Aim To investigate the enhanced efficacy and reduced toxicity of GanoExtra in combination with cyclophosphamide(CTX)on inhibiting lung metastasis and immune function in mice.Methods The CCK-8 method was used to verify the cytotoxic effects of Gano-Extra on MCF-7 and 4T1 tumor cells.In vivo experi-ment,a mouse model of lung metastasis of breast canc-er was established by injecting 4T1 tumor cells into the tail vein,which was divided into four groups including 4T1 model group,CTX group,GanoExtra group and GanoExtra+CTX group.The control group was set.After 21 days,the mice were euthanized under anes-thesia,and the body weight of the mice was recorded.Average lung index and spleen index were calculated.The mouse spleen lymphocyte transformation experi-ment was used to determine the activity of spleen cells.The NK cell activity assay was used to determine the activity of NK cells.Blood cells were determined in mouse blood samples.Flow cytometry was used to de-termine the levels of CD4+and CD8+T cells in blood samples.ELISA was used to measure the levels of TNF-α and IL-6 in serum.HE staining was used to ob-serve the pathological morphological changes in tumors and various tissues;and CFSE staining was used to de-termine the proliferative effect of GanoExtra on CD8+cells.Results In vitro GanoExtra at 50 mg·L-1 sig-nificantly inhibited the activity of MCF-7 and 4T1 tumor cells.In the breast cancer pulmonary metastasis model,compared with the model group,the spleen in-dex and blood WBCs content were significantly re-duced,while the activity of NK cells,spleen cells,and the proportion of RBCs,CD 3+and CD 8+T cells in the blood were significantly increased.At the end of the treatment,compared with the CTX group,the number of lung metastases and lung index of the Gano-Extra+CTX group were significantly reduced,and the levels of HGB,CD8+cells,IL-6,and TNF-α in the blood of mice were significantly increased.GanoExtra at 10 mg·L-1 significantly promoted the proliferation of CD8+T cells in vitro.Conclusions GanoExtra can enhance the inhibitory effect of CTX on tumor metasta-sis,alleviate adverse reactions such as splenomegaly and pulmonary enlargement caused by CTX,and have a health-promoting function of promoting the prolifera-tion of CD8+T cells to enhance the immune efficacy of the body.

Immunotherapy is an important breakthrough in canc-er treatment.Unfortunately,low drug concentration in tumor sites almost ineffectively initiates immune responses and thereby severely limits immune therapy applications in clinics.Nanoma-terials are well-recognized drug delivery system in cancer thera-py.Nanographene oxide(NGO)have shown immense perti-nence for anti-cancer drug delivery owing to their ultra-high sur-face area,chemical stability,good biocompatibility and excel-lent photosensitivity.In addition,functionalized modifications on the surface of NGO increase tumor targeting and minimize cy-totoxicity.This study focuses on reviewing the literature and up-dates on NGO in drug delivery and discussing the possibilities and challenges of NGO in cancer synergetic therapy.

