Kupffer cells (KCs), as residents and sentinels of the liver, are involved in the formation of hepatic fibrosis (HF). However, the biological functions of circular RNAs (circRNAs) in KCs to HF have not been determined. In this study, the expression levels of circRNAs, microRNAs, and messenger RNAs (mRNAs) in KCs from a mouse model of HF mice were investigated using microarray and circRNA-Seq analyses. circDcbld2 was identified as a candidate circRNA in HF, as evidenced by its up-regulation in KCs. Silver staining and mass spectrometry showed that Wtap and Igf2bp2 bind to cirDcbld2. The suppression of circDcbld2 expression decreased the KC inflammatory response and oxidative stress and inhibited hepatic stellate cell (HSCs) activation, attenuating mouse liver fibrogenesis. Mechanistically, Wtap mediated the N ⁶-methyladenosine (m6A) methylation of circDcbld2, and Igf2bp2 recognized m6A-modified circDcbld2 and increased its stability. circDcbld2 contributes to the occurrence of HF by binding miR-144-3p/Et-1 to regulate the inflammatory response and oxidative stress. These findings indicate that circDcbld2 functions via the m6A/circDcbld2/miR-144-3p/Et-1 axis and may act as a potential biomarker for HF treatment.

Objective:To investigate the association of urinary cadmium levels with peripheral leukocyte classification counts among middle-aged and older adults aged 40 to 89 years in selected areas of China.Methods:The research was based on the survey of the impact of soil quality of agricultural land on human health in typical areas conducted in 2019-2020. A total of 5 600 middle-aged and older adults aged 40 to 89 years were included by using a multi-stage stratified random sampling method. Baseline characteristics of the subjects were collected and physical examinations were performed. Random midstream urine was collected to measure urinary cadmium and urinary creatinine and fasting venous blood was collected to measure the leukocyte count, neutrophil count, lymphocyte count, monocyte count and eosinophil count. The linear mixed effect model was used to analyse the association of urinary cadmium levels with leukocyte classification counts, and the dose-response relationship between them was analyzed by using the restricted cubic spline (RCS) function.Results:The age of the subjects was (63.17±12.02) years; 2 851 (50.91%) were males; and the M ( Q 1, Q 3) of urinary creatinine-corrected urinary cadmium levels was 2.69 (1.52, 4.69) μg/g·creatinine. After adjusting for confounding factors, the results of linear mixed effects model analysis showed that for each 1-unit increase in urinary creatinine-corrected urinary cadmium level, the percentage change [% (95% CI)] of leukocyte count and lymphocyte count was -1.70% (-2.61%, -0.79%) and -1.57% (-2.86%, -0.26%), respectively. RCS function showed a negative linear relationship between urinary creatinine-corrected urinary cadmium levels and leukocyte counts and lymphocyte counts, respectively (all Pnon-linear>0.05). Conclusion:Urinary cadmium levels are negatively associated with leukocyte count and lymphocyte count among middle-aged and older adults aged 40 to 89 years in selected areas of China.

Normal pregnancy is a contradictory and complicated physiological process. Although the fetus carries the human leukocyte antigen (HLA) inherited from the paternal line, it does not cause maternal immune rejection. As the only exception to immunological principles, maternal–fetal immune tolerance has been a reproductive immunology focus. In early pregnancy, fetal extravillous trophoblast cells (EVTs) invade decidual tissues and come into direct contact with maternal decidual immune cells (DICs) and decidual stromal cells (DSCs) to establish a sophisticated maternal–fetal crosstalk. This study reviews previous research results and focuses on the establishment and maintenance mechanism of maternal–fetal tolerance based on maternal–fetal crosstalk. Insights into maternal–fetal tolerance will not only improve understanding of normal pregnancy but will also contribute to novel therapeutic strategies for recurrent spontaneous abortion, pre-eclampsia, and premature birth.

