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Sphingosine kinase (SphK), sphingosine-1-phosphate (S1P) and S1P receptor (S1PR) are involved in the tumor biological processes such as tumor cell proliferation and migration, and play an important role in the development of cancer. In recent years, researchers have increasingly focused on the interaction between cancer cells and the tumor microenvironment. The tumor microenvironment is genetically stable and can be induced to an antitumor phenotype, which has significant therapeutic advantages. Studies have shown that SphK/S1P/S1PR can regulate multiple aspects of the tumor microenvironment. This review summarizes the effects of SphK and S1P/S1PR signaling on the tumor microenvironment from four perspectives: tumor immune microenvironment, cancer associated fibroblasts, tumor angiogenesis and tumor hypoxic microenvironment, and also outlines potential drug research related to these signal molecules, aiming to elucidate the role of SphK/S1P/S1PR in tumor occurrence and development and provide new ideas for the research of anti-tumor drugs.
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Abstract@#Allergic diseases can occur in all systems of the body, covering the whole life cycle, from children to adults and to old age, can be lifelong onset and even fatal in severe cases. Children account for the largest proportion of the victims of allergic disease, Children s allergies start from scratch, ranging from mild to severe, from less to more, from single to multiple systems and systemic performance, so the prevention and treatment of allergic diseases in children is of great importance, which can not only prevent high risk allergic conditions from developing into allergic diseases, but also further block the process of allergy. At present, there is no consensus on the management system of allergic children in kindergartens and primary schools. The "Consensus on Allergy Management and Prevention in Kindergartens and Primary Schools", which includes the organizational structure, system construction and management of allergic children, provides evidence informed recommendations for the long term comprehensive management of allergic children in kindergartens and primary schools, and provides a basis for the establishment of the prevention system for allergic children.
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AIM: To observe the postoperative changes in macular morphological structure and blood flow density of patients with idiopathic macular epiretinal membrane(IMEM)by optical coherence tomography angiography(OCTA), and explore their correlation with visual acuity.METHOD: Prospective study. A total of 45 cases(45 eyes)with IMEM admitted to our hospital from January 2020 to July 2021 were included. The best corrected visual acuity(BCVA), central macular area thickness(CMT), foveal avascular zone(FAZ)area and changes in blood flow density of superficial capillary plexus(SCP)were observed at 1mo, 1, 3 and 6mo before and after operation.RESULT: The BCVA at 1wk after operation had no significant change compared with preoperative data(P>0.05), while it was improved at other time points(P<0.05). The CMT measured at 1wk after operation was thickened significantly(P<0.05), while it was significantly decreased at 1mo, 3mo and 6mo after operation(P<0.05). The FAZ area measured at 1wk and 1mo after operation had no significant change(P>0.05), while it was significantly enlarged at 3 and 6mo after operation(P<0.05). The SCP measured at 1wk, 1 and 3mo after operation had no significant change(P>0.05), while it was significantly decreased at 6mo after operation(P<0.05). BCVA measured at 3 and 6mo after operation was positively correlated with CMT(r=0.457, 0.615, P=0.032, 0.012).CONCLUSION: The visual acuity of patients with IMEM recovered quickly within 1mo after operation, and then it tended to be stable. However, the recovery of macular foveal morphology and blood flow distribution was slower than that of visual acuity, and there was no obvious correlation with visual acuity.
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AIM: To explore the key genes and molecular markers involved in the retinoblastoma development through bioinformatics.METHODS: The mRNA microarray datasets from the Gene Expression Omnibus(GEO)database were obtained, and the differentially expressed gene(DEG)between retinoblastoma cell lines and normal retinal pigment epithelial(RPE)cell lines were analyzed through gene ontology(GO)and KEGG enrichment analysis. To screen key genes, establish protein-protein interaction(PPI)network, and use receiver operating characteristic(ROC)curve to assess clinical diagnostic efficacy. The RNA expressions of key genes in retinoblastoma cell lines and normal RPE cell lines were compared by qRT-PCR.RESULTS: A total of 121 DEGs were obtained from the retinoblastoma dataset of GSE97508 and GSE110811. KEGG pathway analysis showed that DEG were enriched in phototransduction, cell cycle, and p53 signaling pathways. A total of 9 key genes, including MCM6, DTL, UBE2T, TOP2A, NUSAP1, CENPK, RRM2, RLBP1, and RHO, were obtained from the intersection of PPI network analysis and the top 30 DEG from each dataset. The differentially expressed 9 key genes were verified in GSE24673. ROC analysis showed that the area under the curve(AUC)for UBE2T, RRM2, and RHO was ≥80%, and there was a statistical significance(P>0.05). The mRNA level of UBE2T and RRM2 in retinoblastoma was significantly higher than APRE-19 cell line, while the mRNA level of RHO was significantly lower than that of ARPE-19 cell line.CONCLUSION: UBE2T, RRM2, and RHO may be served as potential molecular markers and potential therapeutic targets for retinoblastoma.
