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The high intra- and inter-tumor heterogeneity of gastric cancer leads to a great difference in the immunotherapy efficacy and the prognosis among patients. Several biomarkers, including programmed death-ligand 1, human epidermal growth factor receptor 2, the features of tumor microenvironment, the peripheral blood inflammatory markers and Claudin18.2 have predictive value in the immunotherapy efficacy and the prognosis of gastric cancer patients, which might help the clinicians find the potential patients who will benefit from immunotherapy, and achieve the goal of precision medicine.
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Objective To investigate the expression of circular-RNA DDX5(circ-DDX5)in breast cancer tissues and its relationship with the clinical stage of breast cancer patients,and to analyze the regulatory mechanism of circ-DDX5 on the proliferation and invasion of human breast cancer cell line.Methods The expression level of circ-DDX5 in breast cancer tissues and its correlation with the clinical stage of breast cancer patients were analyzed by TCGA database.Bioinformatics analysis and dual-luciferase reporter gene experiments verified the targeting rela-tionship between circ-DDX5 and miR-3940.The correlation between circ-DDX5 and miR-3940 expression in breast cancer tissues was analyzed by TCGA database.The expression level of circ-DDX5 in breast cancer SK-BR-3,MDA-MB-231,BT-549,MCF-7,and HCC-1937 cells was detected by RT-qPCR.The circ-DDX5 over-expression plasmid and negative control plasmid were transfected into MDA-MB-231 cells,which were named circ-DDX5 group and NC group,respectively.The proliferation and invasion of MDA-MB-231 cells in the circ-DDX5 group and the NC group were detected by colony formation assay and Transwell assay.The expressions of proliferation pheno-type protein and invasion phenotype protein of MDA-MB-231 cells were detected by Western blot.The expression level of miR-3940 in MDA-MB-231 cells of circ-DDX5 group and NC group was detected by RT-qPCR.Results The expression of circ-DDX5 in breast cancer tissues was lower than that in adjacent tissues(P<0.01)and the ex-pression level of circ-DDX5 was negatively correlated with the clinical stage of breast cancer patients(P<0.01).There was a targeting relationship between circ-DDX5 and miR-3940(P<0.01).The expression of circ-DDX5 and miR-3940 in breast cancer tissue was negatively correlated(P<0.01).The expression of circ-DDX5 in human breast cancer cell lines was lower than that in immortalized breast epithelial cells MCF-10A(P<0.05 or P<0.01).Compared with the NC group,the over-expression of circ-DDX5 could significantly inhibit the proliferation and in-vasion of MDA-MB-231 cells(P<0.01),as well as the proliferation phenotype proteins(cyclin C,CDK3)and in-vasion phenotype proteins(Snail,vimentin)expression(P<0.01)and miR-3940 expression(P<0.01).Conclu-sions The expression of circ-DDX5 in breast cancer tissues and cells is low.circ-DDX5 inhibits the proliferation and invasion of breast cancer MDA-MB-231 cells by targeting the expression of miR-3940.
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Objective:To analyze the clinical and immunological characteristics of children with acute viral infection-related encephalopathy.Methods:Case-control study.A retrospective analysis was conducted on the clinical data of children diagnosed with acute viral infection-related encephalopathy during hospitalization at the Children′s Hospital, Capital Institute of Pediatrics from January 2020 to January 2023.According to the last follow-up modified Rankin scale (mRS) score, these children were divided into a good prognosis group (mRS score ≤2) and a poor prognosis group (mRS score >2), and the clinical and immunological characteristics of the children with different prognoses were analyzed.The binary Logistic regression was used to analyze the risk factors for poor prognosis.Results:A total of 28 children with acute viral infection-related encephalopathy aged 4 months to 11 years were included.There were 16 males (57%) and 12 females (43%). Among the preinfection viruses, there were 16 children of Corona virus disease 2019, 8 children of influenza A virus, 3 children of influenza B virus, and 1 child of norovirus.Among them, there were 21 children with acute necrotizing encephalopathy, 4 children with acute encephalopathy with biphasic seizures and late reduced diffusion, 2 children with mild encephalitis with a reversible splenial lesion, and 1 child with hemorrhagic shock and encephalopathy syndrome.Among the first symptoms, 24 children (85.7%) had consciousness disorders, 23 children (82.1%) had seizures, 17 children (60.7%) had speech disorders, 11 children (39.3%) had involuntary movements, and 10 children (35.7%) had abnormal mental behavior.For the site of lesion, the cranial nuclear magnetic resonance imaging revealed 17 in the thalamus, 10 in the brainstem, 9 in the basal ganglia, 8 in the cerebellar hemisphere, and 4 in the corpus callosum.In the last follow-up evaluation, 17 children had a mRS score of >2, and 11 children had a mRS score of ≤2.Univariate analysis showed that disturbance of consciousness, seizure cluster, brain stem lesion, absolute value of serum T lymphocytes, cerebrospinal fluid(CSF) protein, CSF cytokines [interleukin(IL)-1β, IL-6 and IL-8]were higher in the poor prognosis group than those in the good prognosis group.Multivariate Logistic regression analysis indicated that brain stem disease, CSF IL-1β and T lymphocyte absolute number were independent risk factors for poor prognosis.Conclusions:Brain stem lesions, cerebrospinal fluid IL-1β and the absolute number of T lymphocytes have predictive value for the prognosis of acute viral infection-associated encephalopathy.The more severe the conditions, the lower the T lymphocytes, and the higher the cytokines in some cerebrospinal fluid.