Background::Endometriosis (EM) is a complex benign gynecological disease, but it has malignant biological behavior and can invade any part of the body. Clinical manifestations include pelvic pain, dysmenorrhea, infertility, pelvic nodules, and masses. Our previous study successfully detected circulating endometrial cells (CECs) in the peripheral blood of patients with EM. The purpose of this study is to overcome the limitation of cell size in the previous microfluidic chip method, to further accurately capture CECs, understand the characteristics of these cells, and explore the relationship between CECs and the clinical course characteristics of patients with EM.Methods::Human peripheral venous blood used to detect CECs and circulating vascular endothelial cells (CVECs) was taken from EM patients ( n = 34) hospitalized in the Peking University People’s Hospital. We used the subtraction enrichment and immunostaining fluorescence in situ hybridization (SE-iFISH) method to exclude the interference of red blood cells, white blood cells, and CVECs, so as to accurately capture the CECs in the peripheral blood of patients with EM. Then we clarified the size and ploidy number of chromosome 8 of CECs, and a second grouping of patients was performed based on clinical characteristics to determine the relationship between CECs and clinical course characteristics. Results::The peripheral blood of 34 EM patients and 12 non-EM patients was evaluated by SE-iFISH. Overall, 34 eligible EM patients were enrolled. The results showed that the detection rates of CECs were 58.8% in EM patients and 16.7% in the control group. However, after classification according to clinical characteristics, more CECs could be detected in the peripheral blood of patients with rapidly progressive EM, with a detection rate of 94.4% (17/18). In total, 63.5% (40/63) of these cells were small cells with diameters below 5 μm, and 44.4% (28/63) were aneuploid cells. No significant association was found between the number of CECs and EM stage.Conclusion::The number and characteristics of CECs are related to the clinical course characteristics of patients with EM, such as pain and changes in lesion size, and may be used as biomarkers for personalized treatment and management of EM in the future.

Objective:To investigate the association of urinary cadmium levels with peripheral leukocyte classification counts among middle-aged and older adults aged 40 to 89 years in selected areas of China.Methods:The research was based on the survey of the impact of soil quality of agricultural land on human health in typical areas conducted in 2019-2020. A total of 5 600 middle-aged and older adults aged 40 to 89 years were included by using a multi-stage stratified random sampling method. Baseline characteristics of the subjects were collected and physical examinations were performed. Random midstream urine was collected to measure urinary cadmium and urinary creatinine and fasting venous blood was collected to measure the leukocyte count, neutrophil count, lymphocyte count, monocyte count and eosinophil count. The linear mixed effect model was used to analyse the association of urinary cadmium levels with leukocyte classification counts, and the dose-response relationship between them was analyzed by using the restricted cubic spline (RCS) function.Results:The age of the subjects was (63.17±12.02) years; 2 851 (50.91%) were males; and the M ( Q 1, Q 3) of urinary creatinine-corrected urinary cadmium levels was 2.69 (1.52, 4.69) μg/g·creatinine. After adjusting for confounding factors, the results of linear mixed effects model analysis showed that for each 1-unit increase in urinary creatinine-corrected urinary cadmium level, the percentage change [% (95% CI)] of leukocyte count and lymphocyte count was -1.70% (-2.61%, -0.79%) and -1.57% (-2.86%, -0.26%), respectively. RCS function showed a negative linear relationship between urinary creatinine-corrected urinary cadmium levels and leukocyte counts and lymphocyte counts, respectively (all Pnon-linear>0.05). Conclusion:Urinary cadmium levels are negatively associated with leukocyte count and lymphocyte count among middle-aged and older adults aged 40 to 89 years in selected areas of China.

