ObjectiveTo investigate the dynamic expression profiles and potential regulatory mechanisms of long non-coding RNAs （lncRNAs） in male reproductive system aging. MethodsA naturally aging C57BL/6 mouse model was used and 4 mice were selected each at 3， 15， and 21 months of age. RNA was extracted from seven regions of the male reproductive tract （testis， efferent duct， initial segment of epididymis， caput epididymis， corpus epididymis， cauda epididymis， and vas deferens）， followed by RNA sequencing and bioinformatics analysis. ResultsRegion-specific dynamic expression profiles of lncRNAs were constructed in the testis， epididymis （efferent duct， initial segment， caput， corpus， and cauda）， and vas deferens of male mice. Combined with gene functional enrichment analysis， the functional associations of lncRNAs were elucidated in reproductive system aging. The differentially expressed lncRNAs in the aging testis were primarily involved in hormone biosynthesis and extracellular matrix organization， while those in the initial segment of the epididymis were closely related to cell recognition and epithelial cell migration. A comprehensive lncRNA expression atlas associated with male reproductive aging was established. ConclusionLncRNAs may participate in male reproductive aging through the regulation of the reproductive microenvironment， which provides key molecular targets and a research foundation for understanding age-related fertility decline.

Objective:To investigate the application of (4R)-4-(3-[ 18F]fluoranyl-5-fluorophenyl)-1-((3-methylpyridin-4-yl)methyl)pyrrolidin-2-one( 18F-SynVesT-1), a synaptic vesicle glycoprotein 2A (SV2A) radioactive tracer, in patients with Alzheimer′s disease (AD). Methods:A total of 20 AD patients (2 males, 18 females, age (66.4±8.1) years) with positive β-amyloid (Aβ) deposition and 20 normal controls (NC; 9 males, 11 females, age (62.6±8.6) years ) without Aβ deposition were retrospectively recruited from Huashan Hospital, Fudan University between December 2021 and December 2022. All of them underwent 18F-SynVesT-1 PET/MR and 18F-Florbetapir (AV45) PET/CT scans. Preprocessing of brain 18F-SynVesT-1 PET images was carried out using statistical parametric mapping (SPM). The differences of the uptke of 18F-SynVesT-1 (synaptic density) between two groups based on ROI were compared by using either the independent-sample t test or Mann-Whitney U test. Spearman rank correlation analysis was performed to assess the relationship between synaptic density and cognitive performance. For voxelwise analysis, a general linear model was constructed to analyze differences in synaptic density between the two groups using the independent-sample t test. Furthermore, a multiple linear regression model was developed to explore the relationship between synaptic density and cognitive performance. Results:Compared to the NC group, the AD group exhibited significant widespread reduction in synaptic density across the cortical regions ( P<0.05, false discovery rate (FDR)-corrected), particularly in the medial temporal lobe (0.84±0.09 vs 1.04±0.09; t=-6.95, P<0.001), lateral temporal lobe (1.15±0.13 vs 1.31±0.08; t=-4.56, P<0.001), and lateral parietal lobe (1.24(1.04, 1.26) vs 1.32(1.23, 1.39); z=-3.25, P=0.001). Moreover, synaptic density in extensive cortical regions showed a positive correlation with mini-mental state examination (MMSE) and Montreal cognitive assessment-basic (MoCA-B) scores ( P<0.05, FDR-corrected). Notably, significant associations were observed between MMSE and MoCA-B scores and synaptic density in the lateral temporal lobe ( rs values: 0.71, 0.74, both P<0.001) and medial temporal lobe ( rs values: 0.71, 0.74, both P<0.001). Conclusions:18F-SynVesT-1 PET imaging is a valuable tool for evaluating synaptic density, specifically in the context of AD. The observed widespread reduction in synaptic density across cortical regions of patients with AD are closely related to cognitive decline.