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BACKGROUND:Previous studies have shown that human dental pulp stem cells have good osteogenic differentiation potential and are potential seed cells in bone tissue engineering,and the effect of recombinant human growth hormone on the proliferative osteogenic differentiation of human dental pulp stem cells is still unclear. OBJECTIVE:To explore the effect of recombinant human growth hormone on the proliferation and osteogenic differentiation of human dental pulp stem cells. METHODS:Human dental pulp stem cells were isolated and cultured by tissue block culture method.After screening according to the drug concentration gradient,recombinant human growth hormone containing 10,100,250,500,1 000 μg/L was selected as the experimental group,and 0 μg/L without recombinant human growth hormone was selected as the control group.CCK-8 detection reagents were used on days 1,3,5,and 7 after the drug intervention to detect the proliferation of human dental pulp stem cells.Different concentrations(10,100,250,500,and 1 000 μg/L)of recombinant human growth hormone were added to the osteogenesis induction solution to intervene in human dental pulp stem cells.Alkaline phosphatase activity was detected by alkaline phosphatase staining and semi-quantitative analysis on day 7 of mineralization induction.The mRNA expression levels of osteogenic gene type I collagen,osteocalcin and Runt-related transcription factor 2 were detected by fluorescence quantitative RT-qPCR.Alizarin red staining was performed on day 14 of mineralization induction to detect osteogenic mineralized nodules. RESULTS AND CONCLUSION:(1)CCK-8 assay results showed that from the third day of intervention,the 100,250,500,1 000 μg/L recombinant human growth hormone group could promote the proliferation of human dental pulp stem cells compared with the control group(P<0.01).(2)The alkaline phosphatase activity of human dental pulp stem cells in the 100,250,and 500 μg/L recombinant human growth hormone group was significantly increased compared with the control group(P<0.01).The number of alizarin-stained mineralized nodules in human dental pulp stem cells in the 100,250 μg/L recombinant human growth hormone group was significantly increased compared with the control group(P<0.01).Compared with the control group,the mRNA expression of type I collagen and osteocalcin increased in the 250 μg/L recombinant human growth hormone group(P<0.05,P<0.01).mRNA expression of Runt-associated transcription factor 2 increased in the 100 and 250 μg/L recombinant human growth hormone groups(P<0.01).(3)According to the above results,recombinant human growth hormone at a concentration of 250 μg/L is a more suitable concentration to promote the proliferation and osteogenic differentiation of human dental pulp stem cells.
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With the implementation of Party building in public hospitals in the new era,and the deep integration of Party building of administration departments and healthcare services as well,the high-quality development of hospitals through high-quality Party building is realized,which is a topic that needs to be explored in Party building in public hospitals.The Party build-ing in public hospitals has its unique functional positioning.With the requirements of Party building in the new era and the de-mand for high-quality development of public hospitals,Party building in public hospitals needs to solve the problems of"What","How"and"Well"from the ideological perspective,top-level design and practical level respectively,which are called the"3W"principles.
