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 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.

Background/Aims: Endoscopic radiofrequency ablation (ERFA) is a treatment option for superficial esophageal squamous cell neoplasia (ESCN), with a relatively low risk of stenosis; however, the long-term outcomes remain unclear. We aimed to compare the long-term outcomes of patients with widespread superficial ESCN who underwent endoscopic submucosal dissection (ESD) or ERFA. Methods: We retrospectively analyzed the clinical data of patients with superficial ESCN who underwent ESD or ERFA between January 2015 and December 2021. The primary outcome measure was recurrence-free survival. Results: Ninety-two and 33 patients with superficial ESCN underwent ESD and ERFA, respectively. The en bloc, R0, and curative resection rates for ESD were 100.0%, 90.2%, and 76.1%, respectively. At 12 months, the complete response rate was comparable between the two groups (94.6% vs 90.9%, p=0.748). During a median follow-up of 66 months, recurrence-free survival was significantly longer in the ESD group than in the ERFA group (p=0.004), while no significant differences in overall survival (p=0.845) and disease-specific survival (p=0.494) were observed.Preoperative diagnosis of intramucosal cancer (adjusted hazard ratio, 5.55; vs high-grade intraepithelial neoplasia) was an independent predictor of recurrence. Significantly fewer patients in the ERFA group experienced stenosis compare to ESD group (15.2% vs 38.0%, p=0.016). Conclusions The risk of recurrence was higher for ERFA than ESD for ESCN but overall survival was not affected. The risk of esophageal stenosis was significantly lower for patients who underwent ERFA.

Objective: To evaluate the feasibility of a V-shaped incision in the resection of a superficial parotid gland benign tumor by comparison with a modified Blair incision. To provide a basis for evaluating the clinical application value of the V-shaped incision. Methods: This study was reviewed and approved by the ethics committee, and informed consent was obtained from the patients. Data from 61 patients with a benign tumor on the superficial parotid gland who had surgery at People’s Hospital of Xinjiang Uygur Autonomous Region from September 2021 to September 2023 were collected and analyzed. The maximum diameter of the tumor included in the patient should not exceed 4 cm. The patients were divided into two groups based on the different surgical incisions: a V-shaped incision group (29 cases) and modified Blair incision group (32 cases). Several comparisons were made between the group: operation time; postoperative drainage volume; facial nerve function, pain, and complication in the operation area; and aesthetic effect of the surgical incision. The patients were followed up for 6 months. The 61 patients were further divided into groups based on the locations of the tumors: tumors around the earlobe and tumors in the lower pole of the parotid gland. Results: There were no significant differences in operation time, postoperative House-Brackmann grading system (HBGs) facial nerve function score, and visual analogue scale (VAS) pain score between the two groups (P>0.05). The postoperative drainage volume and Vancouver scar scale (VSS) score of the V-shaped incision group were higher than the modified Blair incision group (P<0.05). The incidence of great auricular nerve numbness was lower in the V-shaped incision group than the modified Blair incision group (P<0.05). The operation time of the V-shaped incision applied to excise the tumor around the earlobe was shorter than the modified Blair incision (P<0.05). Conclusion The V-shaped incision is a concealed facial incision, surgeons should be aware that some patients who receive this incision have a large amount of postoperative drainage and the retroauricular region is prone to scar hyperplasia.

Glaucoma is a group of optic nerve disorders characterized by progressive optic nerve atrophy and visual field defects, which can lead to irreversible blindness. Early diagnosis of glaucoma is essential for preventing visual loss. However, due to the absence of obvious early symptoms, the diagnosis of glaucoma remains challenging. Visual electrophysiological examinations, an objective approach for evaluating visual function, have the potential to be used in the early diagnosis of glaucoma. This review integrates the latest publications to introduce visual electrophysiological examination techniques, including electroretinography(ERG)and visual evoked potential(VEP). It also explores the mechanisms underlying these techniques and their application value in the early diagnosis of glaucoma. In addition, this review summarizes the advantages, limitations, and applicable scenarios of different visual electrophysiological techniques. Finally, the review provides an outlook on the development prospects of visual electrophysiological techniques in the early diagnosis of glaucoma. The findings of this review can assist clinicians in selecting appropriate diagnostic methods, promote the innovation and development of early visual electrophysiological diagnostic techniques for glaucoma, and contribute to reducing the risk of blindness caused by glaucoma.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Background/Aims: Endoscopic radiofrequency ablation (ERFA) is a treatment option for superficial esophageal squamous cell neoplasia (ESCN), with a relatively low risk of stenosis; however, the long-term outcomes remain unclear. We aimed to compare the long-term outcomes of patients with widespread superficial ESCN who underwent endoscopic submucosal dissection (ESD) or ERFA. Methods: We retrospectively analyzed the clinical data of patients with superficial ESCN who underwent ESD or ERFA between January 2015 and December 2021. The primary outcome measure was recurrence-free survival. Results: Ninety-two and 33 patients with superficial ESCN underwent ESD and ERFA, respectively. The en bloc, R0, and curative resection rates for ESD were 100.0%, 90.2%, and 76.1%, respectively. At 12 months, the complete response rate was comparable between the two groups (94.6% vs 90.9%, p=0.748). During a median follow-up of 66 months, recurrence-free survival was significantly longer in the ESD group than in the ERFA group (p=0.004), while no significant differences in overall survival (p=0.845) and disease-specific survival (p=0.494) were observed.Preoperative diagnosis of intramucosal cancer (adjusted hazard ratio, 5.55; vs high-grade intraepithelial neoplasia) was an independent predictor of recurrence. Significantly fewer patients in the ERFA group experienced stenosis compare to ESD group (15.2% vs 38.0%, p=0.016). Conclusions The risk of recurrence was higher for ERFA than ESD for ESCN but overall survival was not affected. The risk of esophageal stenosis was significantly lower for patients who underwent ERFA.