Objective:To evaluate the clinical value of CD4 + T lymphocyte subsets such as helper Th2 in patients with recurrent uveitis (BU) in Beh?et′s disease (BD). Methods:The clinical data of 153 hospitalized patients diagnosed with Beh?et′s disease from January 1, 2020 to June 30, 2023 in the Second Hospital of Shanxi Medical University were retrospectively analyzed. The subsets of CD4 + T lymphocytes were measured, including helper T cells (Th cells) such as Th1, Th2, Th17 and regulatory T cells (Treg cells), biochemical lipid indexes (TC, TG, etc.), the frequency of oral ulcers in the past 1 year, the frequency of genital ulcers in the past 1 year, and drug use before admission;According to whether there was ocular involvement and uveitis, 153 cases of BD were divided into Beh?et non-uveitis group (non-BU group) and Beh?et uveitis group (BU group). The above indexes and independent correlation factors of recurrent BU were compared between BU group and non-BU group;The above indexes and independent correlation factors of recurrent BU were compared between BU group and non-BU group. The levels of cytokines and ICBD total score, the correlation between ICBD total score and various cytokines, and the diagnostic performance of Th2 cells were compared between BU group and non-BU group.The statistical methods were Mann-Whitney U test, independent sample t test, Chi-square test, multiple logistic regression analysis, Pearson correlation analysis and receiver operating characteristic curve (ROC) analysis. Results:①The levels of Th1, Th2, Th17 cells, TC and TG in BU group were higher than those in non-BU group [133.87 (93.38, 229.87)/μl vs. 102.51(64.25, 149.23)/μl] and [9.43 (5.84, 14.13)/μl vs. 6.78(4.23, 9.44)/μl], [15.53 (9.36, 25.27)/μl vs. 9.83(5.46, 14.76)/μl], [4.21 (3.89, 4.90) mmol/L vs. 3.89(3.37, 4.34)mmol/L)], [1.43(1.00, 2.21)mmol/L vs. 0.96(0.69, 1.38)mmol/L], The differences were statistically significant ( Z=-3.24, Z=-3.05, Z=-3.94, Z=-2.25, Z=-3.47; all P<0.05); There was no statistical significance in Chi-square test between the two groups ( χ2=5.69, P>0.05).②The levels of IL-2, IL-10 and total ICBD score in BU group were higher than those in non-BU group, with statistical significance ( Z=-2.12, Z=-2.29, t=-6.48; all P<0.05). ③ The results of multiple logistic regression analysis showed that Th2 was an independent correlation factor for BU [ OR value (95% CI) was 1.143(1.007, 1.298), P=0.039]. The total score of BU patients was correlated with Th2 and Th17 cells. ROC analysis showed that the sensitivity of Th2 in diagnosing BU was 68.8%, the specificity was 49.5% and the area under the curve (95% CI) was 0.697 (0.585, 0.809) (P=0.001). Conclusion:CD4 + T lymphocyte subsets such as the absolute number of Th2 cells are related to BU, which is an important indicator to observe the severity of disease progression in BU patients, and has certain clinical value in evaluating the recurrence of BU in BD patients.

Objective To investigate the factors influencing prognosis in patients with acute myocardial infarction complicated with cardiogenic shock undergoing primary percutaneous coronary intervention(PPCI).Methods Patients with acute myocardial infarction complicated with cardiogenic shock who underwent PPCI at our hospital between January 2015 and December 2019 were enrolled.Clinical baseline characteristics,coronary angiography and PCI-related parameters,and mechanical support information were collected.The patients were followed up for one year and divided into survival and death groups based on their survival status within one year.Differences in various factors between the two groups were compared.Results A total of 40 patients were enrolled,including 26 in the survival group and 14 in the death group.There were no differences in baseline data,diagnosis,risk factors,and comorbidities between the two groups.The survival group had a lower heart rate and higher blood pressure trend at admission compared to the death group.Myocardial enzymes were significantly lower in the survival group compared to the death group(median CK peak:496.00(198.25,2 830.00)U/L vs.3 040.00(405.75,5 626.53)U/L,P=0.003;median CK-MB peak:52.65(31.75,219.50)U/L vs.306.00(27.25,489.63)U/L,P=0.006).When comparing coronary angiography and PCI-related indicators between the two groups,the survival group had a higher rate of complete revascularization compared to the control group(53.85％vs.21.43％,P=0.048).The survival group had a higher proportion of extracorporeal membrane oxygenation(ECMO)combined with intra-aortic balloon pump(IABP)support compared to the control group[38.46％vs.7.14％,P=0.034].Conclusions Survival in patients with acute myocardial infarction complicated with cardiogenic shock undergoing PPCI is associated with lower level of myocardial enzymes,ECMO combined with IABP support and complete revascularization.

