Air Pollution/analysis* ; Environmental Exposure/analysis* ; China/epidemiology* ; Air Pollutants/analysis* ; Particulate Matter/analysis* ; Environmental Monitoring

Astrocytes are the largest glial population in the mammalian brain. However, we have a minimal understanding of astrocyte development, especially fate specification in different regions of the brain. Through lineage tracing of the progenitors of the third ventricle (3V) wall via in-utero electroporation in the embryonic mouse brain, we show the fate specification and migration pattern of astrocytes derived from radial glia along the 3V wall. Unexpectedly, radial glia located in different regions along the 3V wall of the diencephalon produce distinct cell types: radial glia in the upper region produce astrocytes and those in the lower region produce neurons in the diencephalon. With genetic fate mapping analysis, we reveal that the first population of astrocytes appears along the zona incerta in the diencephalon. Astrogenesis occurs at an early time point in the dorsal region relative to that in the ventral region of the developing diencephalon. With transcriptomic analysis of the region-specific 3V wall and lateral ventricle (LV) wall, we identified cohorts of differentially-expressed genes in the dorsal 3V wall compared to the ventral 3V wall and LV wall that may regulate astrogenesis in the dorsal diencephalon. Together, these results demonstrate that the generation of astrocytes shows a spatiotemporal pattern in the developing mouse diencephalon.
Mice ; Animals ; Astrocytes ; Neuroglia/physiology* ; Diencephalon ; Brain ; Neurons ; Mammals

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases. A number of allosteric RIPK1 inhibitors (RIPK1i) have been developed, and some of them have already advanced into clinical evaluation. Recently, selective RIPK1i that interact with both the allosteric pocket and the ATP-binding site of RIPK1 have started to emerge. Here, we report the rational development of a new series of type-II RIPK1i based on the rediscovery of a reported but mechanistically atypical RIPK3i. We also describe the structure-guided lead optimization of a potent, selective, and orally bioavailable RIPK1i, 62, which exhibits extraordinary efficacies in mouse models of acute or chronic inflammatory diseases. Collectively, 62 provides a useful tool for evaluating RIPK1 in animal disease models and a promising lead for further drug development.

Objective:To analyze the association between visceral fat area (VFA) and fatty liver based on quantitative CT (QCT) in people receiving health examination with normal body mass index (BMI).Methods:A cross-sectional study. A total of 1 305 physical examiners who underwent chest CT and QCT examination in the Department of Health Management of Henan Provincial People′s Hospital from January to December 2021 were retrospectively selected as subjects. The physical components at the central level of the lumbar two cone were measured with QCT, including subcutaneous fat area (SFA), VFA and liver fat content (LFC). And the metabolic indexes, such as blood lipids and blood glucose, were collected. The t-test and χ2 test were used to analyze the correlation between the detection rate of fatty live and LFCr and age and gender. According to level of VFA (<100 cm 2, 100-150 cm 2 and≥150 cm 2), the subjects were divided into three groups, and one-way ANOVA and χ2 test were used in comparison between groups. Multiple linear regression was used to analyze the correlation between VFA and metabolic indexes and LFC. Results:Of the 1 305 subjects, there were 634 males and 671 females. The detection rate of fatty liver in normal BMI population was 65.67%, and it was 72.71% and 59.02% respectively in men and women ( χ2=27.12, P<0.001), and the detection rate of fatty liver and LFC increased with age (both P<0.05). With the increase of VFA, the age, BMI, SFA, LFC, total cholesterol (TC), triacylglycerol (TG), low-density lipoprotein cholesterol (LDL-C), fasting blood glucose (FBG), alanine aminotransferase (ALT), blood uric acid and prevalence of fatty liver increased (all P<0.05), and the low-density lipoprotein cholesterol (HDL-C) decreased ( P<0.001). Multiple linear regression analysis showed that after adjustment for age factors, regardless of male or female, LFC was independently positively related with VFA, BMI, and ALT (male β=0.206, 0.145, 0.174, female β=0.194, 0.150, 0.184; all P<0.05). FBG was positively correlated with male independently ( β=0.134; P<0.001). The indicators related to female independently were TC, TG, and blood uric acid ( β=-0.121, 0.145, 0.141, all P<0.05) Conclusion:In the population receiving health examination with normal BMI, the VFA measured by QCT technique is closely related to fatty liver.

