Compound 275# Induces Mitochondria-Mediated Apoptosis and Autophagy Initiation in Colorectal Cancer Cells through an Accumulation of Intracellular ROS.

Colorectal cancer (CRC) is the most common intestinal malignancy, and nearly 70% of patients with this cancer develop metastatic disease. In the present study, we synthesized a novel compound, termed N-(3-(5,7-dimethylbenzo [d]oxazol-2-yl)phenyl)-5-nitrofuran-2-carboxamide (compound 275#), and found that it exhibits antiproliferative capability in suppressing the proliferation and growth of CRC cell lines. Furthermore, compound 275# triggered caspase 3-mediated intrinsic apoptosis of mitochondria and autophagy initiation. An investigation of the molecular mechanisms demonstrated that compound 275# induced intrinsic apoptosis, and autophagy initiation was largely mediated by increasing the levels of the intracellular accumulation of reactive oxygen species (ROS) in CRC cells. Taken together, these data suggest that ROS accumulation after treatment with compound 275# leads to mitochondria-mediated apoptosis and autophagy activation, highlighting the potential of compound 275# as a novel therapeutic agent for the treatment of CRC.

Single Nucleotide Polymorphisms of Paclitaxel-induced Peripheral Sensory Neuropathy in Chinese Han Population.

Objective To study the single nucleotide polymorphisms (SNPs)that predict a patient's risk of grade 2-3 paclitaxel-induced peripheral sensory neuropathy (PSN) in Chinese Han populations.Methods Totally 216 patients received paclitaxel in Peking Union Medical College Hospital from May 2014 to December 2016 were enrolled.DNA was isolated from peripheral blood.Genotyping for eight candidate SNPs was performed on Sequenom-MassARRARYiPLEX platform.Patients were followed up and PSN was assessed by trained physicians according to National Cancer Institute-Common Terminology Criteria for Adverse Events v4.03.Results A total of 209 patients entered the final analysis.Among the candidate SNPs,only rs4141404:A>C(LIMK2) was significantly associated with grade 2/3 PSN (OR:4.32,95%CI:2.37-7.89,P<0.0001).In multivariate logistic regression analysis,both rs4141404:A>C(LIMK2) and history of receiving platinum compound (OR:2.70,95%CI:1.32-5.51,P=0.007) were associated with grade 2/3 PSN.Conclusion rs4141404:A>C(LIMK2) may be the markers of risk of grade 2/3 PSN.

[Application of calcium ionophore A23187 in ICSI for globozoospermia: A report of 2 cases and review of the literature].

OBJECTIVE: To investigate the pathogenesis of globozoospermia, fertilization ability of round-headed sperm, and the application value of assisted oocyte activation in intracytoplasmic sperm injection (ICSI) for the wives of glohozoospermia men. METHODS: We collected oocytes from the wives of 2 globozoospermia patients and randomly divided them into two groups after ICSI to receive calcium ionophore A23187-activation and conventional treatment, respectively. We reviewed the relevant literature published at home and abroad, and discussed the etiology of globozoospermia, fertilization ability of round-headed sperm, and treatment options for this disease. RESULTS: Quality embryos were obtained in the A23187-activation group while no fertilized oocytes, oocyte cleavage, quality embryos, or blastular formation were found in the conventional treatment group. Both women achieved pregnancy and gave birth to healthy neonates after transfer of the quality embryos from the A23187-activation group. CONCLUSION: Calcium ionophore A23187 can be applied to ICSI for the wives of globozoospermia men and bring about desirable clinical outcomes. Meanwhile, attention should be paid to its safety.

Pregnancy with oocytes characterized by narrow perivitelline space and heterogeneous zona pellucida: is intracytoplasmic sperm injection necessary?