Objective To observe the clinical and symptomatic improvement three months after uterine artery embolization(UAE),and to analyze the value of apparent diffusion coefficient(ADC)in MR diffusion weighted imaging(DWI)in assessing the response of fibroids volume after UAE.Methods A total of 40 patients with uterine fibroids were included.The volume changes of fibroids,clinical and symptomatic improvement before and after treatment were recorded,and the efficacy of UAE was comprehensively analyzed.All patients underwent MR DWI before UAE and were evaluated at three months postoperatively by outpatient MR follow-up,with fibroids vol-ume and ADC quantitative measurements were performed to compare the changes in ADC values of fibroids preoperatively and post-operatively at each b value.Pearson correlation analysis was performed to analyze the correlation between baseline ADC values and postoperative fibroids volume reduction.Regression analysis was performed to assess the relationship between ADC and fibroids volume reduction after UAE.And the receiver operating characteristic(ROC)curve were plotted to analyze the predictive value of ADC values for evaluating fibroids volume reduction of more than 30％after UAE.Results The patients'clinical symptoms was improved in the three months after surgery,the volume of fibroids was significantly reduced,and the life quality was improved,the difference was sta-tistically significant(P＜0.05).There was no significant effect on ovarian function,hormone levels did not change significantly com-pared to before surgery,with no statistical significance(P＞0.05).When b=50,1 000 s/mm2,the changes in ADC values before and after uterine fibroids treatment were not significant,with no statistical significance(P＞0.05).However,the changes in ADC values before and after uterine fibroids treatment were significant when b=800 s/mm2 and the difference was statistically significant(P＜0.05).Under the condition of b=800 s/mm2,Pearson correlation analysis showed ADC value had a positive correlation with postoperative uterine fibroids volume reduction rate(r=0.45,P＜0.05),and the area under the curve(AUC)for ADC value to predict the reduction rate of uterine fibroids volume by more than 30％after UAE was 0.787.The cut-off value was 1.143 × 10-3 mm2/s,with sensitivity and specificity of 0.793 and 0.818,respectively.Conclusion UAE is more effective in treating uterine fibroids.The baseline ADC value of uterine fibroids correlated significantly with the volume reduction after UAE.The ADC value can be used to assess the volume response after UAE.

OBJECTIVE: To explore the effects of Zishen Yutai Pills (ZYPs) on the quality of oocytes and embryos, as well as pregnancy outcomes in patients with diminished ovarian reserve (DOR) receiving in vitro fertilization-embryo transfer (IVF-ET). The possible mechanisms, involving the regulation of bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9), were also investigated. METHODS: A total of 120 patients with DOR who underwent their IVF-ET cycle were randomly allocated to 2 groups in a 1:1 ratio. The patients in the treatment group (60 cases) received ZYPs from the mid-luteal phase of the former menstrual cycle by using gonadotropin-releasing hormone (GnRH) antagonist protocol. The patients in the control group (60 cases) received the same protocol but without ZYPs. The primary outcomes were the number of oocytes retrieved and high-quality embryos. Secondary outcomes included other oocyte or embryo indices as well as pregnancy outcomes. Adverse events were assessed by comparison of the incidence of ectopic pregnancy, pregnancy complications, pregnancy loss, and preterm birth. Contents of BMP15 and GDF9 in the follicle fluids (FF) were also quantified with enzyme-linked immunosorbent assay. RESULTS: Compared with the control group, the numbers of oocytes retrieved and high-quality embryos were significantly increased in the ZYPs group (both P<0.05). After treatment with ZYPs, a significant regulation of serum sex hormones was observed, including progesterone and estradiol. Both hormones were up-regulated compared with the control group (P=0.014 and 0.008), respectively. No significant differences were observed with regard to pregnancy outcomes including implantation rates, biochemical pregnancy rates, clinical pregnancy rates, live birth rates, and pregnancy loss rates (all P>0.05). The administration of ZYPs did not increase the incidence of adverse events. The expressions of BMP15 and GDF9 in the ZYPs group were significantly up-regulated compared with the control group (both P<0.05). CONCLUSIONS ZYPs exhibited beneficial effects in DOR patients undergoing IVF-ET, resulting in increments of oocytes and embryos, and up-regulation of BMP15 and GDF9 expressions in the FF. However, the effects of ZYPs on pregnancy outcomes should be assessed in clinical trials with larger sample sizes (Trial reqistration No. ChiCTR2100048441).
Infant, Newborn ; Pregnancy ; Female ; Humans ; Fertilization in Vitro/methods* ; Ovarian Reserve ; Prospective Studies ; Premature Birth ; Embryo Transfer/methods* ; Ovulation Induction/methods* ; Gonadotropin-Releasing Hormone/therapeutic use*

