[Clinicopathological characteristics and outcomes of 122 patients with colorectal cancer metastasize to the ovary].

Objective: To explore the clinicopathological characteristics and prognosis of patients with ovarian metastases from colorectal cancer. Methods: A total of 122 female patients with ovarian metastases from colorectal cancer underwent treatment in Cancer Hospital, Chinese Academy of Medical Sciences between 2010 and 2015 were recruited. The clinicopathological features, treatment details and survival data of these patients were retrospectively analyzed. Kaplan-Maier method was used for survival analysis, log rank test and Cox proportional hazards model were used for prognostic factor analysis. Results: The median overall survival (OS) was 19.7 months. The 1-year, 3-years and 5-years OS rates were 72.1%, 24.7% and 9.9%, respectively. A total of 99 (81.1%) patients underwent oophorectomy. The median OS of patients who underwent oophorectomy was 21.9 months, significantly longer than 10.3 months of patients without oophorectomy (P<0.01). Ovary as the only site of metastasis, primary tumor resection, and oophorectomy were associated with improved survival (all P<0.01). Primary tumor resection and oophorectomy were independent prognostic factors for OS (both P<0.01). Conclusion: Patients with ovarian metastases from colorectal cancer might acquire a survival benefit from surgical resection of the primary tumor and ovaries.

Evolution of diverse Hall effects during the successive magnetic phase transitions in Mn2.5Fe0.6Sn0.9 Kagome-lattice alloy.

Evolution of diverse Hall effects due to successive magnetic transitions has been observed in Mn2.5Fe0.6Sn0.9 by suitable chemical substitution of Fe in Mn3.1Sn0.9. This noncollinear antiferromagnetic alloy exhibits a Neel temperature of 325 K. Upon cooling from 325 K, a magnetic phase transition from noncollinear antiferromagnetism to ferromagnetism occurs at 168 K due to the tilting of magnetization towards c axis. Above this temperature, anomalous Hall resistivity ranged from 0.6 to 1.3 µΩ cm has been observed in noncollinear antiferromagnetic state. Below this temperature, a topological Hall effect (THE) starts to appear due to the non-vanishing scalar spin chirality arising from the noncoplanar spin structure. Further decreasing temperature to 132 K, another magnetic transition happens, resulting in the coexistence of ferromagnetism and antiferromagnetism, so that a Hall plateau with large hysteresis below 70 K is yielded. A hysteresis as high as ∼80 kOe is obtained in ρ xy -H at 15 K. However, the Hall plateau disappears and only anomalous Hall effect (AHE) persists when further decreasing the temperature to 5 K. The present study provides a picture of diverse magneto-transport properties correlated to the variable spin structures driven by magnetic phase transitions.

[Analysis of metastatic colorectal cancer patients treated with regorafenib in real-world practice].

Objective: To evaluate the dose, efficacy and tolerability of regorafenib in a real-world clinical setting of metastatic colorectal cancer patients. Methods: The clinical data of patients with metastatic colorectal cancer who had received at least two previous treatment lines treated with regorafenib from May 2018 to December 2019 at National Cancer Center/Cancer Hospital was retrospectively analyzed. Patients'demographics, treatment, dosimetry, safety and survival data were collected. The primary endpoint was overall survival (OS). Results: A total of 114 patients were enrolled in this study, including male 83 and female 31, with a median age of 61.Of all patients, 83 were treated with regorafenib and 31 were given combination therapy with regorafenib. Starting dose was 80 mg in 57 (50.0%) patients, 120 mg in 24 (21.1%) patients, and 160 mg in 28 (24.6%) patients. Dose increases were observed in 30.9% (25/81) of patients receiving 80 mg and 120 mg as the initial dose. Forty-five (39.5%) and 36 (31.6%) patients took the last daily dose of 80 mg and 120 mg, respectively. Median follow-up time was 8.5 months.Objective response rate (ORR) and disease control rate(DCR) were 1.0% and 52.1%, respectively. The median progression free survivalrate (PFS) was 2.4 moths (95%CI: 0.80-10.57), median OS was 11.0 moths(95%CI: 9.03-not available). The difference of the PFS and OS in the different dose groups was not statistically significant. But patients who received 120 mg regorafenib showed much longer survival with a median OS of 16.7 month. The difference of survival between the regorafenib group and combination group was not statistically significant either. Twenty patients continued with regorafenib as treatment even after progression. These patients had longer survival compared with those (n=52) who stopped regorafenib with median OS of 16.7 month vs 9.1 month (χ(2)=2.305, P=0.116), respectively.There were 7.9%(9/114) of the patients who discontinued regorafenib therapy because of the adverse event, such as hand-foot skin reaction (HFSR), gastrointestinal bleeding, proteinuria and liver function injury. Conclusions: Patients with advanced colorectal cancer who failed to respond to standard therapy have a good survival benefit. The initial dose of 120 mg of regorafenib has a better risk/benefit ratio and is more suitable for patients with advanced colorectal cancer.