Background Di(2-ethylhexyl) phthalate (DEHP) is the highest consumed and the most widely used phthalic acid ester, their effects on lipid metabolism have attracted the attention of many scholars. However, the associated mechanism is still unclear. Objective To observe the effect of DEHP on lipid metabolism in rats, probe its possible mechanism, and provide a research basis for the effect of DEHP on human lipid metabolism. Methods Forty healthy male SD rats were randomly divided into 4 groups: solvent control (0 mg·kg⁻¹ DEHP), low DEHP (187 mg·kg⁻¹), medium DEHP (375 mg·kg⁻¹), and high DEHP (750 mg·kg⁻¹) groups. DEHP was administered by oral gavage for 6 d per week, consecutively 8 weeks. The rats were weighed once a week during the exposure period. At 24 h after the last exposure, the rats were anesthetized with 20% urethane and sacrificed by apical puncture. Rat livers were harvested and weighed before hematoxylin-eosin (HE) histopathological observation. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the mRNA levels of lipid metabolism-related genes Janus kinase 3 (JAK3), signal transducer and activator of transcription 5b (STAT5b), and peroxisome proliferator-activated receptor γ (PPARγ) in liver, and Western blot was used to detect the expression levels of lipid metabolism-related proteins JAK3, STAT5b, and PPARγ in liver. Results Compared with the control group, there was no significant difference in the body weight gain of the rats in each group (P>0.05). The liver organ coefficients of the DEHP exposure groups were higher than that of the control group (P<0.001), and increased with higher DEHP dosages. The level of high-density lipoprotein cholesterol (HDL-C) in serum decreased in all DEHP exposure groups (P<0.05), and the level of low-density lipoprotein cholesterol (LDL-C) in serum increased in the high DEHP group (P<0.05). The results of liver histopathological morphology showed that the hepatocytes of each DEHP group were enlarged and edematous in varying degrees, with loose stroma and irregular arrangement of cells, which were manifested as inflammatory cell infiltration and fatty degeneration of liver cells. Compared to the control group, the mRNA levels of JAK3, STAT5b, and PPARγ in liver tissues of rats in each DEHP group decreased (P<0.001). Compared to the control group, the relative expression levels of JAK3 in each DEHP group decreased (P<0.05), and the relative expression levels of STAT5b and PPARγ in the medium and high DEHP groups decreased (P<0.05). Conclusion DEHP exposure can induce abnormal lipid metabolism in rats, and the mechanism may be related to DEHP inhibiting the activation of JAK3/STAT5b/PPARγ signaling pathway.

Objective To investigate the distribution and imaging manifestations of extrapulmonary bronchogenic cyst(BC)and to make differential diagnosis.Methods The data of 32 patients with extrapulmonary BC confirmed by pathology were collected.The lesion location,CT and MRI findings were analyzed and summarized.All patients underwent plain CT scan,and 27 of them underwent enhanced CT scan.Three patients underwent MRI plain and enhanced scan.Results Of the 32 patients,24 cases were mediastinal BC including 20 cases in the anterior mediastinum and other 4 cases in the posterior mediastinum.8 cases were ectopic BC,including 2 cases in the upper chest wall,4 cases in the gastric cardia,1 case in the greater curvature of the stomach,and 1 case in the left adre-nal gland.All lesions were single with clear boundary.The lesions were mainly round in shape(22 cases),and a few were flat/"D"shape(10 cases).There were no significant differences in the included signs between mediastinal BC and ectopic BC(P＞0.05).Nodular calcification of cyst wall was found in 2 cases.There were 4 cases with CT value＜20 HU and other 28 cases with CT value≥20 HU.The enhanced CT scan in 27 cases showed non-or mild enhancement.MRI showed hypointensity on T1WI in 2 cases,isointensity on T1WI in 1 case,hyperintensity on T2WI in 3 cases,and obvious enhancement on T1WI enhanced scan in 1 case.In addition,30 cases(93.7％)were misdiagnosed as thymic cyst(8 cases),thymoma(12 cases),neurogenic tumor(4 cases),ganglioneuroma(4 cases)and gastric stromal tumor(2 cases).Conclusion Extrapulmonary BC is rare,and most of the lesions are located near the central axis of the body with no obvious enhancement and sometimes cyst wall calcification,which has certain value for clinical diagnosis.

