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.

AIM: To analyze the clinical outcomes of cyclosporine combined with lacrimal plug in the treatment of dry eye in patients with primary Sjögren's syndrome.METHODS: The clinical data of 60 patients(120 eyes)who were admitted to the ophthalmology department and rheumatology and immunology department of Baoding No.1 Central Hospital and were diagonosed with siogren's syndrome dry eye after multidisciplinary consultation from June 2022 to September 2023 were retrospectively analyzed. All the patients received regular treatment of primary Sjögren's syndrome, and they were divided into three groups according to treatment methods: A, B and C, with 20 cases(40 eyes)in each group. The group A received 0.3% sodium hyaluronate eyedrops, the group B received 0.3% sodium hyaluronate eyedrops plus 0.05% cyclosporine eyedrops, and the group C received 0.3% sodium hyaluronate eyedrops plus 0.05% cyclosporine eyedrops combined with binocular lacrimal plugs. The ocular surface disease index(OSDI)score, conjunctival hyperemia score, tear film breakup time(BUT), tear meniscus height(TMH), corneal fluorescein staining(FL)score and tear secretion of the three groups of patients were compared before and at 4, 8 and 12 wk after treatment. The contents of inflammatory factors such as interleukin-6(IL-6), tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)in tears were detected before and at 12 wk after treatment.RESULTS: At 4, 8 and 12 wk after treatment, the scores of OSDI, conjunctival hyperemia score and FL in the three groups of patients were lower than those before treatment, and the BUT, TMH and tear secretion were higher than those before treatment(all P<0.001). The OSDI score of the group C was lower than that of the group A and B, and the group B was lower than the group A(all P<0.001). The BUT, TMH and tear secretion of the group C were higher than those of the group A and B, with the group B higher than the group A(all P<0.001). At 12 wk after treatment, the levels of IL-6, TNF-α and IL-1β in the tears of the three groups of patients were lower than those before treatment, with the group C lower than the group A and B, and the group B lower than the group A(all P<0.001). There was no statistical significant difference in the incidence of adverse reactions among the three groups of patients(P>0.05).CONCLUSION: The combined use of cyclosporine and lacrimal plug is safe and effective in improving the clinical symptoms of patients with moderate and severe dry eye, promoting the function of tear film and cornea, increasing tears secretion, and reducing the level of tear inflammatory factors.

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.

ObjectiveTo study the mechanism of Huanglian Jiedutang （HLJDT） in treating mice with atherosclerosis （AS） by improving ferroptosis. MethodsA total of 10 SPF C57BL/6J mice were selected as a normal group， and 50 ApoE^-/- mice were randomly divided into five groups： model group， low-dose group of HLJDT， medium-dose group of HLJDT， high-dose group of HLJDT， and atorvastatin （ATV） group. ApoE^-/- mice were fed a high-fat diet for eight weeks to establish the AS model， and at the 9th week， they were given normal saline， low， medium， and high doses of HLJDT （3.9， 7.8， 15.6 g·kg^-1·d^-1）， and atorvastatin calcium tablets （0.01 g·kg^-1·d^-1）， respectively， for a total of eight weeks. The formation of aortic plaque in mice was observed by gross oil red O staining and Masson staining. The levels of total cholesterol （TC）， low-density lipoprotein cholesterol （LDL-C）， triglyceride （TG）， and high-density lipoprotein cholesterol （HDL-C） in blood fat were measured by the automatic biochemical analyzer， and the mitochondrial structure of the aorta was observed by transmission electron microscopy. The content of serum superoxide dismutase （SOD） in serum was detected by enzyme-linked immunosorbent assay （ELISA）. The content of reduced glutathione （GSH） in serum was detected by the microplate method， and that of malondialdehyde （MDA） in serum was detected by the TBA method. The protein expression of nuclear factor E₂-associated factor 2 （Nrf2）/glutathione peroxidase 4 （GPX4） signaling pathway was detected by Western blot. ResultsCompared with those of the normal group， the contents of TC， LDL-C， TG， HDL-C， and MDA in the serum and the aortic vascular plaque deposition of the model group were significantly increased （P<0.01）， while the expression levels of SOD and GSH in serum， as well as Nrf2， solute carrier family 7 member 11 （SLC7A11）， and GPX4 in aorta were significantly decreased （P<0.01）. Mice in the model group appeared mitochondrial fragmentation and vacuolation in the aorta， volume atrophy， mitochondrial crista reduction， or a loose and disorganized form. Compared with those in the model group， the aortic vascular plaque deposition was significantly decreased in the low-dose， medium-dose， and high-dose groups of HLJDT and ATV group， and the contents of serum TC， LDL-C， TG， and MDA in serum were significantly decreased （P<0.05， P<0.01）. The contents of serum SOD and GSH and the expression levels of Nrf2， SLC7A11， and GPX4 in the aorta were increased （P<0.05， P<0.01）， and the symptoms of aortic mitochondrial vacuolation were alleviated. The number of cristae was increased， and they were ordered neatly. ConclusionHLJDT can reduce aortic vascular plaque deposition， decrease blood lipid and MDA expression， increase SOD and GSH expression， and ameliorate the pathological changes of ferroptosis， the mechanism of which is related to the Nrf2/GPX4 signaling pathway.