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Objective:To summarize and analyze the clinical characteristics of patients with infective endocarditis (IE) complicated with cerebral hemorrhage.Methods:The clinical data of 15 IE patients with intracerebral hemorrhage diagnosed in the Affiliated Hospital of Xuzhou Medical University from January 2010 to December 2021 were analyzed retrospectively, and their clinical characteristics were analyzed, including the mode of onset, cranial imaging characteristics, associated diseases, echocardiography, hematology, etiology, chest computed tomography (CT), cerebrospinal fluid characteristics, treatment methods and prognosis of patients.Results:Cerebral hemorrhage in IE patients were acute or subacute onset. Head CT scanning showed that cerebral hemorrhage usually occurred in the brain lobe, can be combined with rheumatic heart disease, congenital heart defect or immune system diseases, etc. Ultrasonic cardiogram can be used to determine the location of vegetations in the heart cavity, the damage of the valve and the hemodynamic changes. The hematologic examination showed elevated hemogram and increased erythrocyte sedimentation rate. Staphylococcus aureus or streptococcus viridans were often detected on the etiological examination. Lung infection was often seen on a chest CT, and inflammatory changes were seen in the cerebrospinal fluid. IE was treated with sufficient course of antibiotics and valve replacement with valve damage. The case fatality rate was 3/15.Conclusions:Young patients presented with lobar hemorrhage, headache, fever and rheumatic heart disease should be thought of the possibility of IE combined with cerebral hemorrhage. IE with intracerebral hemorrhage has a poor prognosis and a high mortality.
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Intestinal microorganisms are closely related to human health or disease status. Spinal cord injury is a serious traumatic disease of the nervous system. Recent studies have shown that intestinal flora can affect the progression of spinal cord injury. At the same time, intestinal flora is closely related to spinal cord injury complications such as anxiety, depression, aspiration pneumonia, malnutrition, constipation, neurocystitis and urinary system infection through intestinal-brain axis, intestinal-lung axis and oral-pulmonary axis. In this paper, the intestinal flora will be used as the starting point to explore the relationship between spinal cord injury, intestinal flora and spinal cord injury complications, providing new ideas for the treatment of spinal cord injury patients and the prevention of complications.
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Objective:To investigate the diagnostic value of chest enhanced computed tomography (CT) for mediastinal lymph node metastasis of esophageal cancer and the influencing factors for its accuracy.Methods:The retrospective case-control study was conducted. The clinico- pathological data of 463 patients with esophageal cancer who underwent surgical treatment in the First Affiliated Hospital of Army Medical University from July 2016 to June 2021 were collected. There were 385 males and 78 females, aged (61±8)years. Observation indicators: (1) results of pre-operative chest enhanced CT and postoperative pathological examination; (2) diagnostic value of chest enhanced CT for mediastinal lymph node metastasis of esophageal cancer; (3) influencing factors analysis of the diagnostic accuracy of chest enhanced CT for mediastinal lymph node metastasis of esophageal cancer. Measurement data with normal distribution were represented as Mean± SD, and count data were represented as absolute numbers and (or) percentages. Sensitivity, specificity, positive predictive value, negative predictive value and Youden index were used for authenticity evaluation of diagnostic value of chest enhanced CT for mediastinal lymph node metastasis of esophageal cancer, and accuracy and Kappa value were used for reliability evaluation. The higher the value of above indicators, the higher the authenticity and (or) reliability. The univariate analysis was conducted using the chi-square test, and multivariate analysis was conducted using the binary Logistic regression model after including indicators with P<0.20 of univariate analysis. Results:(1) Results of preoperative chest enhanced CT and postoperative pathological examination. Of the 463 patients with esophageal cancer, mediastinal lymph node metastasis were diagnosed in 90 cases (including 35 cases of true positive and 55 cases of false positive) and no mediastinal lymph node metastasis were diagnosed in 373 cases (including 300 cases of true negative and 73 cases of false negative) by preoperative chest enhanced CT. Mediastinal lymph node metastasis were diagnosed in 108 cases and no mediastinal lymph node metastasis were diagnosed in 355 cases by postoperative patholo-gical examination. (2) Diagnostic value of chest enhanced CT for mediastinal lymph node metastasis of esophageal