[Preliminary study of the relationship between novel coronavirus pneumonia and liver function damage: a multicenter study].

Objective: To analyze the clinical characteristics of cases of novel coronavirus pneumonia and a preliminary study to explore the relationship between different clinical classification and liver damage. Methods: Consecutively confirmed novel coronavirus infection cases admitted to seven designated hospitals during January 23, 2020 to February 8, 2020 were included. Clinical classification (mild, moderate, severe, and critical) was carried out according to the diagnosis and treatment program of novel coronavirus pneumonia (Trial Fifth Edition) issued by the National Health Commission. The research data were analyzed using SPSS19.0 statistical software. Quantitative data were expressed as median (interquartile range), and qualitative data were expressed as frequency and rate. Results: 32 confirmed cases that met the inclusion criteria were included. 28 cases were of mild or moderate type (87.50%), and four cases (12.50%) of severe or critical type. Four cases (12.5%) were combined with one underlying disease (bronchial asthma, coronary heart disease, malignant tumor, chronic kidney disease), and one case (3.13%) was simultaneously combined with high blood pressure and malignant tumor. The results of laboratory examination showed that the alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB), and total bilirubin (TBil) for entire cohort were 26.98 (16.88 ~ 46.09) U/L and 24.75 (18.71 ~ 31.79) U/L, 39.00 (36.20 ~ 44.20) g/L and 16.40 (11.34 ~ 21.15) µmol/L, respectively. ALT, AST, ALB and TBil of the mild or moderate subgroups were 22.75 (16.31 ~ 37.25) U/L, 23.63 (18.71 ~ 26.50) U/L, 39.70 (36.50 ~ 46.10) g/L, and 15.95 (11.34 ~ 20.83) µmol/L, respectively. ALT, AST, ALB and TBil of the severe or critical subgroups were 60.25 (40.88 ~ 68.90) U/L, 37.00 (20.88 ~ 64.45) U/L, 35.75 (28.68 ~ 42.00) g/L, and 20.50 (11.28 ~ 25.00) µmol/L, respectively. Conclusion: The results of this multicenter retrospective study suggests that novel coronavirus pneumonia combined with liver damage is more likely to be caused by adverse drug reactions and systemic inflammation in severe patients receiving medical treatment. Therefore, liver function monitoring and evaluation should be strengthened during the treatment of such patients.

TRIM66 promotes malignant progression of hepatocellular carcinoma by inhibiting E-cadherin expression through the EMT pathway.

OBJECTIVE: The aim of this study was to explore the regulatory role of TRIM66 in the development of hepatocellular carcinoma (HCC), and to investigate its underlying mechanism. PATIENTS AND METHODS: A total of 88 pairs of HCC tissues and para-cancerous tissues were surgically resected. The expression of TRIM66 was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The correlation between TRIM66 expression and clinic-pathologic characteristics of HCC patients was analyzed. Follow-up data of enrolled HCC patients were collected for survival analysis. Subsequently, TRIM66 expression in HCC cells was determined by qRT-PCR as well. By constructing si-TRIM66, the biological performances of transfected HCC cells were determined using cell counting kit-8 (CCK-8), colony formation and transwell assay. Western blot was performed to measure the protein expressions of relative genes in epithelial-mesenchymal transition (EMT) pathway. Finally, HCC cells were co-transfected with si-TRIM66 and pcDNA-E-cadherin, followed by detection of invasive and migratory abilities. RESULTS: TRIM66 was highly expressed in HCC tissues compared with that of para-cancerous tissues. High expression of TRIM66 was positively correlated with tumor stage, lymph node metastasis and distant metastasis, whereas not correlated with age and sex of HCC patients. Kaplan-Meier curves revealed that a higher expression of TRIM66 was associated with worse prognosis of HCC. Similarly, TRIM66 was also highly expressed in HCC cells. The knockdown of TRIM66 in HCC cells significantly inhibited the proliferative, invasive and migratory abilities of transfected cells. However, TRIM66 down-regulation significantly induced cell apoptosis. Western blot results showed that TRIM66 knockdown in HCC cells markedly downregulated the protein expressions of E-cadherin, N-cadherin, Vimentin and ß-catenin. The inhibited migration and invasion of HCC cells resulted from TRIM66 knockdown were partially reversed by E-cadherin overexpression. CONCLUSIONS: TRIM66 is highly expressed in HCC, which is positively correlated with tumor stage, lymph node metastasis and distant metastasis of HCC patients. In addition, TRIM66 promotes the malignant progression of HCC by inhibiting E-cadherin through the EMT pathway.

