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Objective To investigate whether Toll-like receptor 4 (TLR4) inhibition affects liver regeneration during acetaminophen (APAP)-induced liver injury in mice, as well as the mechanism of TLR4 involved in liver regeneration. Methods A total of 78 male CD-1 mice were divided into nine groups using a random number table, i.e., three control groups (normal control group, solvent control group, inhibitor control group) with 6 mice in each group and six experimental groups (APAP 24-hour group, TAK-242+APAP 24-hour group, APAP 48-hour group, TAK-242+APAP 48-hour group, APAP 72-hour group, TAK-242+APAP 72-hour group) with 10 mice in each group. The mice in the experimental groups were given a single dose of intraperitoneally injected APAP (300 mg/kg), and TAK-242 was intraperitoneally injected at a dose of 3 mg/kg at 3 hours before APAP administration. Serum and liver tissue samples were collected at different time points. The biochemical method was used to measure the serum level of alanine aminotransferase (ALT); HE staining was used to observe liver pathological changes; RT-PCR, Western blot, and immunohistochemistry were used to measure the expression levels of Cyclin D1, PCNA, Ki-67, STAT3, and p-STAT3. The t -test was used for comparison of normally distributed continuous data between two groups; a one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t -test was used for further comparison between two groups. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups, and the Kruskal-Wallis H test was used for comparison between multiple groups and further comparison between two groups. Results Compared with the normal control group, the APAP 24-hour and 48-hour groups had a significantly higher serum level of ALT (both P < 0.05), and the TAK-242+APAP 24-hour and 48-hour groups had a significantly higher serum level of ALT than the APAP group at the same time point (both P < 0.05). HE staining showed typical central lobular necrosis in the liver of APAP-treated mice, and the TAK-242+APAP 24-hour and 48-hour groups had a significantly larger necrotic area than the APAP group at the same time point (both P < 0.05). RT-PCR, Western blot, and immunohistochemistry showed that the TAK-242+APAP 24-hour, 48-hour, and 72-hour groups had significantly lower mRNA and protein expression levels of Cyclin D1 than the APAP group at the same time point (all P < 0.05); the TAK-242+APAP 24-hour, 48-hour, and 72-hour groups had a significantly lower mRNA expression level of PCNA than the APAP group at the same time point (all P < 0.05), and the TAK-242+APAP 24-hour and 48-hour groups had a significantly lower protein expression level of PCNA than the APAP group at the same time point (all P < 0.05); the TAK-242+APAP 24-hour and 72-hour groups had a significantly lower mRNA expression level of Ki-67 than the APAP group at the same time point (all P < 0.05), and the TAK-242+APAP 24-hour, 48-hour, and 72-hour groups had a significantly lower protein expression level of Ki-67 than the APAP group at the same time point (all P < 0.05). In addition, the TAK-242+APAP 24-hour and 48-hour groups had a significantly lower phosphorylation level of STAT3 than the APAP group at the same time point (both P < 0.05). Conclusion TLR4 may promote liver regeneration by increasing the phosphorylation level of STAT3 during APAP-induced liver injury in mice.