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Objective To investigate the clinical significance of the chorda arteriae umbilicalis in laparoscopic transabdominal preperi-toneal(TAPP)hernia repair.Methods The clinical data of 60 patients with inguinal hernia admitted to Xinrui Hospital in Xinwu District of Wuxi City from June 2019 to June 2022 were analyzed,and the patients were randomly divided into two groups according to whether the chorda arteriae umbilicalis was used as a marker during operation.Both the control group and the observation group were operated according to the routine procedure.The observation group exposed the chorda arteriae umbilicalis,which was used as a reference to precisely free the surgical plane and gap to complete the parietalization of spermatic cord,meanwhile,the angle formed by the intersection of the deferens and umbilical artery cord was used to assist in fixing the patch.The operation time,time of parietalization of spermatic cord,hospital stay,bladder surface bleeding volume,removal rate of hernial sac,the occurrence of postoperative complications and recurrence of patients were compared between the two groups.Results There was no significant difference in the operation time,removal rate of hernial sac,hospital stay,recurrence rate or the incidence of postoperative complications such as chronic pain,uroschesis of patients between the two groups(P>0.05).The time of parietalization of spermatic cord,bladder surface bleeding volume,and incidence of seroma of patients in the observation group were shorter/lower than those in the control group,the differences were statistically significant(P<0.05).Conclusion The chorda arteriae umbilicalis has a constant morphology and relatively fixed anatomical position and alignment.The chorda arteriae umbilicalis can be used as a reference and guiding mark,especially when the anatomical layer is dense and unclear or strayed into the layer in TAPP hernia repair,whihc can guide to operate at the correct layer,standardize the parietalization of spermatic cord,reduce bleeding and vice-damage,and also assist the fixation of the patch and prevent the displacement of the patch.
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【Objective】 To explore the expression of PCDH9 loss in regulating cell cycle and promoting tumor progression. 【Methods】 The clinical records of 127 cases of prostate cancer treated during 2018 and 2023 were collected, including 87 paraffin tissue samples from the G4-5 group and 40 from the G1-3 group. The expressions of PCDH9, p53, Rb and STAT3 were detected with immunohistochemical staining, and the relationship between their expressions and clinicopathological characteristics was analyzed. 【Results】 The expression deletion rate of PCDH9 in prostate cancer tissues in G4-5 group (44.8% vs.7.5%) was significantly higher than that in G1-3 group (P<0.001). The positive expression rates of p53 and STAT3 were 34.5% and 89.7%, respectively, and the expression loss rate of Rb was 27.6% in G4-5 group. The expression loss rates of PCDH9 and Rb were associated with neuroendocrine-like histological morphology, nerve invasion and vascular invasion (P<0.05). In G4-5 group of prostate cancer, PCDH9 expression was positively correlated with the expressions of p53 (r=0.345, P<0.05), Rb (r=0.503, P<0.05) and STAT3 (r=0.224, P<0.05). 【Conclusion】 PCDH9 is prone to loss of expression in high-group prostate cancer tissues, especially in cases with neuroendocrine-like histological morphology, which may regulate the cell cycle through the STAT3 signaling pathway, thereby promoting tumor progression.
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ObjectiveTo evaluate the effectiveness of Lutongning granules in the treatment of trigeminal neuralgia in animal models and study its mechanism of action, so as to provide laboratory data support for the clinical application of Lutongning granules and precise treatment. MethodMale SD rats were randomly divided into normal group, model group, carbamazepine group (0.06 g·kg-1·d-1), high-dose Lutongning group (2.70 g·kg-1·d-1), and low-dose Lutongning group (1.35 g·kg-1·d-1) according to the stratified basic mechanical pain thresholds, with 10 rats in each group. A trigeminal neuralgia model of rats was prepared by injecting 30% talc suspension into the infraorbital foramen area of the rat. The drug groups were administered 10 mL·kg-1 of drugs by gavage after 2 h of modeling. The normal group and the model group were administered distilled water by gavage under the same conditions once a day for 10 consecutive days. Von Frey brushes were used to determine the mechanical pain threshold of rats. A fully automated blood and body fluid analyzer was employed to detect the blood routine of rats. Hematoxylin and eosin (HE) staining was utilized to detect the pathological changes in the trigeminal ganglion and medulla oblongata tissue. Transmission electron microscopy was used to scan the ultrastructure of the medulla oblongata tissue. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of inflammatory factors interleukin (IL)-1, IL-6, IL-8, tumor necrosis factor (TNF)-α, neuropeptide substance P, and β-endorphins (β-EP) in the serum of rats, and Western blot was used to detect the protein expression levels of IL-1β, purinergic receptor P2X7 (P2X7R), and phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK). ResultCompared with that in the normal group, the pain threshold of rats in the model group was significantly lower (P<0.01). The absolute value of neutrophils (NEUT#) and the percentage of neutrophils (NEUT) were significantly improved, and the percentage of lymphocytes (LYMPH) was significantly reduced (P<0.01). The serum levels of IL-1, IL-6, IL-8, and TNF-α were significantly increased (P<0.01). SP content in brain tissue was significantly increased, and β-EP content was significantly decreased (P<0.01). The relative protein expression of IL-1β, P2X7R, and p-p38 MAPK was significantly increased (P<0.05). HE staining and transmission electron microscopy results of medulla oblongata tissue revealed neuronal degeneration, mild proliferation of microglial cells, reduction in the number of myelinated nerves, and obvious demyelination. The trigeminal nerve fibers of rats were disarranged, and some nerve fibers showed vacuolization. Axons were swollen, and Schwann cells proliferated. Demyelination was observed. Compared with the model group, each administration group significantly increased the pain threshold of rats (P<0.05, P<0.01), reduced NEUT# and NEUT, and elevated LYMPH (P<0.05, P<0.01). The administration group significantly decreased the levels of IL-1, IL-6, IL-8, and TNF-α in serum and SP in brain tissue (P<0.01) and increased the level of β-EP (P<0.01). They significantly down-regulated the protein expression of IL-1β, P2X7R, and p-p38 MAPK(P<0.05, P<0.01) and significantly ameliorated the pathological changes in medulla oblongata tissue and trigeminal nerves of rats. ConclusionLutongning Granules had significant therapeutic effects on trigeminal neuralgia induced by injection of talc into the infraorbital foramen of model rats, and the mechanism may be related to amelioration of P2X7R-mediated neuroinflammation and inhibition of demyelination of myelinated nerves.