MicroRNA-9-5p promotes osteoporosis development through inhibiting osteogenesis and promoting adipogenesis via targeting Wnt3a.

OBJECTIVE: To explore the role of microRNA-9-5p in regulating osteoporosis (OS) development and its underlying mechanism. PATIENTS AND METHODS: MicroRNA-9-5p expression in peripheral blood of 30 OS patients and 30 healthy subjects was examined by quantitative Real-Time-Polymerase Chain Reaction (qRT-PCR). During the processes of osteogenesis and adipogenesis, mRNA levels of microRNA-9-5p, osteogenesis-related genes, and adipogenesis-related genes in marrow stromal stem cells (MSCs) were detected by qRT-PCR as well. After overexpression or knockdown of microRNA-9-5p, the regulatory effects of microRNA-9-5p on osteogenesis-related genes and adipogenesis-related genes in MSCs were accessed by detecting their mRNA and protein levels. Alizarin red staining and oil red staining were performed to determine the osteogenic and adipogenic capacities of MSCs after microRNA-9-5p overexpression, respectively. The dual-luciferase reporter gene assay was conducted to verify the binding condition of microRNA-9-5p and Wnt3a. Finally, rescue experiments were performed to confirm whether microRNA-9-5p could regulate OS development via targeting Wnt3a. RESULTS: Higher expression of microRNA-9-5p was found in OS patients than that of healthy controls. MicroRNA-9-5p expression was downregulated with the prolongation of osteogenic induction, whereas it was upregulated during the process of adipogenic differentiation. Overexpression of microRNA-9-5p downregulated mRNA levels of osteogenesis-related genes (ALP, RUNX2, and OPN), whereas upregulated adipogenesis-related genes (PPARγ, Adipsin, and C/EBPα) in MSCs. The number of calcified nodules became fewer after microRNA-9-5p overexpression in MSCs. MSCs that overexpressed microRNA-9-5p showed more lipid droplets than that of controls. Subsequently, the dual-luciferase reporter gene assay verified that Wnt3a is the target gene of microRNA-9-5p. Both mRNA and protein levels of Wnt3a were negatively regulated by microRNA-9-5p. Rescue experiments indicated that the regulatory effects of microRNA-9-5p on osteogenesis and adipogenesis of MSCs were reversed by Wnt3a overexpression. CONCLUSIONS: MicroRNA-9-5p is lowly expressed in the peripheral blood of OS patients. MicroRNA-9-5p promotes the occurrence and progression of OS through inhibiting osteogenesis and promoting adipogenesis via targeting Wnt3a.

[Influence factors of carotid endarterectomy improving vascular cognitive impairment].

