A randomized trial of eribulin monotherapy versus eribulin plus anlotinib in patients with locally recurrent or metastatic breast cancer.

BACKGROUND: Eribulin mesylate is a novel, nontaxane, microtubule dynamics inhibitor. In this study, we assessed the efficacy and safety of eribulin versus eribulin plus the oral small-molecule tyrosine kinase inhibitor anlotinib in patients with locally recurrent or metastatic breast cancer. PATIENTS AND METHODS: In this single-center, open-label, phase II clinical study (NCT05206656) conducted in a Chinese hospital, patients with human epidermal growth factor receptor 2 (HER2)-negative, locally recurrent or metastatic breast cancer previously treated with anthracycline- or taxane-based chemotherapy were randomized (1 : 1) to receive eribulin alone or in combination with anlotinib. The primary efficacy endpoint was investigator-assessed progression-free survival (PFS). RESULTS: From June 2020 to April 2022, a total of 80 patients were randomly assigned to either eribulin monotherapy or eribulin plus anlotinib combination therapy, with 40 patients in each group. The data cut-off was 10 August 2022. The median PFS was 3.5 months [95% confidence interval (CI) 2.8-5.5 months] for eribulin and 5.1 months (95% CI 4.5-6.9 months) for eribulin plus anlotinib (hazard ratio = 0.56, 95% CI 0.32-0.98; P = 0.04). The objective response rates were 32.5% versus 52.5% (P = 0.07), respectively, and disease control rates were 67.5% versus 92.5% (P = 0.01), respectively. Patients <50 years of age, with an Eastern Cooperative Oncology Group performance status score of 0, visceral metastasis, number of treatment lines of four or more, hormone receptor negative (triple-negative), and HER2 low expression appeared to benefit more from combined treatment. The most common adverse events in both groups were leukopenia (n = 28, 70.0%, patients in the eribulin monotherapy group versus n = 35, 87.5%, patients in the combination therapy group), aspartate aminotransferase elevations (n = 28, 70.0%, versus n = 35, 87.5%), neutropenia (n = 25, 62.5%, versus n = 31, 77.5%), and alanine aminotransferase elevations (n = 25, 62.5%, versus n = 30, 75.0%). CONCLUSION: Eribulin plus anlotinib can be considered an alternative treatment option for HER2-negative locally advanced or metastatic breast cancer.

Activation cross sections for reactions induced by 14 MeV neutrons on natural titanium.

Cross sections for the neutrons around 14 MeV interaction with natural titanium were precisely measured by neutron activation and off-line measurement technique. The fast neutrons were produced by 3H(d,n)4He reaction and the neutron energy was obtained by using the cross section ratio method of 90Zr(n,2n)89Zr to 93Nb(n,2n)92mNb reactions. Experimental cross sections have been acquired for natTi(n,x)46Sc, natTi(n,x)47Sc, 50Ti(n,x)47Ca and 48Ti(n,x)48Sc reactions. The measured cross section data are compared with the experimental data available in the previous literature and evaluated nuclear data from the ENDF/B-VIII.0, JEFF-3.3, JENDL-5, BROND-3.1, CENDL-3.2 and FENDL-3.2b libraries. Furthermore, excitation functions for these reactions were calculated by using the theoretical model based on Talys-1.96 code with default and adjusted parameters. Within experimental error, evaluated nuclear data are mostly consistent with experimental data. The excitation function with adjusted parameters can roughly reproduce the experimental data.

DEVELOPMENT OF AN EXTENDED-RANGE BONNER SPHERE SPECTROMETER FOR CHINA INITIATIVE ACCELERATOR-DRIVEN SYSTEM.

To measure the extended-range neutron spectra and calibrate the extended-range neutron dosemeters of the China initiative Accelerator-Driven System (CiADS), an Extended-range Bonner Sphere Spectrometer (EBSS) has been developed. The EBSS was designed based on the PHITS codes, investigating various combinations of materials and diameters of the neutron moderators and the neutron multipliers for extended-range neutrons. Finally, seven polyethylene-only spheres and seven extended-range spheres were selected and subsequently built. The neutron multipliers of the extended-range spheres embedded concentric shells of lead, copper and tungsten. The response functions of the EBSS were analyzed and experimentally validated. It was subsequently tested with 252Cf neutron source and cosmic ray neutron source. The results demonstrate that the EBSS is capable of accurately measuring neutron spectra.

