Deletion of the foxO1 gene reduces hypoxia tolerance in zebrafish embryos by influencing erythropoiesis.

FoxO1 (Forkhead box O1) belongs to the evolutionarily conserved FoxO subfamily and is involved in diverse physiologic processes, including apoptosis, cell cycle, DNA damage repair, oxidative stress and cell differentiation. FoxO1 plays an important role in regulating the hypoxia microenvironment such as cancers, but its role in hypoxia adaptation remains unclear in animals. To understand the function of foxO1 in hypoxia response, we constructed foxO1a and foxO1b mutant zebrafish using CRISPR/Cas9 technology. It was found that foxO1a and foxO1b destruction affected the hematopoietic system in the early zebrafish embryos. Specifically, FoxO1a and FoxO1b were found to affect the transcriptional activity of runx1, a marker gene for hematopoietic stem cells (HSCs). Moreover, foxO1a and foxO1b had complementary features in hypoxia response, and foxO1a or/and foxO1b destruction resulted in tolerance of zebrafish becoming weakened in hypoxia due to insufficient hemoglobin supply. Additionally, the transcriptional activity of these two genes was demonstrated to be regulated by Hif1α. In conclusion, foxO1a and foxO1b respond to Hif1α-mediated hypoxia response by participating in zebrafish erythropoiesis. These results will provide a theoretical basis for further exploring the function of FoxO1 in hematopoiesis and hypoxia response.

Algorithm of automatic identification of diabetic retinopathy foci based on ultra-widefield scanning laser ophthalmoscopy.

AIM: To propose an algorithm for automatic detection of diabetic retinopathy (DR) lesions based on ultra-widefield scanning laser ophthalmoscopy (SLO). METHODS: The algorithm utilized the FasterRCNN (Faster Regions with CNN features)+ResNet50 (Residua Network 50)+FPN (Feature Pyramid Networks) method for detecting hemorrhagic spots, cotton wool spots, exudates, and microaneurysms in DR ultra-widefield SLO. Subimage segmentation combined with a deeper residual network FasterRCNN+ResNet50 was employed for feature extraction to enhance intelligent learning rate. Feature fusion was carried out by the feature pyramid network FPN, which significantly improved lesion detection rates in SLO fundus images. RESULTS: By analyzing 1076 ultra-widefield SLO images provided by our hospital, with a resolution of 2600×2048 dpi, the accuracy rates for hemorrhagic spots, cotton wool spots, exudates, and microaneurysms were found to be 87.23%, 83.57%, 86.75%, and 54.94%, respectively. CONCLUSION: The proposed algorithm demonstrates intelligent detection of DR lesions in ultra-widefield SLO, providing significant advantages over traditional fundus color imaging intelligent diagnosis algorithms.

Tai Chi Exercise for Cancer-Related Fatigue in Patients With Lung Cancer Undergoing Chemotherapy: A Randomized Controlled Trial.

CONTEXT: Tai Chi is a traditional Chinese health-promoting exercise. It has been shown to enhance mental health and improve psychological condition. OBJECTIVES: We aimed to assess the effectiveness of Tai Chi exercise for cancer-related fatigue in patients with lung cancer undergoing chemotherapy. METHODS: We conducted a randomized trial of Tai Chi exercise as compared with low-impact exercise as a control intervention. Exercises were practiced every other day, a one-hour session for 12 weeks for each of the study groups. The primary end point was a change in total score of the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF). Secondary end points were changes in five subscale scores of the MFSI-SF. All assessments were repeated at three time points, T0: before first course of chemotherapy; T1: before third course of chemotherapy; and T2: at the end of the fourth course of chemotherapy. RESULTS: Between January 2012 and December 2014, 96 patients were enrolled in this trial. At six and 12 weeks, the Tai Chi group had a lower MFSI-SF total score compared with the control group (59.5 ± 11.3 vs. 66.8 ± 11.9, P < 0.05; 53.3 ± 11.8 vs. 59.3 ± 12.2, P < 0.05). At six weeks, the Tai Chi group had lower MFSI-SF general subscale scores (18.1 ± 4.6 vs. 20.4 ± 4.5, P < 0.05) and physical subscale scores (17.5 ± 4.4 vs. 19.1 ± 4.5, P < 0.05), and higher MFSI-SF vigor subscale scores (14.5 ± 3.3 vs. 11.6 ± 3.4, P < 0.05), compared with the control group. But no significant differences were found in emotional subscale (20.2 ± 3.6 vs. 20.0 ± 3.5, P > 0.05) and mental subscale (18.2 ± 4.0 vs. 18.9 ± 3.9, P > 0.05) scores between the Tai Chi group and the control group. At 12 weeks, the MFSI-SF subscale scores showed the same trends as at six weeks. CONCLUSION: Tai Chi is an effective intervention for managing cancer-related fatigue in patients with lung cancer undergoing chemotherapy, especially for decreasing general fatigue and physical fatigue, and increasing vigor.

