OBJECTIVE To investigate the effects of imperatorin （IMP-SD） on malignant biological behavior of gastric cancer （GC） cells by regulating zinc finger and BTB domain 7B （ThPOK）. METHODS Human GC cells MKN-7 were used as the research object and then divided into control group （no treatment）， IMP-SD low-， medium- and high-concentration groups （40， 80 and 160 μmol/L IMP-SD）， si-ThPOK and si-NC group [treated with 160 μmol/L IMP-SD and then transfected with ThPOK small interfering RNA （si-ThPOK） or its negative control （si-NC）]. After treatment， cell clone formation， migration and invasion abilities and apoptosis of MKN-7 cells were detected； the killing activity of NK cells， T cells classification， the protein expressions of ThPOK， programmed death-1 （PD-1） and programmed death-ligand 1 （PD-L1） were all determined. RESULTS Compared with the control group， the number of cell clones， migration number， invasion number， and the protein expressions of PD-1 and PD-L1 were decreased or down-regulated significantly in IMP-SD groups， while the cell apoptotic rate， NK cell killing activity， CD4+ T proportion， the ratio of CD4+ T proportion and CD8+ T proportion （CD4+ T/CD8+ T）， and the protein expression of ThPOK were increased or up-regulated significantly， in a concentration-dependent manner （P＜0.05）. Compared with IMP-SD high-concentration group and si-NC group， the number of cell clones， migration number， invasion number， and the protein expressions of PD-1 and PD-L1 were increased or up-regulated significantly in si-ThPOK group， while the cell apoptotic rate， NK cell killing activity， CD4+ T proportion， CD4+ T/CD8+ T， and the protein expression of ThPOK were decreased or down-regulated significantly （P＜0.05）. CONCLUSIONS IMP-SD may reduce the clonal formation， migration and invasion abilities of GC cells， promote their apoptosis and inhibit their immune escape by promoting ThPOK expression.

OBJECTIVE To investigate the effects of imperatorin （IMP-SD） on malignant biological behavior of gastric cancer （GC） cells by regulating zinc finger and BTB domain 7B （ThPOK）. METHODS Human GC cells MKN-7 were used as the research object and then divided into control group （no treatment）， IMP-SD low-， medium- and high-concentration groups （40， 80 and 160 μmol/L IMP-SD）， si-ThPOK and si-NC group [treated with 160 μmol/L IMP-SD and then transfected with ThPOK small interfering RNA （si-ThPOK） or its negative control （si-NC）]. After treatment， cell clone formation， migration and invasion abilities and apoptosis of MKN-7 cells were detected； the killing activity of NK cells， T cells classification， the protein expressions of ThPOK， programmed death-1 （PD-1） and programmed death-ligand 1 （PD-L1） were all determined. RESULTS Compared with the control group， the number of cell clones， migration number， invasion number， and the protein expressions of PD-1 and PD-L1 were decreased or down-regulated significantly in IMP-SD groups， while the cell apoptotic rate， NK cell killing activity， CD4+ T proportion， the ratio of CD4+ T proportion and CD8+ T proportion （CD4+ T/CD8+ T）， and the protein expression of ThPOK were increased or up-regulated significantly， in a concentration-dependent manner （P＜0.05）. Compared with IMP-SD high-concentration group and si-NC group， the number of cell clones， migration number， invasion number， and the protein expressions of PD-1 and PD-L1 were increased or up-regulated significantly in si-ThPOK group， while the cell apoptotic rate， NK cell killing activity， CD4+ T proportion， CD4+ T/CD8+ T， and the protein expression of ThPOK were decreased or down-regulated significantly （P＜0.05）. CONCLUSIONS IMP-SD may reduce the clonal formation， migration and invasion abilities of GC cells， promote their apoptosis and inhibit their immune escape by promoting ThPOK expression.

