perform burn debridement.Methods:Twelve rat models of burn wound were established and pHLIP-var7-FITC with different concentrations (0.5, 1.5 and 2.0 mg/ml) were injected from the rat tail vein for in vivo fluorescence imaging. By determining the concentration of fluorescent conjugates to the burn wound, the scope of wound injury necrosis was judged by combining pathological sections, and its residue and toxicity in important organs such as heart, liver, kidneys, and brain were detected. The Kruskal-Wallis rank sum test, Bonferroni correction method and one-way analysis of variance were used for data analysis. Results:Within 24 h, the fluorescence photons per unit area of the burn wound in the group of 0.5 mg/ml, 1.5 mg/ml and 2.0 mg/ml were 1.49(1.31, 1.65), 2.46(1.88, 2.68), 2.77 (1.94, 3.10)×10 7 p·s -1·cm -2·Sr -1, with significant differences in the overall distribution of fluorescence photons ( H=73.55, P<0.001). The fluorescence intensity was stronger in the group with higher concentration, but with no significant difference in the number of fluorescence photons between the group of 1.5 mg/ml and 2.0 mg/ml ( P=0.263, Bonferroni correction method). At 14 time points (0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 7.0, 8.0, 12, 24 h), there was no significant difference in the overall mean of fluorescence photons ( F=1.04, P=0.419), and the tissue with burn necrosis seen in tissue sections was highly consistent with the fluorescence imaging region. There was no obvious fluorescence residue in the heart, liver, kidney and brain sections. Conclusion:In superficial second-degree burn tissue, pHLIP-var7-FITC can accurately target and gather on the burn wound within 24 h, showing a clear boundary between burn tissue and normal tissue, which can assist clinical surgical debridement to determine the extent of injury.

ObjectiveTo determine the characteristics， viral load and immunological status of HIV-infected persons and their spouses who became HIV-positive， and the reasons for HIV seroconversion in 55 HIV discordant couples in Dehong Dai and Jingpo Autonomous Prefecture （Dehong Prefecture）， Yunan Province. MethodsData on the 55 couples meeting the criteria of having a previously positive spouse were retrieved from the AIDS Integrated Prevention and Control Data Information System of the China Disease Control and Prevention Information System during 2015-2021. General socio-demographic information， age at diagnosis， exposure history， CD4⁺T lymphocyte count， and antiviral treatment were collected. Descriptive analysis and chi-square test were used to compare the distribution of pre-HIV-positive spouses and their HIV seroconverted spouses. ResultsA total of 55 spouses from HIV discordant couples had HIV seroconversion. Of them， 72.7% （40/55） of pre-HIV-positive spouses were husbands. The most recent CD4⁺T lymphocyte count in the pre-HIV-positive spouses was （328.31±246.27） cells·μL^-1 at the time of diagnosis of their seroconverted spouses， of which 36.3% （20/55） had a CD4⁺T lymphocyte count of less than 200 cells·μL^-1. Furthermore， of those pre-HIV-positive spouses with low CD4⁺T lymphocyte count， 45.0% （9/20） had an undetectable viral load， 15.0% （3/20） <400 copies·mL^-1， and 25.0%（5/20） ≥400 copies·mL^-1. Additionally， 16.4% （9/55） of the pre-HIV-positive spouses did not have a viral load test. The main reasons for HIV seroconversion among HIV-negative spouses in the discordant couples were poor condom use， poor compliance with antiviral therapy， and treatment discontinuation. ConclusionThe follow-up management of HIV discordant couples should be strengthened in Dehong Prefecture， especially the monitoring of viral load levels and immunological status of pre-HIV-positive spouses， to improve their compliance with antiviral therapy and reduce treatment discontinuation， which would effectively prevent and control HIV transmission between spouses.

ObjectiveTo investigate the demographic characteristics， high-risk behavior and first CD4⁺T cell（CD4 cell） counts among newly reported HIV-infected Burmese in Dehong Dai Jingpo Autonomous Prefecture （Dehong Prefecture） from 2019 to 2020. MethodsA cross-sectional survey was conducted among newly reported HIV-infected Burmese cases in Dehong Prefecture from 2019 to 2020 to collect related information and measure their first CD4 cell counts. ResultsAmong 1 228 HIV-infected Burmese cases， 846 （68.9%） were males and 382 （31.1%） were females； 445 （36.2%） were from Kachin， and 210（17.1%） were from Shan. Of them， 960 cases （78.2%） had participated in the first CD4 cell counts testing， and 405 cases （42.2%） had a first CD4 cell counts <350 cells·μL^-1. In the multivariable logistic regression analysis， age ≥30 years （adjusted OR=1.44， 95%CI： 1.07‒1.92） and history of illicit drug use in Myanmar （adjusted OR=0.41， 95%CI： 0.21‒0.79） were independently associated with first CD4 cell counts <350 cells·μL^-1. ConclusionThe first CD4 cell counts are generally low among newly reported HIV-infected Burmese in Dehong Prefecture， especially those aged ≥ 30 years and with a history of intravenous drug use in Myanmar. Therefore， early detection of HIV infection should be strengthened for timely intervention and treatment management among Burmese.