Translabial three-dimensional ultrasound investigation of the levator hiatus in postpartum women.

PURPOSE: This study utilized translabial three-dimensional ultrasound to investigate the morphological characteristics of the levator hiatus and provide sonographic evidence for assessing pelvic floor dysfunction in postpartum women. METHODS: Two-hundred and one singleton primiparae without any complications underwent translabial three-dimensional ultrasound at 6 and 18 weeks after delivery, with 12 participants lost to follow-up at 18 weeks. Fifty nulliparae were enrolled as the control group. Levator hiatal morphology at rest and on Valsalva maneuver was assessed by experienced sonographers, specifically evaluating the anteroposterior diameter, left-to-right diameter, and area. RESULTS: In postpartum women at 6 weeks after delivery, all the levator hiatal parameters were significantly higher compared with those of the control group. At 18 weeks, the hiatal parameters were better than at 6 weeks but still higher than in the nulliparous controls. In all three groups, the hiatal parameters were significantly higher during the Valsalva maneuver than at rest. CONCLUSIONS: Postpartum women are prone to develop pelvic floor dysfunction as shown by an enlarged levator hiatus. Translabial three-dimensional ultrasound can be used to effectively assess the morphology and structural alterations of the levator hiatus in postpartum women, providing reliable pelvic floor imaging for early screening, diagnosis, and prevention of pelvic floor dysfunction.

Gastric metastasis from small cell lung cancer: a case report.

Small cell lung cancer (SCLC) represents a group of highly malignant tumors that give rise to early and widespread metastases at the time of diagnosis. The preferential metastatic sites are the brain, liver, adrenal glands, bone, and bone marrow. However, metastases of the gastrointestinal system, especially the stomach, are rare; most cases of stomach metastasis are asymptomatic and, as a result, are usually only discovered at autopsy. We report a case of gastric metastasis originating from SCLC. The patient was a 66-year-old man admitted to our hospital due to abdominal pain. He underwent gastroscopy, with the pathological report of the tissue biopsy proving it to be a small cell cancer. Immunohistochemistry was positive for CD56, synaptophysin, and pan-cytokeratin. These results confirmed the diagnosis of gastric metastasis of a neuroendocrine small cell carcinoma from the lung.

[Comparison of the displacements of peripheral lung cancer based on 4D CT scan and 3D CT scan assisted with active breathing control].