Objective To investigate the relationship between combined plasma ferritin and triglyceride (TG) concentrations in early pregnancy and the risk of gestational diabetes mellitus (GDM). Methods A total of 1 000 pregnant women who had antenatal care at the Sixth Hospital of Wuhan from January 2021 to January 2023 were selected as the research subjects. The cut-offs of ferritin and TG were analyzed by using unrestricted cube splines. All participants were divided into 4 groups according to the cut‐off values of ferritin and TG. Associations between combined ferritin and TG concentrations and GDM risk were estimated using multivariable logistic regression models. Results A total of 158 (15.8%) participants were diagnosed with GDM. The ferritin and TG levels in early pregnancy of pregnant women in the GDM group were significantly higher than those in the non-GDM group (P<0.05). After adjusting for potential confounders, the OR for the risk of developing GDM after combining ferritin with TG was 2.35 (1.65, 3.35). Couclusion The increase in plasma ferritin and TG concentrations in early pregnancy is positively correlated with the increased risk of GDM. Pregnant women with high plasma ferritin (˃65.7 ng/mL) and high TG (˃1.9mmoL/L) have the greatest risk of GDM.

OBJECTIVE To investigate the effect mechanism of andrographolide （Andro） on neuropathic pain （NP） in rats. METHODS Rats were randomly separated into sham operation group， model group， Andro low-dose （1 mg/kg）， Andro medium-dose （5 mg/kg） and Andro high-dose （10 mg/kg） groups， and sodium ferulic acid （150 mg/kg） group， with 12 rats in each group. Except for sham operation group， other groups used the chronic sciatic nerve compression injury method to induce NP model. After modeling， each group was given relevant dose of Andro intrathecally or sodium ferulate intragastrically. The sham operation group and model group were given a constant volume of normal saline once a day for 14 consecutive days. The mechanical withdrawal threshold （MWT） and thermal withdrawal latency （TWL） of rats were detected in each group after 7 and 14 days of administration. After the last medication， the serum levels of interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， prostaglandin E2 （PGE2）， and substance P （SP） in rats were detected in each group， and the pathological morphology of spinal cord tissue was observed. mRNA and protein expressions of ionized calcium binding adaptor molecule-1 （Iba-1）， growth arrest specific protein 6 （Gas6）， and Axl in spinal cord tissue were determined. RESULTS Compared with model group， MWT and TWL after 7 and 14 days of the administration， the mRNA and protein expressions of Gas6 and Axl after the last medication were all increased significantly in administration groups （P＜0.05）， while the levels of IL-6， TNF-α， PGE2 and SP， mRNA and protein expressions of Iba-1 were all decreased significantly （P＜0.05）； pathological injuries such as the disordered arrangement of spinal cord neurons and dilation and congestion of capillaries had been alleviated to varying degrees. Compared with sodium ferulic acid group， there was no statistically significant difference in the above indicators in the Andro high-dose group （P＞0.05）. CONCLUSIONS Andro may inhibit inflammatory response by activating the Gas6/Axl signaling axis， thereby alleviating NP.