Objective: To investigate the influence factors of carotid endarterectomy(CEA) improving cognitive function in patients with carotid stenosis. Methods: The clinical data of carotid stenosis patients with cognitive impairment who underwent CEA in Nanjing Drum Tower Hospital and the First People's Hospital of Lianyungang from December 2011 to July 2017 were retrospectively analyzed. One week before operation, carotid CT angiography and cranial magnetic resonance imaging were performed, and the cognitive function of patients was evaluated with Montreal Cognitive Scale (MoCA). The magnetic resonance imaging and MoCA were reexamined 4 weeks after the procedure. The patients were divided into improved group (COI+) and un-improved group (COI-) according to whether the cognitive function score was improved or not after operation. The general data, carotid artery occlusiontime, surgical site, preoperative carotid calcification score (CS) and the Fazekas score, pre-operative and post-operative cerebral perfusion parameters, like mean transit time(MTT), time to peak(TTP) and arrivetime (T0), and any new infarcts after operation between the two groups were compared. Results: A total of 70 patients were selected, including 50 patients in group COI+ and 20 patients in group COI-. There were no significant differences in age, gender, hypertension, diabetes mellitus, smoking and drinking habits, as well as in carotid artery occlusiontime and preoperative Fazekas score between the two groups (all P>0.05). The preoperative carotid artery calcification scores of the two groups were 469.75±50.86 and 393.51±77.41, respectively. The changes of pre-and post-operation perfusion parameters between the two groups were statistically significant, with ΔMTT were 7.79±9.51 and 3.03±6.40, ΔTTP were 5.83±8.98 and 1.17±4.77, T0 were 5.89±8.08 and 3.05±5.95, respectively(t=4.844, 2.053, 2.192 and 1.423, respectively, all P<0.05). Proportion of cases with new infarcts after operation(0.38 vs 0.65) or undergoing left CEA (0.66 vs 0.40)between the two groups was statistically different (χ(2)=4.197 and 9.677, respectively, both P<0.05). Conclusion: Higher preoperative CS score, undergoing left CEA, significantly improved cerebral perfusion and without new infarct postoperatively, are independent factors contributing to improving cognitive function through CEA operation.

MiR-7 regulates the PI3K/AKT/VEGF pathway of retinal capillary endothelial cell and retinal pericytes in diabetic rat model through IRS-1 and inhibits cell proliferation.

OBJECTIVE: To investigate the role of miR-7 in diabetic retinopathy and the underlying mechanism. MATERIALS AND METHODS: The rat model of diabetic retinopathy (DR) was established. After that, the endothelial cell (EC) and retinal pericyte (RP) were isolated. QRT-PCR was used to detect the expression of miR-7 and insulin receptor substrate-1 (IRS-1) in ECs and RPs cells while the protein level of IRS1 was detected by Western blot. miR-7 mimic and miR-7 inhibitor were transfected to achieve miR-7 overexpression or knockdown. Cell viability was detected by Cell Counting Kit-8 (CCK-8) assay after miR-7 overexpression or knockdown. Besides, the expression levels of PI3K, AKT, and VEGF were detected by Western Blot. The luciferase reporter assay was performed to investigate whether miR-7 could be combined with IRS-1. Conversely, whether miR-7 could affect IRS-1 was also verified. RESULTS: miR-7 expression was significantly decreased in ECs and RPs of the experimental group compared with the control group, while the mRNA and protein levels of IRS-1 were increased. The CCK-8 assay showed that overexpression of miR-7 decreased the cell activity in ECs and RPs. In contrast, knock-down of miR-7 could increase the cell viability. Besides, Western blot showed that after overexpression of miR-7, the expressions of PI3K, AKT, and VEGF in ECs and RPs cells were down-regulated. Meanwhile, miR-7 knockdown upregulated the protein levels of PI3K, AKT, and VEGF. The luciferase reporter assay suggested that the 3'UTR region of IRS-1 could be combined with miR-7, which may be the downstream target gene for miR-7. Moreover, knockdown of IRS-1 could reverse the effect of the miR-7 inhibitor on cell proliferation in the diabetic model. CONCLUSIONS: MiR-7 was lowly expressed in ECs and RPs cells. Overexpression of miR-7 can down-regulate the expression levels of PI3K, AKT, and VEGF by down-regulating its downstream target gene IRS-1, and ultimately inhibit the proliferation of retinal cells.

[Research advances in the aortic remodeling after thoracic endovascular aortic repair therapy of Stanford type B aortic dissection].

Aortic dissection is one of the most common vascular emergent disease. Thoracic endovascular aortic repair (TEVAR) therapy which created the new era of treatment of Stanford type B aortic dissection (TBAD) has gradually replaced the surgical treatment and becomes the gold standard for treatment of TBAD. Aortic remodeling after TEVAR is the key factor to evaluate the mid-term survival rate and successful treatment of the aortic dissection victims. However, there are few studies on aortic remodeling and lack of unified criteria to evaluate it. This article was to summarize the domestic and abroad research advances which focused on the morphological changes, the regularity, and the evaluation criteria of aorta remodeling after TEVAR.