BACKGROUND: Ventricular remodeling after acute anterior wall ST-segment elevation myocardial infarction (AAMI) is an important factor in occurrence of heart failure which additionally results in poor prognosis. Therefore, the treatment of ventricular remodeling needs to be further optimized. Compound Danshen Dripping Pills (CDDP), a traditional Chinese medicine, exerts a protective effect on microcirculatory disturbance caused by ischemia-reperfusion injury and attenuates ventricular remodeling after myocardial infarction. OBJECTIVE: This study is designed to evaluate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function after AAMI on a larger scale. METHODS: This study is a multi-center, randomized, double-blind, placebo-controlled, parallel-group clinical trial. The total of 268 patients with AAMI after primary percutaneous coronary intervention (pPCI) will be randomly assigned 1:1 to the CDDP group (n=134) and control group (n=134) with a follow-up of 48 weeks. Both groups will be treated with standard therapy of ST-segment elevation myocardial infarction (STEMI), with the CDDP group administrating 20 tablets of CDDP before pPCI and 10 tablets 3 times daily after pPCI, and the control group treated with a placebo simultaneously. The primary endpoint is 48-week echocardiographic outcomes including left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume index (LVEDVI), and left ventricular end-systolic volume index (LVESVI). The secondary endpoint includes the change in N terminal pro-B-type natriuretic peptide (NT-proBNP) level, arrhythmias, and cardiovascular events (death, cardiac arrest, or cardiopulmonary resuscitation, rehospitalization due to heart failure or angina pectoris, deterioration of cardiac function, and stroke). Investigators and patients are both blinded to the allocated treatment. DISCUSSION This prospective study will investigate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function in patients undergoing pPCI for a first AAMI. Patients in the CDDP group will be compared with those in the control group. If certified to be effective, CDDP treatment in AAMI will probably be advised on a larger scale. (Trial registration No. NCT05000411).
Humans ; ST Elevation Myocardial Infarction/therapy* ; Stroke Volume ; Ventricular Remodeling ; Prospective Studies ; Microcirculation ; Ventricular Function, Left ; Myocardial Infarction/etiology* ; Treatment Outcome ; Percutaneous Coronary Intervention/adverse effects* ; Heart Failure/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Randomized Controlled Trials as Topic ; Multicenter Studies as Topic

This study aimed to explore the molecular mechanism of Juanbi Qianggu Formula(JBQGF), an empirical formula formulated by the prestigious doctor in traditional Chinese medicine, in the treatment of rheumatoid arthritis based on network pharmacology and cell function experiments. The main active components and targets of JBQGF were obtained through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and Encyclopedia of Traditional Chinese Medicine(ETCM), and the core targets underwent functional enrichment analysis and signaling pathway analysis. Cytoscape 3.6.0 was used to construct a visualized "active component-target-signaling pathway" network of JBQGF. After screening, nine potential pathways of JBQGF were obtained, mainly including G protein-coupled receptor signaling pathway and tyrosine kinase receptor signaling pathway. As previously indicated, the fibroblast growth factor receptor 1(FGFR1) signaling pathway was highly activated in active fibroblast-like synoviocytes(FLS) in rheumatoid arthritis, and cell and animal experiments demonstrated that inhibition of the FGFR1 signaling pathway could significantly reduce joint inflammation and joint destruction in collagen-induced arthritis(CIA) rats. In terms of the tyrosine kinase receptor signal transduction pathway, the analysis of its target genes revealed that FGFR1 might be a potential target of JBQGF for rheumatoid arthritis treatment. The biological effect of JBQGF by inhibiting FGFR1 phosphorylation was preliminarily verified by Western blot, Transwell invasion assay, and pannus erosion assay, thereby inhibiting matrix metalloproteinase 2(MMP2) and receptor activator of nuclear factor-κB ligand(RANKL) and suppressing the invasion of fibroblasts in rheumatoid arthritis and erosive effect of pannus bone. This study provides ideas for searching potential targets of rheumatoid arthritis treatment and TCM drugs through network pharmacology.
Rats ; Animals ; Synoviocytes ; Matrix Metalloproteinase 2/metabolism* ; Network Pharmacology ; Receptor, Fibroblast Growth Factor, Type 1/therapeutic use* ; Arthritis, Rheumatoid/genetics* ; Signal Transduction ; Fibroblasts ; Drugs, Chinese Herbal/therapeutic use*

