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.

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.

Purpose: Molecular residual disease (MRD) is a promising biomarker in colorectal cancer (CRC) for prognosis and guiding treatment, while the whole-exome sequencing (WES) based tumor-informed assay is standard for evaluating MRD based on circulating tumor DNA (ctDNA). In this study, we assessed the feasibility of a fixed-panel for evaluating MRD in CRC. Materials and Methods: Seventy-five patients with resectable stage I-III CRC were enrolled. Tumor tissues obtained by surgery, and preoperative and postoperative day 7 blood samples were collected. The ctDNA was evaluated using the tumor-agnostic and tumor-informed fixed assays, as well as the WES-based and panel-based personalized assays in randomly selected patients. Results: The tumor-informed fixed assay had a higher preoperative positive rate than the tumor-agnostic assay (73.3% vs. 57.3%). The preoperative ctDNA status failed to predict disease-free survival (DFS) in either of the fixed assays, while the tumor-informed fixed assay-determined postoperative ctDNA positivity was significantly associated with worse DFS (hazard ratio [HR], 20.74; 95% confidence interval [CI], 7.19 to 59.83; p < 0.001), which was an independent predictor by multivariable analysis (HR, 28.57; 95% CI, 7.10 to 114.9; p < 0.001). Sub-cohort analysis indicated the WES-based personalized assay had the highest preoperative positive rate (95.1%). The two personalized assays and the tumor-informed fixed assay demonstrated same results in postoperative landmark (HR, 26.34; 95% CI, 6.01 to 115.57; p < 0.001), outperforming the tumor-agnostic fixed panel (HR, 3.04; 95% CI, 0.94 to 9.89; p=0.052). Conclusion Our study confirmed the prognostic value of the ctDNA positivity at postoperative day 7 by the tumor-informed fixed panel. The tumor-informed fixed panel may be a cost-effective method to evaluate MRD, which warrants further studies in future.

Objective:To investigate the allele distribution of aldehyde dehydrogenase 2 (ALDH2) gene polymorphism in elderly patients with type 2 diabetes mellitus (T2DM) and to analyze its correlation with the presence and severity of coronary stenosis.Methods:A total of 94 elderly patients with T2DM who were admitted to the Affiliated Hospital of Jining Medical University from March 2020 to March 2022 were selected as the observation group, and 50 age- gender-matched healthy subjects were selected as the control group. The observation group was further divided into stenosis group and non-stenosis group based on the presence of coronary stenosis. Clinical data were collected from all participants, and blood samples were taken for analysis. The ALDH2 gene polymorphism (rs671 locus) was detected using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technology. The distribution of ALDH2 genotypes was observed in elderly patients with T2DM, and multivariate logistic regression analysis was used to identify independent factors associated with the development of coronary stenosis in elderly patients with T2DM. The degree of coronary stenosis was compared between patients with different genotypes.Results:The allele A frequency of ALDH2 gene (rs671 locus) was significantly higher in the observation group than in the control group ( P<0.05). The proportion of patients with diabetes duration≥5 years and smoking history in the stenosis group was significantly higher than that in the non-stenosis group (all P<0.05). Serum levels of glucose (GLU), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) were significantly higher in the stenosis group than in the non-stenosis group, while high-density lipoprotein cholesterol (HDL-C) level was significantly lower in the stenosis group than in the non-stenosis group (all P<0.05). The proportion of ALDH2 genotypes AA and allele A frequency were significantly higher in the stenosis group than in the non-stenosis group (all P<0.05). Long duration of diabetes, low HDL-C level, and ALDH2 genotypes AA were independent risk factors for the development of coronary stenosis in elderly patients with T2DM (all P<0.05). The proportion of patients with three or more coronary artery lesions in the stenosis group with genotype AA was significantly higher than that in the stenosis group with genotypes GG and GA (all P<0.05). Conclusions:ALDH2 gene polymorphism is associated with the development of T2DM in elderly patients, and allele A carriers may have a higher risk of developing coronary stenosis and more severe disease severity.

