Objective We aimed to establish and evaluate a rat model of post-infectious irritable bowel syndrome(PI-IBS)with the pattern of liver depression and spleen deficiency coupled with dampness.Methods First,200 rats were randomly divided into the normal group,the infection group,the infection+stress group,the infection+stress+external dampness group,and the acetic acid+stress group(n=40 rats per group)for eight weeks.The rats were treated with Trichinella spiralis infection,chronic restraint stress,an artificial high-humidity climate,and/or acetic acid enema.Weight growth rate,24-hour food intake and water intake,and the fecal moisture percentage were recorded.The open field test and the sucrose consumption test were used to determine the behavioral characteristics of rats in each group.The abdominal withdrawal reflex(AWR)test was used to determine visceral sensitivity.The contents of 5-hydroxytryptamine(5-HT)and aquaporin 4(AQP4)in colon tissue were detected by ELISA.Results Compared with the normal group,the weight growth rate of rats in the infection+stress+external dampness group and the acetic acid+stress group was lower from Week 1 to Week 8 of modeling.The 24-hour food intake of rats in the infection+stress+external dampness group and the infection+stress group was lower than that in the normal group from Week 2 to Week 8 of modeling.At the end of week 2 of modeling,the 24-hour water intake of rats in the infection+stress+external dampness group,the acetic acid+stress group,and the infection+stress group was lower than that in the normal group.The fecal moisture percentage of rats in the infection+stress+external dampness group was higher than that in the normal group at the end of Week 1,6,and 8(P＜0.05).At the end of Week 4 of modeling,the total distance in the open field test in the infection+stress+external dampness group and the acetic acid+stress group was shorter than that in the normal group.The sugar preference rate in the infection+stress+external dampness group was lower than that in the normal group at the end of 1,4,and 8 weeks and lower than that in the acetic acid+stress group at the end of Week 4 and 8(P＜0.05).The AWR scores of rats in the infection+stress+external dampness group were higher than those in the normal group after week 1 at 60 and 80 mmHg(1 mmHg≈0.133 kPa),after Week 4 at 40,60,and 80 mmHg,and after Week 6 and 8 at 20,40,and 80 mmHg(P＜0.05).At the end of Week 2 and 4,a large number of inflammatory cells were infiltrated in the colonic mucosa of the intervention groups,and the inflammation score was higher than that of the normal group(P＜0.05).At the end of weeks 6 and 8,the inflammatory cell infiltration in the intestinal mucosa of the intervention groups was not obvious,and the colonic mucosa returned to normal.At the end of weeks 6 and 8,the 5-HT content was higher in the infection+stress group,the infection+stress+external dampness group,and the acetic acid+stress group than in the normal group(P＜0.05).After Week 4,the AQP4 content was lower in the infection+stress+external dampness group and the acetic acid+stress group than that in the normal group(P＜0.05).After week 6,compared to the normal group,the AQP4 content was lower in all groups except for the acetic acid+stress group,and the AQP4 content in the infection+stress+external dampness group was lower than that in the acetic acid+stress group.After week 8,only in the infection+stress+external dampness group the AQP4 content was lower than in the normal group(P＜0.05).Conclusion The combination of Trichinella spiralis infection,chronic restraint stress,and an artificial high-humidity climate can be used to prepare a relatively stable and reliable rat model of PI-IBS with the pattern of liver depression and spleen deficiency with dampness.

Conventional chemotherapy based on cytotoxic drugs is facing tough challenges recently following the advances of monoclonal antibodies and molecularly targeted drugs. It is critical to inspire new potential to remodel the value of this classical therapeutic strategy. Here, we fabricate bisphosphonate coordination lipid nanogranules (BC-LNPs) and load paclitaxel (PTX) to boost the chemo- and immuno-therapeutic synergism of cytotoxic drugs. Alendronate in BC-LNPs@PTX, a bisphosphonate to block mevalonate metabolism, works as both the structure and drug constituent in nanogranules, where alendronate coordinated with calcium ions to form the particle core. The synergy of alendronate enhances the efficacy of paclitaxel, suppresses tumor metastasis, and alters the cytotoxic mechanism. Differing from the paclitaxel-induced apoptosis, the involvement of alendronate inhibits the mevalonate metabolism, changes the mitochondrial morphology, disturbs the redox homeostasis, and causes the accumulation of mitochondrial ROS and lethal lipid peroxides (LPO). These factors finally trigger the ferroptosis of tumor cells, an immunogenic cell death mode, which remodels the suppressive tumor immune microenvironment and synergizes with immunotherapy. Therefore, by switching paclitaxel-induced apoptosis to mevalonate metabolism-triggered ferroptosis, BC-LNPs@PTX provides new insight into the development of cytotoxic drugs and highlights the potential of metabolism regulation in cancer therapy.