Background Dibutyl phthalate (DBP) is one of the most commonly used plasticizers, and has been found to relate to allergic asthma. However, mechanisms behind the phenomenon linking DBP and allergic asthma are still not well comprehended. Objective To investigate the role of endoplasmic reticulum stress in DBP-exacerbated allergic asthma. Methods Thirty-two male mice were divided into four groups at random, eight mice in each group: control group, allergic asthma model group (ovalbumin, OVA), OVA+40 mg·kg⁻¹ DBP exposure group (OVA+DBP), and OVA+40 mg·kg⁻¹ DBP+50 mg·kg⁻¹ 4-phenyl butyric acid (4-PBA) group (OVA+DBP+4-PBA). The control group mice were treated with saline via intraperitoneal injection on day 21, 35, 42, and 49, and atomized saline for 30 min per day from day 54 to 60. The OVA group mice were injected with 0.3 mL OVA sensitizing solution via intraperitoneal injection on day 21, 35, 42, and 49, and atomized with 1% OVA solution from day 54 to 60. The OVA+DBP group was treated in the same way as the OVA group to build an allergic asthma model, and was orally exposed to 40 mg·kg⁻¹ DBP from day 1 to 53, plus atomized with 1% OVA solution from day 54 to 60. In order to verify the role of endoplasmic reticulum stress in DBP-exacerbated allergic asthma, 4-PBA was injected intraperitoneally every 2 d from day 1 to 53 in the OVA+DBP+4-PBA group mice. The pathological changes such as airway remodeling, inflammatory cell infiltration, and airway mucous hyperplasia in lung tissues were observed after hematoxylin-eosin (HE) and periodic acid-Schiff (PAS) staining. The contents of total immunoglobulin E (T-IgE) and ovalbumin immunoglobulin E (OVA-IgE) levels in serum, and interleukin (IL)-4, IL-5, IL-13, and IL-17A in alveolar lavage fluid (BALF) were detected by Enzyme-Linked ImmunoSorbent Assay(ELISA). The expression levels of endoplasmic reticulum stress-related proteins including inositol-requiring enzyme 1α (IRE1α), protein kinase R-like endoplasmic reticulum kinase (PERK), and activating transcription factor 6 (ATF6) were detected by immunohistochemistry. Results Compared to the control mice, the OVA mice showed significant asthma-like symptoms, including inflammatory cell infiltration, increased inflammatory cytokines, airway remodeling, and mucous hyperplasia. Compared to the OVA group, long-term exposure to DBP aggravated airway pathological changes in the OVA+DBP mice, and increased the serum T-IgE and OVA-IgE levels (P<0.01), the Th2 (IL-4, IL-5, IL-13) and Th17 (IL-17A) cytokines in BALF (P<0.01), and the expression levels of endoplasmic reticulum stress-related proteins IRE1α, PERK and ATF-6 (P<0.01). In addition, after the 4-PBA treatment, it was found that compared with the OVA+DBP group, the expression levels of endoplasmic reticulum stress-related proteins (IRE1α, PERK and ATF-6) were down-regulated in the OVA+DBP+4-PBA group (P<0.01), the levels of cytokines (IL-4, IL-5, IL-13, and IL-17A) in BALF and T-IgE and OVA-IgE in serum were decreased (P<0.01), and airway remodeling and mucous hyperplasia were significantly alleviated. Conclusion Long-term exposure to DBP could aggravate allergic asthma by activating the endoplasmic reticulum stress pathway. This worsening effect is accompanied by the increase of immunoglobulin IgE levels and the release of Th2 and Th17 cytokines, which in turn leads to lung histopathological changes that affect lung function.

AIM: To investigate the expression levels and clinical significance of hypoxia-inducible factor-1α(HIF-1α)and interleukin-17(IL-17)in conjunctival epithelial cells and tear fluid of patients with dry eyes.METHODS: Retrospective study. A total of 183 dry eye patients admitted to our hospital from February 2021 to March 2023 were selected, and 181 people who were physically healthy in our hospital during the same period were chosen as the control group. HIF-1α and IL-17 expression levels in conjunctival epithelial cells and tear fluid of the two groups of subjects were tested, and the diagnostic value of HIF-1α and IL-17 in conjunctival epithelial cells and tear fluid of the subjects in testing dry eyes was analyzed through receiver operating characteristics(ROC)curves.RESULTS: Compared with the control group, patients in the dry eye group had elevated levels of HIF-1α and IL-17 expression in conjunctival epithelial cells(all P<0.01); and HIF-1α and IL-17 expression increased in tear fluid(all P<0.01). Pearson correlation analysis showed that HIF-1α and IL-17 in the conjunctival epithelium and tear fluid of dry eye patients were negatively correlated with BUT and Schirmer I test(SⅠt), and positively correlated with corneal fluorescein staining scores(all P<0.05); expression levels of HIF-1α and IL-17 in conjunctival epithelial cells and tear fluid of dry eye patients showed positive correlation(all P<0.001). The area under the ROC curve showed that the AUC for the combined diagnosis of HIF-1α and IL-17 in conjunctival epithelium was significantly greater than the AUC for HIF-1α alone in conjunctival epithelium(Z=5.574, P<0.001). The AUC of IL-17 alone in conjunctival epithelial cells(Z=4.351, P<0.001)and the AUC of the combined HIF-1α, IL-17 in tear fluid were significantly greater than the AUC of HIF-1α alone(Z=3.583, P<0.001)and the AUC of IL-17 alone(Z=4.303, P<0.001).CONCLUSION: Conjunctival epithelial cells and tear fluid of dry eye patients have elevated expression levels of HIF-1α and IL-17, and joint detection of HIF-1α and IL-17 expression levels is of great value in the diagnosis of dry eye.