The 3-succinate-30-stearyl glycyrrhetinic acid(18-GA-Suc) was inserted into glycyrrhetinic acid(GA)-tanshinone Ⅱ_A(TSN)-salvianolic acid B(Sal B) liposome(GTS-lip) to prepare liver targeting compound liposome(Suc-GTS-lip) mediated by GA receptors. Next, pharmacokinetics and tissue distribution of Suc-GTS-lip and GTS-lip were compared by UPLC, and in vivo imaging tracking of Suc-GTS-lip was conducted. The authors investigated the effect of Suc-GTS-lip on the proliferation inhibition of hepatic stellate cells(HSC) and explored their molecular mechanism of improving liver fibrosis. Pharmacokinetic results showed that the AUC_(Sal B) decreased from(636.06±27.73) μg·h·mL~(-1) to(550.39±12.34) μg·h·mL~(-1), and the AUC_(TSN) decreased from(1.08±0.72) μg·h·mL~(-1) to(0.65±0.04) μg·h·mL~(-1), but the AUC_(GA) increased from(43.64±3.10) μg·h·mL~(-1) to(96.21±3.75) μg·h·mL~(-1). The results of tissue distribution showed that the AUC_(Sal B) and C_(max) of Sal B in the liver of the Suc-GTS-lip group were 10.21 and 4.44 times those of the GTS-lip group, respectively. The liver targeting efficiency of Sal B, TSN, and GA in the Suc-GTS-lip group was 40.66%, 3.06%, and 22.08%, respectively. In vivo imaging studies showed that the modified liposomes tended to accumulate in the liver. MTT results showed that Suc-GTS-lip could significantly inhibit the proliferation of HSC, and RT-PCR results showed that the expression of MMP-1 was significantly increased in all groups, but that of TIMP-1 and TIMP-2 was significantly decreased. The mRNA expressions of collagen-I and collagen-Ⅲ were significantly decreased in all groups. The experimental results showed that Suc-GTS-lip had liver targeting, and it could inhibit the proliferation of HSC and induce their apoptosis, which provided the experimental basis for the targeted treatment of liver fibrosis by Suc-GTS-lip.
Humans ; Liposomes ; Hepatic Stellate Cells ; Glycyrrhetinic Acid/pharmacology* ; Liver ; Liver Cirrhosis/genetics* ; Collagen/pharmacology*

Pancreatic cancer is a highly malignant tumor with a poor prognosis. It is very hard to treat pancreatic cancers for their high heterogeneity, complex tumor microenvironment, and drug resistance. Currently, gemcitabine plus nab-paclitaxel, capecitabine and FOLFIRINOX are standard chemotherapy for resectable or advanced metastatic pancreatic cancer. Considering the limited efficacy and toxic side effects of chemotherapy, targeted and immune drugs have gradually attracted attention and made some progress. In this article, we systematically reviewed the chemotherapeutic drugs, targets and related targeted drugs, and immunotherapy drugs for pancreatic cancer.

AIM: To optimize the technique of intravenous injection of Evans blue and retinal preparations in mice, improving the accuracy and repeatability of staining experiment of retinal preparations.METHODS: C57BL/6 male mice were intravenous injected with 10g/L(1%)Evans Blue 0.3mL and circulated in vivo for 10 or 20min, and the eyes were removed after sacrificed and fixed in 4% paraformaldehyde for 20, 40 or 60min. When failure of intravenous injection, the experiment was remediated by intraperitoneal injection of 1% Evans Blue 0.3mL, circulated in vivo for 3h and fixed for 60min to observe morphology, distribution and leakage of the retinal vessels. Besides, we compared the morphology, distribution and leakage of the retinal vessels after intravenous injection with those after intraperitoneal injection to determine the optimal conditions for in vivo circulation time and retinal preparations.RESULTS: After intravenous injection, compared to the retinal vascular condition under 20min in vivo circulation time of Evans blue and 20 or 40min of fixation, with 10min of in vivo Evans blue circulation and 60min of fixation, the morphology of retinal vascular was more intact with less retinal vascular leakage, and the vascular branches are clear. When intravenous injection failed, remediated results from intraperitoneal injection showed that the morphology and distribution of retinal vessels were intact. There was no significant difference in morphology, distribution and leakage of the retinal vessels after 3h of intraperitoneal Evans blue circulation compared to 10min intravenous Evans blue circulation.CONCLUSION: This experiment optimizes the protocol, improves the accuracy and reproducibility of retinal preparations, and provides a reference for the study of related retinal vascular diseases.