This study aims to explore the mechanism of lung and gut protection by Tanreqing Capsules on the mice infected with influenza virus based on "the lung-gut axis". A total of 110 C57BL/6J mice were randomized into control group, model group, oseltamivir group, and low-and high-dose Tanreqing Capsules groups. Ten mice in each group underwent body weight protection experiments, and the remaining 12 mice underwent experiments for mechanism exploration. Mice were infected with influenza virus A/Puerto Rico/08/1934(PR8) via nasal inhalation for the modeling. The lung tissue was collected on day 3 after gavage, and the lung tissue, colon tissue, and feces were collected on day 7 after gavage for subsequent testing. The results showed that Tanreqing Capsules alleviated the body weight reduction and increased the survival rate caused by PR8 infection. Compared with model group, Tanreqing Capsules can alleviate the lung injury by reducing the lung index, alleviating inflammation and edema in the lung tissue, down-regulating viral gene expression at the late stage of infection, reducing the percentage of neutrophils, and increasing the percentage of T cells. Tanreqing Capsules relieved the gut injury by restoring the colon length, increasing intestinal lumen mucin secretion, alleviating intestinal inflammation, and reducing goblet cell destruction. The gut microbiota analysis showed that Tanreqing Capsules increased species diversity compared with model group. At the phylum level, Tanreqing Capsules significantly increased the abundance of Firmicutes and Actinobacteria, while reducing the abundance of Bacteroidota and Proteobacteria to maintain gut microbiota balance. At the genus level, Tanreqing Capsules significantly increased the abundance of unclassified＿f＿Lachnospiraceae while reducing the abundance of Bacteroides, Eubacterium, and Phocaeicola to maintain gut microbiota balance. In conclusion, Tanreqing Capsules can alleviate mouse lung and gut injury caused by influenza virus infection and restore the balance of gut microbiota. Treating influenza from the lung and gut can provide new ideas for clinical practice.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Lung/metabolism* ; Mice, Inbred C57BL ; Capsules ; Orthomyxoviridae Infections/virology* ; Gastrointestinal Microbiome/drug effects* ; Male ; Humans ; Female ; Influenza A virus/physiology* ; Influenza, Human/virology*

This study aimed to investigate the effect and underlying mechanisms of Zexie Decoction against liver injury in rats with hyperlipidemic acute pancreatitis(HLAP). The network pharmacology-related databases were used to screen the active components and potential targets of Zexie Decoction, as well as the disease targets of HLAP. A protein-protein interaction(PPI) network of the overlapping targets was constructed. Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis and Gene Ontology(GO) functional enrichment analysis were performed on the overlapping targets. Sprague-Dawley(SD) rats were randomly divided into sham group, model group, low-dose Zexie Decoction group, and high-dose Zexie Decoction group. Enzyme-linked immunosorbent assay(ELISA) kits were used to detect serum biochemical indicators. Hematoxylin-eosin(HE) staining was used to observe the pathological morphology of the pancreas and liver tissues, while oil red O staining was employed to assess hepatic steatosis. Immunofluorescence staining was used to detect the expression of IL-1β and NLRP3 in pancreatic tissues. Western blot analysis was conducted to evaluate the expression levels of proteins related to oxidative stress, endoplasmic reticulum stress, the PI3K/AKT signaling pathway, and autophagy. Network pharmacology predictions identified 721 targets of Zexie Decoction and 2 486 targets associated with HLAP, with 279 overlapping targets. GO enrichment analysis yielded 1 112 entries, and KEGG enrichment analysis identified 179 signaling pathways. Experimental results showed that Zexie Decoction could reduce the levels of lipid metabolites, serum enzymes, and inflammatory cytokines in HLAP rats, alleviate pathological damage to the pancreas and liver, decrease hepatic lipid accumulation, and decrease the expression of IL-1β and NLRP3 in pancreatic tissues. In addition, Zexie Decoction significantly upregulated the expression of antioxidant stress-related proteins NRF2 and HO-1, downregulated the expression of endoplasmic reticulum stress-related proteins BiP, xBP1s, p-eIF2α, eIF2α, and ATF4, inhibited the expression of PI3K and phosphorylation of AKT, increased the expression of autophagy-related proteins Beclin1, ATG3, ATG5, and ATG12, and reduced the expression of p62. In conclusion, Zexie Decoction can improve HLAP, and its mechanism may be associated with alleviating oxidative stress and endoplasmic reticulum stress, inhibiting the PI3K/AKT pathway, and inducing autophagy in hepatocytes.
Animals ; Rats, Sprague-Dawley ; Drugs, Chinese Herbal/administration & dosage* ; Network Pharmacology ; Rats ; Pancreatitis/genetics* ; Hyperlipidemias/genetics* ; Male ; Liver/injuries* ; Protein Interaction Maps/drug effects* ; Signal Transduction/drug effects* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Interleukin-1beta/genetics* ; Humans