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ObjectiveTo investigate the effects of Biling Qutong prescription （BLQT） on serum levels of NOD-like receptor thermal protein domain associated protein 3 （NLRP3）， purinergic ligand-gated ion channel 7 receptor （P2X7R）， fibronectin （FN）， and hepatic steatosis in patients with type 2 diabetes mellitus （T2DM） complicated with gouty arthritis （GA）. MethodSixty-four patients diagnosed with T2DM comorbid with GA and treated at the First Affiliated Hospital of Anhui University of Chinese Medicine from January 2019 to December 2022 were enrolled and randomly divided into a BLQT group （Chinese medicine group， 32 cases） and the ibuprofen group （western medicine group， 32 cases）. Thirty healthy individuals who underwent routine health examinations during the same period were assigned to the control group. The BLQT group and the western medicine group received basic treatment along with BLQT and ibuprofen， respectively. After 8 weeks of continuous treatment， the traditional Chinese medicine syndrome score （TCMSS） of the patients was evaluated before and after treatment. The differences in fasting plasma glucose （FPG）， 2-hour postprandial plasma glucose （2 h PG）， glycated hemoglobin （HbA1c）， fasting insulin （FINS）， homeostasis model assessment of insulin resistance （HOMA-IR）， serum uric acid （SUA）， serum creatinine （SCr）， total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， controlled attenuation parameter （CAP）， liver stiffness measurement （LSM）， NLRP3， P2X7R， and FN levels before and after treatment were compared. Adverse drug reactions that occurred during treatment were recorded. ResultThe TCMSS for joint redness， swelling， pain， joint burning， yellow urine， and red tongue with yellow and greasy coating， as well as total score were significantly reduced in both the BLQT group and the western medicine group as compared with those before treatment （P<0.05， P<0.01）. The BLQT group also showed a significant reduction in symptom scores such as dry mouth， polyuria， polydipsia， and slippery and rapid pulse （P<0.01）. Compared with the western medicine group after treatment， the BLQT group exhibited a more significant reduction in all symptom scores and total score （P<0.05， P<0.01）. The BLQT group and the western medicine group showed a decrease in FPG， 2 h PG， HbA1c， SCr， SUA， TG， TC， and LDL-C levels （P<0.05， P<0.01） after treatment， and the BLQT group showed decreased HOMA-IR， ALT， AST， and HDL-C levels （P<0.05， P<0.01） compared with those before treatment. When compared with the western medicine group after treatment， the BLQT group showed a more significant reduction in all laboratory parameters except for HDL-C （P<0.05， P<0.01）. Before treatment， NLRP3， P2X7R， and FN levels in both the BLQT group and the western medicine group were higher than those in the control group （P<0.01）. After treatment， NLRP3 and P2X7R levels in both groups significantly decreased （P<0.01）， and FN levels in the BLQT group also decreased significantly （P<0.01）. When compared with the western medicine group after treatment， the BLQT group showed a more significant reduction in NLRP3， P2X7R， and FN levels （P<0.01）. Before treatment， CAP and LSM levels in both the BLQT group and the western medicine group were higher than those in the control group （P<0.01）. After treatment， CAP and LSM levels in both groups decreased （P<0.05， P<0.01）. Compared with the western medicine group after treatment， the BLQT group showed a more significant reduction in CAP and LSM （P<0.01）. The incidence of adverse reactions was 3.13% （1/32） in the BLQT group and 15.63% （5/32） in the western medicine group， with no significant difference. ConclusionBLQT has good efficacy in patients with T2DM complicated with GA， which can significantly alleviate joint redness， swelling， heat， pain， limited mobility， dry mouth， and polydipsia， reduce blood glucose， uric acid， and lipid levels， suppress the high expression of NLRP3， P2X7R， and FN， and improve hepatic steatosis.
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Objective:To analyze the clinical and laboratory characteristics of acute myeloid leukemia (AML) patients with NPM1 mutation, and to explore the prognostic factors.Methods:A total of 77 AML patients with NPM1 gene mutation admitted to Hebei Yanda Ludaopei Hospital from May 1st 2012 to December 31st 2021 were enrolled in the study, including 34 male and 43 female patients. The median age was 40 (3, 68) years old. Patients were selected and divided into 4 groups according to the morphological FAB classification. There were 29 cases (37.7%) of M1 type, 13 cases (16.9%) of M2 type, 23 cases (29.9%) of M4 type, and 12 cases (15.5%) of M5 type. The clinical characteristics, bone marrow/peripheral blood cell morphology, immunophenotype, cytogenetics, molecular biology and overall survival of different groups were retrospectively analyzed, and the risk factors affecting the prognosis of AML were also explored. Cox multivariate regression was used to analyze the clinical influencing factors of survival and prognosis.Results:The white blood cell counts were highest in M4 and M5 patients and lowest in M2 patients, while no significant difference in the red blood