PURPOSE: This retrospective study analyzed fertilization protocols and pregnancy outcomes for oocytes with with narrow perivitelline space and heterogeneous zona pellucid (NPVS/HZP). METHODS: In 63 in-vitro fertilization cycles filled with NPVS/HZP oocytes (abnormal oocytes group) and 521 cycles with normal oocytes (normal oocytes group), major clinical and laboratory parameters were recorded and compared in different fertilization cycles (conventional IVF cycles, rescue ICSI cycles, and traditional ICSI cycles). RESULTS: NPVS/HZP oocytes meant lower MIIoocytes rates in both IVF and ICSI cycles compared with normal oocytes (p < 0.05). The 2PN rates for abnormal oocytes were significantly lower than those for normal oocytes in both conventional IVF cycles (58.8% VS 71.3%, P < 0.05) and rescue ICSI cycles (58.0% VS 78.0%, P = 0.0000). The high-quality embryo rates in normal oocytes groups were significantly higher than those in abnormal oocytes groups in different fertilization cycles (52.2% VS 35.0%, P < 0.01; 42.9% VS 23.9%, P < 0.001; 50.6% VS 31.0%, P = 0.0000, respectively). No clinical pregnancy was obtained from abnormal oocytes in 11 conventional IVF cycles. The clinical pregnancy rates in rescue ICSI and traditional ICSI cycles were comparatively lower in abnormal oocytes groups, but there was no significant difference as compared with normal oocytes groups (35.0% VS 48.1% and 26.7% VS 50.7%, P > 0.05, respectively). CONCLUSIONS: Retrieval of oocytes characterized by NPVS/PZP from cycle to cycle was one of the reasons for obscure infertility. ICSI may be the right way to avoid fertilization failure and get pregnancy in women with NPVS/HZP oocytes.

Evaluation of the developmental potential of metaphase I oocytes from stimulated intracytoplasmic sperm injection cycles.

The objective of the present study was to evaluate the developmental potential and clinical application value of metaphase I (MI) oocytes obtained from stimulated intracytoplasmic sperm injection (ICSI) cycles. ICSI was performed on MI oocytes immediately after denudation (Group A), or on in vitro-matured (IVM) oocytes following culture; oocytes in culture were further divided into two groups, being cultured for either 3-5 h (Group B) or 24-28 h (Group C). Metaphase II oocytes from the same cycle(s) isolated for ICSI served as the control group (Group D). The rates of normal fertilisation, cleavage and high-quality embryos were compared among the four groups. High-quality embryos were transferred whenever possible, and pregnancy rates were evaluated. Results showed that normal fertilisation rates for Groups B, C and D were significantly higher than that of Group A (68.6%, 57.8%, 74.5% and 30.1%, respectively; P<0.01). The rate of high-quality embryos in Group B was comparable with Group D; the rate for Group C was significantly lower than that of the other groups (P<0.05). Two clinical pregnancies were achieved after transfer of embryos from IVM oocytes. In vitro maturation of MI oocytes for a short period of time may increase the number of available embryos; however, overnight in vitro culture of MI oocytes did not improve results.

Dynamic modulation of cytoskeleton during in vitro maturation in human oocytes.

OBJECTIVE: To investigate the role of cytoskeleton in several important dynamic events during in vitro maturation of human oocytes. STUDY DESIGN: Human germinal vesicle stage oocytes were divided randomly into control and study groups. After cultured for 24 hours, chromatin state and position, spindle formation and migration, cortical granules, and mitochondria distribution were evaluated. RESULTS: In colchicine group, spindles did not form. Cortical granules migrated to the cortex but mitochondria maintained the peripheral distribution pattern in most of the oocytes. In cytochalasin B group, the migration of spindle and chromosomes to the cortex was prohibited. Microfilaments disruption influenced cortical granules migration but not redistribution of mitochondria. CONCLUSION: Meiosis progression could not go beyond metaphase I stage when microtubule or microfilament polymerization was prohibited in human oocytes. The migration of cortical granules to the cortex and redistribution of mitochondria to the inner cytoplasm were mediated by microfilaments and microtubules, respectively.

[Infection of human papillomavirus 16/18 DNA in patients with head and neck squamous cell carcinoma and its relationship with expression of Ki-67 and P53 protein].