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@#Hemodynamics plays a vital role in the development and progression of cardiovascular diseases, and is closely associated with changes in morphology and function. Reliable detection of hemodynamic changes is essential to improve treatment strategies and enhance patient prognosis. The combination of computational fluid dynamics with cardiovascular imaging technology has extended the accessibility of hemodynamics. This review provides a comprehensive summary of recent developments in the application of computational fluid dynamics for cardiovascular hemodynamic assessment and a succinct discussion for potential future development.
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Objective To investigate the effects of Helicobacter pylori(Hp)on the proliferation,migration,apoptosis and inflammatory response of human umbilical vein endothelial cells(HUVEC)through activation of STAT3/nuclear factor κB(NF-κB)pathway.Methods HUVEC were divided into control group(without Hp infection)and Hp group(multiplicity of infection=25).Cell morphology was observed with inverted microscopy,proliferation was detected by CCK-8 assay and plate cloning assay,and the migration ability was examined by Transwell migration as-say and wound healing assay.Flow cytometry was used to detect the apoptotic rate.Real-time fluo-rescence quantitative PCR was employed to measure the mRNA expression of cytotoxin-associat-ed gene A(CagA),IL-6,IL-8,IL-1β and TNF-α.Western blotting was applied to determine the protein expression of Cyclin D1,proto-oncogene C-Myc,MMP-2,MMP-9,PCNA,Bax,Bcl-2 and STAT3/NF-κB signaling pathway.Results Hp infection resulted in suppressed proliferation and migration abilities,decreased protein levels of Cyclin D1,PCNA,C-Myc,MMP-2,MMP-9 and Bcl-2,elevated protein levels of Bax,p-STAT3/STAT3,p-NF-KB p65/NF-κB p65,raised apoptotic rate,and significantly increased mRNA levels of IL-6,IL-8,IL-1β and TNF-α(2.71±0.05 vs 1.06±0.41,1.42±0.02 vs 0.92±0.11,2.50±0.29 vs 1.00±0.10,5.34±0.57 vs 1.00±0.16;P<0.01)when compared with the control group.Conclusion Hp infection inhibits proliferation and migra-tion,and induces apoptosis and inflammatory response in HUVEC through activation of the STAT3/NF-κB pathway.
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ObjectiveThe human angiotensin converting enzyme2 (hACE2) transgenic mouse model was used to clarify the antiviral efficacy of BD-77 against a novel coronavirus SARS-CoV-2 and explore the action mechanism of BD-77 against SARS-CoV-2. MethodSARS-CoV-2 Omicron and Delta variant strains-infected VeroE6 cell models were established and administered with BD-77 to observe the antiviral effect of BD-77 in vitro. A kit was used to detect the effect of BD-77 in vitro on the binding of spike S protein of SARS-CoV-2 virus (Delta/Omicron) to angiotensin converting enzyme2 (ACE2). Chromatography was adopted to detect the binding of BD-77 to the S protein and N protein of the novel coronavirus. hACE2 transgenic C57BL/6 mice were divided into a blank control group, SARS-CoV-2 infection group, BD-77 administration groups of 37.5 mg·kg-1 and 75 mg·kg-1, with eight mice in each group. The pneumonia model of SARS-CoV-2-infected hACE2 transgenic mice was built to observe the survival of the mice, detect the virus titer of the lung tissue of the mice, and observe the lesions in the lung tissue. ResultBD-77 had a certain inhibitory effect on Omicron and Delta variant strains in vitro, with median inhibitory concentration (IC50) of 526.3 mg·L-1 and 653.0 mg·L-1, respectively. BD-77 had no significant inhibitory effect on the binding of the S protein of WT, Omicron, and Delta variant strains of SARS-CoV-2 to ACE2 and had no binding effect with the S protein and N protein of the novel coronavirus. No mice in the blank group died, while the mortality rate of SARS-CoV-2-infected mice was 75%. There was a large amount of virus replication in the lung tissue of the mice and large areas of inflammatory infiltration in the lung tissue and interstitium. Compared with the model group, BD-77 administration groups of 37.5 mg·kg-1 and 75 mg·kg-1 could reduce the mortality of mice, significantly lower the virus titer in the lung tissue of mice (P<0.05), and improve lung lesions. ConclusionBD-77 demonstrated significant inhibitory effects against SARS-CoV-2 virus in vitro and in vivo. However, its mechanism of action did not involve direct inhibition of the virus itself or intervention in the virus-host binding process. This finding suggests that the mechanism of action of BD-77 needs to be thoroughly investigated and elucidated by further experiments.