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

AIM:To establish and evaluate a colonoids model of intestinal barrier dysfunction with irritable bowel syndrome(IBS).METHODS:The colonic recess of 20～22 g male C57BL/6 mice were isolated and cultured in ma-trix glue to proliferate and differentiate into 3D hollow spheres with colonic epithelioid structure.The following experi-ments were carried out:(1)Colonoids and colonic tissues of mice were detected by immunofluorescence to identify colo-noids.(2)Fluorescein isothiocyanate dextran 4(FD4)evaluated the epithelial barrier function of colonoids.(3)To ex-plore the changes in the epithelial barrier of colonoids induced by interferon-γ(IFN-γ)at different concentrations and time points.FD4 and HE staining were used to evaluate the barrier function.RT-qPCR was used to detect the mRNA expres-sion of occludin and zonula occludens-1(ZO-1)in tight junctions of colonoids.Immunofluorescence was used to detect the distribution and localization of occludin and ZO-1 proteins.RESULTS:(1)The expression of EdU proliferation and in-testinal epithelial cell lineage markers in colonoids was consistent with that in mouse colonic tissues.(2)In the control group,FD4 did not infiltrate the colonoids lumen,but FD4 significantly infiltrated the colonoids lumen induced by ethyl-ene glycol-bis(β-aminoethyl ether)-N,N,N',N'-tetraacetic acid(EGTA).(3)From 18 h,the IFN-γ at 60,100,200 and 240 ng/mL could significantly infiltrate into the cavity of colonoids(0.033,0.032,0.042 and 0.001),and the barri-er injury of colonoids could be seen by HE staining.After 18 h,all concentrations of IFN-γ could significantly decrease the mRNA expression of occludin and ZO-1,and the fluorescence of occludin and ZO-1 decreased significantly(P<0.05).CONCLUSION:(1)The cultured organoids are colonoids with complete epithelial barrier.(2)IFN-γ could in-duce the decrease of the transcriptional levels of occludin and ZO-1 in the tight junction of colonoids,the decrease of the expression of corresponding proteins,and the change of localization and distribution,thus increasing the epithelial perme-ability of colonoids.This model is highly consistent with the pathophysiological state of IBS colonic mucosal barrier dys-function,which provides a new tool and method for studying the direction of colonic mucosal barrier dysfunction in IBS.

Objective:Analyzing the relationship between negative life events and depressive symptoms in university freshmen,and the mediating effects of neuroticism and the moderating role of exercise frequency.Meth-ods:A sampling of 8 079 university freshmen,and the Patient Health Questionnaire was used to assess depressive symptoms,the Eysenck Personality Inventory-Neuroticism subscale to assess neuroticism,the self-administered questionnaire to assess the number of negative life events that the participants had experienced and the exercise fre-quency.Model 4 in the Process plug-in was used to test the mediating effect of neuroticism,and Model 7 to test the moderating role of exercise frequency.Results:The numbers of negative life events were positively correlated with the depressive symptoms scores(r=0.16,P＜0.01),and were positively correlated with the neuroticism scores(r=0.26,P＜0.01).The neuroticism scores were positively correlated with the depressive symptoms scores(r=0.52,P＜0.01).Neuroticism score partially mediated between negative life events and depressive symptoms score,with a mediating effect of 78.4％,and exercise frequency score moderated between negative life events and neuroti-cism scores(β=-0.05,P=0.032).Conclusion:Negative life events are associated with depressive symptoms,neuroticism plays a mediating role,and exercise frequency could moderate negative life events and neuroticism.