OBJECTIVE: To detect the infection of human papillomavirus (HPV) 16/18 in patients with head and neck squamous cell carcinoma and explore the relationship between HPV infection and expressions of Ki-67 and P53 proteins in tumor tissue. METHOD: The level of HPV 16/18 DNA was measured by real time polymerase chain reaction, and Ki-67 and P53 proteins were measured by immunohistochemistry in tissues from head and neck squamous cell carcinoma. RESULTS: HPV 16/18 DNA was detected in 62.8% of our patients. In each cancer tissue sample, Ki-67 protein was expressed between 2% to 70%. P53 protein was expressed in 46.15% of our patients. No significant relation was found between HPV 16/18 DNA level and sex, smoking, drinking, and tumor clinical stages. However, level of HPV 16/18 DNA was found to have positive relation with tumor pathological grades and negative relation with P53 protein expression. No relation with Ki-67 protein expression was found. CONCLUSION: Head and neck squamous cell carcinoma may be initiated by HPV 16/18 infection and the mechanism in carcinogenesis involves abnormal expression in P53 protein.

Expanded activated autologous lymphocyte infusions improve outcomes of low- and intermediate-risk childhood acute myeloid leukemia with low level of minimal residual disease.

The presence of minimal residual disease (MRD) is a risk factor for relapse among children with acute myeloid leukemia (AML), and eliminating MRD can usually improve survival rates. To investigate the effect of expanded activated autologous lymphocytes (EAALs) combined with chemotherapy on eliminating MRD and improving survival rates of children with AML, we retrospectively analyzed the results of 115 children with low- or intermediate-risk AML with MRD treated at the Pediatric Hematological Center, Peking University People's Hospital, between January 2010 and January 2016. The patients were assigned to the chemotherapy plus EAAL (combined therapy) group (n = 61) and chemotherapy group (n = 54). The MRD-negativity rates were 95.1% (58/61) in the combined therapy group and 63.0% (34/54) in the chemotherapy group (P < 0.0001) during consolidation treatment. The 5-year event-free survival rate was higher in the combined therapy group than in the chemotherapy group (86.3 ± 4.6% vs. 72.1 ± 6.1%, P = 0.025). No severe adverse event was observed after EAAL infusion. The present study showed that EAAL combined with chemotherapy could improve the MRD-negativity rate and event-free survival rate among children with AML with low level MRD-positive status.

[Predictors of residual lesion in cervix after conization in patients with cervical intraepithelial neoplasia and microinvasive cervical cancer].

OBJECTIVE: To determine the clinicopathological factors predicting residual lesions after conization in patients with cervical intraepithelial neoplasia (CIN) and microinvasive carcinoma of cervix (MIC). METHODS: The clinical data of 77 patients with CIN3, 20 patients with stage Ia1 cervical cancer, and 8 patients with stage 1a2 cervical cancer, totally 105 patients, aged (43 + 6), who received further surgery within 3 months after conization, 95 receiving hysterectomy, 2 receiving repeated conization, and 8 receiving radical hysterectomy and pelvic lymph node dissection, were evaluated. The demographic features, clinical and pathological parameters, and the correlation thereof with the post-conization residual lesions were analyzed retrospectively. RESULTS: Residual lesions were found in the specimens obtained from hysterectomy or repeated conization of 53 of the 105 patients (50.5%), among which 38 were CIN2 or less severe lesions. Univariate analysis showed that menopausal status, procreation status, cervical cytology, method of conization, and range of resection were not correlated with the presence of post-conization residual lesion, while age < or = 45 (P < 0.05, odd ratio [OR] = 4.68) and positive resection margin (P < 0.05, OR = 5.40) were risk factors of residual lesion. There were no differences in the proportion of post-conization residual lesion among the patients with MIC, CIN 3, CIN2 or less severe lesions. Multivariate logistic analysis showed that only the positive resection margin was an independent risk factor of residual lesion after conization (P < 0.05, OR = 4.20). CONCLUSIONS: Although severity of the cervical disease is the most important factor in determining post-conization treatment, it is not a predicting factor for post-conization residual lesion. Only the positive resection margin was an independent risk factor of residual lesion after conization.

