Diabetic macular edema(DME), a serious complication of diabetic retinopathy(DR), is a chronic condition caused by multiple factors. Throughout its progression, inflammatory factors and vascular endothelial growth factor(VEGF)play a critical role. Anti-VEGF drugs have shown significant effectiveness in the treatment of DME; however, some patients may experience persistent DME after injection or require frequent injections. Dexamethasone intravitreal implants(DEX implants)serve as a sustained-release implant characterized by a reasonable release profile and high bioavailability. They offer safe, effective, and prolonged anti-inflammatory effects, aiding in the repair of retinal barrier and reduction of exudation. To further enhance patients' visual quality, exploring the efficacy of DEX implants in combination with existing treatment regimens has great clinical significance. This review primarily discusses the research advancements in DEX implants, focusing on their pharmacological properties, indications for use, and their combination with existing drugs and treatment methods. It also evaluates the advantages and disadvantages of combination therapy or switching to DEX implants compared to current standard treatments, aiming to provide guidance for personalized treatment options for patients with DME.

ObjectiveTo clarify the anti-inflammatory and lung-protective effects of Yantiao prescription on lipopolysaccharide （LPS）-induced acute lung injury （ALI）， and to explore the impact of Yantiao prescription on the metabolic pathways of arachidonic acid （AA） in vivo. MethodsThirty male C57BL/6J mice were randomly divided into the following groups based on body weight： normal group， model group， dexamethasone group （2 mg·kg^-1）， low-dose Yantiao prescription group （18 g·kg^-1）， and high-dose Yantiao prescription group （36 g·kg^-1）， with 6 mice in each group. The ALI mouse model was established by intraperitoneal injection of LPS. The treatment groups received oral gavage once a day for 7 consecutive days， and serum and lung tissue were collected at the end of the experiment. The content of pro-inflammatory cytokines tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） in serum was detected by enzyme-linked immunosorbent assay （ELISA）. Hematoxylin-eosin （HE） staining was used to assess lung tissue pathology. The wet/dry weight ratio （W/D） and myeloperoxidase （MPO） activity in lung tissue were measured. The content of AA metabolites in serum and lung tissue was measured by liquid chromatography triple quadrupole-mass spectrometry （LC-MS/MS）. ResultsCompared with the conditions in the normal group， the content of serum pro-inflammatory cytokines TNF-α， IL-1β， and IL-6 in the model group was significantly increased （P<0.01）. The alveolar structure in mice was severely damaged， with markedly thickened alveolar walls and extensive inflammatory cell infiltration. The W/D ratio and MPO activity in lung tissue were significantly increased （P<0.01）. The content of AA metabolites， including prostaglandin D₂ （PGD₂）， prostaglandin E₂ （PGE₂）， 11（S）-hydroxy-eicosatetraenoic acid ［11（S）-HETE］， and 5-hydroxy-eicosatetraenoic acid （5-HETE） in serum and lung tissue was significantly increased （P<0.05）， while the content of 11，12-epoxyeicosatrienoic acid （11，12-EET） and 14，15-epoxyeicosatrienoic acid （14，15-EET） in serum was significantly decreased （P<0.01）. Compared with the results in the model group， the content of serum pro-inflammatory cytokines TNF-α， IL-1β， and IL-6 in the dexamethasone group， low-dose Yantiao prescription group， and high-dose Yantiao prescription group was significantly reduced （P<0.05）. Mild thickening of alveolar walls， scattered inflammatory cell infiltration， and relatively intact tissue structure with improved alveolar architecture were observed. The W/D ratio and MPO activity in lung tissue were significantly reduced （P<0.01）. The content of AA metabolites PGD₂， PGE₂， 11（S）-HETE， and 5-HETE in serum from the dexamethasone group was significantly decreased （P<0.05）， while the content of 14，15-EET in serum significantly increased （P<0.01）， and the content of 5-HETE in lung tissue significantly decreased （P<0.01）. In the low-dose and high-dose Yantiao prescription groups， the content of AA metabolites PGD₂， PGE₂， 11（S）-HETE， and 5-HETE in serum and lung tissue was significantly decreased （P<0.05）， while the content of 11，12-EET in both serum and lung tissue was significantly increased （P<0.05）. ConclusionYantiao prescription has significant protective effects against LPS-induced ALI， which are related to its regulation of AA metabolic pathways in vivo.

