AIM:To compare the clinical efficacy of defocus rigid gas permeable contact lenses(RGPCL)and highly aspherical lenslets(HAL)for myopia control in children and adolescents with moderate to high myopia.METHODS:A retrospective study was conducted, enrolling patients aged 8-17 y with moderate to high myopia who presented to Sichuan Eye Hospital, Aier Eye Hospital Group between January 2022 and January 2024. Subjects were divided into the RGPCL group and the HAL group according to myopia correction modalities. Refractive diopters, axial length, corneal curvature, and visual quality were examined at 6 and 12 mo after lens wear, and relevant data were statistically analyzed.RESULTS:A total of 96 eyes from 96 cases were enrolled, with 48 cases(48 eyes, 8 males and 40 females)allocated to the RGPCL group with a median age of 12.00(11.50, 15.00)y, and 48 cases(48 eyes, 14 males and 34 females)to the HAL group with a median age of 13.00(12.00,14.00)y. At the 6-month follow-up, no significant changes in spherical diopters were observed in either group relative to baseline. Spherical diopters increased in both groups at the 12-month visit, with a significantly smaller increment in the RGPCL group(P<0.01). At the 6- and 12-month follow-up visits, the magnitude of changes in cylindrical refractive power was markedly larger in the RGPCL group relative to the HAL group(P<0.01). At the 6-and 12-month follow-up visits, axial length in both groups had increased relative to baseline, and no significant intergroup difference was detected in axial elongation(P>0.05). At 6 and 12 mo of lens wear, no significant difference in K1,K2 was found in the HAL group compared with baseline, while the K2 value decreased significantly in the RGPCL group(P<0.0167). The RGPCL group achieved substantially higher scores in four domains including visual clarity, image scaling, glare tolerance, visual field range and total at both follow-up time points(all P<0.001).CONCLUSION:Defocus RGPCL yields superior performance in slowing the progression of spherical and cylindrical, as well as providing better overall visual experience, when compared with HAL.

OBJECTIVE To analyze the development history， current status， and major challenges of central （cloud） pharmacies within China’s close-knit county-level medical communities， and to provide references for improving the overall effectiveness of the primary-level pharmaceutical supply and support system.METHODS Policy documents and practical case data related to central （cloud） pharmacies in county-level medical communities from 31 provinces （autonomous regions and municipalities） in China were collected. A qualitative approach combining policy text analysis and comparative case analysis was employed to longitudinally trace and cross-sectionally compare the development history and current status of central （cloud） pharmacies， identify existing problems， and propose targeted recommendations. RESULTS &CONCLUSIONS The development of central （cloud） pharmacies in China has undergone three stages： initial exploration， pilot expansion and mechanism deepening， and high-level promotion with local responses. While adhering to national policy directives， various regions have conducted diverse explorations in organizational and legal forms， management models， and institutional frameworks. However， several challenges remain， including insufficient policy guidance， an imperfect mechanism for drug coordination and supply security， weaknesses in hardware infrastructure and information technology development， and the need to strengthen statistical monitoring and outcome evaluation systems. It is recommended that the construction of central （cloud） pharmacies should be oriented toward achieving their fundamental functions， improve the institutional framework， adopt differentiated construction models tailored to local conditions， enhance the coordinated drug supply and support system， strengthen information technology infrastructure and professional capacity building， unify evaluation standards， and improve performance assessment mechanisms， so as to elevate the overall effectiveness of the primary-level pharmaceutical supply and support system.