Association of aldehyde exposure with bone mineral density in the national health and nutrition examination survey (NHANES 2013-2014).

PURPOSE: The association between aldehyde exposure and bone health in humans remains unclear. This study was to evaluate the association of serum aldehydes with bone mineral density (BMD) and osteopenia/osteoporosis. METHODS: We analyzed the US National Health and Nutrition Examination Survey cross-sectional data from 2013 to 2014. Weighted multivariate-adjusted linear regression and logistic regression models were used to assess the association between specific aldehydes and osteopenia/osteoporosis. Associations between aldehyde combinations and BMD were also evaluated using the restricted cubic spline (RCS) method. RESULTS: Compared with men in the first tertile, those in the third tertile of propanaldehyde concentration were negatively associated with proximal femur and lumbar spine BMD. Significant inverse associations were observed between benzaldehyde exposure and trochanter BMD in women. Benzaldehyde increased the risk of osteopenia/osteoporosis 2.75-fold [95% confidence interval (CI) = 1.06, 7.11] in the highest tertile in women compared to the lowest tertile concentration. In males, the prevalence of total femur, femur neck, and trochanter osteopenia/osteoporosis was significantly higher in the highest versus the lowest tertile of propanaldehyde exposure, with odds ratios (ORs) of 6.84 (95% CI = 2.33, 20.04), 2.72 (95% CI = 1.18, 6.27), and 3.26 (95% CI = 1.25, 8.56), respectively. RCS regression also showed decreased BMD continuously with increasing serum mixed aldehyde levels. CONCLUSIONS: Serum aldehyde concentrations were associated with low BMD and high osteopenia/osteoporosis risk in adults, with propanaldehyde and benzaldehyde being the most critical. Co-exposure to aldehyde combinations was negatively correlated with BMD.

Survival analysis of 80 elderly patients with esophageal squamous cell carcinoma receiving definitive concurrent chemoradiotherapy with S-1.

PURPOSE: This single-center retrospective study aimed to observe survival and prognosis of elderly patients with esophageal cancer receiving radical radiotherapy combined with S1 chemotherapy, and to preliminarily explore whether hematologic indicators or inflammatory indicators before radiotherapy are prognostic factors. MATERIAL AND METHODS: We retrospectively collected data of 80 elderly patients with esophageal cancer who had received radical concurrent chemoradiotherapy from January 2015 to July 2018. The patients were older than 70 years. Radiation therapy was delivered with intensity-modulated irradiation therapy (IMRT) or volumetric modulated arc therapy (VMAT), while the chemotherapy regimen was S1 alone. Toxicities were evaluated in accordance with the criteria of the Radiation Therapy Oncology Group. Baseline hematologic basic nutritional indicators, such as hemoglobin (HGB), albumin (ALB), and prealbumin (PAB), along with inflammatory indicators, such as the ratio of neutrophils to lymphocytes (NLR), the ratio of platelets to lymphocytes (PLR), were collected to preliminarily analyze their relationship with progression and survival. RESULTS: The median follow-up time was 39 months (range 30-65 months). The median overall survival and progression-free survival times were 24 and 17 months, respectively. The 1-, 2-, and 3-year overall survival rates were 76.5%, 48.1%, and 31.3%, respectively. The 1-, 2-, and 3-year progression-free survival rates were 57.5%, 37.8%, and 29.4%, respectively. T stage, clinical staging, and lesion region were independent prognostic factors for OS. No significant associations with prognosis were observed either for baseline hematologic or for inflammatory indicators (all P>0.05). The rates of esophagitis (grade 2 and above) and hematologic toxicity were 60% and 45%, respectively. CONCLUSION: Oral S-1 combined with definitive concurrent radiotherapy for elderly patients with esophageal cancer has a significant survival benefit. The toxicities are well tolerated. It seems that prognosis does not correlate with baseline hematologic nutritional indicators and inflammatory indicators.

[DALYs for breast cancer in China, 2000-2050: trend analysis and prediction based on GBD 2019].