AIM: To compare the clinical outcomes of extended depth-of-focus intraocular lenses(EDOF IOLs)using either micromonovision implantation or mixed implantation of EDOF and diffractive bifocal IOLs.METHODS: This retrospective clinical trial included 130 patients(260 eyes), who were divided into two groups. Group RR comprised 70 patients(140 eyes)bilaterally implanted with ZXR00 IOLs(Tecnis ZXR00, where one target was -0.5 D to -0.75 D and the other was 0 to -0.25 D). Group RM comprised 60 patients(120 eyes)unilaterally implanted with both ZXR00 and ZMB00 IOLs(Tecnis ZMB00, 0 to -0.25 D). Postoperative outcomes were compared after 3 mo, including visual acuity, defocus curves, stereoacuity, modulation transfer functions(MTFs), higher-order aberrations, and Visual Function-14(VF-14)questionnaire responses.RESULTS: Group RR had superior bilateral intermediate vision, while the group RM had superior bilateral near vision(both P<0.05). Group RM also exhibited superior MTFs and reduced higher-order aberrations(both P<0.05). Stereoacuity and VF-14 questionnaire results showed no statistically significant difference between groups(P>0.05).CONCLUSION: The implantation of micromonovision has significantly improved near vision. IOLs and their collocation can be customized according to individual patient needs to achieve precise treatment and provide cataract patients with high-quality vision.

AIM: To compare the clinical outcomes of extended depth-of-focus intraocular lenses(EDOF IOLs)using either micromonovision implantation or mixed implantation of EDOF and diffractive bifocal IOLs.METHODS: This retrospective clinical trial included 130 patients(260 eyes), who were divided into two groups. Group RR comprised 70 patients(140 eyes)bilaterally implanted with ZXR00 IOLs(Tecnis ZXR00, where one target was -0.5 D to -0.75 D and the other was 0 to -0.25 D). Group RM comprised 60 patients(120 eyes)unilaterally implanted with both ZXR00 and ZMB00 IOLs(Tecnis ZMB00, 0 to -0.25 D). Postoperative outcomes were compared after 3 mo, including visual acuity, defocus curves, stereoacuity, modulation transfer functions(MTFs), higher-order aberrations, and Visual Function-14(VF-14)questionnaire responses.RESULTS: Group RR had superior bilateral intermediate vision, while the group RM had superior bilateral near vision(both P<0.05). Group RM also exhibited superior MTFs and reduced higher-order aberrations(both P<0.05). Stereoacuity and VF-14 questionnaire results showed no statistically significant difference between groups(P>0.05).CONCLUSION: The implantation of micromonovision has significantly improved near vision. IOLs and their collocation can be customized according to individual patient needs to achieve precise treatment and provide cataract patients with high-quality vision.