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ObjectiveTo observe the therapeutic effect of BD-77 by nebulized inhalation on animal models of various respiratory viral infections and investigate the mechanism of broad-spectrum antiviral action of BD-77 using proteomics. MethodThe influenza virus H1N1/FM1 experiment used ICR mice and divided them into a normal group, model group, Tamiflu group, and BD-77 groups of 75 and 37.5 g·L-1 for inhalation of 20 min and 25 min. Human coronavirus 229E and OC43 experiment divided the BALB/c mice into a normal group, model group, chloroquine phosphate group, and BD-77 groups of 75, 37.5, 18.75, and 9.375 g·L-1, with 10 mice in each group. Influenza virus H1N1/FM1 and human coronaviruses 229E and OC43 infection-induced pneumonia models were used to detect mouse lung index, and real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the viral load in lung tissue. Enzyme-linked immunosorbent assay (ELISA) was used to detect related inflammatory factors in lung tissue, and proteomics analysis was performed on the lung tissue of OC43-infected mice. ResultCompared with that in the normal group, the lung index of mice in each infection group was significantly increased (P<0.01), and viral nucleic acid could be detected in the lung tissue of mice infected with human coronaviruses 229E and OC43. The levels of interleukin-6 (IL-6), IL-10, and tumor necrosis factor-α (TNF-α) in the lung tissue of mice infected with human coronavirus 229E were all significantly increased (P<0.01). BD-77 could significantly reduce the lung index of mice infected with influenza virus H1N1/FM1 and human coronaviruses 229E and OC43 (P<0.05, P<0.01), cut down the viral load in the lungs of mice infected with human coronaviruses 229E and OC43 (P<0.01), and lower the contents of IL-6, IL-10, and TNF-α in the lung tissue of mice infected with human coronavirus 229E (P<0.01). Proteomics analysis of the lung tissue of OC43-infected mice showed that BD-77 regulated the AMPK signaling pathway, TNF signaling pathway, NOD-like signaling pathway, IL-17 signaling pathway, Forkhead box protein O (FoxO) signaling pathway, transforming growth factor-β (TGF-β) signaling pathway, and other signaling pathways. ConclusionNebulized inhalation of BD-77 is effective in treating pneumonia caused by influenza virus H1N1/FM1 and human coronaviruses 229E and OC43 infection in mice and may exert its antiviral effects by regulating the balance of cellular metabolism, enhancing the immune function of the host, and attenuating inflammatory responses.
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Objective:To investigate clinical treatment regimens for ocular lesions in patients with severe ocular rosacea.Methods:A total of 28 patients (34 eyes) with severe rosacea complicated by blepharokeratoconjunctivitis were collected from outpatient department of the Affiliated Eye Hospital of Nanjing Medical University from December 1, 2019 to May 30, 2021. They were randomly divided into two groups: group A (13 cases, 16 eyes) topically treated with sodium hyaluronate 0.3% eye drops and levofloxacin 0.5% eye drops, and group B (15 cases, 18 eyes) topically treated with sodium hyaluronate 0.3% eye drops alone. Patients in both groups also received oral minocycline hydrochloride 100 mg every day for the first 2 weeks, and then 50 mg every day for the next 6 weeks. Meanwhile, all patients received same physical therapies such as meibomian gland massage, eyelid hot compresses and eyelid margin cleaning. LogMAR visual acuity, tear break-up time (BUT) , ocular surface disease index (OSDI) score, and meibomian gland function grading examination results in the two groups were recorded before and 8 weeks after treatment. Paired t test was used to compare within-group differences in the parameters before and after treatment, and two-independent-sample t test to compare intergroup differences after treatment. Results:After 8-week treatment, both group A and group B showed significantly increased LogMAR visual acuity ( t = 3.10, 2.15, P = 0.007, 0.046, respectively) , improved BUT ( t = 3.44, 2.85, P = 0.003, 0.011, respectively) , but significantly decreased OSDI scores ( t = 7.12, 9.33, respectively, both P < 0.001) and meibomian gland function scores ( t = 13.73, 16.82, respectively, both P < 0.001) compared with those before treatment. After treatment, no significant differences were observed in the LogMAR visual acuity ( P = 0.721) , BUT ( P = 0.189) , OSDI scores ( P = 0.808) and meibomian gland function scores ( P = 0.191) between the two groups. No adverse drug reactions occurred during the treatment. During the follow-up period (8 months or shorter) , no recurrence of ocular lesions was observed. Conclusion:Without topical antibiotics, oral minocycline hydrochloride combined with topical sodium hyaluronate eye drops is still effective for the treatment and prevention of recurrence of ocular lesions in patients with severe ocular rosacea.