cell, hemoglobin, and platelet counts( P>0.05). Morphologically, there were significant differences in the percentage of blasts and blasts with cup-like nuclei on bone marrow (BM) and peripheral blood (PB). The proportion of blasts in BM and PB was the highest in M1 and the lowest in M2 ( P<0.001). The positive rate of blasts with cup-like nuclei was the highest in M1 and the lowest in M5 of BM ( P<0.001), while the highest in M2 and the lowest in M5 of PB ( P=0.006). The scores of myeloperoxidase and chloroacetate esterase were all the highest in M1 and the lowest in M5 ( P<0.001, 0.001, respectively). In terms of molecular biology, the occurence rate of blasts combined with DNMT3A mutation was the highest in M4 and the lowest in M2 ( P=0.044), while those combined with FLT3-ITD mutation was the highest in M4 and the lowest in M5 ( P=0.002). In immunophenotype, there were significant differences in the expression positivities of seven antigens including HLA-DR, CD56, CD11c, CD15, CD14, CD96 and cMPO ( P<0.05). Multivariate COX regression analysis showed that no recurrence after treatment ( P<0.001), complete remission after treatment ( P=0.015) and transplantation ( P<0.001) were correlated with overall survival (OS). No recurrence after treatment ( P=0.033), transplantation ( P=0.027), no mutation of FLT3-ITD ( P=0.040), and hemoglobin concentration ( P=0.023) were associated with relapse-free survival (RFS). Survival analysis by Kaplan-Meier curve showed that there was no significant difference in survival time between the M1, M2, M4 and M5 groups in OS and RFS. Conclusion:There were significant differences in the white blood count, the percentage of blasts and blasts with cup-like nuclear morphology, cytochemical staining (MPO integration, CE integration and percentage of NAS-DCE), gene mutation (DNMT3A and FLT3-ITD) and immunophenotypes (HLA-DR, CD56, CD11c, CD15, CD14, CD96 and cMPO) between the four groups. The multivariate analysis revealed that no recurrence after treatment and transplantation were independent prognostic factors in NPM1 mut AML patients. On the other hand, FLT3-ITD mutation and hemoglobin concentration were associated with RFS and complete remission after treatment was associated with OS in the entire NPM1 mut cohort.
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Radiotherapy plays an important role in the treatment of advanced esophageal cancer. Under the premise of effective systemic treatment, selecting patients who may benefit from local radiotherapy can effectively relieve symptoms and improve quality of life, and it is expected to prolong the survival time of patients. Moreover, immunotherapy plays an increasingly significant role in advanced esophageal cancer, and the efficacy of radiotherapy combined with immunotherapy is promising.
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E-cigarettes have gained considerable popularity worldwide recently， which have also drawn the attention of adolescents and pregnant women. However， recent studies have uncovered the negative effects of e-cigarettes on our cardiovascular system， respiratory system， nervous system， blood system and so on. Furthermore， several studies indicate that e-cigarettes can significantly impair users’ reproductive ability. In this review， we collected the most recent studies on the effects of e-cigarettes on reproductive system based on human studies， animal studies and in vitro preclinical studies. In addition， the review shows the urgency of setting e-cigarettes exposure standards. As a result， we recommend setting strict limits on the production and sales of e-cigarettes， thus encouraging consumers to consume reasonably.
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Objective:To compare the efficacy and adverse events of salvage radiotherapy and other treatments for recurrent esophageal cancer after chemoradiotherapy in this Meta-analysis.Methods:Databases including PubMed, Embase, Cochrane Library, CNKI and Wanfang data were searched from the inception to April 2020 to collect the clinical trials which comparatively analyzed the efficacy and safety between radiotherapy and other treatments for recurrent esophageal cancer after chemoradiotherapy. Meta-analysis was performed using RevMan 5.1 software. RR and 95% CI were used to describe the differences among different groups. Results:According to the inclusion and exclusion criteria, a total of 11 clinical trials involving 842 patients were included. Meta-analysis showed that the overall survival in the salvage radiotherapy group was significantly lower than that in the salvage esophagectomy group ( RR=0.40, 95% CI: 0.27-0.61, P<0.001), whereas significantly higher than that in the chemotherapy group ( RR=2.91, 95% CI: 1.43-5.95, P=0.003). There was no significant difference in the treatment-related mortality between the salvage radiotherapy and salvage esophagectomy groups ( RR=0.53, 95% CI: 0.14-1.98, P=0.350), but the incidence was significantly higher in the salvage esophagectomy group (1.7%-11.4% vs. 1.9%-2.8%). Conclusion:Salvage radiotherapy is an effective treatment for recurrent esophageal cancer after chemoradiotherapy, which can be regarded as one choice for clinical patients.