Pelvic Exenteration for Recurrent and Persistent Cervical Cancer.

BACKGROUND: Pelvic exenteration (PE) for primary and recurrent cervical cancer has resulted in favorable survival outcomes, but there are controversies about specific prognosis factors, and up to now, there have been no published reports from China. This study aimed to share our experiences of PE, which were performed in a single institution. METHODS: From January 2009 to January 2016, 38 patients with recurrent or persistent cervical cancer were included in the study, and they were followed up until January 2017. Epidemiological and clinicopathological characteristics of patients were compared for survival outcomes in univariate and Cox hazard regression analysis. RESULTS: There were thirty-one and seven patients with recurrent and persistent cervical cancer, respectively. The median age of patients was 45 years (range 29-65 years). Total, anterior, and posterior PE consisted of 52.6%, 28.9%, and 18.4% of cases, respectively. Early and late complications occurred in 21 (55.3%) patients and 15 (39.5%) patients, respectively. Two (5.3%) patients died due to complications related to surgeries within 3 months after PE. The median overall survival (OS) and disease-free survival (DFS) were 28.5 months (range 9-96 months) and 23 months (range 4-96 months), respectively, and 5-year OS and DFS were 48% and 40%, respectively. Cox hazard regression analysis showed that, the margin status of the incision and mesorectal lymph node status were independent risk factors for OS and DFS. CONCLUSION: In our patients with recurrent and persistent cervical cancer, the practice of PE might achieve favorable survival outcomes. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03291275; https://clinicaltrials.gov/ct2/show/NCT03291275?term=NCT03291275&rank=1.

Resveratrol improves in vitro maturation of oocytes in aged mice and humans.

OBJECTIVE: To evaluate the effects of resveratrol on oocyte maturation in aged mice and humans. DESIGN: Experimental laboratory study. SETTING: University-based reproductive medicine center. PATIENT(S): A total of 64 women 38-45 years of age undergoing intracytoplasmic sperm injection (ICSI) and 48-52-week-old female C57BL/6J mice. INTERVENTION(S): In vitro culture in the presence of three different concentrations of resveratrol (0.1, 1.0, and 10 µm) or dimethylsulfoxide. MAIN OUTCOME MEASURE(S): Parameters of oocyte nuclear maturation, fertilization, immunofluorescence intensity of mitochondria, and normal morphology of spindle and chromosome of oocytes undergoing in vitro maturation (IVM) in aged mice and humans; blastocyst formation and levels of SRIT1, CAT, SOD1, and GPX4 gene expressions in aged mice. RESULT(S): Resveratrol at 1.0 µm significantly increased first polar body emission rate in oocytes derived from aged mice and humans, and an increased percentage of fertilization and blastocyst formation was observed in aged mice. In addition, immunofluorescence intensity of mitochondria and normal morphology of spindle and chromosome of oocytes undergoing IVM were notably improved compared with control samples in aged mice and human. Furthermore, the use of resveratrol exhibited enhanced expression patterns of SRIT1, CAT, SOD1, and GPX4 in aged mice. CONCLUSION(S): Resveratrol induced oocyte maturation and blastocyst formation in aged mice, and improved oocyte maturation and quality was examined in aged humans. In conclusion, 1.0 µm resveratrol was the appropriate concentration in IVM medium.

[Spindle and chromosome configuration of human in vitro matured oocytes after slow freezing-fast thawing].

OBJECTIVE: To evaluate the development of immature oocytes after freezing-thawing by conventional cryopreservation method for mature oocytes. METHODS: Immature oocytes were collected from stimulated ovaries of intracytoplasmic sperm injection (ICSI) cycles. Immature oocytes were in vitro matured directly or after slow freezing-fast thawing and immunostained for tubulin and chromatin and at last visualized by confocal microscopy. RESULTS: No statistical difference was found in maturity rate between freezing groups and the controls. There was a statistically significant increase in abnormalities of chromosome (23.7% vs. 50%) and spindle (28.9% vs. 53.9%) in the GV freezing group compared with the GV control (P < 0.05). MI groups gave the same results. But we did not find any statistical difference between GV frozen group and MI frozen group. CONCLUSIONS: Cryopreservation decreases the ability of immature oocytes to form normal meiosis spindle and induce abnormal division of chromosomes. This suggests that the routine slow freezing-fast thawing procedure for mature oocyte couldn't preserve the ability well to form normal meiosis spindle during in vitro maturation.