Objective To analyze the characteristics of imported malaria epidemic from overseas in Wuhan, to explore the management mechanism of on-site cases, and to accumulate experience for the treatment of imported malaria in large cities after malaria elimination. Methods The epidemiological data on imported malaria from abroad during the period of malaria elimination (2010-2019) in Wuhan were collected. The gender, age and severe illness-related factors of the cases were analyzed. Based on the characteristics of the epidemic and the current situation of prevention and control, the content and experience of the “Municipal-District 24-7” case mechanism were discussed. Results The medical resources in Wuhan were the best in the central region, resulting in a large number of imported malaria cases, with a total of 474 cases reported from 2010 to 2019 (40.79% of the total number of cases in Hubei Province), including 359 cases of falciparum malaria, 36 severe cases and one death (the death rate was 0.28%). The patients were mainly young and middle-aged men aged 20 to 49 years old (97.26%). There were many referral cases (40.30%), and there was no seasonal clustering of cases reported. The undiagnosed proportion at the first visit was 44.85%, and the time of attack-diagnosis was 4 days or more in 61.00% of cases. The occurrence of severe cases was related to unconfirmed diagnosis at the first visit (χ²=35.46, P<0.001) and attack-diagnosis time (Z=-6.49, P<0.001). Conclusion Imported malaria occurs frequently in Wuhan, mainly falciparum malaria. However, “Municipal-District 24-7” case mechanism has effectively curbed the occurrence of severe and death cases and provided valuable experience for case management in similar cities in China.

Objectives To investigate the effects of low level of ambient NO₂ on the death of cardiovascular and cerebrovascular diseases in Enshi city and to identify sensitive population, so as to provide a scientific basis for formulating health policies. Methods The data of air pollutants, meteorological factors and death of cardiovascular and cerebrovascular diseases in Enshi city from 2015 to 2018 were collected. The generalized additive model based on Poisson distribution was used to analyze the effects of low ambient NO₂ level on the death risk of cardiovascular and cerebrovascular diseases in Enshi city. A subgroup analysis was performed on age, gender, and season. Results The average concentrations of major gaseous air pollutants in Enshi city from 2015 to 2018 were NO₂ (21.40 μg/m³), SO₂ (9.68 μg/m³), CO (0.88 mg/m³), and O₃ (61.21 μg/m³), respectively, all of which did not exceed the national secondary standard. The results of single pollutant model analysis showed that each 1 μg/m3 increase in NO₂ concentration in lag0 day was associated with a 0.33% increase (95% CI: 0.06 - 0.72) (P>0.05) in mortality risk of cardiovascular and cerebrovascular diseases. In the female population, each 1 μg/m3 increase in NO2 concentration in lag01 day was associated with a 0.92% increase (95% CI: 0.26 - 1.56) (P<0.05) in mortality risk of cardiovascular and cerebrovascular diseases. In the cold season, each 1 μg/m3 increase in NO₂ concentration in lag0 day was associated with a 0.62% increase (95% CI: 0.12 - 1.12) (P<0.05) in mortality risk of cardiovascular and cerebrovascular diseases. The results of the two-pollutant model showed that after controlling other gaseous pollutants (SO₂, CO or O₃), the effect of NO₂ on the mortality risk of cardiovascular and cerebrovascular diseases in women and the whole population in cold season still existed. Conclusion The low ambient level of NO₂ in Enshi city was significantly associated with increased mortality risk of cardiovascular and cerebrovascular diseases in female population as well as in cold seasons in the whole population. Attention should be paid to the health protection of special populations in areas with low ambient pollution level of NO₂ in special seasons.