Objective:To investigate the effects of ribonucleic acid for injection Ⅱ, often called RNA Ⅱ for short, combined with chemotherapeutic drug cyclophosphamide (CTX) on the tumor inhibition and survival of sarcoma cell S180 tumor-bearing mice.Methods:The solid transplanted tumor mouse model of sarcoma cell S180 and peritoneal fluid tumor mouse model were established respectively. CTX (25 mg/kg, once for 2 days) alone or combined with low-dose (25 mg/kg, once a day) and medium-dose (50 mg/kg, once a day) RNA Ⅱ were injected intraperitoneally into solid transplanted tumor mice for 10 d. CTX (25 mg/kg, once for 2 days) alone, medium-dose (50 mg/kg, once a day) or high-dose (100 mg/kg, once a day) RNA Ⅱ alone or combined with CTX were injected intraperitoneally into peritoneal effusion tumor mice until all mice died. The two models were set up for modeling groups without drug treatment, 8 mice in each group. The body mass of solid transplanted tumor mice after administration was weighed, the tumor tissue in vivo was taken out and weighed after the mice were executed, and the tumor inhibition rate was calculated. The body mass of peritoneal effusion tumor mice after administration was weighed, the growth rate of body mass was calculated, the survival curve of each group was drawn, and the life extension rate was calculated.Results:(1) Solid transplanted tumor mice: the body mass of mice in each administration group was lower than that in the modeling group after administration. During the administration period, the tumor volume in the modeling group was much higher than that in each administration group. From the 8th day of administration, the tumor volume in vivo in the CTX group began to be larger compared with that in the two combined administration groups. After stopping the administration and killing the mice, the weighing showed that the tumor mass of each administration group was lower than that in the modeling group (all P < 0.01), the tumor mass of CTX + RNA Ⅱ low-dose group and CTX + RNA Ⅱ medium-dose group was lower than that of CTX group (all P < 0.05), and the tumor inhibition rate of the two groups was higher than that of CTX group (83.6%, 77.2% vs. 58.5%). (2) Peritoneal effusion tumor mice: after administration for 12 d, the body mass growth rate of mice in CTX group was increased rapidly and reached the highest, and the body mass growth rate of mice in the two combined administration groups was lower than that in other groups. The life prolongation rates of RNA Ⅱ high-dose group and CTX group were 48.2% and 53.2% respectively, which had the same effect on life prolongation. The life prolongation rate in RNA Ⅱ medium-dose group was 20.9%. The life prolongation rates of CTX + RNA Ⅱ medium-dose group and CTX + RNA Ⅱ high-dose group were 94.2% and 105.0% respectively. Conclusions:RNA Ⅱ combined with CTX can significantly prolong the survival time of sarcoma cell S180 tumor-bearing mice, increase the tumor inhibition rate and improve the quality of life of the mice. Both of them have a synergistic effect.

Leishmaniasis is a prevalent cause of death and animal morbidity in underdeveloped countries of endemic area. However, there is few vaccine and effective drugs. Antimicrobial peptides are involved in the innate immune response in many organisms and are being developed as novel drugs against parasitic infections. In the present study, we synthesized a 5-amino acid peptide REDLK, which mutated the C-terminus of Pseudomonas exotoxin, to identify its effect on the Leishmania tarentolae. Promastigotes were incubated with different concentration of REDLK peptide, and the viability of parasite was assessed using MTT and Trypan blue dye. Morphologic damage of Leishmania was analyzed by light and electron microscopy. Cellular apoptosis was observed using the annexin V-FITC/PI apoptosis detection kit, mitochondrial membrane potential assay kit and flow cytometry. Our results showed that Leishmania tarentolae was susceptible to REDLK in a dose-dependent manner, disrupt the surface membrane integrity and caused parasite apoptosis. In our study, we demonstrated the leishmanicidal activity of an antimicrobial peptide REDLK from Pseudomonas aeruginosa against Leishmania tarentolae in vitro and present a foundation for further research of anti-leishmanial drugs.