AIM: To investigate the relationship between objective ocular torsion and near stereopsis in patients with primary superior oblique overaction(PSOOA).METHODS: Retrospective study. A total of 59 strabismus patients with PSOOA who underwent strabismus surgery at Renmin Hospital of Wuhan University between January 2019 and November 2023 were collected. Based on the collected fundus photographs and the position of the fovea relative to the horizontal line through the optic disc, the eyes were categorized as incyclotorsion, excyclotorsion, or no cyclotorsion. Additionally, the fovea-disc angle(FDA)and the relationship between objective ocular torsion status, FDA, and near stereopsis function in the patients were further measured and analyzed.RESULTS: Totally 59 patients(92 eyes)showed superior oblique overaction. There were no cases of excyclotorsion, 32 cases with no cyclotorsion, and 27 cases with incyclotorsion. The total binocular FDA was significantly smaller in the no-cyclotorsion group compared with the incyclotorsion group(2.83°±2.89° vs 16.12°±5.74°, P<0.001). The preservation rates of near stereopsis were 66% and 15% in the no-cyclotorsion and incyclotorsion groups, respectively, with a significant statistical difference(P<0.001), and the preservation rates of fine near stereopsis were 38% and 11% in the no-cyclotorsion and incyclotorsion groups, respectively, with a significant statistical difference(P=0.02). Among all patients, near stereopsis was correlated with total binocular FDA(r=-0.526, P<0.001), with the strongest correlation observed with the FDA of the incyclotorsion(r=-0.546, P<0.001). In the incyclotorsion group, there was no correlation between near stereopsis and total binocular FDA(r=-0.366, P=0.060), with a negative correlation between near stereopsis and the FDA of both the incyclotorsion and the overaction(r=-0.424, P=0.028; r=-0.485, P=0.010). In the no-cyclotorsion group, near stereopsis was not correlated with total binocular FDA, incyclotorsion FDA, or overaction FDA.CONCLUSION:PSOOA patients with incyclotorsion have a lower preservation rate of near stereopsis than those without cyclotorsion. Near stereopsis function of patients with PSOOA is negatively correlated with total binocular FDA, especially the greater the FDA of the incyclotorsion and overaction, the worse the near-stereoscopic function.

ObjectiveTo compare the differences in intestinal absorption of nanophase（NP） formed by single decoction and combined decoction of Ginseng Radix et Rhizoma（GRR） and Zingiberis Rhizoma Recens（ZRR） in rats， and to investigate the effects of new NP formed by the combined decoction on the absorption of main components in GRR and ZRR. MethodDifferential centrifugation and dialysis techniques were used to enrich NP in the single and combined decoctions of GRR and ZRR， respectively. The microstructure， particle size， Zeta potential and concentration of the NP were analyzed by transmission electron microscope， particle size analyzer and nanoparticle tracking analyzer. Based on everted gut sac model， the index components in the intestinal absorption solution of NP from the single and combined decoctions were analyzed by ultra-performance liquid chromatography-triple quadrupole tandem mass spectrometry（UPLC-QqQ-MS/MS）. The per unit area actual value of cumulative intestinal absorption（Q_actual）， absorption rate constant（K_a） and apparent permeability coefficient（P_app） were used as the evaluating indexes to investigate the absorption characteristics of the aforementioned NP in the duodenum， jejunum， ileum and colon. ResultIrregularly spherical NP was present in the single and combined decoctions， and the contents of components in NP of the combined decoction were mostly lower than those in the single decoction. In these NP， ten components could be absorbed into the intestinal sac， with the main absorption site being the small intestine， and the P_app was greater than 1×10^-5 cm·min^-1. Compared with NP in the single decoction， the Q_actual and K_a of ginsenoside Rb₁， ginsenoside Rf， 4-gingerol and 6-shogaol were significantly increased in NP of the combined decoction， while ginsenoside Re and 6-gingerol were significantly decreased（P<0.01）. Except for ginsenoside Re and ginsenoside Rd， the P_app of the remaining constituents was significantly increased in NP of the combined decoction（P<0.01）. In addition， the maximum intestinal segment site of Q_actual was shifted forward for ginsenoside Rb₁， ginsenoside Rd and ginsenoside Ro， while shifted backward for ginsenoside Rg₁， ginsenoside Re and 8-gingerol. The maximal intestinal segment sites of K_a and P_app of ginsenoside Rb₁， ginsenoside Rg₁， ginsenoside Rd and ginsenoside Ro shifted forward， while ginsenoside Re and 4-gingerol were shifted backward. ConclusionThe combined decoction of GRR and ZRR is helpful to promote the absorption of the effective components of the two， and changes the absorption behavior of the effective components in some intestinal segments. This study provides a reference for the subsequent research on the compatibility mechanism of the two medicines.