Humans ; Small Cell Lung Carcinoma/drug therapy* ; Lung Neoplasms/drug therapy* ; Colonic Neoplasms/drug therapy* ; Microsatellite Instability ; DNA Mismatch Repair ; Colorectal Neoplasms

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected 660 million people and resulted in 6.7 million deaths. At present, a variety of risk factors related to the severity of COVID-19 have been identified, but whether allergic rhinitis and asthma will affect SARS-CoV-2 infection remains controversial. In general, there is no sufficient evidence to support that allergic rhinitis or asthma is a risk factor for increasing the rate of SARS-CoV-2 infection or aggravating the disease. Some studies even show that atopy may be a protective factor to alleviate SARS-CoV-2 infection, which is related to the decreased expression of angiotensin-converting enzyme 2, the receptor required for SARS-CoV-2 to enter cells, in atopic individuals. This paper reviews the influence of the severity and treatment of allergic rhinitis and asthma on SARS-CoV-2 infection, in order to provide some references for establishing strategies for prevention, risk stratification and treatment of COVID-19.
Humans ; COVID-19 ; SARS-CoV-2/metabolism* ; Peptidyl-Dipeptidase A/metabolism* ; Asthma/therapy* ; Rhinitis, Allergic

Objective: To analyze the clinical characteristics of children with IgE-mediated cow's milk protein allergy (CMPA) and provide a basis for disease management and prevention. Methods: A cross-sectional study was conducted to analyze 142 children aged 0-12 years who were diagnosed with IgE-mediated CMPA in Capital Institute of Pediatrics Affiliated Children's Hospital from 2020 to 2022. There were 79 males (55.6%) and 63 females (44.4%), with an average age of 14 (8, 27) months. 61 cases (43.0%) were in the <1-year-old group, 54 cases (38.0%) in the 1-3-year-old group, and 27 cases (19.0%) in the >3-year-old group. Data on demographic data, clinical manifestations, mean wheel diameter of skin prick test and serum specific IgE level were collected. The serum cow's milk protein sIgE and component sIgE were measured by ImmunoCAP fully automated system of fluorescence enzyme-linked immunosorbent assay, and statistically analyzed using chi-square test, nonparametric tests, correlation. Results: Cutaneous symptoms were the first and most frequent in 142 children (97.9%, 139/142 cases), followed by digestive (29.6%, 42/142 cases) and respiratory symptoms (27.5%, 39/142 cases).The proportion of children with respiratory symptoms after consuming cow's milk was significantly higher in the>3 years age group than those in the infant and toddler groups(66.7% vs 19.7%,χ²=18.396,P<0.01;66.7% vs 16.7%,χ²=20.250,P<0.01), and the symptoms involving ≥3 systems were also significantly higher than those in the other two groups(37.0% vs 13.1%,χ²=6.597,P<0.05;37.0% vs 7.4%,χ²=12.120,P<0.01). The average cow's milk SPT diameter and serum sIgE levels in the>3 years age group were significantly higher than those in the infant and toddler groups (Z=-4.682, P<0.01; Z=-3.498, P<0.01); (Z=-4.463, P<0.01; Z=-6.463, P<0.01). The most common cow's milk component protein were β-lactoglobulin(65.1%,56/86 cases) and casein (57.0%, 49/86 cases). Multiple-sensitization rate of the patients were 54.9%. Egg white (43.7%, 62/142 cases) was the most common co-sensitization food allergen while mold (12.7%, 18/142 cases) and weed pollen (12.7%, 18/142 cases) were the main co-sensitization aeroallergens. The proportion of multiple-sensitization to aeroallergens in the children group was the highest (51.9%, 14/27 cases), followed by the toddler group (29.6%, 16/54 cases), and the infant group was the least (3.3%, 2/61 cases). There was a significant difference among these three groups (χ²=7.476, P<0.05). Conclusion: Skin and mucosal symptoms are the most common in CMPA patients. The proportion of respiratory symptoms and multisystem involvement increased with age as well as the wheal diameter in skin test and serum sIgE level elevated. CMPA patients older than 3 years had the highest proportion of aeroallergen sensitization and airway allergic diseases.
Male ; Animals ; Cattle ; Female ; Child ; Humans ; Milk Hypersensitivity/diagnosis* ; Cross-Sectional Studies ; Food Hypersensitivity ; Allergens ; Immunoglobulin E