Objective To systematically evaluate the similarities between six-gene-modified pig red blood cells and human red blood cells in multiple dimensions, including cell morphology, hematological parameters, microbial safety and serological compatibility, and to verify the feasibility of using six-gene-modified pig red blood cells as an alternative for blood transfusion in cases of traumatic hemorrhage. Methods Blood samples from O-type human donor, six-gene-modified O-type pig and wild-type O-type pig were collected. The pig gene-modified phenotype was identified by flow cytometry. The morphology was observed using field emission scanning electron microscopy and the diameter was measured. Hematological tests, including blood routine, osmotic fragility test, adenosine triphosphate (ATP) and 2,3-diphosphoglycerate (2,3-DPG) content and partial pressure of oxygen at 50% hemoglobin saturation (P50), were conducted to assess the deformability of red blood cells. Real-time fluorescent quantitative polymerase chain reaction was used to screen for zoonotic viruses, and cross-matching was performed using column gel method, condensation amine method and saline tube method. Results The six-gene-modified pig red blood cells successfully knocked out the α-Gal, Neu5Gc and Sda antigens and expressed hCD55. Wild-type pig red blood cells expressed these three antigens but did not express human complement regulatory proteins. All three types of red blood cells presented a biconcave discoid morphology. The diameter of O-type human red blood cells was larger than that of the six-gene-modified porcine red blood cells and wild-type pig red blood cells (all P < 0.05). The average red blood cell volume and average red blood cell hemoglobin of O-type humans were higher than those of the six-gene-modified pig red blood cells, and the distribution width-variable coefficient of O-type human red blood cells was lower than that of the six-gene-modified pig red blood cells (all P < 0.05). There were no statistically significant differences in the permeability fragility, ATP content, 2,3-DPG content, P50 and red blood cell deformability indicators of the three types of red blood cells (all P > 0.05). The screening for zoonotic viruses in human and animal cells of the six-gene-modified pigs and wild-type pigs was negative. The cross-matching results showed that in the column gel method and condensation amine method, the primary and secondary sides of the six-gene-modified pig red blood cells did not agglutinate with human red blood cells, while the wild-type pig red blood cells agglutinated with human red blood cells in all cross-matching methods. Conclusions The six-gene-modified pig red blood cells are highly similar to human red blood cells in terms of morphology, key hematological parameters, energy metabolism, oxygen-carrying capacity, mechanical properties, microbial safety and serological compatibility, providing an experimental basis for the clinical transformation of xenotransfusion.

ObjectiveTo investigate the possible mechanism by which Zhiqiao Gancao Decoction （枳壳甘草汤， ZGD） delays intervertebral disc degeneration （IDD） based on the Hippo-yes-associated protein （YAP）/transcriptional co-activator with PDZ-binding motif （TAZ） signaling pathway. MethodsA total of 50 SD rats were randomly divided into sham surgery group， model group， low-dose ZGD group， high-dose ZGD group， and high-dose ZGD + inhibitor group， with 10 rats in each group. In the sham surgery group， the rats were pierced in the skin and muscle at the Co6/7/8 segments of the tail with a 21G needle （depth approximately 2 mm） without damaging the intervertebral disc. In the other groups， rats were injected with a 21G needle at the Co6/7/8 segments of the tail to establish an IDD model by piercing the tail intervertebral disc 5 mm. One week after modeling， rats in the low-dose and high-dose ZGD groups were given 6.24 and 12.24 g/（kg·d） of the decoction via gastric gavage， respectively. The high-dose ZGD + inhibitor group was given 12.24 g/（kg·d） of the decoction and an intraperitoneal injection of YAP/TAZ inhibitor Verteporfin 10 mg/kg. The sham surgery and model groups were given 5 ml/（kg·d） of normal saline via gavage. The gavage was given once a day， and the intraperitoneal injection was given every other day. After 4 weeks of continuous intervention， the pathological changes of the tail intervertebral discs were observed using HE staining， Oil Red O-Green staining， and Toluidine Blue staining. Immunohistochemistry was used to detect the expression of aggrecan and MMP3 in the nucleus pulposus. TUNEL fluorescence staining was performed to detect apoptosis in the nucleus pulposus， and the apoptosis rate was calculated. Western blot was used to detect the Hippo-YAP/TAZ signaling pathway， including YAP， phosphorylated YAP （p-YAP）， phosphorylated MST1/2 （p-MST1/2）， phosphorylated TAZ （p-TAZ） and apoptosis-related proteins， such as Cleaved Caspase 3， P53， Bcl-2 and Bax. ResultsCompared with sham surgery group， the rats in the model group showed significant degenerative changes in the intervertebral disc. The levels of aggrecan， Bcl-2， and YAP proteins in the nucleus pulposus decreased， while the levels of p-MST1/2， p-YAP， p-TAZ， P53， Bax， Cleaved Caspase 3， MMP3 proteins， and the apoptosis rate increased （P < 0.01）. Compared with the model group， the drug intervention groups showed partial recovery in intervertebral disc degeneration. The levels of aggrecan， Bcl-2， and YAP proteins increased， while the levels of p-MST1/2， p-YAP， p-TAZ， P53， Bax， Cleaved Caspase 3， MMP3 proteins， and the apoptosis rate decreased （P＜0.05 or P＜0.01）. The high-dose ZGD group showed more significant recovery in intervertebral disc degeneration compared to the low-dose ZGD group， with a decrease in the levels of p-MST1/2， p-YAP， p-TAZ， P53， Bax， Cleaved Caspase 3， MMP3 proteins， and apoptosis rate， and an increase in the levels of aggrecan， Bcl-2， and YAP proteins （P＜0.05 or P＜0.01）. Compared with the high-dose ZGD group， the high-dose ZGD + inhibitor group showed a reduced recovery in intervertebral disc degeneration， with an increase in the levels of p-MST1/2， p-YAP， p-TAZ， P53， Bax， Cleaved Caspase 3， MMP3 proteins， and apoptosis rate， and a decrease in the levels of aggrecan， Bcl-2， and YAP proteins （P＜0.05 or P＜0.01）. ConclusionZGD may delay intervertebral disc degeneration by inhibiting the phosphorylation of YAP in the nucleus pulposus， maintaining the function of the Hippo-YAP/TAZ signaling pathway， and reducing apoptosis of nucleus pulposus cells.