Objective The aim of the study was to investigate how morphine(Mor)effects mitochondrial dynamics change of H9c2 induced by hypoxia/reoxygenation(H/R).Methods Myocardial H9c2 cells were divided into blank group(without treatment),model group(H/R treatment),control group(5 μmol·L-1 Mor treatment)and experimental group(H/R+5 μmol·L-1 Mor treatment).The content of reactive oxygen species(ROS),mitochondrial membrane potential(MMP),and complex of Ⅰ and Ⅲ activity were detected using ROS,tetramethylrhodamine ethyl ester(TMRE),and mitochondrial complex of Ⅰ and Ⅲ activity detection kits,respectively.The morphology of mitochondria and lysosomes was observed by transmission electron microscope electron microscopy(TEM);Western blot was used to detect the expression of GTPase kinetic protein 1(Drp1),cytochrome c oxidase Ⅳ(COX Ⅳ)and transporters of the outer mitochondrial membrane(TOM20).Results The nuclear membrane was smooth and complete;the mitochondrial size was consistent;the crest arrangement was neat;vacuolization was reduced or even disappeared;the mitochondrial matrix electron density was increased;the number of autophagosomes was decreased in the experimental group.The contents of ROS in blank group,model group,control group and experimental group were 1.03±0.04,1.53±0.10,1.06±0.06 and 1.10±0.11;MMP were 1.00±0.15,0.80±0.16,1.06±0.19 and 1.00±0.19;the activities of complex of Ⅰ were 1.00±0.08,2.28±0.82,1.05±0.26 and 1.13±0.37;the activities of complex of Ⅲ were 1.00±0.09,2.13±0.38,0.83±0.22 and 0.96±0.11;the expression of Drp1 protein were 1.00±0.14,1.27±0.07,0.97±0.21 and 0.93±0.17;the expression of fission protein 1(Fis1)protein were 1.00±0.16,1.33±0.18,1.17±0.25 and 0.99±0.05;the expression of COX Ⅳ protein were 1.00±0.25,0.62±0.08,0.79±0.26 and 0.97±0.16;the expression of TOM20 protein were 1.00±0.13,0.67±0.15,0.75±0.13 and 0.89±0.05.The above indexes of model group were significantly different from those of blank group(P＜0.05,P＜0.01,P＜0.001,P＜0.000 1).The above indexes of experimental group were significantly different from those of model group(P＜0.05,P＜0.01,P＜0.001,P＜0.000 1).Conclusion Morphine may inhibit mitophagy and fission,and alleviated mitochondrial oxidative stress damage by decreasing the activity of respiratory chain complex of Ⅰ and Ⅲ,thus maintaining mitochondrial dynamic homeostasis and alleviating H/R-induced myocardial cell damage.