cancer. Authenticity evaluation of diagnostic value of chest enhanced CT for medias-tinal lymph node metastasis of esophageal cancer showed that sensitivity, specificity, positive predic-tive value, negative predictive value and Youden indexes were 32.41%(35/108), 84.51%(300/355), 38.89%(35/90), 80.43%(300/373), 0.169, respectively. Reliability evaluation showed that accuracy and Kappa value were 72.35%(335/463) and 0.180 ( P<0.05), respectively. (3) Influencing factors analysis of the diagnostic accuracy of chest enhanced CT for mediastinal lymph node metastasis of esophageal cancer. Results of univariate analysis showed that the tumor diameter and the depth of tumor invasion were related factors affecting the diagnostic accuracy of chest enhanced CT for mediastinal lymph node metastasis of esophageal cancer ( χ2=7.65, 6.07, P<0.05). Results of multi-variate analysis showed that the tumor diameter ≥2.1 cm was an independent risk factor affecting the diagnostic accuracy of chest enhanced CT for mediastinal lymph node metastasis of esophageal cancer ( odds ratio=2.05, 95% confidence interval as 1.23?3.43, P<0.05). Conclusions:The clinical value of chest enhanced CT for diagnosing mediastinal lymph node metastasis of esophageal cancer is limited, and the consistency with pathological results is quite different. The tumor diameter ≥2.1 cm is an independent risk factor affecting the diagnostic accuracy of chest enhanced CT for mediastinal lymph node metastasis of esophageal cancer
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Objective:To investigate the efficacy and safety of using diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) mismatch to guide intravenous thrombolysis in patients with ischemic stroke beyond a 4.5-h time window.Methods:Patients with acute ischemic stroke received intravenous thrombolysis with alteplase in the Stroke Center of Hefei Second People's Hospital from July 2019 to June 2021 were retrospectively enrolled. According to the time of onset, they were divided into the time window group and the beyond time window group. The demographic and baseline clinical data of both groups were recorded and compared. The primary outcome measure was the clinical outcome assessed by the modified Rankin Scale (mRS) at 90 d after onset. 0-2 points were defined as good outcome, and >2 were defined as poor outcome. The secondary outcome measure was symptomatic intracranial hemorrhage (sICH). Multivariate logistic regression analysis was used to determine the independent risk factors for poor outcomes. Results:A total of 244 patients with acute ischemic stroke were enrollded, including 146 males (58.8%), aged 61.4±8.47 years. The median time from onset to thrombolysis was 142 min, and the median baseline National Institutes of Health Stroke Scale (NIHSS) score was 7. Thirty-six (14.8%) patients exceeded the 4.5 h time window, and 69 (28.3%) patients had poor outcomes. There were no significant differences in the good outcome rate (71.2% vs. 75.0%; χ2=0.224, P=0.636), any intracranial hemorrhage (9.6% vs. 13.9%; χ2=0.233, P=0.629) and the incidence of sICH (5.3% vs. 5.6%; χ2=0.000, P=1.000) between the time window group and the beyond time window group. Univariate analysis showed that the proportion of patients with atrial fibrillation or cardiogenic embolism and the baseline NIHSS score in the poor outcome group were significantly higher than those in the good outcome group (all P<0.05), while there was no statistical difference in the proportion of patients receiving intravenous thrombolysis beyond the time window. Multivariate logistic regression analysis showed that only the baseline NIHSS score was an independent risk factor for poor outcomes (odds ratio 1.681, 95% confidence interval 1.457-1.940; P<0.001). Conclusions:Compared with the patients who received intravenous thrombolysis within 4.5 h after onset, intravenous thrombolysis in patients with acute ischemic stroke beyond the 4.5 h time window guided by DWI-FLAIR mismatch results in similar clinical outcomes, and does not increase the incidence of intracranial hemorrhage.
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Peripheral T-cell lymphoma (PTCL) is a group of heterogeneous diseases originating from retrothymic T lymphocytes or mature natural killer (NK) cells. With the innovation of medical technology, the prognosis of patients with PTCL has been greatly improved. However, there are still some patients who are refractory or relapsed after treatment and have poor prognosis. In recent years, the applications of second-line chemotherapy regimen, hematopoietic stem cell transplantation and several new drugs (histone deacetylase inhibitors, dihydrofolate reductase inhibitors, aurora A kinase inhibitors, phosphatidylinositol 3-kinase inhibitors, targeted therapy, etc.) have played an important role in the treatment of relapsed/refractory PTCL patients. Meanwhile, the choice of transplantation programs and the combination of new drug-based schemes have also become research hotspots.