The reversal of the spontaneous exchange bias effect and zero-field-cooling magnetization in La1.5Sr0.5Co1-xFexMnO6: the effect of Fe doping.

The crystal structure, electronic structure and magnetic properties were systematically studied in a series of Fe-doped La1.5Sr0.5CoMnO6 double perovskites. The X-ray diffraction patterns of the samples are all refined with a rhombohedral (R3[combining macron]c) structure. The parameters a and c continuously increase with increasing Fe doping concentration x. X-ray photoelectron spectroscopy (XPS) spectra of the Mn, Co, and Fe 2p core levels, consistent with the soft X-ray absorption spectroscopy (XAS) spectra of Mn, Co, and Fe L2,3 edges, indicate that their valence states are Mn3+ and Mn4+, Co2+ and Co3+, and Fe3+, respectively. However, relative to samples with x ≤ 0.1, there is an abrupt change of photon energy in the Co- and Fe-2p XAS spectra for x ≥ 0.2, implying the spin state transition is from high to low. In addition, this is further confirmed by a comparison between the calculated effective spin moment from the paramagnetic data and the theoretical value. Interestingly, we demonstrate the reversal of both zero-field-cooling magnetization and the sign switching of the spontaneous exchange bias (SEB) with the doping concentration from magnetic measurements. The magnetization reverses from positive to negative with the temperature decreasing across the compensation temperature at the critical concentration x = 0.2. Meanwhile, the exchange bias field of the SEB reverses from large negative values to positive ones. Our findings allow us to propose that the spin state transition caused by inhomogeneity is considered to play an important role in the reversal of the magnetization and the SEB effect.

[Effect of inhibiting perivascular adhesion on intimal hyperplasia of the vein grafts in rabbits].

Objective: To investigate the effect of preventing perivascular adhesion with topical application of sodium hyaluronate on intimal hyperplasia of the vein grafts in rabbits. Methods: Twenty-four male New Zealand white rabbits, aged 5 months, were randomly divided into 2 groups: Group A and B (n=12 rabbits per group). Artery defect model was established by cutting about 1 cm artery from the middle part of the dissociated left common carotid artery. A section about 3 cm was cut from the right external jugular vein, and the harvested vein was inverted and end-to-end anastomosed to the artery defect. After anastomosis, the adventitia and two anastomosis of the grafted veins in group A was applied 0.2 ml sodium hyaluronate locally to, and corresponding site in Group B was served as a control, but with the sterile normal saline. The grafted veins were obtained 1, 2 and 4 weeks after operation, HE staining and Masson staining were preformed for histological changes of grafted vein wall, proliferating cell nuclear antigen (PCNA) and platelet-derived growth factor (PDGF) immunohistochemistry staining were conducted for proliferation and expression and distribution of PDGF of the grafted vein. Results: The macroscopic and histological observation showed that the perivascular adhesions in Group A were looser when compared with those in Group B. The thickness of the intima, the degree of intima hyperplasia of 2 groups at different time points were as follows: at 1 week after operation, group A[(25.5±3.9) µm, (1.2±0.1) ]and group B[(26.2±4.2)µm, (1.2±0.1)]; at 2 weeks after operation, group A[(44.3±2.5)µm, (1.2±0.1)]and group B[(51.0±3.8)µm, (1.4±0.0)]; at 4 weeks after operation, group A[(69.9±6.8)µm, (1.5±0.1)] and group B[(84.4±6.4)µm, (1.7±0.1)]. Group A was inferior to group B in terms of the above three parameters 2 and 4weeks after operation (P<0.05). Cell proliferation index of intima and that of media were as follows: at 1 week after operation, group A (7.4±2.2), (21.5±3.2) and group B (11.5±2.0), (28.6±4.5); at 2 weeks, group A (20.0±3.2), (35.8±3.4) and group B (26.8±4.1), ( 42.6±4.2); at 4 weeks, group A (11.4±2.0), (22.1±2.7) and group B (15.5±2.4, 28.6±3.9). Group A was inferior to group B in terms of cell proliferation index of intima and media 1, 2 and 4 weeks after operation (P<0.05). The percentage of PDGF-positive cells of intima, media and adventitia was as follows: at 1 week after operation, group A (7.7±1.6), (19.6±3.7), (2.5±1.5) and group B (7.6±2.4), (20.6±4.4), (10.3±2.3); at 2 weeks after operation, group A (11.4±2.6), (19.8±3.1), (12.9±3.3) and group B (19.5±3.5), ( 30.6±5.2), (30.5±5.8); at 4 weeks after operation, group A (6.2±1.9), ( 11.1±2.8), (10.2±2.4) and group B (10.5±2.0), (18.6±3.2), (26.5±3.8). Group A was inferior to group B in terms of the percentage of PDGF-positive cells of intima, media and adventitia 2 and 4 weeks after operation (P<0.05) and Group A was inferior to group B that of adventitia 1 week after operation (P<0.05). Conclusion: Preventing perivascular adhesion with topical application of sodium hyaluronate can inhibit intimal hyperplasia.