Objective: To evaluate the safety and immunogenicity of hepatitis E vaccine(HEV)in Maintenance hemodialysis(MHD)patients. Methods: Based on an open-labeled controlled trial, from May 2016 to March 2018, 35 eligible MHD patients were recruited in the Hemodialysis Center of Zhongshan Hospital Affiliated to Xiamen University as the experimental group, and 70 MHD patients with matched age, gender and underlying diseases as the control group. The experimental group received HEV at 0, 1 and 6 months according to the standard vaccination procedures, while the control group received routine diagnosis and treatment without vaccine and placebo injection to observe the safety and immunogenicity of the vaccine. The safety of vaccine in MHD population was evaluated by the incidence of adverse reactions/events in the experimental and control groups. The immunogenicity of HEV in MHD patients was evaluated by comparing the data from the phase Ⅲ clinical trial. Results: The overall incidence of adverse reactions/events was 17.1% (18/105), and there were no grade 3-4 adverse reactions/events related to vaccination. In the experimental group, the incidence of local adverse reactions/events was 20.0% (7/35), and the incidence of systemic adverse reactions/events was 17.1% (6/35).There was no significant difference in the incidence of systemic adverse reactions/events between the experimental group and the control group (P>0.05). There were 23 patients receiving 3 doses with the standard schedule. The positive rate of HEV-IgG antibody was 100% and the GMC was 14.47(95%CI:13.14-15.80) WU/ml, which showed no significant difference compared with the 46 patients in Phase Ⅲ clinical trial (t=-1.04, P>0.05). Conclusion: Recombinant HEV has good safety and immunogenicity in MHD patients.
Clinical Trials, Phase III as Topic ; Female ; Hepatitis E ; Humans ; Immunogenicity, Vaccine ; Immunoglobulin G ; Male ; Renal Dialysis ; Viral Hepatitis Vaccines/adverse effects*

Objective: To evaluate the value of Hadad-Bassagasteguy flap (HBF) in endoscopic endonasal approaches (EEA) skull base reconstruction by radioanatomic measurements on CT of the skull base of Chinese adults. The following data in terms of anterior skull base defect and reconstruction, sphenoid platform area and middle skull base defect and reconstruction including sphenoid platform and sella area, clivus area defect and reconstruction, and HBF were collected and assessed. Methods: CT image data of 42 Chinese adults were selected to obtain radioanatomic measurement data related to HBF, anterior skull base defect and reconstruction, middle skull base defect and reconstruction, and defect and reconstruction of clivus area. SPSS 26.0 software was used to analyze the data. Results: The radioanatomic measurement data about HBF and skull base of 42 Chinese adults were obtained. The width of the leading edge of HBF [(37.49±2.86) mm] was 6 mm more than the anterior skull base width at the level of the anterior ethmoidal artery [(30.87±8.61) mm], and the width of the trailing edge of HBF [(42.61±3.95) mm] was also 6 mm more than the anterior skull base width at the level of the sphenoethmoidal junction [(26.79±2.79) mm]. The total length of HBF including the pedicle [(79.68±4.96) mm] was 6 mm more than the length of the anterior skull base reconstruction [(54.06±8.67) mm], and the length of HBF without pedicle [(46.27±3.14)] mm was 6 mm more than the length of anterior skull base defect [(30.87±8.61) mm]. The trailing edge width was 6 mm more than the planum sphenoidal width at the level of the optic strut [(30.87±8.61) mm]. The total length of HBF including the pedicle was 6 mm more than the length of the planum sphenoidal, and the sella reconstruction [(64.44±10.25) mm], also was 6 mm more than the length of the planum sphenoidal reconstruction [(73.61±8.28) mm]. The length of HBF without pedicle was 6 mm more than the length of the planum sphenoidal, and the sella defect [(27.88±3.74) mm], also was 6 mm more than the length of the planum sphenoidal defect [(15.50±3.38) mm]. The width of the leading edge of HBF and the width of the trailing edge were both 6 mm more than the width of clivus reconstruction at the level of the foramen lacerum [(21.68±2.30) mm]. The total length of HBF including pedicles was 6 mm more than the clivus reconstruction length [(67.09±5.44) mm], while the length of HBF without pedicles was also 6 mm more than the clivus defect length [(37.19±3.80) mm]. Conclusions: In this study, the radiosanatomic measurements ensured that HBF could provide sufficient tissue flap for the reconstruction of the anterior skull base and sphenoid plateau and extend the reconstruction area to sella and clivus. Preoperative radiosanatomic measurement can be used to predict the size of HBF required for skull base reconstruction, which provides important guidance for flap harvest.
Adult ; Endoscopy ; Humans ; Nose/surgery* ; Reconstructive Surgical Procedures ; Skull Base/surgery* ; Skull Base Neoplasms/surgery* ; Sphenoid Bone ; Surgical Flaps