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Objective: To explore the trend of disease burden of degenerative mitral valve disease (DMVD) in the Chinese population from 1990 to 2019. Methods: Based on the 2019 Global Burden of Disease database (GBD 2019), the number of patients, the number of new cases, the number of deaths, the disability-adjusted life years (DALY) as well as the prevalence, incidence and death rate, DALY rate and their age-standardized rates were used to analyze the trend of the burden of DMVD in the Chinese population from 1990 to 2019. Results: In 2019, the number of patients, the number of new cases, and the number of deaths with DMVD in China were 461.2, 27.0 and 0.129 ten thousand, respectively, which increased by 209.0%, 199.1% and 13.2% when compared with 1990. In 2019, the age-standardized prevalence, incidence and death rate were 228.1/100 000, 12.7/100 000 and 0.075/100 000, respectively. Compared with 1990, the change of the age-standardized prevalence, incidence and death rate were 32.6%, 42.8% and -54.1%, respectively. In addition, the 2019 data also showed that the age-standardized prevalence and incidence were higher in females than in males (the age-standardized prevalence was 190.1 (181.5-198.9)/100 000 for males and 262.0 (250.3-273.9)/100 000 for females); the age-standardized incidence was 10.5 (10.0-11.0)/100 000 for males and 14.9 (14.3-15.6)/100 000 for females. The age group with the largest number of DMVD patients was 65 to 69 years old, and the highest incidence was 60 to 64 years old. From 1990 to 2019, DALY caused by DMVD showed an upward trend in China, from 46 439 person-years in 1990 to 69 402 person-years in 2019, with an increase of 49.4%. While the age-standardized DALY rate continued to decline, from 5.5/100 000 in 1990 to 3.8/100 000 in 2019, with a drop of 30.8%. The DALY and the age-standardized DALY rate of females were always higher than that of males in different years. Conclusion: From 1990 to 2019, DALY and the age-standardized prevalence and incidence of DMVD in China shows an increasing trend, and the disease burden caused by DMVD is severe in China.
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Aged , China/epidemiology , Cost of Illness , Disabled Persons , Female , Humans , Incidence , Male , Middle Aged , Mitral Valve , Quality-Adjusted Life YearsABSTRACT
Objective:To explore the risk factors of hypocalcemia and the correlation between calcium supplementation and clinical parameters after parathyroidectomy (PTX) in maintenance hemodialysis patients with secondary hyperparathyroidism (SHPT), and to analyze the effect of calcium supplementation after PTX on the long-term prognosis of patients.Methods:This study was a single-center retrospective study. The patients who underwent PTX in maintenance hemodialysis patients with SHPT in the Huashan Hospital affiliated to Fudan University from October 2014 to March 2021 were retrospectively enrolled. Total PTX with auto transplantation or total PTX alone were the surgical procedures. According to the postoperative requirement of calcium in the first week, the patients were divided into two groups: high calcium supplement (>16.05 g/week) group and low calcium supplement group (≤16.05 g/week). According to the average serum calcium level in the first week after operation, the patients were divided into hypocalcemia group (≤2.1 mmol/L) and non-hypocalcemia group (>2.1 mmol/L) and the differences of clinical parameters between the two groups were compared. The correlation between clinical parameters and the postoperative calcium requirement was examined through Pearson or Spearman correlation analysis. The influencing factors for hypocalcemia after PTX were examined through logistic regression analysis. The survival curve was made by Kaplan-Meier method, and the difference of cumulative survival rate between the two groups was compared by log-rank test.Results:A total of 98 maintenance hemodialysis patients with SHPT were enrolled. The levels of serum calcium, phosphorus, and intact parathyroid hormone (iPTH) after the operation decreased significantly than those of preoperation (all P<0.05). Multiple linear regression analysis showed age ( β=-0.160, P=0.030), iPTH ( β=0.004, P=0.025) and C-reactive protein ( β=0.186, P=0.011) were correlated with postoperative calcium requirement. Preoperative alkaline phosphatase ( OR=1.002, 95% CI 1.000-1.004, P=0.018) and hemoglobin ( OR=0.977, 95% CI 0.954-1.000, P=0.048) independently predicted the occurrence risk of postoperative hypocalcemia through multivariate logistic regression analysis. The recurrence rate of high calcium supplement group was higher than that of low calcium supplement group (10.26% vs 0, P=0.023) and there was no significant difference in all-cause mortality between the two groups (17.95% vs 5.08%, P=0.086). The recurrence rate between the hypocalcemia group and non-hypocalcemia group was no significantly different (8.3% vs 1.8%, P=0.451) and there was no significant difference in all cause mortality between the two groups (12.5% vs 12.7%, P=1.000). Kaplan-Meier survival curve showed that the cumulative survival rate between the two groups was no significantly different (log-rank test χ2=0.147, P=0.702). Conclusions:PTX is a safe and effective therapeutic method to reduce the level of iPTH and improve the metabolism of calcium and phosphorus in SHPT patients. Age, iPTH and C-reactive protein are correlated with the postoperative requirement of calcium in the first week. Preoperative alkaline phosphatase and hemoglobin are independent risk factors for postoperative hypocalcemia. Correcting preoperative electrolyte disorder, improving infection and anemia can reduce the incidence of hypocalcemia after PTX.