Objective: Based on the data of Global Burden of Disease 2019 data, to analyze the past, current, and future burden of disability-adjusted life years (DALYs) in China and compare with the international status. Methods: The total number of DALYs, age-standardized DALY rate, and the composition of different subgroups were extracted and described to analyze the time trend in 2000-2019 and the current situation in 2019 for Chinese female breast cancer. The burden of DALYs in 2050 was predicted by Joinpoint using average annual percent change (AAPC). Results: In 2000-2019, the ranking of DALYs caused by female breast cancer in China rose from the fourth to the second in all female cancers. The total DALYs increased by 48.4%, of which the years lived with disability increased from 4.8% to 8.8%. The age-standardized DALY rate only slightly decreased (AAPC=-0.3%; which increased during 2016-2019, AAPC=1.6%). In 2019, the age-standardized DALY rate for breast cancer in China was 278.0/100 000. The DALYs were 2.88 million (accounting for 14.2% of the global burden and 12.1% of all female cancers burden in China), 26.5% of which attributed known risk factors (overweight and obesity were the largest: 0.34 million DALYs, but some common breast cancer risk factors were not available on the platform, such as menstruation and fertility). In 2050, the prediction suggests that the total DALYs caused by female breast cancer in China will reach 3.80 million person-years-5.16 million person-years, increasing 32.1%-79.4% over 2019. From 2000 to 2019, the peak age of DALYs and DALY rate became older, and the DALYs among females aged 65 years and above increased faster than those younger than 65 years (AAPC were 4.8% and 1.3%, respectively). In 2019, females aged 45-74 (the starting age recommended by local guidelines for breast cancer screening) contributed 74.3% of the total DALYs. Conclusions: Over the past 20 years, the age-standardized DALY rate for breast cancer in female populations in China has not changed obviously. Without the continuous expansion of effective intervention and population aging, the burden of DALYs for female breast cancer in China will increase. DALYs for breast cancer attributed leading risk factors were still limited.

SPL36 Encodes a Receptor-like Protein Kinase that Regulates Programmed Cell Death and Defense Responses in Rice.

Lesion mimic mutants spontaneously produce disease spots in the absence of biotic or abiotic stresses. Analyzing lesion mimic mutants' sheds light on the mechanisms underlying programmed cell death and defense-related responses in plants. Here, we isolated and characterized the rice (Oryza sativa) spotted leaf 36 (spl36) mutant, which was identified from an ethyl methanesulfonate-mutagenized japonica cultivar Yundao population. spl36 displayed spontaneous cell death and enhanced resistance to rice bacterial pathogens. Gene expression analysis suggested that spl36 functions in the disease response by upregulating the expression of defense-related genes. Physiological and biochemical experiments indicated that more cell death occurred in spl36 than the wild type and that plant growth and development were affected in this mutant. We isolated SPL36 by map-based cloning. A single base substitution was detected in spl36, which results in a cysteine-to-arginine substitution in SPL36. SPL36 is predicted to encode a receptor-like protein kinase containing leucine-rich domains that may be involved in stress responses in rice. spl36 was more sensitive to salt stress than the wild type, suggesting that SPL36 also negatively regulates the salt-stress response. These findings suggest that SPL36 regulates the disease resistance response in rice by affecting the expression of defense- and stress-related genes.

Acceptability and practicability of self-management for patients with Parkinson's disease based on smartphone applications in China.

BACKGROUND: China has had about 1.2 billion mobile-phone users, and this number continues to grow. However, mobile-health services (mHealth) are currently in the initial stage, and have not yet prevailed in China. Additionally, the prevalence of Parkinson's disease (PD) in China is 1700/100,000 (≥65 years). Indeed, these PD patients would benefit from mHealth to manage their disease. Therefore, we designed a study to determine attitudes toward smartphone applications (apps) for chronic condition self-management, and to discover the practicality of these apps among PD patients in China. METHODS: We selected 204 participants with PD between 52 and 87 years old and surveyed their attitudes concerning the use of smartphone apps for chronic condition management via questionnaires. RESULTS: Among the participants, 65.19% had smartphones. Among these smartphone users, 82.84% expressed a preference for using apps for PD management. This group tended to be younger and more frequent web users with higher education and better medication compliance, and they tended to have a longer PD course and worse conditions (P < 0.001, P = 0.001, P < 0.001, P = 0.041, P < 0.001, P = 0.013). Additionally, the willingness to apply apps for PD self-management was positively related to education (P < 0.001) and negatively related to age and PD course (P = 0.017, P < 0.001). CONCLUSION: In China, patients with PD have a generally positive attitude towards self-management through smartphone apps. Consequently, improving the coverage of smartphones with practical and handy apps is a promising strategy for PD self-management.

