In recent years, with the endless emergence of meibomian gland dysfunction(MGD)diagnostic equipment, rich treatment methods, and in-depth clinical and basic research on MGD at home and abroad, the understanding of MGD has entered a new stage. MGD-related dry eye is considered to be the main cause of lipid abnormal dry eye, and its occurrence and development is a chronic and multi-factorial pathological process. This article reviews the pathogenesis, imaging analysis and clinical treatment progress of MGD-related dry eye, in order to provide scientific evidence and ideas for clinical diagnosis and therapy of MGD-related dry eye.

BACKGROUND: The primary limitation to kidney transplantation is organ shortage. Recent progress in gene editing and immunosuppressive regimens has made xenotransplantation with porcine organs a possibility. However, evidence in pig-to-human xenotransplantation remains scarce, and antibody-mediated rejection (AMR) is a major obstacle to clinical applications of xenotransplantation. METHODS: We conducted a kidney xenotransplantation in a brain-dead human recipient using a porcine kidney with five gene edits (5GE) on March 25, 2024 at Xijing Hospital, China. Clinical-grade immunosuppressive regimens were employed, and the observation period lasted 22 days. We collected and analyzed the xenograft function, ultrasound findings, sequential protocol biopsies, and immune surveillance of the recipient during the observation. RESULTS: The combination of 5GE in the porcine kidney and clinical-grade immunosuppressive regimens prevented hyperacute rejection. The xenograft kidney underwent delayed graft function in the first week, but urine output increased later and the single xenograft kidney maintained electrolyte and pH homeostasis from postoperative day (POD) 12 to 19. We observed AMR at 24 h post-transplantation, due to the presence of pre-existing anti-porcine antibodies and cytotoxicity before transplantation; this AMR persisted throughout the observation period. Plasma exchange and intravenous immunoglobulin treatment mitigated the AMR. We observed activation of latent porcine cytomegalovirus toward the end of the study, which might have contributed to coagulation disorder in the recipient. CONCLUSIONS 5GE and clinical-grade immunosuppressive regimens were sufficient to prevent hyperacute rejection during pig-to-human kidney xenotransplantation. Pre-existing anti-porcine antibodies predisposed the xenograft to AMR. Plasma exchange and intravenous immunoglobulin were safe and effective in the treatment of AMR after kidney xenotransplantation.
Transplantation, Heterologous/methods* ; Kidney Transplantation/methods* ; Heterografts/pathology* ; Immunoglobulins, Intravenous/administration & dosage* ; Graft Survival/immunology* ; Humans ; Animals ; Sus scrofa ; Graft Rejection/prevention & control* ; Kidney/pathology* ; Gene Editing ; Species Specificity ; Immunosuppression Therapy/methods* ; Plasma Exchange ; Brain Death ; Biopsy ; Male ; Aged

Age-related macular degeneration(AMD)is a prevalent retinal degenerative disease closely linked to age and stands as a leading cause of central vision loss among the elderly. Under physiological condition, microglia in the retina plays crucial roles in tissue homeostasis, immune surveillance, and tissue repair. However, in pathological state, microglia can be abnormally activated and migrate to AMD lesion sites, which results in exacerbating damage to retinal pigment epithelial cells and photoreceptor cells, thus promoting the progression of AMD. This review focuses on the origins, distribution, and functional changes of microglia under physiological and pathological conditions. Recent advances in microglia-targeted therapies for AMD are also summarized, which provides a theoretical basis for the development of novel treatment strategies.