OBJECTIVE: To compare the position, displacement, degree of inclusion (DI) and matching index (MI) of the gross tumor volume (GTV) for peripheral lung cancer based on 4-dimensional CT (4D CT) and 3-dimensional CT (3D CT) assisted with active breathing control (ABC). METHODS: Eighteen patients with peripheral lung cancer underwent 4D CT simulation scan during free breathing and 3D CT simulation scans in end-inspiratory hold (CTEIH) and end-expiratory hold (CTEEH) in turn. The 4D CT images from each respiratory cycle were sorted into 10 phases. phase 0 was defined as end-inspiratory phase (CT0), and phase 50 was defined as end-expiratory phase (CT50). The GTVs were delineated separately on CT0, CT50, CTEIH and CTEEH images, and then GTV0, GTV50, GTVEIH and GTVEEH were constructed, respectively. RESULTS: The median distances between the centroids of GTV0 and GTVEIH, GTV50 and GTVEEH were 3.9 mm and 3.4 mm in all patients, 3.2 mm and 3.1 mm in the upper lobe group, and 5.0 mm and 4.7 mm in the lower lobe group, respectively. In the upper lobe group, the GTV0 and GTVEIH were 65.9% and 63.1%, and the median mutual DIs of GTV50 and GTVEEH were 67.5%, 63.1%, respectively. In the lower lobe group, the GTV0 and GTVEIH were 35.3% and 21.4%, and the median mutual DIs of GTV50 and GTVEEH were 27.8% and 24.8%, respectively. In the upper lobe group, the median MI of GTV0 and GTVEIH was 0.5, and the median MI of GTV50 and GTVEEH was 0.6. In the lower lobe group, the median MI of GTV0 and GTVEIH was 0.2, and the median MI of GTV50 and GTVEEH was 0.3. Whether in the upper or lower lobe groups, all the differences between displacements of centroid positions of GTVEIH and GTVEEH (ABC displacement) and GTV0 and GTV50 (4D displacement ) were <1 mm in three dimensional directions (all P>0.05). CONCLUSIONS: The target displacement of tumors based on 3D CT scanning in end-inspiratory hold and end-expiration hold can be used to construct internal target volume instead of that based on 4D CT scanning in extreme phase for peripheral lung cancers, but spatital mismatches of GTVs are obvious between extreme phases in 4D CT and corresponding phases in 3D CT assisted with ABC, especially for tumors of smaller volume and with larger motion amplitude.

[Measurement of intrafraction displacement of the mediastinal metastatic lymph nodes of non-small cell lung cancer based on four-dimensional computed tomography (4D-CT)].

OBJECTIVE: To measure the intrafraction displacement of the mediastinal metastatic lymph nodes of non-small cell lung cancer (NSCLC) based on four-dimensional computed tomography (4D-CT), and to provide the basis for the internal margin of metastatic mediastinal lymph nodes. METHODS: Twenty-four NSCLC patients with mediastinal metastatic lymph nodes confirmed by contrast enhanced CT (short axis diameter ≥ 1 cm) were included in this study. 4D-CT simulation was carried out during free breathing and 10 image sets were acquired. The mediastinal metastatic lymph nodes and the dome of ipsilateral diaphragma were separately delineated on the CT images of 10 phases of breath cycle, and the lymph nodes were grouped as the upper, middle and lower mediastinal groups depending on the mediastinal station. Then the displacements of the lymph nodes in the left-right, anterior-posterior, superior-inferior directions and the 3-dimensional vector were measured. The differences of displacement in three directions for the same group of metastatic lymph nodes and in the same direction for different groups of metastatic lymph nodes were compared. The correlation between the displacement of ipsilateral diaphragma and mediastinal lymph nodes was analyzed in superior-inferior direction. RESULTS: The displacements in left-right, anterior-posterior and superior-inferior directions were (2.24 ± 1.55) mm, (1.87 ± 0.92) mm and (3.28 ± 2.59) mm for the total (53) mediastinal lymph nodes, respectively. The vectors were (4.70 ± 2.66) mm, (3.87 ± 2.45) mm, (4.97 ± 2.75) mm and (5.23 ± 2.67) mm for the total, upper, middle and lower mediastinal lymph nodes, respectively. For the upper mediastinal lymph nodes, the displacements in left-right, anterior-posterior and superior-inferior directions showed no significant difference between each other (P > 0.05). For the middle mediastinal lymph nodes, the displacements merely in anterior-posterior and superior-inferior directions showed significant difference (P = 0.005), while the displacements were not significantly different in the left-right and anterior-posterior, left-right and superior-inferior directions (P > 0.05). The displacements of the total and the lower mediastinal lymph nodes in left-right and superior-inferior, or anterior-posterior and superior-inferior directions were significantly different (P < 0.05), but was not significantly different in left-right and anterior-posterior directions (P > 0.05). The displacements of different group of mediastinal lymph nodes in a single direction or vector showed no significant difference (P > 0.05). In the superior-inferior direction, the correlation between the displacements of ipsilateral diaphragma and mediastinal lymph nodes were not statistically significant (P > 0.05). CONCLUSIONS: During free breathing, the differences between the intrafractional displacement of mediastinal metastatic lymph nodes in the same direction and its station were not statistically significant. The displacements of the total mediastinal metastatic lymph nodes in the superior-inferior direction were greater than that in the left-right and anterior-posterior directions, especially for the middle and lower mediastinal metastatic lymph nodes. There was no significant correlation between the displacements of ipsilateral diaphragma and the mediastinal metastatic lymph nodes in the superior-inferior direction, so it was unreasonable to estimate and predict the displacement of mediastinal metastatic lymph nodes by the displacement of ipsilateral diaphragma.