Atomically dispersed Ni in cadmium-zinc sulfide quantum dots for high-performance visible-light photocatalytic hydrogen production.

Catalysts with a single atom site allow highly tuning of the activity, stability, and reactivity of heterogeneous catalysts. Therefore, atomistic understanding of the pertinent mechanism is essential to simultaneously boost the intrinsic activity, site density, electron transport, and stability. Here, we report that atomically dispersed nickel (Ni) in zincblende cadmium-zinc sulfide quantum dots (ZCS QDs) delivers an efficient and durable photocatalytic performance for water splitting under sunlight. The finely tuned Ni atoms dispersed in ZCS QDs exhibit an ultrahigh photocatalytic H2 production activity of 18.87 mmol hour-1 g-1. It could be ascribed to the favorable surface engineering to achieve highly active sites of monovalent Ni(I) and the surface heterojunctions to reinforce the carrier separation owing to the suitable energy band structures, built-in electric field, and optimized surface H2 adsorption thermodynamics. This work demonstrates a synergistic regulation of the physicochemical properties of QDs for high-efficiency photocatalytic H2 production.

MFN2 contributes to metabolic disorders and inflammation in the aging of rat chondrocytes and osteoarthritis.

OBJECTIVE: Metabolic disorders and inflammation of chondrocytes are major pathological changes in aging cells and osteoarthritis (OA). Recent studies demonstrated age-related mitochondrial dysfunction may be a key contributing factor in the development of OA. Mitofusin 2 (MFN2) is a key regulator of mitochondrial fusion, cell metabolism, autophagy and apoptosis. This study was performed to ascertain whether MFN2 was involved in the aging of chondrocytes and OA. METHODS: Metabolic measurements were taken in rat chondrocytes between different ages (3-week, 5-month, 12-month). MFN2 activity was detected in both human and rat chondrocytes during aging and OA. Then, knockdown of MFN2 with small interfering RNA (siRNA) was performed to confirm whether MFN2 contributes to metabolic changes. Lentiviruses were used to establish MFN2-overexpression/knockdown OA models both in vivo and in vitro to confirm whether MFN2 contributes to OA progress. Further, regulatory mechanism of MFN2 was assessed and interaction between MFN2 and PARKIN was performed. RESULTS: A metabolic shift to mitochondrial respiration was confirmed in rat chondrocytes during aging. MFN2 expression was elevated in both human and rat chondrocytes during aging and OA. Knockdown of MFN2 with siRNA reversed the age-related metabolic changes in rat chondrocytes. Overexpression of MFN2 exacerbated inflammation and OA progress, while knockdown of MFN2 ameliorated inflammation and OA progress. Further, MFN2 could be ubiquitinated by PARKIN, declined PARKIN expression during aging and OA might result in elevated MFN2 expression. CONCLUSIONS: Elevated MFN2 contributes to metabolic changes and inflammation during aging of rat chondrocytes and osteoarthritis.

Calcium-calmodulin-dependent protein kinase type 2 induces apoptosis of hepatocytes after liver transplantation.

OBJECTIVE: The warm ischemia-reperfusion injury confines the prevalence of allografts. To improve the success rate of allotransplantation, we designed experiments to study the mechanism of calcium-calmodulin-dependent protein kinase type 2 (CaMK II) in ischemia-reperfusion (I/R) injury. MATERIALS AND METHODS: We established the I/R model in SD rats and performed the liver transplantation (LT). As a result, the expression of CaMK II in tissues was detected. CaMK II was interfered with and overexpressed by the transference of the lentivirus vector, and the hepatocyte apoptosis and viability were inspected. At the same time, the content of cytochrome c and apoptosis-inducing factor (AIF) were determined. The measurement of mitochondrial membrane potential and detection of intercellular calcium levels were performed. RESULTS: The expression of CaMK II significantly increased and is highly corresponded with the duration of warm ischemia. In BRL-3A cells and liver tissues, increased cellular apoptosis and less viability had been observed in the CaMK II overexpression group. Cytochrome c and AIF were also largely increased compared to the interfered group. Moreover, apparent mitochondrial membrane potential loss has also been detected in the CaMK II overexpression group. CONCLUSIONS: It suggested that CaMK II induces cell apoptosis. Our findings may give a novel indication that inhibition of CaMK II could be a new way for the therapy of warm ischemia-reperfusion injury after LT in future clinical practice.