Objective To investigate the expression of long non-coding RNA(LncRNA)PICSAR in ovarian canc-er,and explore the effects of LncRNA PICSAR on the proliferation,migration,invasion and apoptosis of ovarian cancer cells as well as its possible mechanism of action.Methods The expression levels of LncRNA PICSAR in o-varian cancer tissue and cell line A2780,OVCAR-3,HO-8910 and normal ovarian tissue and cell line IOSE386 were detected by fluorescence quantitative PCR.Ovarian cancer cell lines with the highest expression of LncRNA PICSAR were divided into control group and experimental group,and transfected with negative control small inter-fering RNA(siRNA-NC)or PICSAR knockout small interfering RNA(siRNA-PICSAR)by liposome transfection technique,respectively.The effects of LncRNA PICSAR knockdown on the invasion,migration,proliferation and apoptosis of ovarian cancer cells were analyzed by cell counting assay(CCK-8),clonogenic assay,scratch assay,transwell assay and flow cytometry and so on.The expression levels of autophagy related proteins and apoptosis-re-lated proteins in each group were determined by Western blot.Ovarian cancer cells were treated with rapamycin and hydroxychloroquine as autophagy activator and inhibitor,and Western blot assay was used to detect apoptosis.Results The expression level of LncRNA PICSAR in ovarian cancer tissues was higher than that in normal ovarian tissues.Compared with IOSE386 cell line,LncRNA PICSAR expression levels in ovarian cancer cell lines HO-8910,OVCAR-3 and A2780 increased.Compared with the si-NC group,the proliferation,invasion and migration ability of ovarian cancer cells in si-PICSAR group decreased,and the apoptosis rate increased.The autophagy level of ovarian cancer cells in si-PICSAR group was lower than that in si-NC group.After transfection with siRNA-PIC-SAR,rapamycin activated autophagy to reduce apoptosis,while hydroxychloroquine inhibited autophagy to promote apoptosis.Conclusion LncRNA PICSAR is highly expressed in ovarian cancer tissues and cell lines,and the ma-lignant biological behavior of ovarian cancer cells can be inhibited by knockout of LncRNA PICSAR.The knock-down of LncRNA PICSAR may promote the apoptosis of ovarian cancer cells by regulating autophagy.

Objective:To observe alterations in center retinal thickness (CRT) in patients diagnosed with central retinal artery occlusion (CRAO) before and after undergoing superselective arterial thrombolysis (IAT) treatment.Methods:A retrospective clinical study. From August 2022 to September 2023, 12 patients (12 eyes) diagnosed with CRAO and treated with IAT at the ophthalmology department of Shenzhen Second People's Hospital. Among these patients, there were 8 males (8 eyes) and 4 females (4 eyes), all experiencing unilateral onset. The mean age was (47.00±15.06) years. The mean duration from onset to thrombolysis was (30.00±30.42) h. All eyes underwent best corrected visual acuity (BCVA) and optical coherence tomography (OCT) assessments; additionally, 6 eyes underwent Fluorescein fundus angiography (FFA). BCVA assessments were conducted using a standard logarithmic chart and transformed into logarithm of the minimum angle of resolution (logMAR) values for statistical analysis. The OCT measured CRT at various locations around the macular fovea (M), including upper (S1, S3), lower (I1, I3), nasal (N1, N3), and temporal (T1, T3) areas at 1 mm and 3 mm distances from the fovea. CRT was defined as the vertical distance between the inner retinal boundary membrane and the inner interface of the retinal pigment epithelial layer. Pre- and post-IAT examinations were performed using the same equipment and methodologies within a 24-hour interval. Changes in CRT at different macular points were compared and observed, while arterial imaging time changes were assessed in 6 eyes that underwent FFA. Paired t-tests were utilized to analyze logMAR BCVA, CRT at different locations, and arterial imaging time pre- and post-treatment. Results:Prior to IAT treatment, the logMAR BCVA for the affected eye was 3.48±1.42, while the arterial imaging time for the 6 eyes undergoing FFA examination was (27.50±5.47) s. After 24 hours, the logMAR BCVA had improved to 2.35±1.59 for the affected eye, with 9 eyes showing varying degrees of BCVA improvement. The arterial imaging time was (24.17±7.28) s post-treatment. The differences in logMAR BCVA and arterial imaging time before and after treatment were found to be statistically significant ( t=2.489, 3.262; P<0.05). Additionally, the comparison of CRT at S3 ( t=2.871), I1 ( t=2.325), and T3 ( t=3.446) before and after treatment yielded statistically significant differences ( P<0.05). Conversely, the comparison of CRT at S1 ( t=1.879), I3 ( t=1.915), N1 ( t=2.001), N3 ( t=1.987), T1 ( t=2.180), and M ( t=-0.490) showed no statistically significant differences ( P>0.05). Conclusions:IAT treatment for CRAO has been shown to be effective in achieving therapeutic effects by reducing CRT in the macular area. However, the short-term improvement in retinal edema in the macular area is limited.