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Objective:To evaluate the safety and efficacy of n-butyl cyanoacrylate (NBCA) in treating great saphenous vein(GSV) incompetence.Methods:60 patients (60 limbs) with GSV incompetence were randomly divided into NBCA glue group (30 cases) and radiofrequency ablation(RFA) group in 30 cases. The clinical outcomes, venous clinical severity score(VCSS), and quality of life using the Aberdeen varicose vein questionnaire(AVVQ) were evaluated. The primary endpoint is the occlusion rate of GSV at 3 months after surgery.Results:For the two groups, the occlusion rate of GSV was 100% immediately after surgery and at 3 months follow-up. AVVQ and VCSS were improved in the two groups( P<0.05). In terms of complications, the NBCA group had scleroma in 3 cases, pain and skin redness in 1 case respectively, but no ecchymosis and numbness. In the RFA group, numbness occurred in 1 case, skin redness in 2 cases, scleroma in 3 cases, ecchymosis and pain in 4 cases respectively. The incidence of ecchymosis and total complications in the NBCA group was significantly lower than that in the RFA group( P<0.05). No DVT or other adverse event occurred in both groups. Conclusion:NBCA and RFA have the same short-term closure rate. Furthermore, the NBCA treatment requires less equipment, no use of tumescent anesthetic, and has lower incidence in terms of complications than that of RFA.
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Objective:To explore the status of microsatellite instability (MSI) and its relationship with clinicopathological characteristics of patients with endometrial carcinoma.Methods:The clinical data of 365 patients with endometrial carcinoma who received surgery in Shanxi Province Cancer Hospital between January 2020 and December 2021 were retrospectively analyzed. Immunohistochemistry was used to detect the expressions of 4 DNA mismatch repair (MMR) proteins (MLH1, MSH2, MHS6, and PMS2), estrogen receptor (ER), progesterone receptor (PR), and p53 mutant protein in postoperative cancer tissue samples from 365 patients with endometrial carcinoma. All patients were divided into MSI group (1 or more non-expression of MMR protein) and microsatellite stability (MSS) group (4 proteins were all expressed), and the clinicopathological characteristics of patients in both groups were compared. φ efficient was used to analyze the correlation of MSI with ER, PR, p53 mutant protein expressions. Results:There were 72 cases (19.7%) in MSI group and 293 cases (80.3%) in MSS group; and the age of all patients was (53±19) years (21-83 years). There were statistically significant differences in the proportion of MSI patients in endometrial carcinoma patients with different age [>50 years vs. ≤50 years: 22.1% (61/276) vs. 12.4% (11/89)], tumor diameter [≤2 cm vs. > 2 cm: 25.9% (30/116) vs. 16.8% (42/249)], International Federation of Gynecology and Obstetrics (FIGO) staging [stage Ⅲ-Ⅳ vs. stage Ⅰ-Ⅱ: 31.1% (14/45) vs. 18.1% (58/320)], histological type [type Ⅰ vs. type Ⅱ: 21.7% (71/327) vs. 2.6% (1/38)] (all P < 0.05). There were no statistically significant differences in the proportion of MSI patients with different depth of invasion, degree of differentiation, lymph node metastasis, vascular involvement, and lesion location (all P > 0.05). Among 327 cases of type Ⅰendometrial carcinoma, 1 case was mucinous adenocarcinoma (MSS status), and the other 326 cases were endometrioid adenocarcinoma. Of the 72 patients with MSI, 71 cases were endometrioid carcinoma and the other was 1 of 3 mixed carcinomas in type Ⅱ endometrial carcinoma. There was a negative correlation between MSI and mutant p53 ( φ coefficient was -0.11, P = 0.031), and φ coefficient of the correlation of MSI with ER and PR was -0.03 and -0.06, while there were no statistically significant differences ( P value was 0.578 and 0.255, respectively). Conclusions:Endometrioid adenocarcinoma is the main type of endometrial cancer patients with MSI. MSI in endometrial cancer is correlated with age, FIGO staging, tumor diameter and histological type of patients, while negatively correlated with mutant p53.
