Di-(2-ethylhexyl)phthalate(DEHP)is an environmental pollutant commonly found in plastic products and has toxic effects on female reproductive system.DEHP can interfere with the synthesis of progesterone,testosterone and estradiol through female hypothalamic-pituitary-ovarian axis,aggravate insulin resistance and obesity by affecting glucose and lipid metabolism,and cause ovarian damage through inducing oxidative stress,excessive autophagy and pyroptosis of oocyte or granulosa cells.It can also alter epigenetic genes relating to follicular development and prevent follicles from mature.These factors are closely contribute to the pathogenesis of polycystic ovary syndrome.We systematically summarizes the mechanism of DEHP interfering with ovarian function and inducing polycystic ovary syndrome,in order to provide help for the prevention and treatment of female reproductive injury from environmental pollutant.

AIM To investigate the effects of Zhuangyao Shuanglu Tongnao Formula on neuronal apoptosis in rats with cerebral ischemia-reperfusion injury based on the study of oxidative stress and inflammatory response.METHODS The rats were randomly divided into the sham operation group,the model group,the edaravone group(3.0 mg/kg),the low,medium and high dose groups(9.0,18.0,36.0 g/kg)of Zhuangyao Shuanglu Tongnao Formula,with 18 rats in each group.The middle cerebral artery occlusion/reperfusion was conducted by thread embolism method to simulate cerebral ischemia reperfusion injury in rats followed by 6 days corresponding drugs administration.Subsequently,the rats had their neurological function deficit scored by Zeal Longa scoring method;their sizes of cerebral infarction areas measured by TTC staining;their pathological damage and apoptosis of neurons in hippocampal CA1 area of ischemic penumbra of the brain tissue detected by HE staining and TUNEL staining;their SOD activity and levels of GSH,MDA,IL-6,IL-1β,TNF-α in brain tissue detected by kits;and their protein expressions of Bax,Bcl-2,caspase-3,cleaved-capase-3,TLR4,NF-κB p65,Nrf2,HO-1 in rat brain tissue determined by Western blot.RESULTS Compared with the model group,the groups intervened with edaravone,medium and high dose of Zhuangyao Shuanglu Tongnao Formula displayed improvements in the scores of nerve function defects,the rate of cerebral infarction,the rate of neuronal apoptosis,the levels of IL-6,IL-1β,TNF-α and MDA in the ischemic penumbra of brain tissues,the protein expressions of Bax and TLR4,the ratio of cleaved-capase-3/caspase-3 and p-NF-κB p65/NF-κB p65(P＜0.05),the levels of GSH,the activity of SOD and the protein expressions of Bcl-2,Nrf2 and HO-1(P＜0.05).CONCLUSION Being an inhibitor of oxidative stress and inflammatory response,Zhuangyao Shuanglu Tongnao Formula can alleviate brain injury in rats with cerebral ischemia reperfusion injury through the inhibition of neuronal apoptosis and improvement of neural function mediated by the inhibition of TLR4/NF-κB signal pathway and activation of Nrf2/HO-1 signal pathway.