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Objective:To explore the effects of dietary phosphate restriction education on serum phosphorus level, dietary phosphate intake and the knowledge of hyperphosphatemia in maintenance hemodialysis (MHD) patients.Methods:This study was a retrospective cohort study. A total of 116 hemodialysis patients in Huashan Hospital, Huadong Hospital and Tongji Hospital from October 2019 to December 2020 were enrolled in this study. They were divided into short-term group (84 cases) and long-term group (32 cases). The short-term group did not receive education or received education≤60 minutes. Meanwhile, the long-term group received education>60 minutes. Serum phosphorus level, dietary phosphate intake and knowledge of hyperphosphatemia were compared between the two groups after 4 weeks.Results:At baseline, age [64(56, 69) years old vs 65(60, 73) years old, Z=-1.493, P=0.136], the proportion of males [58.3%(49/84) vs 56.3%(18/32), χ2=0.041, P=0.839], dialysis age [55(26, 130) months vs 53(20, 132) months, Z=-0.062, P=0.951], body mass index, diabetes history, single-pool Kt/V, proportion of calctriol used, blood calcium, blood phosphorus, intact parathyroid hormone and dietary protein, dietary phosphorus and dietary phosphorus protein ratio had no statistical significance between short-term group and long-term group (all P>0.05). Adequate dietary phosphate restriction education reduced dietary phosphate intake [777.98(653.81, 943.16) mg/d vs 896.56(801.51, 1 015.51) mg/d, Z=-2.903, P=0.004], phosphate/protein ratio [13.16(11.52, 14.21) mg/g vs 15.27(13.31, 17.48) mg/g, Z=-3.929, P<0.001] and serum phosphorus level [(1.42±0.37) mmol/L vs (1.85±0.44) mmol/L, t=4.984, P<0.001]. Meanwhile, such education significantly improved achievement rate of serum phosphorus (62.5% vs 41.7%, χ2=4.034, P=0.045). In addition, patients in long-term group answered more questions correctly (completely correct plus partially correct) about the causes (93.8% vs 72.6%, χ2=6.120, P=0.013), poor prognosis (78.1% vs 52.4%, χ2=6.372, P=0.012) of hyperphosphatemia as well as the types of food with high phosphate (65.6% vs 52.4%, χ2=1.650, P=0.199). Conclusion:Adequate dietary phosphate restriction education reduces serum phosphorus level and dietary phosphate intake, and improves the knowledge of hyperphosphatemia in MHD patients.
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Objective:To explore the clinical characteristics, causes, diagnosis and treatment of transplant renal artery stenosis after pediatric-to-adult kidney transplantation.Methods:Between July 2014 and March 2019, clinical data were retrospectively reviewed for 25 en-bloc and 27 single kidney transplant cases.Results:One en-bloc(4.0%)and two single kidney recipients(7.4%)were diagnosed as renal artery stenosis at Month 13-23 months post-transplantation.It was higher than the rate of stenosis in adult-to-adult transplant cases(1.1%)during the same period.As compared with recipients without stenosis, stenotic ones had younger pediatric donors( P<0.05)and yet similar body weight of donors as well as recipients( P>0.05). The inner diameters of stenonotic sites were(1.40-1.63)mm and predominant stenotic site was proximal renal artery rather than anastomotic site.The remaining parts of major renal arteries varied from 2.31 to 4.93 mm in diameter.It was normal in children with a corresponding age.All three cases responded well to percutaneous transluminal angioplasty and stenting. Conclusions:The cause of stenosis may be an undeveloped local artery diameter due to extensive tissue dissection around artery.Therefore cautious selections of infantile single renal graft for adult recipients and preserving surrounding tissue of renal artery assist in the prevention of graft arterial stenosis.