Background:The preferred treatment for uncomplicated type B dissection (thoracic endovascular aortic repair [TEVAR] or medical) is still under debate.Since 2001,our center has performed TEVAR for uncomplicated type B dissection.Based on our data,5-and 10-year survival rates among patients with uncomplicated type B dissection after TEVAR were 96.5％ and 83.0％,respectively.We,therefore,believe that TEVAR is preferable for uncomplicated type B dissections.This study analyzed the impact of a pre-operative smoking history on long-term survival after TEVAR in patients with uncomplicated type B dissections.Methods:From May 2001 to December 2013,data from 751 patients with type B dissections were collected and analyzed.Patients were divided into two groups (337 smoking patients and 414 non-smoking patients).The Kaplan-Meier method and log-rank test were used to compare survival curves of the two groups.Multivariable analyses using the Cox proportional hazards model were used to estimate the effects of smoking on survival rates.Results:The 5-and 10-year survival rates of non-smokers were 97.6％ (95％ confidence interval [CI],96.0％-99.2％) and 87.0％ (95％ CI,81.6％-92.7％),respectively,and 94.9％ (95％ CI,92.2％-97.7％) and 73.8％ (95％ CI,62.3％-87.5％) for smokers,respectively (Log-rank test,P =0.006).Multivariable analyses showed that smoking increased the risk of death during follow-up,2.1-fold when compared to non-smokers (P =0.039).Conclusion:A pre-operative smoking history increases long-term mortality rates after TEVAR in patients with uncomplicated type B dissections.

Objective To observe the clinical efficacy and safety of losartan potassium tablets combined with cyclophosphamide injection in the treatment of focal segmental glomerulosclerosis. Methods A total of90 patients of focal segmental glomerulosclerosis were randomly divided into control group (n = 41 cases) and treatment group (n = 49 cases) .Control group received cyclophosphamide 0. 6-1. 0 g per time, intravenous infusion, once every 3 to 4 weeks. Treatment group was given losartan potassium 50 mg per, orally in the morning, qd, on the basis of control group. Two groups were treated for 3 months. The clinical efficacy, renal function and adverse drug reactions were compared between two groups.Results After treatment, the total effective rates of treatment and control groups were 91. 84％ (45 cases/49 cases) and 73. 17％ (30 cases/41 cases) with significant difference (P < 0. 05) . After treatment, the main indexes of treatment and control groups were compared: urea nitrogen were (9. 37 ± 1. 55) and (10. 24 ± 1. 89) mmol · L-1, creatinine were (119. 95 ± 15. 51) and (138. 34 ± 15. 24) μmol · L-1, proteinquantitation were (0. 86 ± 0. 12) and (1. 33 ± 0. 18) g · 24 h-1, the differences were statistically significant (all P < 0. 05) . Adverse drug reactions of two groups were gastrointestinal reactions, elevated transaminase and bone marrow suppression. The total incidences of adverse drug reactions in the treatment and control groups were 18. 37％ and14. 63％ without significant difference (P> 0. 05) . Conclusion Losartan potassium tablets combined with cyclophosphamide injection have a definitive clinical efficacy in the treatment of focal segmental glomerulosclerosis, which can effectively control the proteinuria and improve the renal function, without increasing the incidence of adverse drug reactions.