[Displacement of the silver clips in surgical cavity based on four-dimensional CT images for patients undertaking external-beam partial breast irradiation after breast-conserving surgery].

OBJECTIVE: To explore the displacement of the selected clips and the center of the geometry consisted of all the clips in the surgical cavity measured on the basis of four-dimensional computed tomography (4D-CT) simulation images. METHODS: Fourteen breast cancer patients after breast-conserving surgery were recruited for external beam partial-breast irradiation (EB-PBI), and received large aperture CT simulation. The 4D-CT image data sets were collected when the patient was in the free breathing state. Using the Varian Eclipse treatment planning system, the selected four clips in the cavity were separately delineated on the CT images from 10 phases of the breath cycle, and all of the clips in the cavity were marked to obtain the geometry. Then the displacement of the four selected clips and the center of the geometry in the left-right (LR), anterior-posterior (AP), and superior-inferior (SI) directions were measured. The differences of the displacement were compared. RESULTS: The displacements in the AP and SI directions were always greater than the displacement in LR direction for the same selected clip. The difference of the displacements in the same direction of the different selected clips was not statistically significant (P>0.05). The displacements of the geometry center consisted of all of the clips in the LR, AP, SI directions were (1.34±0.39) mm, (2.01±1.02) mm and (1.89±1.03) mm, respectively, and the difference of the displacements between LR and AP, LR and SI were all statistically significant (P<0.05). In the same directions (LR, AP and SI), the displacement of geometry center was always greater than the displacement of the selected clips, and the difference except SI direction was all statistically significant (P<0.05). In the SI direction, the association between the displacement of geometry center and the upper clip, geometry center and the lower clip was statistically significant (P<0.05). CONCLUSION: When the target for EB-PBI is defined on the basis of 4D-CT simulation images, the displacement of the selected clips at the border of the surgical cavity is not qualified to substitute the displacement of the target defined basing on all of the clips in the surgical cavity.

Effect of educational and psychological intervention on the quality of life of asthmatic patients.

OBJECTIVE: To evaluate the effects of educational and psychological intervention on the quality of life and psychological status of patients with asthma. METHODS: Asthmatic patients were randomized to study (n = 228) and control (n = 146) groups. Both groups received conventional pharmacotherapy for asthma. The study group also received education and psychological counseling. We assessed quality of life, mood states, and asthma knowledge before and after the educational and psychological interventions. RESULTS: The study group's mean quality-of-life score was higher than that of the control group immediately after the intervention (130.2 +/- 25.1 vs 111.6 +/- 27.4, P < .001) and 3 months after the intervention (144.4 +/- 16.9 vs 121.5 +/- 25.6, P < .001). The study group's mean asthma-knowledge score was higher immediately after the intervention (9.0 +/- 1.2 vs 7.5 +/- 1.8, P < .001) and 3 months after the intervention (9.4 +/- 0.8 vs 7.5 +/- 1.5, P < .001). Two weeks after the intervention the mean increment of the asthma-knowledge score in the study group was greater than that in the control group (1.8 +/- 1.6 vs 0.6 +/- 1.7, P = or < .01). The study group's mean Profile of Mood States score was lower than that of the control group immediately after the intervention (12.0 +/- 18.5 vs 23.0 +/- 22.7, P < .001) and 3 months following the intervention (10.2 +/- 7.5 vs 22.8 +/- 11.4, P < .001). CONCLUSIONS: Education and psychological counseling improves the quality of life and alleviates the psychological distress in patients with asthma. These interventions also enhance patient's understanding of this chronic disease.

G-CSF mobilized PBMCs contribute to the liver function of cirrhotic rats.