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ObjectiveTo evaluate the efficacy of Zishui Bugan decoction on perimenopausal insomnia of liver-kidney deficiency type and the safety. MethodA randomized， double-blind， placebo-controlled trial was designed. To be specific， 72 patients of perimenopausal insomnia with Liver-kidney deficiency were randomized into the treatment group and the control group at the ratio of 1∶1 and they were respectively treated with Zishui Bugan decoction and placebo for 3 weeks. The Pittsburgh sleep quality index （PSQI）， modified Kupperman index， traditional Chinese medicine （TCM） syndrome score， self-rating anxiety scale （SAS） score， and self-rating depression scale （SDS） score， were compared before and after treatment to determine the clinical efficacy， with adverse effects recorded. ResultThe total effective rate for insomnia was 85.3%（29/34） in treatment group and 17.6%（6/34） in control group（Z=-5.582，P<0.01）. After treatment， PSQI score， modified Kupperman index， TCM syndrome score， and SAS score were improved in both groups （P<0.05， P<0.01）， particularly the treatment group which showed significant difference from the control group （P<0.05，P<0.01）. The safety indicators were insignificantly different between two groups before and after treatment. No related adverse effects were reported in both groups during the treatment. ConclusionZishui Bugan decoction can improve the sleep quality and alleviate the menopausal symptoms， such as depression and anxiety， which shows ideal efficacy and safety for the perimenopausal insomnia with liver-kidney deficiency type.
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ObjectiveTo explore the intervention effect of Erxian decoction on intestinal microflora after ovariectomy in rats by 16S rRNA gene sequencing. MethodThirty-two female healthy SD rats were randomly divided into a Sham operation （Sham） group， a model （OVX） group， an estrogen （E） group， and an Erxian decoction （EXD） group， with 8 rats in each group. The rats in the E group and the EXD group received 1.8×10-4 g·kg-1 estradiol valerate solution and 9 g·kg-1 Erxian decoction， respectively， and those in the Sham group and the OVX group received an equal volume of distilled water once a day for 16 weeks. After 16 weeks， the levels of serum estrogen and blood lipid were detected. The fecal DNA was extracted， followed by 16S rRNA gene sequencing and analysis. ResultCompared with the Sham group， the OVX group showed reduced serum estrogen level （P<0.01） and increased serum levels of total cholesterol （TC） and low-density lipoprotein cholesterol （LDL-C） （P<0.05）. Compared with the OVX group， the E group and the EXD group showed increased serum estrogen level （P<0.01） and reduced TC and LDL-C （P<0.05）. Alpha diversity showed that there was no significant change in intestinal microflora diversity after ovariectomy. Beta diversity showed that there were significant differences in the structure of intestinal microflora in the four groups. The intervention of Erxian decoction could improve the changes in intestinal microflora after ovariectomy. LEfSe was used to analyze the differential flora in the four groups. The results showed that the Sham group and the OVX group had 3 differential bacterial phyla and 18 differential bacterial genera， the OVX group and the E group had 1 differential bacterial phylum and 12 differential bacterial genera， and the OVX group and the EXD group had 3 differential bacterial phyla and 5 differential bacterial genera. Estrogen intervention could reverse the change trend of Ruminococcus 1， Anaerovibrio， and Turicibacter in the OVX group. Erxian decoction intervention could reverse the change trend of Bacteroidetes， Firmicutes， Prevotella 9， Ruminococcaceae UCG-014， Ruminococcus 1， and Fusicatenibacter in the OVX group. ConclusionThe structure and function of intestinal microflora in ovariectomized rats changed obviously， and Erxian decoction could ameliorate the change.