Diabetic macular edema (DME) is the main cause of vision loss in diabetic patients, its pathogenesis is complicated, and the clinical treatment is not good. DME is extremely harmful to vision. With the deepening of relevant studies, its related pathological mechanism has become more and more clear, and the treatment methods have also changed accordingly. In recent years, the rapid development of intracocular fluid cytokine detection technology has provided a more reasonable explanation of the mechanism of DME and made the choice of treatment more reasonable. However, the acquisition of intraocular fluid is an invasive operation with a certain risk of infection. If the level of relevant cytokines in intraocular fluid can be linked with the relevant imaging indicators, it will provide a better choice for the treatment and prognosis monitoring of DME and reduce the risk of invasive operation, and further clinical studies are needed to explore its correlation in the future.

Objective:To quantify the associations between periconceptional maternal homocysteine (HCY) and offspring′s birth weight and risk of small for gestational age (SGA) infant.Methods:The 19 984 mother-child pairs in this prospective cohort study were recruited from the Shanghai preconception cohort; the infants were delivered from 1 st September 2016 to 11 th November 2022. A standardized questionnaire was used to collect the mothers′ demographic information, medical history, dietary supplement use, and maternal complications during pregnancy, and their serum samples were collected. Serum HCY, folate, and vitamin B 12 were measured using chemiluminescent microparticle immunoassay based on serum sample drawn at enrollment. Birth weight data were obtained from medical records. Multiple imputation methods were applied to handle missing data in key variables. Multivariable linear regression and Poisson regression models were used to analyze the relationship between maternal HCY concentration during the periconceptional period and the birth weight and SGA risk of the offspring. Results:A total of 9 452 pairs were enrolled preconceptionally and the remaining 10 532 pairs were enrolled in early pregnancy. The proportion of mothers whose pregnancy age was greater than 35 years was 9.2% (1 832/19 984), the proportion of primiparous women was 76.5% (15 283/19 984), the proportion of pre-pregnancy overweight and obesity was 14.0% (2 804/19 984), the proportion of using folic acid supplements before pregnancy was 21.4% (4 272/19 984), and the proportion of those who supplemented with folic acid during early pregnancy was 85.2% (8 976/10 532); gestational diabetes mellitus was in 6.2% (1 245/19 984), gestational hypertensive syndrome in 3.6% (711/19 984). The birth weight of the offspring was (3 297±468) g, and there were 1 962 SGA children (9.8%). The HCY concentration in the overall population in appropriate for gestational age during the periconceptional period was (7.9±3.2) μmol/L, with (8.3±3.7) μmol/L in the preconception subgroup and (7.3±2.4) μmol/L in the early pregnancy subgroup. After adjustment for the covariates of perinatal demographic information, adverse pregnancy outcomes, serum folate and vitamin B 12, increased maternal periconceptional HCY was significantly associated with lower offspring birth weight ( β=-2.30, 95% CI -4.43--0.16, P=0.035). Only the early pregnancy subgroup was significantly associated with lower offspring birth weight ( β=-7.39, 95% CI-11.50--3.21, P<0.001). No association was found between peripregnancy HCY and offspring SGA risk. However, elevated HCY in early pregnancy was associated with an increased risk of SGA in the offspring ( RR=1.05, 95% CI 1.01-1.08, P=0.002). Periconceptional vitamin B 12 was a mediator of the association between HCY and offspring birth weight, accounting for 16.5%, 41.2% and 5.4% of its total effect in the overall periconceptional population, the pre-pregnancy subgroup and the early pregnancy subgroup, respectively. Conclusions:Maternal periconceptional HCY level is associated with lower birth weight in offspring, but not with the risk of SGA. Elevated maternal HCY in early pregnancy subgroup may be associated with increased risk of SGA in offspring.

Organ shortage has become one of the major challenges hindering the development of organ transplantation. Xenotransplantation is one of the most valuable methods to resolve global organ shortage. In recent years, the development of genetic engineering technique and research and development of new immunosuppressant have provided novel theoretical basis for xenotransplantation. International scholars have successively carried out researches on xenotransplantation in genetically modified pigs to non-human primates or brain death recipients, making certain substantial progresses. However, most of the researches are still in the preclinical stage, far from clinical application. Therefore, according to the latest preclinical experimental research progress at home and abroad, the history of xenotransplantation, the development of gene modification technology, xenotransplantation rejection and immunosuppression regimens were reviewed, aiming to provide reference for subsequent research of xenotransplantation, promote clinical application of xenotransplantation and bring benefits to more patients with end-stage diseases.