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Objective:To investigate the clinical safety of daratumumab (DARA) in patients with relapsed/refractory multiple myeloma (MM).Methods:The diagnosis and treatment process of 2 cases of relapsed/refractory MM treated in Huadong Hospital of Fudan University in 2020 were retrospectively analyzed, the related laboratory indicators indexes after using DARA were analyzed, and the related literature was reviewed.Results:After using DARA, the 2 patients rapidly developed tumor lysis syndrome (TLS) such as high potassium, high phosphorus, high uric acid, low calcium and kidney damage, which eventually led to the death of patients.Conclusions:Patients with high tumor load treated by DARA are prone to TLS, which is often life-threatening. Clinicians should be alert to the occurrence of such events.
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Objective:To systematically evaluate the efficacy and safety of demethylation drugs intreatment of myelodysplastic syndrome (MDS), and to provide reliable basis and guidance for clinical application of these drugs.Methods:The randomized controlled trials (RCT) of demethylation drugs for treatment of MDS published in the PubMed, Web of Science, Embase, Cochrane Library, Chinese Journal Full-text Database (CNKI), Chinese Biomedical Literature Database (CBM) and VIP database from January 2000 to December 2019 were searched by computer. RevMan 5.3 software was used for Meta-analysis of the efficacy and safety.Results:Seven RCT studies involving 1 172 patients were obtained. Meta-analysis showed that the complete remission rate ( OR = 6.26, 95% CI 1.74-22.49, P = 0.005), partial remission rate ( OR = 4.65, 95% CI 1.51-14.29, P = 0.007), overall response rate ( OR = 14.14, 95% CI 7.27-27.51, P < 0.01), hematology improves ( OR = 3.47, 95% CI 1.44-8.32, P = 0.005) in the demethylation drug treatment group were better than those in the best supportive treatment group. Meanwhile, the overall survival of patients in azacytidine group was improved ( HR = 0.62, 95% CI 0.50-0.77, P < 0.01). In terms of adverse reactions, demethylation drugs increased the incidence of neutropenic fever ( OR = 4.19, 95% CI 2.26-7.76, P < 0.01). However, there was no significant difference in the incidence of neutropenia, thrombocytopenia, anemia, infection, nausea, liver damage and fatigue between the two groups (all P > 0.05). Conclusions:The effect of demethylation drugs in treatment of MDS is obvious, the remission rate can be improved, and azacytidine can prolong the patients' survival, but demethylation drugs increase the incidence of neutropenia fever. In the clinical application of demethylation drugs, it is necessary to further carefully evaluate their clinical safety.
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AIM:To detect the levels of Fusobacterium nucleatum in Uygurs of Xinjiang with normal glucose tolerance (NGT) or type 2 diabetes mellitus (T2DM) and to analyze the correlation between Fusobacterium nucleatum level and type 2 diabetes mellitus.METHODS:Blood and fecal samples were collected from Uygurs of Xinjiang with NGT or T2DM respectively.16SrDNA quantitative real-time PCR technology was used to detect the levels of Fusobacterium nucleatum in fecal samples.The correlations between Fusobacterium nucleatum and BMI,TC,TG,HDL and LDL levels were analyzed by Pearson.RESULTS:(1) The levels of Fusobacterium nucleatum in Uygurs T2DM group were significantly higher than those in Uygurs NGT group (P =0.011).(2) Fusobacterium nucleatum was positively correlated with the levels of BMI (r =0.335,P =0.049),TC(r =0.472,P =0.011)and LDL(r =0.368,P =0.029).CONCLUSION:The levels of Fusobacterium nucleatum may be closely related to lipid metabolism of T2DM in Uygurs.