Objective To investigate the clinical effect of unilateral percutaneous vertebroplasty(PVP)combined with 3D printing technology for the treatment of thoracolumbar osteoporotic compression fracture.Methods A total of 77 patients with thoracolumbar osteoporotic compression fractures from October 2020 to April 2022 were included in the study,all of which were vertebral body compression fractures caused by trauma.According to different treatment methods,they were di-vided into experimental group and control group.Thirty-two patients used 3D printing technology to improve unilateral transpedicle puncture vertebroplasty in the experimental group,there were 5 males and 27 females,aged from 63 to 91 years old with an average of(77.59±8.75)years old.Forty-five patients were treated with traditional bilateral pedicle puncture vertebroplasty,including 7 males and 38 females,aged from 60 to 88 years old with an average of(74.89±7.37)years old.Operation time,intraoperative C-arm X-ray times,anesthetic dosage,bone cement injection amount,bone cement diffusion good and good rate,complications,vertebral height,kyphotic angle(Cobb angle),visual analogue scale(VAS),Oswestry disability index(ODI)and other indicators were recorded before and after surgery,and statistically analyzed.Results All patients were followed up for 6 to 23 months,with preoperative imaging studies,confirmed for thoracolumbar osteoporosis com-pression fractures,two groups of patients with postoperative complications,no special two groups of patients'age,gender,body mass index(BMI),time were injured,the injured vertebral distribution had no statistical difference(P＞0.05),comparable data.Two groups of patients with bone cement injection,bone cement dispersion rate,preoperative and postoperative vertebral body height,protruding after spine angle(Cobb angle),VAS,ODI had no statistical difference(P＞0.05).The operative time,intra-operative fluoroscopy times and anesthetic dosage were statistically different between the two groups(P＜0.05).Compared with the traditional bilateral puncture group,the modified unilateral puncture group combined with 3D printing technology had shorter operation time,fewer intraoperative fluoroscopy times and less anesthetic dosage.The height of anterior vertebral edge,kyphosis angle(Cobb angle),VAS score and ODI of the affected vertebrae were statistically different between two groups at each time point after surgery(P＜0.05).Conclusion In the treatment of thoracolumbar osteoporotic compression fractures,3D printing technology is used to improve unilateral puncture PVP,which is convenient and simple,less trauma,short operation time,fewer fluoroscopy times,satisfactory distribution of bone cement,vertebral height recovery and kyphotic Angle correction,and good functional improvement.

Objective To elucidate the bidirectional causal relationship between lipid profiles and colorectal cancer(CRC)by using the two-sample and two-step Mendelian randomization(MR)methods,and to explore the mediating role and proportion of immune cells as intermediary factors.Methods The pooled statistical data related to the study were screened,and 179 lipids and CRC were analyzed using two-sample and two-step MR with the inverse variance weighted method.Simultaneously,the causal effect was verified via Bayesian weighted MR.Two-step MR analysis was conducted to determine whether a mediated effect was exerted on immune cell traits.Sensitivity,heterogeneity,and pleiotropy analyses were performed to verify the reliability of the study results.Results The causal relationship between nine lipid traits and CRC was preliminarily identified,and no reverse causal effect was found(P>0.05).The validity of the results was verified via Bayesian weighted MR(P<0.05).Twenty-seven types of immune cells were suggested to exert a causal effect on CRC.The causal effect of phosphatidylcholine(O-18:2_20:4)on CRC was determined via mediation analysis(OR:0.8579,95% CI=0.7395-0.9952,P=0.0429).The CD127-mediated proportion on CD45RA+CD4+T cells was 9.14% (β=-0.1052,P=0.0155).Conclusion A causal relationship exists between lipid traits and CRC,and the intervention of CD127 on CD45RA+CD4+T cell helps phosph-atidylcholine reduce the risk of CRC.

As the backbone force of China's social and economic construction, the health status of workers is closely related to the nation's productivity and social development. Currently, cancers have become one of the major diseases threatening the health of workers. However, there are still many shortcomings in the cancer screening services for the workers. To standardize cancer screening services for workers, ensure the quality of screening services, and improve the overall screening effectiveness, 19 institutions, including Peking Union Medical College Hospital of the Chinese Academy of Medical Sciences, have jointly formulated the Group Standard "Specification for service of cancer screening for workers (T/CHAA 023-2023)". This standard follows the principles of "legality, scientific rigor, advancement, and feasibility" and combines the frontier scientific advances in cancer screening. It clarifies the relevant requirements for service principles, service design, service delivery, service management, service evaluation, and improving worker cancer screening. Implementing this group standard will help connect the common screening needs of workers, employers, and cancer screening service providers, standardize the screening process, improve screening quality, and ultimately increase the early diagnosis rate and survival rate of cancer patients. Consequently, this group standard will help safeguard workers' health rights and interests, ensure the labor force resources, promote the comprehensive coordinated and sustainable development of society, and contribute to realizing the "Healthy China 2030" strategic policy.