The amygdala is an important hub for regulating emotions and is involved in the pathophysiology of many mental diseases, such as depression and anxiety. Meanwhile, the endocannabinoid system plays a crucial role in regulating emotions and mainly functions through the cannabinoid type-1 receptor (CB₁R), which is strongly expressed in the amygdala of non-human primates (NHPs). However, it remains largely unknown how the CB₁Rs in the amygdala of NHPs regulate mental diseases. Here, we investigated the role of CB₁R by knocking down the cannabinoid receptor 1 (CNR1) gene encoding CB₁R in the amygdala of adult marmosets through regional delivery of AAV-SaCas9-gRNA. We found that CB₁R knockdown in the amygdala induced anxiety-like behaviors, including disrupted night sleep, agitated psychomotor activity in new environments, and reduced social desire. Moreover, marmosets with CB₁R-knockdown had up-regulated plasma cortisol levels. These results indicate that the knockdown of CB₁Rs in the amygdala induces anxiety-like behaviors in marmosets, and this may be the mechanism underlying the regulation of anxiety by CB₁Rs in the amygdala of NHPs.
Animals ; Callithrix ; Receptors, Cannabinoid ; Anxiety ; Amygdala ; Cannabinoids ; Phenotype

The testis is pivotal for male reproduction, and its progressive functional decline in aging is associated with infertility. However, the regulatory mechanism underlying primate testicular aging remains largely elusive. Here, we resolve the aging-related cellular and molecular alterations of primate testicular aging by establishing a single-nucleus transcriptomic atlas. Gene-expression patterns along the spermatogenesis trajectory revealed molecular programs associated with attrition of spermatogonial stem cell reservoir, disturbed meiosis and impaired spermiogenesis along the sequential continuum. Remarkably, Sertoli cell was identified as the cell type most susceptible to aging, given its deeply perturbed age-associated transcriptional profiles. Concomitantly, downregulation of the transcription factor Wilms' Tumor 1 (WT1), essential for Sertoli cell homeostasis, was associated with accelerated cellular senescence, disrupted tight junctions, and a compromised cell identity signature, which altogether may help create a hostile microenvironment for spermatogenesis. Collectively, our study depicts in-depth transcriptomic traits of non-human primate (NHP) testicular aging at single-cell resolution, providing potential diagnostic biomarkers and targets for therapeutic interventions against testicular aging and age-related male reproductive diseases.
Animals ; Male ; Testis ; Sertoli Cells/metabolism* ; Transcriptome ; Spermatogenesis/genetics* ; Primates ; Aging/genetics* ; Stem Cells

【Objective】 To analyze the basic characteristics of whole blood donors from blood stations before and after the outbreak of COVID-19. 【Methods】 After excluding invalid data, data related to the basic characteristics of whole blood donors collected from 26 blood stations in China during 2018 to 2021 were statistically analyzed, including the trend of total whole blood donors, the number of repeated blood donors, the frequency of blood donation, the average age of donors and the recruitment of first-time blood donors. 【Results】 Affected by the epidemic, 8 out of 14 indicators were with large variations, accounting for 57%. The overall growth rate of total whole blood donors during the epidemic was higher than before the epidemic (P<0.05).The number of repeated blood donors has shown an increased trend, with a higher number during the epidemic than before (P<0.05). The frequency of blood donation was lower during the epidemic than before(P<0.05).Average ages of blood donors and female blood donors fluctuated widely during the epidemic, both higher than those before the epidemic(P<0.05).The donation rate of first-time blood donors <25 years old and ≥25 years old varied widely and irregularly during the epidemic (both P<0.05). The percentage of first-time blood donors fluctuated irregularly during the epidemic, with overall percentage lower than that before the epidemic(P<0.05). 【Conclusion】 Whole blood donors from 26 blood stations increased after the outbreak of COVID-19, and some indicators in certain areas showed significant fluctuations during the epidemic.

The construction of a countywide community for medical and health services is designed to upgrade the service capacity of primary medical and health institutions, to promote resource sharing and collaborative services, and promote the hierarchical medical system. Huzhou of Zhejiang province has launched its initiative in building a countywide community for medical services since 2018. The authors summarized its main practices in promoting the integration of the management system and optimizing operating mechanism of countywide medical and health institutions, promoting the reform of the county medical and health governance system, as well as the achievements and shortcomings, with a view to providing reference for promoting the high-quality development of the countywide medical and health service system.