Transmembrane proteins (TMEM) are a type of membrane protein. Most proteins in this family are located in the phospholipid bilayer of the cell membrane, while a smaller portion is found in the membranes of cellular organelles. Transmembrane protein 43 (TMEM43) is a member of the TMEM protein family and is encoded by the TMEM43 gene. This protein consists of 400 amino acids and has 4 transmembrane domains and 1 membrane-associated domain. TMEM43 is localized to various biological membranes within the cell, such as the cell membrane and nuclear membrane, where it forms transmembrane channels for various ions. Additionally, TMEM43 is expressed in many species, showing high genetic similarity, especially with the four transmembrane domains being highly conserved. Current studies on the TMEM43 gene are still in its early stages, mainly focusing on its association with arrhythmogenic right ventricular cardiomyopathy (ARVC) and cancer. However, recent studies suggest that pathogenic mutations in TMEM43 may cause auditory neuropathy spectrum disorder (ANSD). Patients with TMEM43 p.Ser372Ter exhibited late-onset progressive ANSD. Impact of TMEM43 pathogenic mutations on individual hearing was likely mediated through effects on gap junction (GJ) structures on glia-like supporting cells (GLS), cell membranes. The TMEM43 p.Arg372Ter pathogenic mutation primarily affected the structure and function of TMEM43 protein, leading to premature termination of protein translation and the production of a truncated protein. Abnormal TMEM43 protein significantly reduced K⁺ influx in GLS cells, disrupting the endolymphatic K⁺ circulation and cochlear microenvironment homeostasis. When K⁺ circulation was obstructed, the endocochlear potential (EP) became abnormal, impairing the physiological function of hair cells and potentially leading to hearing impairment. However, it is important to note that studies on the mechanism is limited, and more experimental evidence is needed to confirm this hypothesis. Currently, there is a significant gap in research on TMEM43 and hearing loss, with many issues remaining unresolved. While TMEM43 has been studied in relation to hearing loss in humans, zebrafish, mice, and rats, the research is still preliminary. Detailed investigations into the molecular pathogenic mechanisms, the impact of mutations on hearing damage, and related therapeutic strategies are needed. Additionally, as a newly identified hearing loss-related gene, the mutation frequency and incidence of hearing disorders associated with TMEM43 have not been effectively quantified. For example, the ClinVar database listed 829 mutation sites for the TMEM43 gene, with only three mutations related to auditory neuropathy: c.605A>T (p.Asn202Ile), c.889T>A (p.Phe297Ile), and c.1114C>T (p.Arg372Ter). Aside from the aforementioned TMEM43 c.1114C>T (p.Arg372Ter) mutation observed in patients, the other two mutations were experimentally induced and have not been found in patients. Consequently, these mutations have been classified as unknown significance. We reviewed the current understanding of TMEM43 and hearing loss, analyzed its role in ear development and sound conduction, and explored the impact of TMEM43 gene variations on hearing loss, aiming to provide new insights for future research and precision medicine related to TMEM43.

Background Polystyrene microplastics (PS-MPs) attract widespread public attention due to their adverse effects on mammalian reproductive systems. However, it is currently unclear whether ferroptosis is related to testicular damage and decreased sperm quality in mice exposed to PS-MPs. Objective To clarify the reproductive damage in male mice exposed to PS-MPs and investigate the mechanism of ferroptotic effects. Methods Five-week-old male BALB/c mice were randomly divided into four experimental groups, including one control group and three PS-MPs groups at low dose (0.5 mg·kg⁻¹), medium dose (5 mg·kg⁻¹), and high dose (50 mg·kg⁻¹), respectively, with 6 mice in each group. The treatment was delivered by gavage for 35 consecutive days (one time per day). After the mice were neutralized, the wet weights of testis and epididymis were measured, and organ coefficients were then calculated. Sperm was counted by hematimetry, and sperm motility and adenosine triphosphate (ATP) level were evaluated using CCK-8 and CellTiter Glo ® Kit 2.0 Assay respectively. In addition, serum testosterone, follicle-stimulating hormone, and luteinizing hormone were determined using ELISA kit, total testicular iron content was measured using tissue iron kit, and pathological changes in testicular tissue were observed after hematoxylin-eosin (HE) staining. We also used glutathione (GSH), malondialdehyde (MDA), and superoxide dismutase (SOD) assays to examine their changes to better understand the physiological status of testicular tissue. Finally, the expression levels of ferroptosis-associated proteins glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) were detected by Western blotting. Results Compared with the control group, the testicular index in the high dose group decreased, and the epididymal index decreased in all dose groups (P<0.05). The results of sperm quality analysis showed that the sperm count in each dose group was lower than that of the control group; the sperm motility decreased, sperm malformation rate increased, and ATP level in sperm decreased in the medium and high dose groups. The results of HE staining showed that the spermatogenic epithelium was disordered and the arrangement of spermatogenic cells were loose in the low dose group, the spermatogenic gap was enlarged in the middle dose group, and the cells in the high dose group were vacuolated and even azoospermic. The results of serum sex hormone levels showed that the serum testosterone levels decreased in each dose group, the serum follicle-stimulating hormone levels decreased in the medium and high dose groups, and the serum luteinizing hormone levels decreased in the high dose group (P<0.05). The iron content in the testicular tissue homogenate of the high dose group increased (P<0.05). The levels of GSH and SOD in the homogenate of testicular tissue decreased in the medium and high dose groups, while the levels of MDA increased (P<0.05). The results of Western blotting showed that the protein expression level of GPX4 in the testis in the high dose group was lower than that in the control group. The protein expression levels of SLC7A11 in the medium and high dose groups were lower than that in the control group. The results of correlation analysis showed that the expression level of GPX4 was positively correlated with sperm count, and negatively correlated with MDA level (P<0.05). SLC7A11 expression level was positively correlated with sperm count, and negatively correlated with sperm malformation rate and MDA level (P<0.05). Conclusion PS-MPs exposure leads to decreased sperm quality, testicular damage, and decreased serum sex hormone levels in male mice, and its mechanism of action may involve ferroptosis.