Fungal keratitis represents a significant cause of blindness, with current therapeutic approaches yielding limited success. The disease's onset and progression are primarily driven by fungal virulence factors and the host's immune response. The innate immune system is the first to respond, with neutrophils playing a pivotal role in the antifungal defense. Although neutrophils are critical for pathogen clearance, their excessive or abnormal activation can lead to tissue damage, exacerbating the disease. Thus, elucidating the mechanisms underlying neutrophil activity in fungal keratitis is crucial for refining treatment strategies. This article aims to systematically review the principal antimicrobial mechanisms employed by neutrophils, including phagocytosis, degranulation, and the formation of neutrophil extracellular traps(NETs). Furthermore, it explores the crosstalk between neutrophils and macrophages, alongside their collective impact and underlying mechanisms in the context of fungal keratitis. Exploration of the mechanisms of fungal keratitis facilitates precise intervention and enhances the efficacy of treatment.

OBJECTIVE To explore the effect and mechanism of Zhiqiao gancao decoction （ZQGCD） on pathological angiogenesis of degenerative intervertebral disc. METHODS The rats were randomly divided into sham operation group （normal saline）， model group （normal saline）， hypoxia inducible factor-1α （HIF-1α） inhibitor （YC-1） group [2 mg/（kg·d）， tail vein injection]， and ZQGCD low-dose， medium-dose and high-dose groups [3.06， 6.12， 12.24 g/（kg·d）]， with 8 rats in each group. Except for sham operation group， lumbar disc degeneration model of rat was constructed in all other groups. After modeling， they were given relevant medicine once a day， for consecutive 3 weeks. After the last medication， pathological changes and angiogenesis of the intervertebral disc tissue in rats were observed； the levels of inflammatory factors [interleukin-1β （IL-1β）， IL-6， tumor necrosis factor-α （TNF-α）] and the expressions of angiogenesis-related proteins [HIF-1α， vascular endothelial growth factor （VEGF）， VEGF receptor 2 （VEGFR2）， angiotensin 1（Ang 1）， Ang 2] in the com intervertebral disc tissue in rats were all determined. In cell experiment， the primary nucleus pulposus cells were isolated and cultured from rats， and cellular degeneration was induced using 50 ng/mL TNF-α. The cells were divided into blank control group （10% blank control serum）， TNF-α group （10% blank control serum）， YC-1 group （10% blank control serum+0.2 mmol/L YC-1）， and 5%， 10%， 15% drug-containing serum group （5%， 10%， 15% drug-containing serum）. After 24 hours of intervention， the nucleus pulposus cells were co-cultured with HUVEC. The expressions of Collagen Ⅱ， matrix metalloproteinase-3 （MMP-3） in nucleus pulposus cells were detected. HUVEC proliferation， migration and tube forming ability were detected， and the expression levels of the HIF-1α/VEGF/Ang signal axis and angiogenesis- related proteins （add MMP-2， MMP-9） in HUVEC were detected. RESULTS Animal experiments had shown that compared with model group， the positive expression of CD31 in the intervertebral disc tissues of rats in each drug group was down-regulated （P＜ 0.05）， the levels of inflammatory factors and angiogenesis-related proteins were decreased significantly （P＜0.05）， and the pathological changes in the intervertebral disc were alleviated. Cell experiments had shown that compared with TNF-α group， the expression of Collagen Ⅱ in nucleus pulposus cells of all drug groups was significantly up-regulated （P＜0.05）， and the expression of MMP-3 was significantly down-regulated （P＜0.05）； the proliferation， migration and tubulogenesis of HUVEC were significantly weakened （P＜0.05）. The mRNA and protein expressions of HIF-1α， VEGF， Ang 2 as well as the expression of angiogenesis-related proteins （except for the expression of Ang 2 mRNA and HIF-1α， VEGFR2， Ang 2 protein in 5% drug- containing serum group） were significantly down-regulated （P＜0.05）. CONCLUSIONS ZQGCD may inhibit the HIF-1α/VEGF/ Ang signal axis to weaken the angiogenic ability of vascular endothelial cells， improve pathological angiogenesis in the intervertebral disc， and delay the degeneration of the intervertebral disc.