Objective:To investigate the efficacy and safety of geritinib in the treatment of acute myeloid leukemia (AML) with FLT3 mutation.Methods:The clinical data of 5 AML patients with FLT3 mutation who were diagnosed in the University of Hong Kong-Shenzhen Hospital, Shenzhen People's Hospital, Shenzhen Second People's Hospital, Shenzhen University General Hospital from March 2020 to April 2021 were retrospectively analyzed. Relapsed patients concurrently received two- or three-drug chemotherapy combined with geritinib. Blood routine was checked once a week; liver function and renal function were checked once every 2 weeks during treatment. Bone marrow puncture was performed once every 1 to 3 months to monitor the bone marrow morphology, minimal residual disease (MRD) and FLT3 mutation expression levels. The efficacy, side effects, overall survival of these patients were analyzed after treatment with geritinib.Results:The white blood cell was increased in all the 5 patients at the initial diagnosis. FLT3 mutations analysis showed FLT3-internal tandem duplication (ITD) (3 cases) and FLT-3 tyrosine-kinase domain (TKD) (2 cases). Among 5 patients, 1 patient was relapse-free with maintenance therapy of oral geritinib after hematological stem cell transplantation (HSCT) for 60 days; among other 4 relapsed and refractory patients, 1 female patient after pregnancy relapsed after transplantation and then achieved complete remission followed by the maintenance therapy with geritinib after oral geritinib, 1 16-year-old patient achieved treatment outcome close to the complete remission after treatment with geritinib, 1 patient achieved complete remission after treatment with geritinib, and then underwent haplo-HSCT followed by the maintenance therapy with geritinib and the other 1 relapsed patient achieved complete remission after treatment with geritinib. After transplantation, 3 patients receiving maintenance treatment of geritinib did not relapse. The main side effects included anemia, decreased neutrophil count, rash, and increased aminotransferase. The median follow-up time of 5 patients was 15 months (6-20 months). All 5 cases survived until the last follow-up in November 2021 and 4 patients were disease-free.Conclusions:Relapsed and refractory AML patients with FLT3 mutation can achieve complete remission after treatment with geritinib and get a chance for transplantation. Geritinib may reduce the risk of recurrence after transplantation and improve survival rate. No serious side effects occur in geritinib treatment.

Objective:To explore the relationship between the changes of total cholesterol (TC), C-reactive protein (CRP), vascular endothelial growth factor (VEGF) and the degree of false lumen thrombosis after thoracic endovascular aortic repair (TEVAR) and its clinical significance.Methods:A total of 95 patients with aortic dissection admitted to the Affiliated Hospital of Jining Medical College from June 2015 to July 2020 were selected for retrospective study. All patients were treated with TEVAR. According to the disappearance of false lumen detected by computed tomography (CT) angiography six months after operation, 95 patients were divided into complete disappearance group ( n=43) and incomplete disappearance group ( n=52). The levels of plasma TC, CRP and VEGF in the two groups were compared before operation and 1 and 3 months after operation, as well as the degree of false lumen thrombosis. Spearman′s method was used to analyze the relationship between the levels of plasma TC, CRP and VEGF and the degree of postoperative false lumen thrombosis; multivariate logistic regression was used to analyze the factors affecting the disappearance of false lumen after TEVAR; The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to analyze the value of each index in predicting the complete disappearance of false lumen. Results:The plasma levels of TC, CRP and VEGF in the complete disappearance group were lower than those in the incomplete disappearance group 1 and 3 months after operation (all P<0.05). The degree of false lumen thrombosis in the complete disappearance group was significantly different from that in the incomplete disappearance group 1 and 3 months after operation (all P<0.05). The plasma levels of TC, CRP and VEGF 1 and 3 months after TEVAR were negatively correlated with the degree of false lumen thrombosis (all P<0.05). Multivariate logistic regression analysis showed that the plasma levels of TC, CRP and VEGF 1 and 3 months after operation were correlated with the disappearance of false lumen (all P<0.05). With the passage of time, the AUC of each index to predict the complete disappearance of false lumen gradually increased. At 3 months after operation, the AUC of TC, CRP, VEGF and combined prediction of the complete disappearance of false lumen were 0.706, 0.899, 0.781 and 0.943, respectively (all P<0.05). Conclusions:The changes of plasma TC, CRP and VEGF levels after TEVAR are related to the degree of false lumen thrombosis and the disappearance of false lumen in patients with aortic dissection. Combined examination of the three can be an effective method to predict the complete disappearance of false lumen.