The European Society of Cardiology (ESC) released the "2024 ESC guidelines for the management of elevated blood pressure and hypertension" on August 30, 2024. This guideline updates the 2018 "Guidelines for the management of arterial hypertension." One notable update is the introduction of the concept of "elevated blood pressure" (120-139/70-89 mm Hg). Additionally, a new systolic blood pressure target range of 120-129 mm Hg has been proposed for most patients receiving antihypertensive treatment. The guideline also includes numerous additions or revisions in areas such as non-pharmacological interventions and device-based treatments for hypertension. This article interprets the guideline's recommendations on definition and classification of elevated blood pressure and hypertension, and cardiovascular disease risk assessment, diagnosing hypertension and investigating underlying causes, preventing and treating elevated blood pressure and hypertension. We provide a comparison interpretation with the 2018 "Guidelines for the management of arterial hypertension" and the "2017 ACC/AHA guideline on the prevention, detection, evaluation, and management of high blood pressure in adults."

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.

ObjectiveTo establish a rapid analytical method for identifying the differential components in Poria cocos medicinal materials based on ultra performance liquid chromatography-quadrupole-electrostatic field orbital trap high-resolution mass spectrometry（UPLC-Q-Orbitrap-MS）， combined with mass defect filtering（MDF） and molecular network integration techniques. MethodsUPLC-Q-Orbitrap-MS was used for MS data acquisition and identification of P. cocos medicinal materials， with the help of MDF for the study of cleavage behavior and structural identification of triterpenoids. According to the similarity of MS/MS fragmentation patterns of each component， global natural product social molecular network（GNPS） was established， and Cytoscape 3.6.1 was used to screen molecular clusters with similar structures and the the structure of main compound classes were identified and confirmed. Multivariate statistical analyses such as principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） were used to screen the differential components of the five P. cocos medicinal materials with the variable importance in the projection（VIP） value>1 and P<0.05 as the criteria. ResultsA total of 66 compounds were identified by database comparison， 8 compounds were newly identified by MDF， 28 compounds were newly identified by GNPS， and a total of 102 chemical compounds were identified， including 43 triterpenoids， 16 saccharides， 26 amino acids and peptides， 3 nucleosides， and 14 other compounds. Triterpenoids were predominant in Poriae Cutis and wild Fushen， amino acids and peptides were the most abundant in Poria and cultivated Fushen， carbohydrates were the most abundant in Poriae Cutis. Type Ⅰ and Ⅱ triterpenoids had higher amounts in Poria and cultivated Fushen， type Ⅲ triterpenoids were more abundant in Poriae Cutis， all four types of triterpenoids were higher in Fushenmu， and type Ⅰ， Ⅱ， and Ⅳ triterpenoids were higher in wild Fushen. A total of 12 common differential chemical constituents were screened， including serine， guanosine， gallic acid， 2-octenal， maltotriose， trametenolic acid， dehydroeburicoic acid， dehydrotrametenolic acid， poricoic acid A， poricoic acid B， poricoic acid E and G， but the relative contents of them varied significantly among different medicinal materials. ConclusionAmong the five P. cocos medicinal materials， the types of constituents are generally similar， but their relative contents differed significantly among these medicinal materials， especially in the distribution of triterpenoids. The integration of UPLC-Q-Orbitrap-MS， MDF and GNPS can provide a reference for the rapid qualitative analysis of other Chinese medicines.

ObjectiveTo establish a rapid analytical method for identifying the differential components in Poria cocos medicinal materials based on ultra performance liquid chromatography-quadrupole-electrostatic field orbital trap high-resolution mass spectrometry（UPLC-Q-Orbitrap-MS）， combined with mass defect filtering（MDF） and molecular network integration techniques. MethodsUPLC-Q-Orbitrap-MS was used for MS data acquisition and identification of P. cocos medicinal materials， with the help of MDF for the study of cleavage behavior and structural identification of triterpenoids. According to the similarity of MS/MS fragmentation patterns of each component， global natural product social molecular network（GNPS） was established， and Cytoscape 3.6.1 was used to screen molecular clusters with similar structures and the the structure of main compound classes were identified and confirmed. Multivariate statistical analyses such as principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） were used to screen the differential components of the five P. cocos medicinal materials with the variable importance in the projection（VIP） value>1 and P<0.05 as the criteria. ResultsA total of 66 compounds were identified by database comparison， 8 compounds were newly identified by MDF， 28 compounds were newly identified by GNPS， and a total of 102 chemical compounds were identified， including 43 triterpenoids， 16 saccharides， 26 amino acids and peptides， 3 nucleosides， and 14 other compounds. Triterpenoids were predominant in Poriae Cutis and wild Fushen， amino acids and peptides were the most abundant in Poria and cultivated Fushen， carbohydrates were the most abundant in Poriae Cutis. Type Ⅰ and Ⅱ triterpenoids had higher amounts in Poria and cultivated Fushen， type Ⅲ triterpenoids were more abundant in Poriae Cutis， all four types of triterpenoids were higher in Fushenmu， and type Ⅰ， Ⅱ， and Ⅳ triterpenoids were higher in wild Fushen. A total of 12 common differential chemical constituents were screened， including serine， guanosine， gallic acid， 2-octenal， maltotriose， trametenolic acid， dehydroeburicoic acid， dehydrotrametenolic acid， poricoic acid A， poricoic acid B， poricoic acid E and G， but the relative contents of them varied significantly among different medicinal materials. ConclusionAmong the five P. cocos medicinal materials， the types of constituents are generally similar， but their relative contents differed significantly among these medicinal materials， especially in the distribution of triterpenoids. The integration of UPLC-Q-Orbitrap-MS， MDF and GNPS can provide a reference for the rapid qualitative analysis of other Chinese medicines.