T2 mapping in dermatomyositis/polymyositis and correlation with clinical parameters.

AIM: To explore the T2-mapping signal characteristics of the thigh muscles in patients with dermatomyositis/polymyositis (DM/PM) and to investigate the correlation between thigh muscle T2 values, clinical parameters, and serum creatinine kinase (CK). MATERIALS AND METHODS: Forty-two patients with DM/PM proven by diagnostic criteria were enrolled in the study along with 13 healthy control subjects. Both T2-mapping and conventional magnetic resonance imaging (MRI) images were obtained in the thigh musculature of all subjects. The T2 values of thigh muscles were compared between the DM/PM patients and control groups. Thirty-one DM/PM patients were evaluated with manual muscle testing (MMT) and serum CK levels. A Spearman correlation coefficient model was used to correlate the mean T2 values and clinical assessments. The Kruskal-Wallis test and receiver operating characteristic (ROC) curves were also utilised. p-Values <0.05 reflected statistical significance. RESULTS: The T2 value of all oedematous muscles was greater on average than that of the unaffected muscles of the DM/PM patients (p<0.05) and the muscles of healthy volunteers (p<0.05). The T2 value of unaffected muscles in DM/PM patients was also greater than that of the normal muscles in healthy volunteers (p<0.05). The area under the curves (AUCs) for T2 relaxation time values was 0.72 with respective sensitivity and specificity of 72.6% and 65.4%. The mean T2 relaxation time of the 31 patients group and the MMTs (p<0.05) was correlated without serum CK levels (p>0.05). CONCLUSION: T2 mapping is not only quantitatively used for subclinical muscle involvement in DM/PM, but also be used to demonstrate severity of damaged muscles in DM/PM.

[Prognostic value of pretreatment neutrophil-to-lymphocyte ratio (NLR) in locally advanced non-small cell lung cancer patients treated with thoracic radiation].

Objective: The aim of this retrospective study was to evaluate the prognostic significance of pretreatment Neutrophil-to-Lymphocyte Ratio(NLR) in locally advanced non-small cell lung cancer(NSCLC) patients treated with thoracic radiotherapy. Methods: We retrospectively analyze 420 patients who received thoracic radiotherapy alone, sequential chemoraiotherapy or concurrent chemoradiotherapy for locally advanced stage NSCLC from January 2007 to December 2010 of our hospital. The patients were divided into two groups (high NLR group and low NLR group) with appropriate cutoff point using the receiver operating characteristic (ROC) curve method. The survival curve was established by Kaplan-Meier method. The Log-rank test was used to compare the survival of the two NLR groups and the multivariate analysis was carried out by Cox regression model. Results: Among the 420 patients, 99 received radiotherapy alone, 139 received sequential chemoradiotherapy and 182 received concurrent chemoradiotherapy. 345 patients died and 75 were still alive. The median follow-up time was 5.2 years and the median overall survival was 22 months. The cut-off value of pretreatment NLR was 2.1. The 5-year PFS and OS rates in high NLR group and low NLR group were 10.6% vs 15.7% (P=0.033) and 15.5% vs 22.7% (P=0.012). Multivariate analysis confirmed that pretreatment NLR (hazard ratio 1.06, P=0.041) was independent prognostic factor of OS. Conclusions: Our study revealed that the pretreatment NLR is the independent prognostic factor of OS in patients with locally advanced stage NSCLC treated with thoracic radiotherapy. However, NLR is still greatly influenced by patient's condition and treatment which needs further research.

Statistically optimal estimation of Greenland Ice Sheet mass variations from GRACE monthly solutions using an improved mascon approach.