The influence of age at menarche, menstrual cycle length and bleeding duration on time to pregnancy: a large prospective cohort study among rural Chinese women.

OBJECTIVE: To investigate the relations among age at menarche (AAM), menstrual cycle length, menstrual bleeding duration and time to pregnancy in a large cohort of rural Chinese women. DESIGN: A prospective cohort study. SETTING: Local family-planning service agencies and maternal/child care service centres. POPULATION: A total of 391 320 rural women of reproductive age who participated in the National Free Pre-pregnancy Checkups and were planning to conceive were enrolled. METHODS: Menstrual characteristics were collected via face-to-face interviews. The Cox proportional hazards model were used to estimate the fecundability ratios (FRs) and 95% confidence intervals for each measure relative to its reference category. MAIN OUTCOME MEASURES: Time to pregnancy. RESULTS: Women with an AAM later than 14 years of age were less likely become pregnant compared with women with AAM at 13-14 years of age (FR 0.93, 95% CI 0.92-0.94). Those with menstrual cycle lengths >29 days were less likely to come pregnant (FR 0.91, 95% CI 0.90-0.92) compared with the reference cycle length of 27-29 days. Women with bleeding durations of <4 (FR 0.88; 95% CI 0.86-0.91) or >5 days (FR 0.91; 95% CI 0.90-0.91) showed lower FRs compared with those reporting 4-5 days of bleeding. The associations were independent of maternal age, ethnicity, education level, occupation, tobacco use, alcohol use and body mass index. CONCLUSION: A later onset of menarche, longer menstrual cycle length, both shorter (<4 days) and longer (>5 days) bleeding duration were associated with a lower FR and longer time to pregnancy in rural Chinese women. TWEETABLE ABSTRACT: A later menarche, longer cycle, shorter or longer bleeding duration were associated with lower fecundity.

Exosomes miR-126a released from MDSC induced by DOX treatment promotes lung metastasis.

Acquired resistance to chemotherapy remains a major stumbling block in cancer treatment. Chronic inflammation has a crucial role in induction of chemoresistance and results, in part, from the induction and expansion of inflammatory cells that include myeloid-derived suppressor cells (MDSCs) and IL-13+ Th2 cells. The mechanisms that lead to induction of activated MDSCs and IL-13+ Th2 cells have not yet been identified. Here we demonstrated that doxorubicin (DOX) treatment of 4T1 breast tumor-bearing mice led to the induction of IL-13R+miR-126a+ MDSCs (DOX-MDSC). DOX-MDSC promote breast tumor lung metastasis through MDSC miR-126a+ exosomal-mediated induction of IL-13+ Th2 cells and tumor angiogenesis. The induction of DOX-MDSC is regulated in a paracrine manner. DOX treatment not only increases interleukin (IL)-33 released from breast tumor cells, which is crucial for the induction of IL-13+ Th2 cells, but it also participates in the induction of IL-13 receptors and miR-126a expressed on/in the MDSCs. IL-13 released from IL-13+Th2 cells then promotes the production of DOX-MDSC and MDSC miR-126a+ exosomes via MDSC IL-13R. MDSC miR-126a+ exosomes further induce IL13+ Th2 cells in a positive feed-back loop manner. We also showed that MDSC miR-126a rescues DOX-induced MDSC death in a S100A8/A9-dependent manner and promotes tumor angiogenesis. Our findings provide insight into the MDSC exosomal-mediated chemoresistance mechanism, which will be useful for the design of inhibitors targeting the blocking of induction of miR-126a+ MDSCs.

Translocation breakpoints of chromosome 4 in male carriers: clinical features and implications for genetic counseling.

