Sepsis-acquired weakness (SAW) is a common complication in critically ill patients, yet significant gaps remain in both mechanistic understanding and therapeutic interventions for this condition. SAW not only prolongs the duration of mechanical ventilation and hospitalization but is also closely associated with increased mortality. Even if these SAW patients survive, they often experience long-term physical dysfunction after hospital discharge, leading to diminished quality of life. Emerging evidence suggests that sustained mitochondrial dysfunction may constitute a pivotal pathophysiological basis for the development and progression of SAW, primarily encompassing five key aspects: dysregulated mitochondrial quality control (MtQC), impaired oxidative phosphorylation (OXPHOS), exacerbated oxidative stress, disrupted Ca²⁺; homeostasis, and their mediation of diverse myofiber injuries. This article systematically elucidates the central role of mitochondrial dysfunction in the pathogenesis of SAW. Furthermore, we explore potential therapeutic strategies targeting mitochondrial function, including mitigating mitochondrial oxidative stress, optimizing nutritional support, and supplementing with muscle-derived mesenchymal stem cells. These insights provide a critical theoretical framework for understanding SAW mechanisms and developing clinical interventions, with particular emphasis on the translational value of mitochondrial-targeted therapies in improving outcomes for septic patients.
Humans ; Sepsis/metabolism* ; Mitochondria/metabolism* ; Muscle Weakness/etiology* ; Oxidative Stress ; Oxidative Phosphorylation

OBJECTIVE: CRISPR-Cas protects bacteria from exogenous DNA invasion and is associated with bacterial biofilm formation and pathogenicity. METHODS: We analyzed the type I-F CRISPR-Cas system of Legionella pneumophila WX48, including Cas1, Cas2-Cas3, Csy1, Csy2, Csy3, and Cas6f, along with downstream CRISPR arrays. We explored the effects of the CRISPR-Cas system on the in vitro growth, biofilm-forming ability, and pathogenicity of L. pneumophila through constructing gene deletion mutants. RESULTS: The type I-F CRISPR-Cas system did not affect the in vitro growth of wild-type or mutant strains. The biofilm formation and intracellular proliferation of the mutant strains were weaker than those of the wild type owing to the regulation of type IV pili and Dot/Icm type IV secretion systems. In particular, Cas6f deletion strongly inhibited these processes. CONCLUSION The type I-F CRISPR-Cas system may reduce biofilm formation and intracellular proliferation in L. pneumophila.
Legionella pneumophila/pathogenicity* ; CRISPR-Cas Systems ; Biofilms/growth & development* ; Phenotype ; Bacterial Proteins/metabolism* ; Gene Deletion

Endo-beta-N-acetylglucosaminidase (ENGase) is widely distributed in various organisms. The first reported ENGase activity was detected in Diplococcus pneumoniae in 1971. The protein (Endo D) was purified and its peptide sequence was determined in 1974. Three ENGases (Endo F1-F3) were discovered in Flavobacterium meningosepticum from 1982 to 1993. After that, the activity was detected from different species of bacteria, yeast, fungal, plant, mice, human, etc. Multiple ENGases were detected in some species, such as Arabidopsis thaliana and Trichoderma atroviride. The first preliminary crystallographic analysis of ENGase was conducted in 1994. But to date, only a few ENGases structures have been obtained, and the structure of human ENGase is still missing. The currently identified ENGases were distributed in the GH18 or GH85 families in Carbohydrate-Active enZyme (CAZy) database. GH18 ENGase only has hydrolytic activity, but GH85 ENGase has both hydrolytic and transglycosylation activity. Although ENGases of the two families have similar (β/α)8-TIM barrel structures, the active sites are slightly different. ENGase is an effective tool for glycan detection andglycan editing. Biochemically, ENGase can specifically hydrolyze β‑1,4 glycosidic bond between the twoN-acetylglucosamines (GlcNAc) on core pentasaccharide presented on glycopeptides and/or glycoproteins. Different ENGases may have different substrate specificity. The hydrolysis products are oligosaccharide chains and a GlcNAc or glycopeptides or glycoproteins with a GlcNAc. Conditionally, it can use the two products to produce a new glycopeptides or glycoprotein. Although ENGase is a common presentation in cell, its biological function remains unclear. Accumulated evidences demonstrated that ENGase is a none essential gene for living and a key regulator for differentiation. No ENGase gene was detected in the genomes of Saccharomyces cerevisiae and three other yeast species. Its expression was extremely low in lung. As glycoproteins are not produced by prokaryotic cells, a role for nutrition and/or microbial-host interaction was predicted for bacterium produced enzymes. In the embryonic lethality phenotype of the Ngly1-deficient mice can be partially rescued by Engase knockout, suggesting down regulation of Engase might be a solution for stress induced adaptation. Potential impacts of ENGase regulation on health and disease were presented. Rabeprazole, a drug used for stomach pain as a proton inhibitor, was identified as an inhibitor for ENGase. ENGases have been applied in vitro to produce antibodies with a designated glycan. The two step reactions were achieved by a pair of ENGase dominated for hydrolysis of substrate glycoprotein and synthesis of new glycoprotein with a free glycan of designed structure, respectively. In addition, ENGase was also been used in cell surface glycan editing. New application scenarios and new detection methods for glycobiological engineering are quickly opened up by the two functions of ENGase, especially in antibody remodeling and antibody drug conjugates. The discovery, distribution, structure property, enzymatic characteristics and recent researches in topical model organisms of ENGase were reviewed in this paper. Possible biological functions and mechanisms of ENGase, including differentiation, digestion of glycoproteins for nutrition and stress responding were hypothesised. In addition, the role of ENGase in glycan editing and synthetic biology was discussed. We hope this paper may provide insights for ENGase research and lay a solid foundation for applied and translational glycomics.