Objective To understand the impact of system reform of salt industry on iodine nutrition of people in Gansu Province, and to provide a scientific basis for policy adjustment of relevant departments. Methods The investigation period (2014-2021) was divided into two sub-periods: before system reform of salt industry (2014-2016) and after system reform of salt industry (2017-2021). Thirty counties were selected according to the method of ^“population proportional probability sampling (PPS)^” in 2014. According to the iodine deficiency disease monitoring program of Gansu Province, from 2016 to 2021, children aged 8-10 years and pregnant women were taken as research objects to collect urine samples for urine iodine detection. Children in 2014 and 2018 were selected to measure thyroid volume. Results A total of 90 989 children urine iodine samples were investigated, and the median urinary iodine (MUI) of children was 194.70µg/L; 7 663 and 83,326 children's urinary iodine samples were investigated in the two periods, the MUI was 180.73 µg/L and 196.00 µg/L, respectively, and the difference was statistically significant (P<0.05). A total of 44 741 pregnant women's urinary iodine samples were investigated, and the MUI of pregnant women was 176.50 µg/L; 4 480 and 40 261 pregnant women's urinary iodine samples were investigated in the two periods, the MUI was 160.61 µg/L and 178.10 µg/L, respectively, and the difference was statistically significant (P<0.05). The thyroid volume of 1 555 children and 8 509 children was investigated in the two periods, the median thyroid volume was 2.70 mL and 2.55 mL , respectively, and the difference was statistically significant (P<0.05). The rates of goiter in children were 3.15% and 1.26%, respectively, and the difference was statistically significant (P<0.05). Conclusion The iodine nutrition of people in Gansu Province has not fluctuated significantly after the reform of salt industry system and has maintained an appropriate level. It is necessary to pay attention to the potential risk of insufficient iodine nutrition level and thyroid health of key populations such as children and pregnant women and strengthen health education of scientific iodine supplementation.

OBJECTIVE To study the intervention effect of Hippophae rhamnoides oil on glucocorticoid resistance in superantigen-induced atopic dermatitis （AD） mice，and to explore the mechanism of action. METHODS Fifty mice were randomly divided into 5 groups，i.e. normal control group （group A），model group （group B），dexamethasone intervention group （positive control，group C），H. rhamnoides oil intervention group （group D），dexamethasone+H. rhamnoides oil intervention group （group E），with 10 mice in each group. Except for group A，other groups were given 2，4-dinitrochlorobenzene+staphylococcal enterotoxin B to induce the AD mice model. Starting from the 7th day of the experiment，groups C，D and E were given dexamethasone （1.5 mg/kg） and/or H. rhamnoides oil （10 mL/kg） intragastrically，once a day，for 28 consecutive days. After the last medication，the pathomorphological changes of ear tissue were observed by 节作用。E-mail：57667478@qq.com HE staining； the serum levels of immunoglobulin E （IgE） and interleukin 4 （IL-4） were detected by enzyme-linked immunosorbent assay. Positive cell count of glucocorticoid receptor α （GRα） and GRβ in the ear tissue of mice was detected by tyramide signal amplification. The expressions of GRα protein，GRβ protein，and protein kinase B （AKT）/ribosomal protein S6 kinase 1，S6K1 （S6K1） signaling pathway-related proteins were determined by Western blot assay. RESULTS Compared with group B，the skin inflammation in the left ear of the mice was significantly reduced in groups C，D and E，the serum levels of IgE and IL-4 were decreased significantly in groups D and E （P＜ 0.05），while the number of GRα positive cells and GRα protein expression were increased significantly （P＜0.05）； the protein levels of G protein inhibitory subunit 1 （Gαi1），Gαi3，phosphorylated S6K1 （p-S6K1） and phosphorylated AKT （p-AKT） were decreased significantly （P＜0.05）； the number of GRβ positive cells and protein expression of GRβ was decreased significantly in group E（P＜0.05）. Compared with group C，the skin inflammation in the left ear of the mice was almost clear away in group E，the serum levels of IgE and IL-4 were decreased significantly （P＜0.05）； the number of GRα positive cells and GRα protein expression were increased significantly in groups D and E （P＜0.05）； the protein levels of GRβ，Gαi1，p-S6K1 and p-AKT were all decreased significantly in groups D and E（P＜0.05）； and protein level of Gαi3 was decreased significantly in group E （P＜0.05）. CONCLUSIONS H. rhamnoides oil has an intervention effect on superantigen-induced glucocorticoid resistance of AD mice，which may be exerted by inhibition of the Gαi1/3-induced AKT/S6K1 signaling pathway.