Cytogenetic analysis remains a powerful and cost-effective technology, and has wide applicability in genetic counseling for infertile males. Chromosomal rearrangements are thought to be one of the major genetic factors that influence male infertility. Some carriers with balanced reciprocal translocation have been identified as having oligozoospermia or azoospermia, and there is an association between balanced translocation and recurrent abortion. Researchers have reported the involvement of chromosome 4 translocations in male factor infertility and recurrent miscarriages. A translocation breakpoint might interrupt the structure of an important gene, and it is associated with reproductive failure. However, the clinical characteristics of the breakpoints in chromosome 4 translocations have not been studied. Here, we report the breakpoints in chromosome 4 translocation and the clinical features presented in carriers to enable informed genetic counseling of these patients. Of 82 patients with balanced reciprocal translocations, 14 were carriers of the chromosome 4 translocation: four presented with pregestational infertility (clinical manifestations: oligozoospermia, severe oligozoospermia, or azoospermia), whereas 10 presented with gestational infertility (able to conceive but with a tendency to miscarry). The breakpoint at 4q12 was associated with pregestational infertility, whereas the breakpoints at 4q13, 4q21, 4q25, and 4q32 were associated with gestational infertility. However, the breakpoint at 4q35 was associated with both pregestational and gestational infertility. Chromosome 4 translocation carriers with pregestational or gestational infertility should be counseled on chromosomal breakpoints and the different technologies available to assist reproduction.

Translocation breakpoints of chromosome 1 in male carriers: clinical features and implications for genetic counseling.

Reciprocal translocation is closely associated with male infertility and recurrent miscarriages. Balanced reciprocal translocations associated with reproductive failures are predominantly observed on chromosome 1. Additionally, infertile male patients present a number of breakpoints throughout chromosome 1. A translocation breakpoint might interrupt the structure of an important gene, leading to male infertility. Here, we report the breakpoints on chromosome 1 translocation and the clinical features presented in carriers, to enable informed genetic counseling of these patients. Balanced reciprocal translocations were found in 1.57% of the tested patients. Among 82 patients, 23 patients (28.05%) were carriers of the chromosome 1 translocation: 12 presented pre-gestational infertility with clinical manifestations of azoospermia or oligozoospermia, while 11 patients presented gestational infertility (able to conceive but with a tendency to miscarry or give birth to a stillborn). The breakpoint at 1p22 was predominantly observed in these patients; additionally, breakpoints at 1p31.2, 1p10, and 1q25 were associated with gestational infertility. Breakpoints at 1p13, 1q12, and 1q21 were associated with pre-gestational infertility. These results suggested that breakpoints at 1p32, 1p13, and 1q21 were predominantly associated with pre-gestational infertility, while that at 1q25 was associated with gestational infertility. Chromosome 1 translocation carriers with infertility presenting as azoospermia or oligospermia should be counseled on chromosomal breakpoints and the different molecular technologies available to facilitate reproduction.

Chromosome 7 translocation breakpoints in male carriers: clinical features and implications for genetic counseling.

Balanced reciprocal translocations are associated with reproductive failure. Some reciprocal translocation carriers exhibit azoospermia or oligozoospermia, and an association exists between these chromosomal abnormalities and recurrent abortion. Previous reports have indicated the involvement of chromosome 7 translocations in male infertility and recurrent miscarriage. A translocation breakpoint can occur within an important gene, interrupting its structure and leading to male infertility. However, clinical characteristics resulting from chromosome 7 translocation breakpoints have not been studied. Here, we report such breakpoints and their associated clinical features, to enable informed genetic counseling of carriers. Balanced reciprocal translocations were found in 1.57% of the tested patients. Among these 82 individuals, 14 (17.07%) carried a chromosome 7 translocation, of which, five presented with pregestational infertility and clinical manifestations of oligozoospermia or necrospermia, while nine presented with gestational infertility (i.e., were able to conceive, but often resulting in miscarriage). Breakpoints at 7q31 and 7q36 were associated with pregestational infertility, whereas those at 7p10, 7q21.2, 7q22, and 7q32 were connected to gestational infertility. However, the breakpoint at 7p15 was associated with both. Chromosome 7 translocation carriers with pregestational or gestational infertility should be counseled on chromosomal breakpoints and the various molecular technologies available for assisted reproduction.