Intraoperative cell salvage (IOCS) has been widely applied as an important blood conservation measure in surgical operations. However, there is currently a lack of clinical practice guidelines for the implementation of IOCS in patients with malignant tumors. This report aims to provide clinicians with recommendations on the use of IOCS in patients with malignant tumors based on the review and assessment of the existed evidence. Data were derived from databases such as PubMed, Embase, the Cochrane Library and Wanfang. The guideline development team formulated recommendations based on the quality of evidence, balance of benefits and harms, patient preferences, and health economic assessments. This study constructed seven major clinical questions. The main conclusions of this guideline are as follows: 1) Compared with no perioperative allogeneic blood transfusion (NPABT), perioperative allogeneic blood transfusion (PABT) leads to a more unfavorable prognosis in cancer patients (Recommended); 2) Compared with the transfusion of allogeneic blood or no transfusion, IOCS does not lead to a more unfavorable prognosis in cancer patients (Recommended); 3) The implementation of IOCS in cancer patients is economically feasible (Recommended); 4) Leukocyte depletion filters (LDF) should be used when implementing IOCS in cancer patients (Strongly Recommended); 5) Irradiation treatment of autologous blood to be reinfused can be used when implementing IOCS in cancer patients (Recommended); 6) A careful assessment of the condition of cancer patients (meeting indications and excluding contraindications) should be conducted before implementing IOCS (Strongly Recommended); 7) Informed consent from cancer patients should be obtained when implementing IOCS, with a thorough pre-assessment of the patient's condition and the likelihood of blood loss, adherence to standardized internally audited management procedures, meeting corresponding conditions, and obtaining corresponding qualifications (Recommended). In brief, current evidence indicates that IOCS can be implemented for some malignant tumor patients who need allogeneic blood transfusion after physician full evaluation, and LDF or irradiation should be used during the implementation process.