OBJECTIVE: To study the in vitro and in vivo antitumor effects of the polysaccharide of Alocasia cucullata (PAC) and the underlying mechanism. METHODS: B16F10 and 4T1 cells were cultured with PAC of 40 µg/mL, and PAC was withdrawn after 40 days of administration. The cell viability was detected by cell counting kit-8. The expression of Bcl-2 and Caspase-3 proteins were detected by Western blot and the expressions of ERK1/2 mRNA were detected by quantitative real-time polymerase chain reaction (qRT-PCR). A mouse melanoma model was established to study the effect of PAC during long-time administration. Mice were divided into 3 treatment groups: control group treated with saline water, positive control group (LNT group) treated with lentinan at 100 mg/(kg·d), and PAC group treated with PAC at 120 mg/(kg·d). The pathological changes of tumor tissues were observed by hematoxylin-eosin staining. The apoptosis of tumor tissues was detected by TUNEL staining. Bcl-2 and Caspase-3 protein expressions were detected by immunohistochemistry, and the expressions of ERK1/2, JNK1 and p38 mRNA were detected by qRT-PCR. RESULTS: In vitro, no strong inhibitory effects of PAC were found in various tumor cells after 48 or 72 h of administration. Interestingly however, after 40 days of cultivation under PAC, an inhibitory effect on B16F10 cells was found. Correspondingly, the long-time administration of PAC led to downregulation of Bcl-2 protein (P<0.05), up-regulation of Caspase-3 protein (P<0.05) and ERK1 mRNA (P<0.05) in B16F10 cells. The above results were verified by in vivo experiments. In addition, viability of B16F10 cells under long-time administration culture in vitro decreased after drug withdrawal, and similar results were also observed in 4T1 cells. CONCLUSIONS Long-time administration of PAC can significantly inhibit viability and promote apoptosis of tumor cells, and had obvious antitumor effect in tumor-bearing mice.
Mice ; Animals ; Alocasia/metabolism* ; MAP Kinase Signaling System ; Caspase 3/metabolism* ; Apoptosis ; RNA, Messenger/metabolism*

To clone and express the K26 gene of Leishmania isolated from three types of visceral leishmaniasis epidemic ar-eas in China and evaluate its effect on detecting specific antibodies against visceral leishmaniasis.The K26 fragments from Leishmania isolated KS-6,SC6 and JIASHI-1 was synthesized and cloned into pET32a vector.The recombinant plasmid pET32a-K26 was transformed into Escherichia coli BL21 strains and induced by isopropyl-β-D-thiogalactopyranoside(IPTG).The expressed recombinant protein was purified by the His-tagged affinity column(Ni-NTA).Serum samples of 110 visceral leishmaniasis patients were used for evaluating the sensitivity by ELISA.Serum samples from patients with malaria,schisto-somiasis japonica,cystechinococcosis,toxoplasmosis,paragon-imiasis,clonorchiosis and 40 healthy people were used for eval-uating the specificity.Detection results of ELISA were compared with that of rK39 strip of American InBios company.Comparation among three K26 antigens were given by x2 test.The sensitivity of the recombinant K26 protein of KS-6,SC6 and JIASHI-5 strains of Leishmania and rK39 strip test to detect the sera of patients with visceral leishmaniasis was 90.00％(99/110),92.73％(102/110),90.91％(100/110)and 93.64％(103/110),respectively.There was no cross reactivity with malaria(10),schistosomiasis japonica(10),cystechinococcosis(10),toxoplasmosis(5),paragonimiasis(5)and clonorchiosis(5),and 40 sera from healthy people were also negative.The specificity was 100.00％.There was no statistical difference in the sensitivity of the recombinant K26 protein of KS-6,SC6 and JIASHI-1 strains of Leishmania and rK39 strip test,x2 values are 0.97,0.07 and 0.57 respectively and the P values are 0.33,0.79 and 0.45,respectively.There was no statis-tical difference in the sensitivity of three K26 antigens(x2=0.53,P=0.97).Conclusion The recombinant K26 antigen has po-tential application value in the diagnosis of visceral leishmaniasis.

Leonurine(SCM-198)was discovered as one of the active constituents of the Herba Leonuri(HL).Now it can be artificially synthesized.Several recent researches has proven that it exhibits anti-inflammatory effect in several systems in animal models and cell culture in vitro.The key mechanism involves downgrading the activity of nuclear transcription factor-κB(NF-κB),thereby inhibiting the phosphorylation of several signal pathways such as PI3K/Akt,MAPK,ERK,and JNK,or upregulating the activity of Nrf2 related pathways,resulting in downregulated expression of inflammatory cytokines such as tumor necrosis factor-α(TNF-α),IL-1β,IL-2,IL-6,IL-8,inducible nitric oxide synthase(iNOS),cyclooxygenase-2(COX-2),chemokines,adhesion molecules,etc.Owing to the advantages of high safety and efficiency,the ease of administration,as well as its effectiveness in many organs and systems,leonurine has a widely prospect for future research and clinical applications.This article reviews the progress in the fundamental research of leonurine in multiple inflammation-related disease,and it could be expect to offer new possibilities for the treatment of these disease.