Defined as a common gynecologic en-docrine disease,endometriosis is characterized by the presence of endometrium outside of the uterus cavity,affecting about 10%to 15%of reproductive-aged women worldwide.Moreover,Asian women tend to have a nine-fold increased risk of endome-triosis compared with their white counterparts in Europe and the United States.Endometriosis not only causes chronic pelvic pain,dysmenorrhea,painful sex and other pain symptoms,but also leads to infertility,pushing the patients into a state of fatigue,high sensitivity and anxiety,thus reduc-ing their quality of life.As the aging of Chinese pop-ulation intensifies and the women's childbearing age delays,it is highly urgent to find solutions to those gynecological endocrine diseases such as en-dometriosis,which hamper women's fertility.In re-cent years,studies have shown that patients with endometriosis have abnormal serum lipid metabo-lism and an increased risk of cardiovascular diseas-es.At the same time,as a type of cholesterol-lower-ing drug,statins can inhibit the progression of en-dometriosis at the cellular and animal levels.Also,a few clinical studies have exhibited that statins ex-ert a positive effect on the treatment of endometri-osis.Therefore,this article aims to review the re-searches regarding the relationship between endo-metriosis and the cardiovascular disease,as well as the research progress of statin therapy on endome-triosis based on the level of cells,animals and hu-man beings.

Objective:To explore the clinical application value of pre-breathing mode in double-low imaging of 320-slices computed tomography(CT)for pulmonary artery.Methods:A total of 100 patients who underwent CT pulmonary angiography(CTPA)for suspected pulmonary embolism(PE)in Liuzhou People's Hospital from July 2021 to September 2022 were prospectively selected as the research subjects and they were randomly divided into observation group and control group,with 50 cases in each group.The patients of the control group adopted conventional breathing mode(the breathing password was activated after reaching the threshold,and the scan was triggered after 6 s),while the patients of the observation group adopted the pre-breathing mode(the breathing password was activated after 1 or 2 seconds,and the scan was triggered after reaching the threshold).Both two groups adopted double low-technique scan of 320 slices CT.The differences in delay time,radiation dose,the points of subjective and objective image quality,and other indicators were compared between the two groups.Results:The volume CT dose index(CTDIvol),dose length product(DLP),effective dose(ED)and delay time of the observation group were significantly lower than those of the control group(t=76.230,30.225,12.282,7.088,P<0.05),respectively.The comparison of the subjective points of image qualities between the two groups indicated that there were 25 cases with 5 points,23 cases with 4 points and 2 cases with 3 points in the observation group,and there were 21 cases with 5 points,26 cases with 4 points and 3 cases with 3 points in the control group.There was no significant difference in the averagely subjective points of image qualities between two groups(P>0.05).The signal-to-noise ratio(SNR)and signal to noise ratio(CNR)of the observation group were significantly lower than those of the control group,and the noise level(SD)of the observation group was significantly higher than that of the control group(t=25.441,23.886、11.426,P<0.05),respectively.The CT values of the artery trunk of right pulmonary,artery branch of right pulmonary,artery trunk of left pulmonary and artery branch of left pulmonary in the observation group were significantly higher than those in the control group(t=2.256,2.225,2.042,2.277,P<0.05),respectively.Conclusion:The pre-breathing mode can effectively improve CTPA image quality,and reduce radiation dose and the dosage of contrast agent,which clinical application effect is significant.It is worth learning.