On the basis of the recently recognized potential of bone marrow stem cells to give rise to hepatocytes, we here investigated the role of G-CSF priming PBMCs played in the liver of cirrhotic rats. The animal model of liver cirrhosis was induced by injecting CCl4 in SD rats, and G-CSF was administered in hematopoietic stem cell mobilization doses. After the liver cirrhosis model was established, the female cirrhotic rats were divided into two groups. Group I only received G-CSF mobilization, group II received G-CSF mobilized PBMCs transplanted from the male cirrhotic rats. PKH26 staining and sex-determining region for the Y-chromosome gene were used to trace the transplanted cells. Liver function related factors were assayed under the animal automatic biochemistry analyzer, and the liver pathological changes were evaluated by HE staining. The comparative liver functions of the two groups were investigated by analysis of two sample t-tests. A P value of <0.05 was considered as significant in all analyses. Our results showed that the transplanted PBMCs could locate in the livers of the female rats. In addition, compared with the group I, rats in group II displayed significant liver improvement in serum ALB, ALT, AST and TBIL (p<0.05). However, the semi-quantitative classification of the liver pathological changes in both groups did not indicate a significant difference (p>0.05). The results indicated that mobilized PBMC transplant could contribute to liver function in cirrhotic livers, which might be an alternative therapy for liver cirrhosis.

[The relationship between Ridit analysis and rank sum test for one-way ordinal contingency table in medical research].

OBJECTIVE: To explore several numerical methods of ordinal variable in one-way ordinal contingency table and their interrelationship, and to compare corresponding statistical analysis methods such as Ridit analysis and rank sum test. METHODS: Formula deduction was based on five simplified grading approaches including rank_r(i), ridit_r(i), ridit_r(ci), ridit_r(mi), and table scores. Practical data set was verified by SAS8.2 in clinical practice (to test the effect of Shiwei solution in treatment for chronic tracheitis). RESULTS: Because of the linear relationship of rank_r(i) = N ridit_r(i) + 1/2 = N ridit_r(ci) = (N + 1) ridit_r(mi), the exact chi2 values in Ridit analysis based on ridit_r(i), ridit_r(ci), and ridit_r(mi), were completely the same, and they were equivalent to the Kruskal-Wallis H test. Traditional Ridit analysis was based on ridit_r(i), and its corresponding chi2 value calculated with an approximate variance (1/12) was conservative. The exact chi2 test of Ridit analysis should be used when comparing multiple groups in the clinical researches because of its special merits such as distribution of mean ridit value on (0,1) and clear graph expression. The exact chi2 test of Ridit analysis can be output directly by proc freq of SAS8.2 with ridit and modridit option (SCORES =). CONCLUSION: The exact chi2 test of Ridit analysis is equivalent to the Kruskal-Wallis H test, and should be used when comparing multiple groups in the clinical researches.

[A multicentre comparative clinical study of uterine cavity shaped device Cu300, TCu220C and TCu380A in ten years].

OBJECTIVE: To observe the clinical effects of uterine cavity shaped device (UCD) Cu300, TCu220C and TCu380A in ten years. METHODS: Two thousand, six hundred and ninety-nine rural parous women were randomized into three groups. UCD Cu300 group had 899 cases, TCu220C group and TCu380A group each had 900 cases. Follow-up visits were performed at 3, 6, 12 months and 2, 3, 5, 10 years after insertion. RESULTS: The cumulative pregnancy rates in the 10th year for UCD Cu300, TCu220C and TCu380A were 2.56, 4.82, and 4.01 per 100 women, respectively. UCD Cu300 group was significantly lower than other two groups (P < 0.05). The expulsion rates were 4.54, 5.46 and 9.68 per 100 women, respectively. TCu380A was significantly higher than UCD Cu300 and TCu220C (P < 0.001). The rates of removal for bleeding and pain for UCDCu300, TCu220C and TCu380A were 6.71, 5.58 and 6.80 per 100 women, respectively, no statistical difference was shown. The cumulative continuation rates were 74.86, 66.22 and 63.56 per 100 women at the 10 th year, UCD Cu300 was the highest, TCu380A was the lowest (P < 0.01). CONCLUSIONS: UCD Cu300, TCu220C and TCu380A are effective for long-term contraception. They are worthy of wide spreading in rural areas.