[Comparison of vitrification and slow-freezing of human day 3 cleavage stage embryos: post-vitrification development and pregnancy outcomes].

OBJECTIVE: To compare the effects of vitrification with slow-freezing on the developmental ability of day 3 cleavage stage embryos. METHODS: Patients who had no less than 4 high quality embryos were included in this study. These embryos were cryopreserved using the methods of vitrification or slow-freezing. In the cryopreserved embryo transfer cycles, the embryos which were cryopreserved using one of the methods were chosen randomly. The developmental ability of embryos was compared between these two groups. RESULTS: A total of 80 patients were included in this study with 160 embryos. In the group of slow-freezing, 73 (91%) embryos were survived and achieved 15 (38%) clinical pregnancies. Among these, 3 were twins and the implantation rate was 25% (18/73). In the group of vitrification, 71 (89%) embryos were survived and achieved 19 (48%) clinical pregnancies. Among these, 9 were twins and the implantation rate was 39% (28/71), which was significantly higher than the slow-freezing group (P < 0.05). Otherwise, the clinical pregnant rate and multiple pregnant rate was higher in the group of vitrification than the slow-freezing group, but had no significance. CONCLUSION: Vitrification is more benefit for the developmental ability of the thawed embryos and more suitable for the cryopreservation of day 3 cleavage stage embryos.

[Study of symptoms in terminally ill patients with ovarian carcinoma].

OBJECTIVE: To investigate symptom characteristics and their their prevalence in terminally ill patients with ovarian carcinoma. METHODS: A retrospective study was carried out based on clinical data of 98 terminally ill patients with ovarian carcinoma who died in our hospital during January 1995 to December 2004. Fifteen most common symptoms were analyzed with a focus on the followings: symptom incidence, survival time after symptom occurrence, regularity of symptom cluster, and common causes of death. Fifteen symptoms were: pain, cachexia, pleural effusion and ascites, dyspnea, fever, intestinal obstruction, renal failure, bone marrow depression, lung infection, hemorrhage, deep venous thrombosis (DVT), intestinal or pancreatic fistula, mycotic infection, jaundice and emergency conditions. RESULTS: (1) The most prevalent symptom was pleural effusion and ascites (63%), followed by pain (60%), cachexia (59%), dyspnea (52%) and intestinal obstruction (49%). (2) The symptom which lasted longest survival time was mycotic infection (77 days), followed by intestinal or pancreatic fistula (75 days), intestinal obstruction (67 days), pain (60 days) and cachexia (60 days). Symptoms such as bone marrow depression, renal failure, dyspnea and emergency conditions were comparatively critical associated with shorter survival times (14, 13, 12, 7 days, respectively). (3) Terminal symptoms occurred typically in clusters, with 4.9 +/- 1.5 symptoms per case. Of 98 cases, 84 cases (86%) had 4 or more symptoms, with the median survival time of 63 days from the last day of anti-cancer therapy, and a slow death process. The remaining 14 cases (14%) with 3 or fewer symptoms survived only 25 days, of which 10 cases (71%) died of emergency diseases. The survival time for two groups was significantly different (P<0.01). (4) The first four causes of death were as follows: intestinal obstruction (30%), infection (15%), emergencies (12%) and treatment complications (5%). CONCLUSION: Symptom characteristics and regularity are seen in terminally ill patients with ovarian carcinoma, the understanding of which is helpful for the improvement of symptom management and patients' quality of life.

[Survival prediction for terminal gynecologic cancer patients].