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ObjectiveTo investigate the survival and adverse reactions of patients with unresectable cholangiocarcinoma after stereotactic body radiation therapy (SBRT). MethodsA total of 27 patients with unresectable solitary cholangiocarcinoma without metastasis who underwent SBRT in The Fifth Medical Center of Chinese PLA General Hospital from February 2012 to July 2020 were enrolled. The prescribed dose to planning target volume was 42-60 Gy in 5-8 fractions, with 5-11 Gy/fraction. Among these patients, five patients were also treated with chemotherapy and transcatheter arterial chemoembolization. The 6-, 12-, 18-, and 24-month overall survival (OS) rates, progression-free survival (PFS) rates, and local control (LC) rates were used as the assessment indices for treatment outcome; Common Terminology Criteria for Adverse Events v.4.03 was used to evaluate adverse reactions; the Kaplan-Meier method was used to calculate OS, PFS, and LC rates. ResultsThe median follow-up time was 17 months. For all 27 patients, the 6-, 12-, 18-, and 24-month OS rates were 100%, 88%, 57.5%, and 47.9%, respectively; the 6-, 12-, 18-, and 24-month PFS rates were 74.1%, 58.6%, 47.9%, and 35.9%, respectively; the 6-, 12-, 18-, and 24-month LC rates were 96.3%, 91.9%, 84.8%, and 76.4%, respectively. No grade 3 or above toxic reactions were observed. Five patients were diagnosed with radiation-induced liver injury, but there was no death due to radiation-induced liver injury. ConclusionSBRT is safe and effective in the treatment of unresectable cholangiocarcinoma, with relatively high survival rate, PFS rate, and LC rate and low toxicity, and therefore, SBRT can be used as an alternative treatment method for patients with cholangiocarcinoma who are not candidates for surgery.
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Rectal cancer is one of the most common gastrointestinal malignancies in China. Accurate and reasonable assessment of the preoperative staging of rectal cancer can significantly enhance treatment outcomes and improve patient prognosis. Magnetic resonance imaging is the technique of choice for local staging of rectal cancer and has significant advantages in the diagnosis of rectal primary tumors (T) and peri-intestinal lymph nodes (N). In this review paper, the research ideas and progress of traditional radiomics and deep learning methods for preoperative TN staging prediction of rectal cancer were reviewed around multimodal magnetic resonance images, with the aim of providing new ideas for realizing fully automated TN staging algorithms for rectal cancer.
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Objective:To explore the characteristics of gut microbiota in the preoperative, short-term postoperative and long-term postoperative period at (15.61±4.51) months in children with ventricular septal defect (VSD) of congenital heart disease (CHD) treated with cardiopulmonary bypass (CPB).Methods:A prospective study was conducted.In Guangzhou Women and Children′s Medical Center, 13 patients with VSD who were scheduled for CPB and additional 10 age- and gender-matched healthy infants as pre-CPB control group from January 2021 to January 2022 were enrolled.Fecal samples were collected at pre- and early post-CPB.Meanwhile, 18 gender- and CHD diagnosis and operation-matched patients at (15.61±4.51) months after CPB and 8 healthy age- and gender-matched children as long-term control group after CPB were also enrolled, and fecal samples were collected.16S rRNA sequencing of fecal samples from all subjects were performed and comparing the differences in gut microbiota between two groups via comparing alpha and beta diversity, parameter test or nonparametric test, and LEfSe analysis.Results:Compared with those of pre-CPB control group, there was a significant difference in the composition of gut microbiota in the preoperative period of VSD children, with significantly increased abundances of Enterobacteriaceae and Shigella, and decreased abundance of Bifidobacterium (all P<0.05). The diversity of gut microbiota was comparable in VSD children before CPB and in the short period time after CPB (all P>0.05), except for the abundances of Clostridium and Streptococcus (all P<0.05), and there was no significant difference in the relative abundances of other highly abundant gut bacteria between the two periods (all P>0.05). Compared with that in VSD children in the short period time after CPB, the abundances of short-chain fatty acids-producing microbes were significantly higher at (15.61±4.51) months postoperatively (all P<0.05), and the gut bacteria profile was similar to that of the long-term control group after CPB (all P>0.05). Conclusions:Gut microbiota imbalance exists in VSD children before CPB.The gut microbiota profile is not influenced by CPB, which returns normal at (15.61±4.51) months postoperatively.