Objective To assess the efficacy of clear lens extraction combined with extended depth of focus(EDOF)intraocular lens(IOL)implantation in enhancing visual quality and concurrently opening peripheral angle structures in patients diagnosed with primary angle closure suspect(PACS)and presbyopia.Methods A total of 80 patients with PACS,presbyopia,and transparent lenses were enrolled and divided into two groups based on the type of implanted lens:a control group(n=46)and an experimental group(n=34).The control group underwent clear lens extraction followed by monofocal intraocular lens implantation,while the experimental group underwent clear lens extraction followed by extended depth of focus(EDOF)intraocular lens implantation.Preoperative and postoperative evaluations at 3 months included visual acuity,intraocular pressure,anterior segment structure,defocus curve,and Catquest 9SF-CN questionnaire scores.Adverse events were recorded to assess safety.Results Regarding the angular structure,after 3 months of treatment,results indicated significant increases in central ante-rior chamber depth,angle opening distance at 750 μ m,angle recess area at 750 μ m,trabecular-iris space area at 750 μm,and trabecular-iris angle at 750 μm in both groups compared to preoperative values(all P<0.01).However,no significant differences were observed between the two groups(all P>0.05).For the defocusing curve,visual acuity in the experimental group improved from+1.0 D to-4.0 D after 3 months of treatment(all P<0.05),while the control group showed improvements at+0.5 D,-0.5 D,-1.0 D,-2.0 D,-3.0 D,-3.5 D,and-4.0 D(all P<0.05).Postoperatively at 3 months,the experimental group exhibited superior visual acuity to the control group at-1.0 D to-4.0 D(all P<0.05).According to the Catquest 9SF-CN scale,scores in both groups significantly im-proved after 3 months of treatment(P<0.01),with the experimental group scoring higher than the control group(P<0.01).During the study,transient intraocular pressure elevation occurred in 7 patients(3 in the control group and 4 in the experimental group),but no serious adverse reactions were reported in either group.Conclusions In patients with pseudoexfoliation glaucoma combined with presbyopia,significant improvements in angle structures were observed following clear lens extraction.The implantation of an EDOF IOL notably enhanced postoperative visual quality compared to monofocal IOLs.