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Objective@#To illuminate the effect of NALP3 inflammasome on regulating the expression of cytokines of macrophages in periodontitis.@*Methods@#RAW264.7 cells were cultured and divided into three groups. The first group stayed normal as control, the second group was stimulated by 1 mg/L Porphyromonas gingivalis (Pg) lipopolysaccharide (LPS), the third group was pretreated with AC-YVAD-CMK (caspase-1 inhibitor) before stimulated with 1 mg/L Pg LPS. RAW264.7 cells pretreated with various concentrations (0, 5, 10, 25, 50, 75, 100, 200 μmol/L) of AC-YVAD-CMK for 2 h, and stimulated by 1 mg/L Pg LPS for 24 h in the third group. After that, cell survival rate were detected by cell counting kit-8. Every group cells gene transcription of NALP3 and interleukin-1β (IL-1β) were detected by quantitative real-time PCR (qPCR) after 6 h, protein expression of NALP3 and IL-1β were separately detected by Western blotting and enzyme linked immunosorbent assay (ELISA) after 24 h, respectively.@*Results@#It is observed that treatment with 5, 10, 25, 50, 75, 100, 200 μmol/L AC-YVAD-CMK did not significantly affect the viability of RAW264.7 cells. qPCR showed that mRNA expression of IL-1β level (1.03±0.08, 5.48±0.22, 4.31±0.20) and NALP3 level (0.96±0.05, 2.62±0.44, 1.73±0.09). Western blotting showed that protein expression of NALP3 level (1.00±0.10, 2.34±0.04, 1.64±0.04), ELISA showed protein secretion of IL-1β level ([40.20±0.25], [61.50±1.81], [52.40±1.91] ng/L). After stimulated by Pg LPS, mRNA and protein expression of IL-1β (P<0.01, P<0.01) and NALP3 (P<0.01, P<0.01) significantly increased; but the expression of IL-1β (P=0.002, P=0.027) and NALP3 (P<0.01, P<0.01) were decreased when pretreated with AC-YVAD-CMK.@*Conclusions@#NALP3 inflammasome signal pathway can be activated by Pg LPS in RAW264.7. Block of the pathway can inhibit Pg LPS-induced secretion of cytokines.
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Objective To investigate the characteristics of nerve injury and incidence of carpal tunnel syndrome(CTS)indiabeticpatientsbymeasuringthenerveconductionvelocity(NCV). Methods Atotalof387 inpatients with type 2 diabetes were selected in Kaifeng Central Hospital from July 1, 2011 to October 1, 2014. The abnormal rates of NCV between left and right or male and female for the same name nerve were compared. The examinations to median nerves were paid particular attention and the segmental test was performed. Results Among 387 patients, 333 cases showed abnormal NCV, and 162 patients (41. 9%) presented with CTS. The incidence of sensory nerve injury was higher than that of motor nerve injury. The nerve injury often occurred in the dominant hand, but the injury of bilateral hand were also found in some patients. In 162 patients with CTS, 91 patients presented with clinical manifestations and signs, and the rest were without discomfort in their hands. The percentages of SCV(34. 1%vs 25. 6%, P=0. 012) and MCV (40. 3% vs 29. 5%, P=0. 020) abnormality in the right median nerve were higher than those in the left side. No significant difference of the other nerves was found between left and right. Significant differences in the percentages of abnormality in SCV of the left median nerve (21. 4%vs 30. 5%, P=0. 047) and the right median nerve (28. 6%vs 40. 1%, P=0. 013) between man and woman were found. The abnormal rates of other nerves were without statistically significant between man and women. Conclusions The incidence of CTS is high in diabetic patients. Usually, it firstly occurs in sensory nerves, followed by motor nerves, especially in the dominant hand.
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Intravascular large B cell lymphoma is a rare subtype of diffuse large B cell lymphoma. Abnormal proliferation of intravascular lymphoma cells is its pathological feature with aggressive clinical behavior such as easy invasive feature, rapid disease progression, poor prognosis and low survival rate. We review the progress in recent research on classification, diagnosis, treatment and prognosis of intravascular large B cell lymphoma.
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Objective To explore the efficient, cheaper and practical water treatment process in removing algae toxins. Methods The different water treatment methods were used and the optimal combination was selected. The removing efficiency for different processes was compared and validated by beaker test. The enzyme-linked immunosorbent assay (ELISA) was conducted in microcystin testing. Results Coagulating sedimentation could remove a small part of microcystin (removing efficiency was from 4.3% to 29.7% ). When oxidants were applied in pretreatment processes, such as ozone combined with coagulant, 83.3% to 91.9% microcystin could be removed. The cost-benefit analysis showed these processes only increased 0.03 to 0.14 yuan RMB cost per cubic meter of water, for example, by using ozone pretreatment and oxidation plus adsorption processes. Conclusion On the basis of general water treatment, ozone(O3), potassium permanganate(KMnO4), chlorine, dioxide(ClO2)and powdered activated carbon(PAC) are effective for removing microcystin in pretreatment processes and the processes are cheaper and practical.