AIM To investigate the clinical effects of Tongdu Huoxue Decoction on patients with cervical spondylosis of vertebral artery type.METHODS Eighty-five patients were randomly assigned into control group (44 cases) for 14-day administration of Betahistine Hydrochloride Tablets,and observation group (41 cases) for 14-day administration of both Tongdu Huoxue Decoction and Tongdu Huoxue Decoction.The changes in clinical effects,hemorheological indices ( vertebral artery resistance index,vertebral artery systolic blood flow velocity,vertebral artery diastolic blood flow velocity),TCM syndrome scores,disease-related serum indices ( NSE,NPY,NF-κB),cervical motion indices ( flexion and extension range of motion,cervical curvature,horizontal vertebral displacement),hemodynamic indices ( whole blood high shear viscosity,whole blood low shear viscosity,plasma viscosity) and incidence of adverse reactions were detected.RESULTS The observation group demonstrated higher total effective rate than the control group ( P<0.05 ).After the treatment,the two groups displayed decreased vertebral artery resistance index,disease-related serum indices,TCM syndrome scores,horizontal vertebral displacement,hemodynamic indices ( P<0.05 ),and increased vertebral artery systolic blood flow velocity,vertebral artery diastolic blood flow velocity,flexion and extension range of motion,cervical curvature ( P<0.05 ),especially for the observation group ( P<0.05 ).No significant difference in incidence of adverse reactions was found between the two groups (P>0.05).CONCLUSION For the patients with cervical spondylosis of vertebral artery type,Tongdu Huoxue Decoction can safely and effectively improve TCM syndrome scores and cervical motion,whose mechanisms may contribute to the regulation of hemorheology,hemodynamics and disease-related serum indices.

AIM To investigate the clinical effects of Tongdu Huoxue Decoction on patients with cervical spondylosis of vertebral artery type.METHODS Eighty-five patients were randomly assigned into control group (44 cases) for 14-day administration of Betahistine Hydrochloride Tablets,and observation group (41 cases) for 14-day administration of both Tongdu Huoxue Decoction and Tongdu Huoxue Decoction.The changes in clinical effects,hemorheological indices ( vertebral artery resistance index,vertebral artery systolic blood flow velocity,vertebral artery diastolic blood flow velocity),TCM syndrome scores,disease-related serum indices ( NSE,NPY,NF-κB),cervical motion indices ( flexion and extension range of motion,cervical curvature,horizontal vertebral displacement),hemodynamic indices ( whole blood high shear viscosity,whole blood low shear viscosity,plasma viscosity) and incidence of adverse reactions were detected.RESULTS The observation group demonstrated higher total effective rate than the control group ( P<0.05 ).After the treatment,the two groups displayed decreased vertebral artery resistance index,disease-related serum indices,TCM syndrome scores,horizontal vertebral displacement,hemodynamic indices ( P<0.05 ),and increased vertebral artery systolic blood flow velocity,vertebral artery diastolic blood flow velocity,flexion and extension range of motion,cervical curvature ( P<0.05 ),especially for the observation group ( P<0.05 ).No significant difference in incidence of adverse reactions was found between the two groups (P>0.05).CONCLUSION For the patients with cervical spondylosis of vertebral artery type,Tongdu Huoxue Decoction can safely and effectively improve TCM syndrome scores and cervical motion,whose mechanisms may contribute to the regulation of hemorheology,hemodynamics and disease-related serum indices.