Objective:To discuss the value of pubo-femoral distance(PFD) in the diagnosis of infants with developmental dysplasia of the hip(DDH).Methods:Nine hundred and thirty-one infants with DDH and normal infants diagnosed by clinical examination and ultrasonography were involved from February 2022 to June 2023 in Beijing Jishuitan Hospital. The ultrasonographic examination included Graf method and pubo-femoral distance measurement. Statistical analysis was made on the measurements of PFD of different types of hips.Results:Among all the hips, 1 359 hips were Graf type Ⅰ, 274 hips were Graf type Ⅱa, 166 hips were Graf type Ⅱb, 31 hips were Graf type Ⅱc, 7 hips were Graf type D, 13 hips were Graf type Ⅲ, and 12 hips were Graf type Ⅳ. The PFD of these hips were (0.34±0.07)cm, (0.35±0.08)cm, (0.35±0.08)cm, (0.51±0.11)cm, (0.67±0.09)cm, (0.95±0.26)cm, (1.27±0.30)cm, respectively. There was no significant difference in PFD between hips of Graf Ⅰ, Graf Ⅱa and Graf Ⅱb ( P>0.05), but there was significant difference in PFD between hips of the other Graf types ( P<0.05). The area under curve(AUC) of the PFD for the diagnosis of stability of the hips in infants was 0.959 with the cut-off value of 0.435 cm, the sensitivity and specificity were 88.9% and 90.4%, respectively. Conclusions:The PFD has great value in the evaluation of the stability of hip joint, and the cut-off value is 0.435 cm.

Objective:To explore the high-frequency ultrasonographic and clinical features of superficial intravascular tumors.Methods:Thirteen superficial intravascular tumor patients who underwent ultrasound examination form Beijing Jishuitan Hospital during 2016-2020 were retrospectively analyzed. The location, anatomic blood vessels, shape, size, boundary, internal echo, blood flow and clinical characteristics of the tumors were analyzed.Results:Among the 13 cases, most of the tumors were oval like or long strip, and a few were round like. All 11 cases of primary intravascular tumors showed hypoechoic mass; 2 cases of intravascular metastasis or recurrence showed solid hypoechoic with hyperechoic mass. Arterial blood flow spectrum was detected in 12 cases. Two patients with glomus tumor showed typical tenderness at the fixed point. Two patients had a history of bone tumors in the upper or lower extremities.Conclusions:High frequency ultrasound can clearly recognize the location of the superficial intravascular tumors, describe the morphological characteristics and sonographic features of the tumor, then help to make a more accurate qualitative diagnosis.

Rabdosia serra(R.serra),an important component of Chinese herbal tea,has traditionally been used to treat hepatitis,jaundice,cholecystitis,and colitis.However,the chemical composition of R.serra and its effect against colitis remain unclear.In this study,the chemical composition of the water extract of R.serra was analyzed using ultra performance liquid chromatography coupled with a hybrid linear ion trap quadrupole-orbitrap mass spectrometer(UPLC-LTQ-Orbitrap-MS).A total of 46 compounds,comprising ent-kaurane diterpenoids,flavonoids,phenolic acids,and steroids,were identified in the water extract of R.serra,and the extract could significantly alleviate dextran sulfate sodium salt-induced colitis by improving colon length,upregulating anti-inflammatory factors,downregulating proinflammatory fac-tors,and restoring the balance of T helper 17/T regulatory cells.R.serra also preserved intestinal barrier function by increasing the level of tight junction proteins(zonula occludens 1 and occludin)in mouse colonic tissue.In addition,R.serra modulated the gut microbiota composition by increasing bacterial richness and diversity,increasing the abundance of beneficial bacteria(Muribaculaceae,Bacteroides,Lactobacillus,and Prevotellaceae_UCG-O01),and decreasing the abundance of pathogenic bacteria(Turi-cibacter,Eubacterium_fissicatena_group,and Eubacterium_xylanophilum_group).Gut microbiota depletion by antibiotics further confirmed that R.serra alleviated colitis in a microbiota-dependent manner.Overall,our findings provide chemical and biological evidence for the potential application of R.serra in the management of colitis.