Objective:To explore the chain mediating effect of basic activity of daily living and nutritional status the effects on comorbidity and frailty, so as to provide guidance for preventing and delaying the frailty of elderly patients with cardiovascular disease and abnormal glucose metabolism.Methods:The cross-sectional study method was adopted, 300 elderly patients with cardiovascular disease and abnormal glucose metabolism who were hospitalized in the cardiovascular medicine ward of Shandong Provincial Hospital Affiliated to Shandong First Medical University, were selected as the study objects from January to August 2022, and were surveyed using General Information Questionnaire, Frailty Scale, Charlson Comorbidity Index Scale, Barthel Index Rating Scale and Mini Nutritional Assessment-Short Form were used to investigate them.Results:A total of 300 questionnaires were collected and 291 valid questionnaires were returned. Out of 291 patients, 167 were male and 124 were female, with an age of (69.55 ± 7.01) years. Comorbidities in elderly patients with cardiovascular disease and abnormal glucose metabolism were positively correlated with frailty ( r=0.414, P<0.01), and negatively correlated with basic activity of daily living and nutritional status ( r=-0.399, -0.373, both P<0.01). Basic activity of daily living was positively correlated with nutritional status ( r=0.575, P<0.01) and negatively correlated with frailty ( r=-0.825, P<0.01). Nutritional status was negatively correlated with frailty ( r=-0.695, P<0.01). The chain mediating model showed that comorbidities had a significant direct effect on frailty (effect value of 0.102), basic activity of daily living partially mediated between comorbidity and frailty (effect value of 0.125). Basic activity of daily living and nutritional status partially chained between comorbidity and frailty (effect value of 0.036). Conclusions:The chain mediating roles of basic activity of daily living and nutritional status between comorbidity and frailty was established. Healthcare professionals should pay attention to the improvement of basic activity of daily living in elderly patients with cardiovascular diseases and abnormal glucose metabolism, guide them to have a reasonable diet to achieve balanced nutrition, and delay the onset and development of frailties.

In November 2023, the seventh National Nucleic Acid Vaccine Conference was held to deeply discuss the immune mechanism, safety risks, advantages, and disadvantages of nucleic acid vaccines, and review the safety and effectiveness of COVID-19 vaccines developed by nucleic acid vaccine technology. Some prospectives were formed in the meeting that in the post-pandemic era, nucleic acid vaccine technology will play a role in the following areas: dealing with pathogens that are difficult to be prevented by traditional vaccines, promoting the upgrading of traditional live attenuated vaccines, contributing to the development of multivalent and combined vaccines, and rapid response to emerging and re-emerging infectious diseases. These views point out the direction for the future development of nucleic acid vaccine technology.

Objective To explore the efficacy of Tongluo Kaibi tablet combined with intra-articular injection of hypertonic glucose in the treatment of knee osteoarthritis(KOA).Methods A total of 82 patients with KOA admitted to Ganzhou Hospital of Traditional Chinese Medicine from January to December 2023 were selected and divided into control group and observation group according to random number table method,with 41 cases in each group.The control group was given diclofenac sodium oral administration+intra-articular injection of sodium hyaluronate,and the observation group was given Tongluo Kaibi tablet oral administration+intra-articular injection of hypertonic glucose.Both groups were treated for 8 weeks.The clinical efficacy,visual analogue scale(VAS)score,Lysholm knee joint score and inflammatory factor levels were compared between two groups.Results The total effective rate of observation group was significantly higher than that of control group(χ2=6.187,P<0.001).After 8 weeks of treatment,VAS score,tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),matrix metalloproteinase 3(MMP-3)in both groups were significantly lower than before treatment,and Lysholm knee joint scores were significantly higher than before treatment(P<0.05).VAS score,TNF-α,IL-1β and MMP-3 levels in observation group were significantly lower than those in control group,and Lysholm knee joint score was significantly higher than that in control group(P<0.05).Conclusion Tongluo Kaibi tablet combined with intra-articular injection of hypertonic glucose can help KOA patients relieve knee pain,reduce the level of inflammatory factors and improve knee joint function,and the therapeutic effect is accurate.