We present an improved mascon approach to transform monthly spherical harmonic solutions based on GRACE satellite data into mass anomaly estimates in Greenland. The GRACE-based spherical harmonic coefficients are used to synthesize gravity anomalies at satellite altitude, which are then inverted into mass anomalies per mascon. The limited spectral content of the gravity anomalies is properly accounted for by applying a low-pass filter as part of the inversion procedure to make the functional model spectrally consistent with the data. The full error covariance matrices of the monthly GRACE solutions are properly propagated using the law of covariance propagation. Using numerical experiments, we demonstrate the importance of a proper data weighting and of the spectral consistency between functional model and data. The developed methodology is applied to process real GRACE level-2 data (CSR RL05). The obtained mass anomaly estimates are integrated over five drainage systems, as well as over entire Greenland. We find that the statistically optimal data weighting reduces random noise by 35-69%, depending on the drainage system. The obtained mass anomaly time-series are de-trended to eliminate the contribution of ice discharge and are compared with de-trended surface mass balance (SMB) time-series computed with the Regional Atmospheric Climate Model (RACMO 2.3). We show that when using a statistically optimal data weighting in GRACE data processing, the discrepancies between GRACE-based estimates of SMB and modelled SMB are reduced by 24-47%.

Molecular characterization, expression, and functional analysis of chicken TRAF6.

Tumor necrosis factor receptor-associated factor 6 (TRAF6) is a crucial adaptor molecule of the interleukin-1 receptor/Toll-like receptor (IL-1/TLR) superfamily, which can trigger downstream signaling cascades involved in innate immunity. The function of TRAF6 has been clarified in mammals but is poorly understood in chicken. In our study, we investigated TRAF6 function in birds, particularly in chicken innate immune responses, by cloning and characterizing chicken TRAF6 (chTRAF6). The full-length coding sequence of chTRAF6 comprised 1638 bp and encoded a 545-amino acid protein, which shares high sequence similarity with TRAF6 of other species and consists of four structurally conserved domains. Quantitative real-time polymerase chain reaction revealed that chTRAF6 was widely expressed in all tested tissues and its expression was induced in chicken embryo fibroblast cells treated with poly(I:C) and poly(dA:dT). Increased expression of chTRAF6 was observed both in vitro and in vivo following infection with Newcastle disease virus in chickens. Taken together, these results suggest that chTRAF6 plays a vital role in host defense against viral infection in chicken.

Effect of different doses of dexmedetomidine on median effective concentration of propofol for anesthesia induction: a randomized controlled trial.

OBJECTIVE: Dexmedetomidine, a highly selective α2-adrenergic receptor agonist with sedative and analgesic properties, is used as an anesthetic adjunct. We determined the effects of different dexmedetomidine doses on the median effective concentration (EC50) of propofol and bispectral index (BIS) values during anesthesia induction. PATIENTS AND METHODS: This randomized, prospective, case-control clinical trial involved 120 patients (56 women; physical status, American Society of Anesthesiologists grades I or II) scheduled to undergo surgery requiring general anesthesia from July 15th, 2014 to June 15th, 2015. The patients were divided into groups of 30 and received dexmedetomidine (0.5 µg/kg, group L; 0.75 µg/kg, group M; 1 µg/kg, group H) with propofol for loss of consciousness or propofol only (control group, group C). EC50, BIS, hemodynamics, and side effects were assessed. RESULTS: The EC50 of propofol was significantly lower in the dexmedetomidine groups than in group C, and decreased with increasing dexmedetomidine dose (p < 0.05). BIS values significantly decreased after 2 min of dexmedetomidine infusion in all dexmedetomidine groups; the values at 8 and 10 min were lower in the dexmedetomidine groups than in group C. The heart rate was lower in the dexmedetomidine groups than in group C. The incidence of bradycardia at loss of consciousness increased with increasing dexmedetomidine dose. CONCLUSIONS: Dexmedetomidine significantly and dose-dependently reduced the EC50 of propofol and BIS values during anesthesia induction. A loading dexmedetomidine dose of 0.5 µg/kg significantly reduced the EC50 of propofol and BIS value, and was associated with a lower incidence of bradycardia than higher doses.

In vitro proliferation and differentiation of hepatic oval cells and their potential capacity for intrahepatic transplantation.