Objective:To evaluate the correlation between corneal biomechanical parameters and Schlemm canal (SC) and trabecular meshwork (TM) in patients with myopia.Methods:Eighty-one consecutive patients who underwent refractive surgery at Wuhan EyeGood Ophthalmology Hospital from May to December 2021 were enrolled.Patients were divided into two groups according to spherical equivalent (SE) and axial length (AL), including 39 patients with 39 eyes in low to moderate myopia group (SE: -0.5 to -6.0 D, AL<26 mm) and 42 patients with 42 eyes in high myopia group (SE≤-6.0 D, AL≥26 mm).Another 20 cases (20 eyes) from the same period of health examinations were included as a healthy control group, with 10 males and 10 females.All subjects' right eye data were included for analysis.The corneal biomechanical parameters were measured with Corvis ST.The morphology of the SC and TM was observed with Zeiss Cirrus HD-OCT 5000.The differences in corneal biomechanical parameters, nasal SC (SC-N) area, temporal SC (SC-T) area, nasal TM (TM-N) width and thickness and temporal TM (TM-T) width were compared between the two groups.Correlations between corneal biomechanical parameters and SC, TM and biomechanically corrected intraocular pressure (bIOP) in myopic patients were analyzed using Pearson linear correlation analysis.The study followed the Declaration of Helsinki, and the study protocol was reviewed and approved by the Ethics Committee of Wuhan EyeGood Ophthalmology Hospital (No.AGQGSS-06).All patients were aware of the purpose and significance of this study and voluntarily signed the informed consent form.Results:The distance between the two peaks of the cornea at highest concavity (PD) was (5.49±0.28)mm in high myopia group, which was higher than (5.36±0.28)mm in low to moderate myopia and (5.05±0.29)mm in healthy control group, and the radius of curvature at highest concavity (HCR) and the stress-strain index (SSI) values in high myopia group were lower than those in low to moderate myopia and healthy control groups, with statistically significant differences (all P<0.05).The SC-T area and SC-N area were significantly higher and TM-T thickness was lower in high myopia group than those in low to moderate myopia and healthy control groups (all P<0.05).PD was positively correlated with SC-N area in myopic patients ( r=0.26, P=0.02).bIOP was negatively correlated with PD, the amount of corneal displacement at highest degree of concavity (DA), inverse concave radius (IR) and deformation amplitude ratio (DA ratio) ( r=-0.79, -0.81, -0.45, -0.50; all P=0.00) and positively correlated with stiffness parameters at applanation 1 (SP-A1) and SSI ( r=0.45, 0.46; all P=0.00). Conclusions:PD values are greater in myopic patients.The greater the PD, the greater the SC-N area.The greater the refractive error, the longer the AL, and the thinner the TM thickness.

Objective To explore the function and molecular mechanisms of matrix metalloproteinase 19(MMP-19)in colorectal cancer(CRC)and liver metastasis of CRC(CRLM).Methods This study comprehen-sively analyzed transcriptomic data,single-cell data,and clinical information of CRC and CRLM patients retrieved from public databases,namely The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO).RNA sequencing analysis was carried out to identify biological functions associated with MMP-19 expression.The differ-ential expression of MMP-19 between primary lesions and liver metastatic lesions was evaluated using quantitative real-time polymerase chain reaction(qRT-PCR),Western blotting,and immunohistochemistry.In vitro functional assays were performed to validate the impact of MMP-19 on the proliferation,invasion,and migration of colorectal cancer cells.Results MMP-19 was highly expressed in CRC tissues and was significantly correlated with poor prognosis in both CRC and CRLM patients.Sequencing results and functional enrichment analysis demonstrated that MMP-19 is involved in epithelial-mesenchymal transition,amino acid and protein transport,cell proliferation,extracellular matrix organization,and the mitogen-activated protein kinase(MAPK)signaling pathway.Single-cell analysis revealed that the expression of MMP-19 in macrophages and dendritic cells was higher in both CRC primary tumors and liver metastases compared to normal tissues.In vitro experiments confirmed that MMP-19 enhances the proliferation,invasion,and migration capabilities of colorectal cancer cells.Conclusion MMP-19 has been shown to play a crucial role in promoting the development and progression of CRC.It increases the risk of postoperative recurrence and liver metastasis through inducing epithelial-mesenchymal transition and remodeling the immune microenvironment.Given these findings,MMP-19 emerges as a promising novel target for the diagnosis and treatment of both CRC and CRLM.

IL-2 is a multifunctional cytokine whose main functions include activating and maintaining T cell survival.Re-search has shown that the level and function of IL-2 in peripheral blood of patients with systemic lupus erythematosus(SLE)have sig-nificantly decreased,and are associated with the activity of SLE disease.In recent years,the decrease in IL-2 level has been found to play a crucial role in the occurrence and development of SLE,and is one of the important mechanisms for T cell homeostasis imba-lance and immune regulation disorders in SLE patients.The low-dose IL-2 treatment regimen for SLE based on this discovery has en-tered clinical application.However,there is still considerable controversy regarding the mechanism of decreased IL-2 level and sup-pressed functions in SLE patients.Clarifying this mechanism is of great significance for further clarifying the occurrence and develop-ment mechanism of SLE and developing new treatment regimens.