Humans ; Retrospective Studies ; Tetanus/epidemiology* ; China/epidemiology*

Objective: To analyze the efficacy and safety of letermovir in primary prophylaxis of cytomegalovirus (CMV) reactivation in patients receiving haploidentical hematopoietic stem cell transplantation. Methods: This retrospective, cohort study was conducted using data of patients who underwent haploidentical transplantation at Peking University Institute of Hematology and received letermovir for primary prophylaxis between May 1, 2022 and August 30, 2022. The inclusion criteria of the letermovir group were as follows: letermovir initiation within 30 days after transplantation and continuation for≥90 days after transplantation. Patients who underwent haploidentical transplantation within the same time period but did not receive letermovir prophylaxis were selected in a 1∶4 ratio as controls. The main outcomes were the incidence of CMV infection and CMV disease after transplantation as well as the possible effects of letermovir on acute graft versus host disease (aGVHD), non-relapse mortality (NRM), and bone marrow suppression. Categorical variables were analyzed by chi-square test, and continuous variables were analyzed by Mann-Whitney U test. The Kaplan-Meier method was used for evaluating incidence differences. Results: Seventeen patients were included in the letermovir prophylaxis group. The median patient age in the letermovir group was significantly greater than that in the control group (43 yr vs. 15 yr; Z=-4.28, P<0.001). The two groups showed no significant difference in sex distribution and primary diseases, etc. (all P>0.05). The proportion of CMV-seronegative donors was significantly higher in the letermovir prophylaxis group in comparison with the control group (8/17 vs. 0/68, χ²=35.32, P<0.001). Three out of the 17 patients in the letermovir group experienced CMV reactivation, which was significantly lower than the incidence of CMV reactivation in the control group (3/17 vs. 40/68, χ²=9.23, P=0.002), and no CMV disease development observed in the letermovir group. Letermovir showed no significant effects on platelet engraftment (P=0.105), aGVHD (P=0.348), and 100-day NRM (P=0.474). Conclusions: Preliminary data suggest that letermovir may effectively reduce the incidence of CMV infection after haploidentical transplantation without influencing aGVHD, NRM, and bone marrow suppression. Prospective randomized controlled studies are required to further verify these findings.
Humans ; Cytomegalovirus ; Retrospective Studies ; Cohort Studies ; Prospective Studies ; Cytomegalovirus Infections/prevention & control* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Graft vs Host Disease/prevention & control* ; Recurrence ; Antiviral Agents/therapeutic use*

Objective: To analyze the detection rate, clinical significance, and prognosis of Epstein-Barr virus (EBV) in the cerebrospinal fluid (CSF) of patients following allogeneic hematopoietic stem cell transplantation. Methods: A retrospective analysis was performed on 1100 patients who underwent the CSF virus test after allogeneic hematopoietic stem cell transplantation in Peking University People's Hospital between January 2017 and June 2022. Among them, 19 patients were screened positive for EBV in their CSF, and their clinical characteristics, treatment, and prognosis were analyzed. Results: Among 19 patients with EBV-positive cerebrospinal fluid, 12 were male and 7 were female, with 5 patients aged <18 years and 12 aged ≥18 years, with a median age of 27 (5-58) years old. There were 7 cases of acute myeloid leukemia, 8 of acute lymphocytic leukemia, 2 of aplastic anemia, 1 of Hodgkin's lymphoma, and 1 of hemophagocytic syndrome. All 19 patients underwent haploid hematopoietic stem cell transplantation, including 1 secondary transplant. Nineteen patients had neurological symptoms (headache, dizziness, convulsions, or seizures), of which 13 had fever. Ten cases showed no abnormalities in cranial imaging examination. Among the 19 patients, 6 were diagnosed with EB virus-related central nervous system diseases, with a median diagnosis time of 50 (22-363) days after transplantation. In 9 (47.3%) patients, EBV was detected in their peripheral blood, and they were treated with intravenous infusion of rituximab (including two patients who underwent lumbar puncture and intrathecal injection of rituximab). After treatment, EBV was not detected in seven patients. Among the 19 patients, 2 died from EBV infection and 2 from other causes. Conclusion: In patients who exhibited central nervous system symptoms after allogeneic hematopoietic stem cell transplantation, EBV should be screened as a potential pathogen. EBV detected in the CSF may indicate an infection; however, it does not confirm the diagnosis.
Humans ; Male ; Female ; Adolescent ; Adult ; Middle Aged ; Herpesvirus 4, Human ; Epstein-Barr Virus Infections/complications* ; Rituximab/therapeutic use* ; Retrospective Studies ; Clinical Relevance ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Lymphoproliferative Disorders/drug therapy*