Hepatic oval cells (HOCs) are recognized as facultative liver progenitor cells that play a role in liver regeneration after acute liver injury. Here, we investigated the in vitro proliferation and differentiation characteristics of HOCs in order to explore their potential capacity for intrahepatic transplantation. Clusters or scattered HOCs were detected in the portal area and interlobular bile duct in the liver of rats subjected to the modified 2-acetylaminofluorene and partial hepatectomy method. Isolated HOCs were positive for c-kit and CD90 staining (99.8% and 88.8%, respectively), and negative for CD34 staining (3.6%) as shown by immunostaining and flow cytometric analysis. In addition, HOCs could be differentiated into hepatocytes and bile duct epithelial cells after leukemia inhibitory factor deprivation. A two-cuff technique was used for orthotopic liver transplantation, and HOCs were subsequently transplanted into recipients. Biochemical indicators of liver function were assessed 4 weeks after transplantation. HOC transplantation significantly prolonged the median survival time and improved the liver function of rats receiving HOCs compared to controls (P = 0.003, Student t-test). Administration of HOCs to rats also receiving liver transplantation significantly reduced acute allograft rejection compared to control liver transplant rats 3 weeks following transplantation (rejection activity index score: control = 6.3 ± 0.9; HOC = 3.5 ± 1.5; P = 0.005). These results indicate that HOCs may be useful in therapeutic liver regeneration after orthotopic liver transplantation.

In vitro proliferation and differentiation of hepatic oval cells and their potential capacity for intrahepatic transplantation

Hepatic oval cells (HOCs) are recognized as facultative liver progenitor cells that play a role in liver regeneration after acute liver injury. Here, we investigated the in vitro proliferation and differentiation characteristics of HOCs in order to explore their potential capacity for intrahepatic transplantation. Clusters or scattered HOCs were detected in the portal area and interlobular bile duct in the liver of rats subjected to the modified 2-acetylaminofluorene and partial hepatectomy method. Isolated HOCs were positive for c-kit and CD90 staining (99.8% and 88.8%, respectively), and negative for CD34 staining (3.6%) as shown by immunostaining and flow cytometric analysis. In addition, HOCs could be differentiated into hepatocytes and bile duct epithelial cells after leukemia inhibitory factor deprivation. A two-cuff technique was used for orthotopic liver transplantation, and HOCs were subsequently transplanted into recipients. Biochemical indicators of liver function were assessed 4 weeks after transplantation. HOC transplantation significantly prolonged the median survival time and improved the liver function of rats receiving HOCs compared to controls (P=0.003, Student t-test). Administration of HOCs to rats also receiving liver transplantation significantly reduced acute allograft rejection compared to control liver transplant rats 3 weeks following transplantation (rejection activity index score: control=6.3±0.9; HOC=3.5±1.5; P=0.005). These results indicate that HOCs may be useful in therapeutic liver regeneration after orthotopic liver transplantation.

Cytogenetic and molecular analysis of infertile Chinese men: karyotypic abnormalities, Y-chromosome microdeletions, and CAG and GGN repeat polymorphisms in the androgen receptor gene.

Chromosome abnormalities, Y-chromosome microdeletions, and androgen receptor gene CAG and GGN repeat polymorphisms in infertile Chinese men featuring severe oligospermia and azoospermia were analyzed. Ninety-six fertile men and 189 non-obstructive infertile men, including 125 patients with azoospermia and 64 with severe oligozoospermia, were studied. Seventeen infertile men (9.0%) carried a chromosome abnormality. Twenty (10.6%) carried a Y-chromosome microdeletion. In the remainder of the patients and controls, GGN and CAG repeats were sequenced. Short GGN repeats (n < 23) appeared to be associated with defective spermatogenesis, with the number of GGN repeats strongly correlated with sperm counts. No significant difference in CAG repeats was found between patients and controls, nor were CAG repeats correlated with sperm counts. However, for CAG repeats ranging between 24 and 25, there was a >2.5-fold risk (OR = 2.539, 95%CI = 1.206-5.344, P < 0.05) of severe oligospermia and azoospermia. Our results confirmed the significant role of chromosome abnormalities, Y-chromosome microdeletions, and GGN repeats in Chinese male infertility.