Objective To observe the curative effect of comprehensive traditional Chinese medicine(TCM)therapy for the treatment of refractory sudden hearing loss(i.e.,suffering sudden hearing loss more than 2 weeks),and to analyze the factors that may affect the prognosis.Methods A retrospective analysis was carried out in 405 hospitalized patients with refractory sudden hearing loss who were treated in the Department of Otorhinolaryngology,the First Affiliated Hospital of Guangzhou University of Chinese Medicine from 2005 to 2022.The patients were all treated by comprehensive TCM therapy including oral administration of Chinese medicine,acupuncture,acupoint seed-pressing application after individualized syndrome differentiation.The overall clinical efficacy was evaluated,and the difference of efficacy in the patients with various courses of disease,degrees of deafness,types of hearing curve,concomitant symptoms and TCM syndrome types,having or not having previous treatment history was analyzed.Results For the 405 patients with refractory sudden hearing loss,the cure rate was 5.7％and the total effective rate was 28.1％.Among the 405 patients,the best efficacy was achieved in the patients with mild hearing loss,low-frequency decline type of hearing curve,and having no previous treatment history,and the differences were statistically significant(P＜0.05 or P＜0.01).There was no significant difference in the efficacy of patients with different courses of disease,with or without concomitant symptoms,or with various syndrome types(P＞0.05).Conclusion The comprehensive TCM therapy has a certain effect on refractory sudden hearing loss.Patients with poor efficacy after conventional western medicine can still benefit from the comprehensive TCM therapy.

Objective To investigate the clinical efficacy of standardized comprehensive pure traditional Chinese medicine(TCM)treatment for short-course sudden deafness and to explore the influencing factors of clinical efficacy.Methods The clinical data of 516 short-course sudden deafness inpatients(TCM group)who were given standardized comprehensive pure TCM treatment were retrospectively analyzed,and their efficacy were compared with the efficacy of 1 024 cases in the Chinese multicenter clinical study of sudden deafness(western medicine group).The analysis was carried out for the influence of the gender,left or right ear,age group,degree of deafness,type of hearing curve,concomitant symptoms(tinnitus,vertigo,and dullness of the ear),and the TCM syndrome types on the efficacy.Results(1)The comparison of baseline data showed that in comparison with the western medicine group,TCM group had relatively low proportion of low-frequency descending type while relatively high proportion of total deafness type,and had relatively high treatment difficulty.The course of treatment in TCM group was shortened by nearly 2/3 in comparison with the western medicine group(12.60 days vs 30 days).(2)Among the 516 patients of the TCM group,175 cases were cured,121 cases were markedly effective,90 cases were effective and 130 cases were ineffective,and the total effective rate was 74.80%.Compared with the 1 024 cases in the western medicine group,there was no significant difference in the overall efficacy or the efficacy evaluated with the hearing curve classification(P＞0.05).(3)Analysis of influencing factors of curative effect showed that the type of hearing curve was closely related to the curative effect of sudden deafness(P＜0.001).The curative effect of low frequency descent type was the best,and the curative effect of total deafness type was the worst.The cure of deafness was correlated with the degree of deafness,the milder the degree of deafness,the greater the likelihood of recovery(P＜0.001).The curative effect of the patients without vertigo was superior to that of the patients with vertigo(P＜0.001).The curative effect of adolescent patients was superior to that of middle-aged and elderly patients(P＜0.05).There was no correlation between TCM syndrome types and curative effect(P＞0.05).Conclusion Standardized comprehensive pure TCM treatment exerts certain curative effect on short-course sudden deafness,and may have some advantages compared with conventional western medicine treatment.The type of hearing curve,degree of deafness,accompanied by vertigo or not,and age group are the influencing factors of the efficacy.

Professor ZHOU Peng has deeply discussed the pathological characteristics of psoriasis vulgaris,emphasizing that the disease is usually manifested deficiency interweaved with excess,leading to frequent recurrence and persistent refractory,which may lead to psychological and emotional problems of patients.This paper further expounds the effect of blood stasis on the pathogenesis,progression and prognosis of psoriasis,and puts forward a new method of combining Lingnan fire needling and filiform needling acupuncture technique to treat psoriasis vulgaris with blood stasis syndrome.Professor ZHOU Peng believes that the treatment principle of this disease is"regulating the mind first,rectifying blood as a base,syndrome differentiating and eliminating pathogenic factors",aiming at comprehensively considering the etiology and symptoms,in order to achieve more effective treatment results.Combined with the analysis of dermoscopic signs,it provides a possible improvement direction for the treatment of psoriasis vulgaris from a new perspective.