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ObjectiveTo explore the molecular mechanism of "transmission between the lung and brain" of influenza based on Janus kinase 1/signal transducer and activator of transcription 1（JAK1/STAT1） signaling pathway and further investigate the intervention effect of Maxing Shigantang （MXSGT）. MethodA total of 100 SPF BALB/c mice were randomly divided into a normal group，a model group，an oseltamivir group （21.63 mg·kg-1·d-1），an antiviral granules group（3.9 g·kg-1·d-1）， and an MXSGT group（6.05 g·kg-1·d-1）， with 20 mice in each group. The pneumonia model was induced in mice except for those in the normal group by intranasal infection of influenza A virus（IAV）. Twenty-four hours after modeling，mice were treated with corresponding drugs， while those in the normal group and the model group received the same amount of normal saline by gavage， once a day for 3 and 7 days. The pathological changes in the lung and brain were observed by hematoxylin-eosin（HE）staining. The mRNA expression of IAV nucleoprotein（NP），JAK1， and STAT1 in the lung and brain was detected by real-time quantitative polymerase chain reaction（Real-time PCR）， and the protein expression of JAK1 and STAT1 in the lung and brain was detected by Western blot. Immunohistochemical method was used to detect the expression of phosphorylated（p）-STAT1 in the lung and brain tissues， and enzyme-linked immunosorbent assay（ELISA） was used to detect the serum levels of interleukin-1β（IL-1β） and interleukin-10（IL-10）. ResultCompared with the normal group， the model group showed obvious pathological changes in the lung tissues and cerebral cortex， increased relative mRNA expression of IAV NP in the lung （P<0.01）， elevated mRNA and protein expression of JAK1 and STAT1 in the lung and brain tissues （P<0.05，P<0.01），up-regulated expression level of p-STAT1 in lung tissues and cerebral cortex （P<0.05，P<0.01）， and increased serum level of IL-1β （P<0.05）. Compared with the model group， the MXSGT group showed alleviated pathological damage to lung tissues and cerebral cortex， decreased relative mRNA expression of IAV NP in lung tissues（P<0.01），reduced mRNA and protein expression levels of JAK1 and STAT1 in lung tissues and brain tissues（P<0.05，P<0.01）， and increased serum level of IL-10（P<0.01）. ConclusionThe abnormal activation of the JAK1-STAT1 signaling pathway may be one of the molecular mechanisms of "transmission between the lung and brain" of influenza. As an effective compound prescription against the influenza virus，MXSGT can alleviate the pathological damage of brain tissues in mice infected with IAV by regulating the level of cytokines mediated by this pathway.
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ObjectiveTo study the effects of Wendantang on the expression of miRNA-219， N-methyl-D-aspartate receptor 2B （NR2B）， disrupted in schizophrenia 1 （DISC1）， and Ca2+/calmodulin-dependent protein kinase Ⅱγ （CaMKⅡγ） in the frontal lobe of rats with schizophrenia. MethodSixty rats were randomly divided into six groups， namely normal group， model group， high-， medium-， and low-dose Wendantang groups， and clozapine group， with 10 rats in each group. Rats in high-， medium-， and low-dose Wendantang groups were intragastric with 40， 20， and 10 g·kg-1 Wendantang， and the ones in clozapine group were intragastric with 0.02 g·kg-1 clozapine， those in normal and model group were intragastric with equal volume of normal saline， once a day. After 21 days of administration， rats in all groups except for the normal group were injected with 0.6 mg·kg-1 dizocilpine maleate （MK-801） into the left abdominal cavity for inducing acute schizophrenia. The stereotypic behavior and ataxia in rats were scored according to SAMS and HOFFMAN criteria. The morphological changes in the prefrontal cortex were observed by hematoxylin-eosin （HE） staining. The protein expression levels of NR2B, DISC1 and CaMKⅡγ in the frontal lobe was detected by Western blot. The mRNA expression levels of miRNA-219 was detected by real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）. ResultCompared with normal group， the model group exhibited significantly increased stereotypic behavior and ataxia scores （P<0.01）， karyopyknosis and karyolysis in most neurons of the prefrontal cortex， and down-regulated NR2B， DISC1， and CaMKⅡγ protein expression （P<0.01） and miRNA-219， NR2B， DISC1， and CaMKⅡγ mRNA expression （P<0.01）. Compared with model group， Wendantang high-， medium-， and low-doses group lowered the scores of stereotypic behavior and ataxia at 50， 60 mmin（P<0.05，P<0.01）. In high- and medium-dose Wendantang groups， the neurons in the prefrontal cortex were densely arranged. The karyopyknosis and karyolysis were alleviated to varying degrees. The NR2B protein expression in the frontal lobe was up-regulated （P<0.01）. In the medium- and low-dose Wendantang groups， the DISC1 protein expression in the frontal lobe was up-regulated （P<0.05，P<0.01）. Wendantang at each dose significantly increased the CaMKⅡγ protein expression （P<0.05） and miRNA-219， NR2B， DISC1， and CaMKⅡγ mRNA expression in the frontal lobe （P<0.05，P<0.01）. ConclusionWendantang improves the scores of stereotypical behavior and ataxia， relieves the karyopyknosis and karyolysis of neurons in the prefrontal cortex， and increases the expression levels of miRNA-219， NR2B， DISC1， and CaMKⅡγ of rats with schizophrenia， so as to alleviate the schizophrenic-like symptoms and schizophrenia.