OBJECTIVE: To construct a scoring system of predicting the survival time of terminal gynecologic cancer patients. METHODS: The clinical data of 91 patients with terminal gynecologic cancers, aged 56 (13-83), who were not suitable to specific anti-cancer therapy and died in the hospital with a mean survival time of 27 days (1-240 days) were analyzed retrospectively. Initially univariate analysis was performed to evaluate the relationship between 19 clinico-biochemical indices and survival time. Multiple logistic regression was used to analyze 9 out of the 19 clinico-biochemical indices which had significant effects on the survival time, and a regression model with 5 indices was constructed by backward selection procedure. The regression coefficient of any category was divided by the maximum regression coefficient so as to get the score of this category. The cores were added together so as to get the overall score of an individual patient. RESULTS: Univariate analysis identified 9 factors independently and significantly influencing the survival time: short breath, Karnofsky performance status (KPS), age, high fever, speed of tumor growth, presence or absence of treatment-related complication, blood urea nitrogen (BUN), creatinine, and platelet. A regression equation was composed of 5 factors: short breath, KPS, age, higher fever, and BUN by multiple logistic regression with a correct classification ability of 83.5%. The 91 patients were then divided into 2 groups based on this prognostic score system: Group A (n = 37) with a score < or = 9.5 and the mean survival time of (65 +/- 7) days, and Group B (n = 54) with a score > or = 10 and the mean survival time of (19 +/- 2) days. 31 of the 37 patients in Group A survived > or = 30 days, and 46 of the 54 patients in Group B died within 29 days. The Kaplan-Meier survival curves of these 2 group were significantly different (P < 0.001). CONCLUSION: A simple, valid, and useful prognostic score system has been established.

[Oocyte activation with calcium ionophore A23187 and puromycin on human oocytes that fail to fertilize after intracytoplasmic sperm injection].

OBJECTIVE: To investigate the effect of assisted oocyte activation with calcium ionophore A23187 and puromycin on human oocytes that fail to fertilize after intracytoplasmic sperm injection (ICSI). METHODS: All 113 discarded oocytes that showed no evidence of fertilization at 16 - 18 hours after in vitro maturation (IVM)-ICSI cycles and conventional ICSI were assigned to four groups according to the time after ICSI: IVM-ICSI 22-hour group (n = 33), IVM-ICSI 44-hour group (n = 18), ICSI 44-hour group (n = 37) and ICSI 68-hour group (n = 25). All unfertilized oocytes were exposed to calcium ionophore A23187 (5 micromol/L) for 5 minutes and subsequently incubated with puromycin (10 microg/ml) for 4 hours. After incubation, the oocytes were cultured in vitro for 3 - 5 days. The activation rate, proportion of oocytes that showed pronucleus formation and cleavage rate were calculated after activation. Sex chromosomal analysis was performed by dual color fluorescence in situ hybridization (FISH) on the embryos that displayed two pronuclei and a second polar body. RESULTS: The combination of calcium ionophore A23187 with puromycin could activate the unfertilized oocytes 22 - 68 hours after ICSI. Best results were achieved in IVM-ICSI 22-hour group, which elicited 88% (29/33) of activation rate, 62% (18/29) of cleavage rate and 28% (5/18) of 4-cell embryos. One embryo in this group developed to the morular stage. The activation rate and developmental potential of the activated embryos in IVM-ICSI 44-hour group, ICSI 44-hour group and ICSI 68-hour group decreased. FISH analysis showed 4 embryos with XX and 9 embryos with XY in 16 embryos. CONCLUSIONS: The combination of calcium ionophore A23187 with puromycin could effectively activate unfertilized oocytes 22 - 68 hours after ICSI. The cultured time of unfertilized oocytes after ICSI affects activation efficiency and developmental potential of the activated embryos. The activated zygotes that display two pronuclei and a second polar body can develop normally.

[Comparison of the outcome of intracytoplasmic single sperm injection between two motile sperm separation methods].