OBJECTIVE: To investigate the efficacy and safety of VDZ (Vedolizumab) in the salvage treatment of glucocorticoid resistance to gastrointestinal graft-versus-host disease (GR-GI GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children. METHODS: The clinical data of 5 patients with refractory GI GVHD who received allo-HSCT in Wuhan Children's Hospital from December 2020 to December 2021 were retrospectively analyzed with VDZ salvage therapy. RESULTS: Among the 5 children with refractory GI GVHD, there were 1 male and 4 female, including 2 cases of extremely severe aplastic anemia, 1 case of acute myeloid leukemia (M2, high-risk), 1 case of fanconi anemia and 1 case of myelodysplastic syndrome. The median age of transplant recipients was 54.4 (12-164) months. The median treatment time from transplantation to VDZ was 1.4 (0.6-6.8) months. On average, 3.5 (2-5) doses of VDZ were received. After receiving treatment, 2 patients achieved a complete response (CR), 2 patients achieved a very good partial response (VGPR), 1 patient was non-responsive (NR) after a short-term partial response (PR). Compared with that before VDZ treatment, the amount of diarrhea, stool color, blood and traits of the children after medication were effectively improved. The median follow-up time was 9.3 (7.23-12.83) months. No disseminated or severe bacterial/fungal infections occurred during VDZ treatment and follow-up, and 2 children died of leukemia recurrence and pulmonary bronchiolitis obliterans. CONCLUSION VDZ salvage treatment of refractory GI GVHD in children has obvious short-term efficacy and good safety.
Child ; Humans ; Female ; Male ; Child, Preschool ; Salvage Therapy ; Glucocorticoids/therapeutic use* ; Retrospective Studies ; Graft vs Host Disease

Preoperative sleep loss can amplify post-operative mechanical hyperalgesia. However, the underlying mechanisms are still largely unknown. In the current study, rats were randomly allocated to a control group and an acute sleep deprivation (ASD) group which experienced 6 h ASD before surgery. Then the variations in cerebral function and activity were investigated with multi-modal techniques, such as nuclear magnetic resonance, functional magnetic resonance imaging, c-Fos immunofluorescence, and electrophysiology. The results indicated that ASD induced hyperalgesia, and the metabolic kinetics were remarkably decreased in the striatum and midbrain. The functional connectivity (FC) between the nucleus accumbens (NAc, a subregion of the ventral striatum) and the ventrolateral periaqueductal gray (vLPAG) was significantly reduced, and the c-Fos expression in the NAc and the vLPAG was suppressed. Furthermore, the electrophysiological recordings demonstrated that both the neuronal activity in the NAc and the vLPAG, and the coherence of the NAc-vLPAG were suppressed in both resting and task states. This study showed that neuronal activity in the NAc and the vLPAG were weakened and the FC between the NAc and the vLPAG was also suppressed in rats with ASD-induced hyperalgesia. This study highlights the importance of preoperative sleep management for surgical patients.
Rats ; Animals ; Hyperalgesia/metabolism* ; Sleep Deprivation/metabolism* ; Rats, Sprague-Dawley ; Periaqueductal Gray/pathology* ; Proto-Oncogene Proteins c-fos/metabolism* ; Pain, Postoperative/pathology*