[Objective] To analyze the prevalence of human T-lymphocyte leukemia virus (HTLV) among blood donors in Guangzhou from 2016 to 2021, and provide a basis for blood collection and supply management in this region. [Methods] A total of 2 116 951 voluntary blood donors were screened for anti-HTLV by enzyme-linked immunosorbent assay (ELISA) from March 2016 to December 2021 in Guangzhou, and the reactive cases were further confirmed by Western blotting (WB). Qualitative data were analyzed by χ2 with spss19 software. The trend of the total positive rate of HTLV confirmation test by WB from 2016 to 2021 was analyzed with the Joinpoint software, and the annual percent change (APC) was used to determine whether the trend changes were statistically significant. [Results] From March 2016 to December 2021, the total positive rate for anti-HTLV by ELISA among voluntary blood donors in Guangzhou was 0.019 7% (416/ 2116 951), and the WB confirmed positive rate was 0.001 1% (23/2 116 951). The total positive rate of HTLV among individual voluntary blood donors in the six main districts (0.002 12%, 19/895 301) was higher than that among group voluntary blood donors (0.000 32%, 3/951 947) (P<0.05). There was no significant difference in the total positive rate of HTLV confirmation between the six main districts (0.001 19%) and the three non-main districts (0.000 37%) (P>0.05). The trend of the total positive rate of HTLV infection in the six main districts and the Guangzhou area(including the six main districts and three non-main districts) showed no significant increase or decrease. [Conclusion] The prevalence of HTLV among blood donors in Guangzhou remains at a low level.

Background: and Purpose This study aimed to investigate the association between residual inflammatory risk (RIR) and vulnerable plaques using high-resolution magnetic resonance imaging (HRMRI) in symptomatic intracranial atherosclerotic stenosis (ICAS). Methods: This retrospective study included 70%–99% symptomatic ICAS patients hospitalized from January 2016 to December 2022. Patients were classified into four groups based on high-sensitivity C-reactive protein (hs-CRP) and low-density lipoprotein cholesterol (LDL-C): residual cholesterol inflammatory risk (RCIR, hs-CRP ≥3 mg/L and LDL-C ≥2.6 mmol/L), RIR (hs-CRP ≥3 mg/L and LDL-C <2.6 mmol/L), residual cholesterol risk (RCR, hs-CRP <3 mg/L and LDL-C ≥2.6 mmol/L), and no residual risk (NRR, hs-CRP <3 mg/L and LDL-C <2.6 mmol/L). Vulnerable plaque features on HRMRI included positive remodeling, diffuse distribution, intraplaque hemorrhage, and strong enhancement. Results: Among 336 included patients, 21, 60, 58, and 197 were assigned to the RCIR, RIR, RCR, and NRR groups, respectively. Patients with RCIR (adjusted odds ratio [aOR], 3.606; 95% confidence interval [CI], 1.346–9.662; P=0.011) and RIR (aOR, 3.361; 95% CI, 1.774–6.368, P<0.001) had higher risks of strong enhancement than those with NRR. Additionally, patients with RCIR (aOR, 2.965; 95% CI, 1.060–8.297; P=0.038) were more likely to have intraplaque hemorrhage compared with those with NRR. In the sensitivity analysis, RCR (aOR, 2.595; 95% CI, 1.201–5.608; P=0.015) exhibited an additional correlation with an increased risk of intraplaque hemorrhage. Conclusion In patients with symptomatic ICAS, RIR is associated with a higher risk of intraplaque hemorrhage and strong enhancement, indicating an increased vulnerability to atherosclerotic plaques.

19 cinnamamide/ester-triazole compounds were designed, synthesized and evaluated for their anti-Alzheimer's disease (AD) activity. Among them, compound 4f displayed excellent anti-β-amyloid protein (Aβ)-mediated cytotoxicity (EC₅₀ = 2.03 ± 2.45 μmol·L^-1) in APPswe cells and acetylcholinesterase inhibiton (IC₅₀ = 4.88 ± 4.70 μmol·L^-1). Further study indicated that, at dosages of (1, 5 and 25 mg·kg^-1), compound 4f was effective in improving spatial learning and memory deficits in Aβ_1-42-impaired mice, which was achieved by promoting the nonamyloidogenic signaling and inhibiting the amyloidogenic pathway, along with the suppression of Aβ-induced Tau phosphorylation. All animal experiments in this study were approved by the Experimental Animal Care and Use Committee of the Institute of Medicinal Biotechnology (IMB-20220908D701). In conclusion, compound 4f holds promise as a lead candidate for AD treatment, and the present study lays the foundation for its subsequent development.