OBJECTIVE: To evaluate the efficiency of density gradient and improved swim-up methods for motile sperm isolation from fresh semen samples in intracytoplasmic sperm injection and embryo transfer (ICSI-ET) program, thus guiding the clinical application. METHODS: The fertilization rate, cleavage rate, high-quality embryo rate, clinical pregnancy rate, sperm abnormal rate and recovery rate of 42 cycles were studied prospectively. The cycles were divided into two groups with respect to the motile sperm isolation methods. RESULTS: No obvious difference was found in the fertilization rate, cleavage rate, high-quality embryo rate and clinical pregnancy rate between the two methods. The abnormal sperm rate induced by the improved swim-up method was significantly higher than that of the density gradient method (P < 0.01). For severe oligozoospermia, the recovery rate of motile sperm with density gradient was higher than that of improved swim-up (P < 0.01). CONCLUSION: In the ICSI-ET, there is no obvious difference in clinical pregnancy outcome between the two methods. The method of improved swim-up can be used for all patients but those with severe oligozoospermia.

Neutrophil Dysfunction in Sepsis.

OBJECTIVE: Sepsis is defined as life-threatening organ dysfunction due to a dysregulated host response to infection. In this article, we reviewed the correlation between neutrophil dysfunction and sepsis. DATA SOURCES: Articles published up to May 31, 2016, were selected from the PubMed databases, with the keywords of "neutrophil function", "neutrophil dysfunction", and "sepsis". STUDY SELECTION: Articles were obtained and reviewed to analyze the neutrophil function in infection and neutrophil dysfunction in sepsis. RESULTS: We emphasized the diagnosis of sepsis and its limitations. Pathophysiological mechanisms involve a generalized circulatory, immune, coagulopathic, and/or neuroendocrine response to infection. Many studies focused on neutrophil burst or cytokines. Complement activation, impairment of neutrophil migration, and endothelial lesions are involved in this progress. Alterations of cytokines, chemokines, and other mediators contribute to neutrophil dysfunction in sepsis. CONCLUSIONS: Sepsis represents a severe derangement of the immune response to infection, resulting in neutrophil dysfunction. Neutrophil dysfunction promotes sepsis and even leads to organ failure. Mechanism studies, clinical practice, and strategies to interrupt dysregulated neutrophil function in sepsis are desperately needed.

Host-guest system of hesperetin and ß-cyclodextrin or its derivatives: Preparation, characterization, inclusion mode, solubilization and stability.

The inclusion complexation behavior, characterization and binding ability of hesperetin with ß-cyclodextrin and its derivatives were investigated in both the solution and solid state by means of XRD, DSC, SEM, (1)H and 2D NMR and UV-vis spectroscopy. The results showed that the water solubility and stability of hesperetin were obviously increased in the inclusion complex with cyclodextrins. This satisfactory water solubility and high stability of the hesperetin/CD complexes will be potentially useful for their application as herbal medicines or healthcare products.

Clinical analysis of primary malignant melanoma of the cervix.

OBJECTIVE: To investigate the clinical and pathological characteristics of primary cervical malignant melanoma, and its prognosis. METHODS: The clinical and pathological data of four patients with primary malignant melanoma of the cervix were analyzed retrospectively. Nerve tissue protein S-100 and monoclonal antibody to melanoma (HMB-45) were measured in all cases by immunohistochemical method. All four patients received radical hysterectomy. Three of them received chemotherapy preoperation or postoperation, and one of them received biotherapy with interferon-gamma and interleukin-2 at the same time. All the cases were followed up. RESULTS: The average age of four patients was 45 years. Clinical symptoms presented with irregular vaginal bleeding, postcoital bleeding, or increase of vaginal discharge. Gynecologic examination showed polypus papilla cauliflower-shaped or nodulated black-brown or black-blue mass on the cervix. All the four cases were pathologically diagnosed with cervical malignant melanoma. S-100 and HMB-45 were positive in all patients. Two patients died at 6 and 41 months postoperation, respectively. The other two patients survived for 3.5 and 7 years postoperation, respectively. CONCLUSIONS: S-100 protein and HMB-45 play very important roles in the diagnosis of primary malignant melanoma of cervix. Radical hysterectomy, chemotherapy combined with dimethyl triazemo imidazole carboxamide and biological therapies may improve the prognosis of the primary malignant melanoma of cervix if the disease could be diagnosed in an early stage.