Objective:To compare the effects of sodium butyrate(Sob)on aged and young asthmatic mice.Methods:Male C57BL/6 mice aged 24 months(n=18)and 4 months(n=18)were divided using randomly generated numbers into 3 groups: a control group, a model group(treated with ovalbumin, OVA), and a treatment group(OVA+ Sob), with 6 mice in each group.The control group was given normal saline as the blank control.Two days before the OVA challenge, the treatment group was given 1 mg/g Sob by intraperitoneal injections and the OVA+ Sob group and the control group were given normal saline intervention.Endpoint evaluation was performed 1 day after the last challenge.Differences in airway hyperresponsiveness(AHR), pathological manifestations of lung tissue sections stained with hematoxylin eosin(HE), and inflammatory factors in lung tissues were compared between aged and young mice and the effects of Sob on asthmatic mice of different ages were evaluated.Results:Under the stimulation of methacholine(Mch), AHR of the O-OVA group was significantly higher than that of the Y-OVA group(6.250 g/L: 276.28±113.62 vs.103.02±19.55, t=3.368, P=0.026; 12.500 g/L: 457.5±157.29 vs.114.76±20.28, t=4.338, P=0.022; 25.000 g/L: 1113.16±256.98 vs.567.87±187.34, t=3.538, P=0.009). HE staining revealed that, compared with the Y-control group, the O-control group exhibited a reduced area of alveolar cavity, partial lung consolidation, proliferation of interstitial fibrous connective tissues, alveolar epithelial cells and capillary endothelial cells.Compared with its control group, the O-OVA group had significantly elevated levels of eotaxin( P=0.035), IL-17A( P=0.004)and IL-1β( P=0.001), among the inflammatory factors, whereas the Y-OVA group had elevated levels of eotaxin( P=0.001), IL-17A( P=0.001), IL-4( P=0.004), KC( P=0.012)and IL-1β( P<0.001). Compared with the O-OVA group, the Y-OVA group had increased levels of IL-4( Z=2.882, P=0.004)but decreased levels of IL-1β( t=2.728, P=0.020). As for the effects of Sob on asthmatic mice of different ages, AHR of the O-OVA+ Sob group was significantly alleviated with stimulation of 12.500 g/L Mch( P=0.015)and 25 g/L Mch( P=0.014), compared with the O-OVA group.With stimulation of 3.125 g/L Mch, AHR of the Y-OVA+ Sob group was significantly decreased( P=0.021)and levels of IL-4( P=0.004)and IL-1β( P=0.014)were significantly reduced in the Y-OVA+ Sob group, compared with the Y-OVA group. Conclusions:The severity of asthma in aged mice is greater than in young mice, perhaps as a result of different immunophenotypes; The alleviating effects of Sob on inflammatory factors in young asthmatic mice may be related to mild AHR in young asthmatic mice, compared with aged asthmatic mice.

Objective:To measure the pubo-femoral distance of hips of the infants diagnosed with Graf type Ⅰ by high frequency ultrasound.Methods:A total of 1 084 infants(2 168 hips) diagnosed with Graf type Ⅰ by ultrasonography were collected in Beijing Jishuitan Hospital from June 2019 to May 2020. The ultrasonographic examinations included Graf method and pubo-femoral distance measurement. The 95% medical reference value was adopted to confirm range of normal values of the pubo-femoral distance. And the differences of the pubo-femoral distance between different gender, age and bilateral hip were compared.Results:The pubo-femoral distance of hips diagnosed with Graf type Ⅰ was (0.27±0.06)cm, the pubo-femoral distance of males was(0.27±0.06)cm, the pubo-femoral distance of females was (0.27±0.07)cm. The 95% medical reference value was 0.15-0.38 cm. The 95% medical reference value of males was 0.15-0.39 cm, and the 95% medical reference value of females was 0.13-0.41 cm. There were no significant differences between the sexes or between the age(all P>0.05). The difference between the bilateral hip joints from the same infant was statistically significant[(0.274±0.064)cm vs (0.265±0.064)cm, P<0.05]. Conclusions:The 95% medical reference value of hip diagnosed with Graf type Ⅰ is 0.15-0.38 cm.