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Pyroptosis is a newly discovered programmed cell death. It is an important natural immune response and has obvious anti-infection function. Studies have shown that pyroptosis plays an important role in the occurrence and development of rheumatoid arthritis. Traditional Chinese medicine（TCM） has unique advantages in the prevention and treatment of rheumatoid arthritis. How to guide TCM to effectively prevent and treat rheumatoid arthritis using pyroptosis theory is a new research hotspot in this field. This paper discussed the overview of pyroptosis theory，its mechanism， signal pathway，and application in the treatment of rheumatoid arthritis as well as the research on the activity of TCM based on pyroptosis theory. It was found that the occurrence of pyroptosis was related to Caspase-1-dependent classical inflammatory body pathway and Caspase-1-independent non classical inflammatory body pathway， and pyroptosis produced distinct regulatory effect on the occurrence，development and treatment of rheumatoid arthritis，which would provide a new strategy for the treatment of rheumatoid arthritis. Additionally，TCM recipes such as Miao ethnomedicine prescription Sidaxue and Duhuo Jishengtang， and a variety of effective components such as punicalagin and paeoniflorin monomer derivatives exerted anti-rheumatic and other biological activities by regulating pyroptosis. This provided a theoretical basis and research ideas for the in-depth study of pyroptosis theory and guiding the prevention and treatment of rheumatoid arthritis with TCM.
ABSTRACT
Pyroptosis is a newly discovered programmed cell death. It is an important natural immune response and has obvious anti-infection function. Studies have shown that pyroptosis plays an important role in the occurrence and development of rheumatoid arthritis. Traditional Chinese medicine（TCM） has unique advantages in the prevention and treatment of rheumatoid arthritis. How to guide TCM to effectively prevent and treat rheumatoid arthritis using pyroptosis theory is a new research hotspot in this field. This paper discussed the overview of pyroptosis theory，its mechanism， signal pathway，and application in the treatment of rheumatoid arthritis as well as the research on the activity of TCM based on pyroptosis theory. It was found that the occurrence of pyroptosis was related to Caspase-1-dependent classical inflammatory body pathway and Caspase-1-independent non classical inflammatory body pathway， and pyroptosis produced distinct regulatory effect on the occurrence，development and treatment of rheumatoid arthritis，which would provide a new strategy for the treatment of rheumatoid arthritis. Additionally，TCM recipes such as Miao ethnomedicine prescription Sidaxue and Duhuo Jishengtang， and a variety of effective components such as punicalagin and paeoniflorin monomer derivatives exerted anti-rheumatic and other biological activities by regulating pyroptosis. This provided a theoretical basis and research ideas for the in-depth study of pyroptosis theory and guiding the prevention and treatment of rheumatoid arthritis with TCM.
ABSTRACT
Glioma is a primary aggressive brain tumor with high recurrence rate. The poor efficiency of chemotherapeutic drugs crossing the blood‒brain barrier (BBB) is well-known as one of the main challenges for anti-glioma therapy. Moreover, massive infiltrated tumor-associated macrophages (TAMs) in glioma further thwart the drug efficacy. Herein, a therapeutic nanosystem (SPP-ARV-825) is constructed by incorporating the BRD4-degrading proteolytic targeting chimera (PROTAC) ARV-825 into the complex micelle (SPP) composed of substance P (SP) peptide-modified poly(ethylene glycol)-poly(d,l-lactic acid)(SP-PEG-PDLLA) and methoxy poly(ethylene glycol)-poly(d,l-lactic acid) (mPEG-PDLLA, PP), which could penetrate BBB and target brain tumor. Subsequently, released drug engenders antitumor effect via attenuating cells proliferation, inducing cells apoptosis and suppressing M2 macrophages polarization through the inhibition of IRF4 promoter transcription and phosphorylation of STAT6, STAT3 and AKT. Taken together, our work demonstrates the versatile role and therapeutic efficacy of SPP-ARV-825 micelle against glioma, which may provide a novel strategy for glioma therapy in future.