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Objective:To explore the effects of Bifidobacterium triple viable capsules combined with Berberine tablets on blood lipid and intestinal flora in patients with hyperlipidemia.Methods:A total of 420 hyperlipidemia patients admitted to the Second Medical Center of PLA General Hospital & National Clinical Research Center for Geriatric Diseases from January 2019 to December 2020 were selected and divided into the observation group and the control group according to the random number table method, with 210 cases in each group. Both groups were routinely given lipid-lowering drugs, the control group was also given Bifidobacterium triple viable capsules orally, and the observation group was combined with Berberine tablets orally on the basis of the control group. The levels of serum inflammatory factor, blood lipid, apolipoprotein and the number of intestinal flora before and after treatment were compared between the two groups. The incidence of adverse reactions was compared between the two groups during the treatment.Results:After treatment, the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), high-sensitivity C-reactive protein (hs-CRP) in the observation group were significantly lower than those in the control group: (26.78 ± 5.63) ng/L vs. (30.06 ± 5.79) ng/L, (12.88 ± 4.76) ng/L vs. (15.45 ± 5.32) ng/L, (8.22 ± 2.80) mg/L vs. (10.26 ± 3.71) mg/L, there were statistical differences ( P<0.05). After treatment, the levels of blood lipid in the observation group were improve better than those in the control group, the levels of apolipoprotein AⅠ in the observation group was higher than that in the control group: (2.00 ± 0.45) g/L vs. (1.72 ± 0.39) g/L; and the levels of apolipoprotein B and apolipoprotein E in the observation group were lower than those in the control group: (1.08 ± 0.18) g/L vs. (1.20 ± 0.22) g/L, (4.80 ± 0.68) g/L vs. (5.12 ± 0.62) g/L, there were statistical differences ( P<0.05). After treatment, the numbers of Bifidobacterium and Lactic acid bacteria in the observation group were higher than those in the control group: (8.80 ± 0.80) lg CFU/g vs. (8.30 ± 0.75) lg cfu/g, (8.85 ± 0.64) lg cfu/g vs. (8.45 ± 0.68) lg cfu/g; and the numbers of Colon bacillus and Enterococcus faecalis in the observation group were lower than those in the control group: (8.20 ± 0.55) lg cfu/g vs. (8.52 ± 0.50) lg cfu/g, (6.42 ± 0.60) lg cfu/g vs.(6.84 ± 0.65) lg cfu/g, there were statistical differences ( P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups ( P>0.05). Conclusions:Bifidobacterium triple viable capsules combined with Berberine tablets in treatment of patients with hyperlipidemia can effectively reduce the level of blood lipid and regulate intestinal flora, with good safety.
ABSTRACT
Objective: To investigate the effect of nuclear factor erythroid 2-related factor 2 (Nrf2) in the alteration of tight junction protein expression in choroid plexus epithelial cells created by lanthanum-activated matrix metalloproteinase 9 (MMP9) . Methods: In October 2020, immortalized rat choroid plexus epithelial cell line (Z310) cells were used as the blood-cerebrospinal fluid barrier in vitro, and were divided into control group and 0.125, 0.25, 0.5 mmol/L lanthanum chloride (LaCl(3)) treatment group. After treating Z310 cells with different concentrations of LaCl(3) for 24 hours, the morphological changes of Z310 cells were observed under inverted microscope, the protein expression levels of MMP9, occludin and zonula occludens-1 (ZO-1) were observed by cellular immunofluorescence method, and the protein expression levels of MMP9, tissue inhibitors of metalloproteinase1 (TIMP1) , occludin, ZO-1 and Nrf2 were detected by Western blotting. The level of reactive oxygen species (ROS) in cells was detected by flow cytometry. Results: Compared with the control group, Z310 cells in the LaCl(3) treatment group were smaller in size, with fewer intercellular junctions, and more dead cells and cell fragments. The expression level of MMP9 protein in cells treated with 0.25 and 0.5 mmol/L LaCl(3) was significantly higher than that in the control group (P<0.05) , and the expression level of TIMP1 and tight junction proteins occudin and ZO-1 was significantly lower than that in the control group (P<0.05) . Compared with the control group, the ROS production level in the 0.25, 0.5 mmol/L LaCl(3) treatment group was significantly increased (P<0.05) , and the Nrf2 protein expression level in the 0.125, 0.25, 0.5 mmol/L LaCl(3) treatment group was significantly decreased (P<0.05) . Conclusion: Lanthanum may increase the level of ROS in cells by down regulating the expression of Nrf2, thus activating MMP9 to reduce the expression level of intercellular tight junction proteins occludin and ZO-1.