Hashimoto's thyroiditis(HT)is a common endocrine disease,which can be classified into the category of goiter disease in traditional Chinese medicine.Professor LIU Min believes that the pathogenesis of HT is closely related to the heart and gallbladder,and its pathogenesis is due to the gallbladder constraint failing to descend and the disturbance of pivot,together with insufficient heart-qi and the disharmony between the nutritive qi and the defensive qi.For the treatment of HT,the modified Chaihu Guizhi Decoction is often used,which is mainly composed of Bupleuri Radix,Cinnamomi Ramulus,Scutellariae Radix,Pinelliae Rhizoma Praeparatum,Ginseng Radix et Rhizoma Rubra,Glycyrrhizae Radix et Rhizoma Praeparata cum Melle,Jujubae Fructus,Paeoniae Radix Alba,Os Draconis,Ostreae Concha,and Zingiberis Rhizoma Recens.Chaihu Guizhi Decoction has the actions of soothing gallbladder and relieving depression,restoring the function of shaoyang pivot,regulating nutritive qi and the defensive qi,and benefiting heart spirit,which exactly accords with the HT's pathogenesis of gallbladder constraint failing to descend and insufficient heart-qi.In the clinical treatment of HT,the modification of the drugs should be performed according to the concurrent syndromes of the patients,and the dosage of the drugs should also be adjusted.In addition to drug treatment,the attention should also be addressed to the adjustment of patients'lifestyle and dietary habits and to the emotional counseling,thus to achieve significant effect.

Objective To explore the effect of targeted inhibition of miR-628-5p by long non-coding RNA(lncRNA)KCNQ1 overlapping transcript 1(KCNQ1OT1)on high glucose(HG)-induced retinal pigment epithelial cell injury.Meth-ods The real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)was performed to detect KCNQ1OT1 expression in serum and aqueous humor of patients with diabetic retinopathy(DR),type 2 diabetes mellitus(T2DM)and uveitis.Human retinal pigment epithelial cells(ARPE-19)were treated with different concentrations of glucose,and their KCNQ1OT1 expression was detected to determine the optimal glucose concentration.ARPE-19 cells were divided into the control(CON)group,HG group,HG+si-NC group,HG+si-KCNQ1OT1 group,HG+miR-NC group,HG+miR-628-5p group,HG+si-KCNQ1OT1+anti-miR-NC group,and HG+si-KCNQ1OT1+anti-miR-628-5p group.The expression levels of KCNQ1OT1 and miR-628-5p in cells were measured by RT-qPCR.The cell apoptosis was detected by flow cytometry.The malondialdehyde(MDA)level and superoxide dismutase(SOD)activity were detected by enzyme-linked immunosorbent assay.The expression level of cleaved Caspase-3 protein was measured by Western blot.The targeting relationship between KCNQ1OT1 and miR-628-5p was detected by dual-luciferase reporter assay.Results The expression levels of KCNQ1OT1 in serum and aqueous humor of DR patients were higher than those of T2DM patients and uveitis patients,and those of uve-itis patients were the lowest(all P＜0.05).Compared with the 0 mmol·L-1 glucose group,the expression levels of KC-NQ1OT1 in ARPE-19 cells in the 5 mmol·L-1 glucose group,15 mmol·L-1 glucose group,and 30 mmol·L-1 glucose group significantly increased,and those in the 30 mmol·L-1 glucose group were the highest(all P＜0.05);thus,30 mmol·L-1 glucose was selected for subsequent experiments.Compared with the CON group,the KCNQ1OT1 expres-sion,apoptosis rate,cleaved Caspase-3 protein expression,and MDA level in the HG group significantly increased,while the SOD activity and miR-628-5p significantly decreased(all P＜0.05).Compared with the HG+si-NC group,the KC-NQ1OT1 expression,apoptosis rate,cleaved Caspase-3 protein expression,and MDA level in the HG+si-KCNQ1OTl group significantly decreased,while the SOD activity significantly increased(all P＜0.05).Compared with the HG+miR-NC group,miR-628-5p and SOD activity in the HG+miR-628-5p group significantly increased,while the apoptosis rate,cleaved Caspase-3 protein expression,and MDA level significantly decreased(all P＜0.05).Compared with the HG+si-KCNQ1OT1+anti-miR-NC group,miR-628-5p and SOD activity in the HG+si-KCNQ1OT1+anti-miR-628-5p group significantly decreased,while the apoptosis rate,cleaved Caspase-3 protein expression,and MDA level significantly increased(all P＜0.05).Conclusion lncRNA KCNQ1OT1 can reduce the HG-induced apoptosis and oxidative damage of ARPE-19 cells by targeted inhibition of miR-628-5p.