Objective To investigate the mechanism by which CDHR2 overexpression inhibits breast cancer cell growth and cell cycle pragression via the PI3K/Akt signaling pathway.Methods Bioinformatic analysis was performed to investigate CDHR2 expression in breast cancer and its correlation with survival outcomes of the patients.Immunohistochemistry was used to examine CDHR2 expressions in surgical specimens of tumor and adjacent tissues from 10 patients with breast cancer.CDHR2 expression levels were also detected in 5 breast cancer cell lines and a normal human mammary epithelial cell line using qRT-PCR and Western blotting.Breast cancer cell lines MDA-MB-231 and MCF7 with low CDHR2 expression were transfected with a CDHR2-overexpressing plasmid,and the changes in cell proliferation and cell cycle were evaluated using CCK-8 assay,EdU assay,and cell cycle assay;the changes in expressions of PI3K/Akt signaling pathway and cell cycle pathway proteins were detected with Western blotting.Results Bioinformatic analysis showed low CDHR2 expression level in both breast cancer and adjacent tissues without significant difference between them(P>0.05),but breast cancer patients with a high expression of CDHR2 had a more favorable prognosis.Immunohistochemistry,qRT-PCR and Western blotting showed that the expression of CDHR2 was significantly down-regulated in breast cancer tissues and breast cancer cells(P<0.01),and its overexpression strongly inhibited cell proliferation,caused cell cycle arrest,and significantly inhibited PI3K and Akt phosphorylation and the expression of cyclin D1.Conclusion Overexpression of CDHR2 inhibits proliferation and causes cell cycle arrest in breast cancer cells possibly by inhibiting the PI3K/Akt signaling pathway.

Objective To investigate the mechanism by which CDHR2 overexpression inhibits breast cancer cell growth and cell cycle pragression via the PI3K/Akt signaling pathway.Methods Bioinformatic analysis was performed to investigate CDHR2 expression in breast cancer and its correlation with survival outcomes of the patients.Immunohistochemistry was used to examine CDHR2 expressions in surgical specimens of tumor and adjacent tissues from 10 patients with breast cancer.CDHR2 expression levels were also detected in 5 breast cancer cell lines and a normal human mammary epithelial cell line using qRT-PCR and Western blotting.Breast cancer cell lines MDA-MB-231 and MCF7 with low CDHR2 expression were transfected with a CDHR2-overexpressing plasmid,and the changes in cell proliferation and cell cycle were evaluated using CCK-8 assay,EdU assay,and cell cycle assay;the changes in expressions of PI3K/Akt signaling pathway and cell cycle pathway proteins were detected with Western blotting.Results Bioinformatic analysis showed low CDHR2 expression level in both breast cancer and adjacent tissues without significant difference between them(P>0.05),but breast cancer patients with a high expression of CDHR2 had a more favorable prognosis.Immunohistochemistry,qRT-PCR and Western blotting showed that the expression of CDHR2 was significantly down-regulated in breast cancer tissues and breast cancer cells(P<0.01),and its overexpression strongly inhibited cell proliferation,caused cell cycle arrest,and significantly inhibited PI3K and Akt phosphorylation and the expression of cyclin D1.Conclusion Overexpression of CDHR2 inhibits proliferation and causes cell cycle arrest in breast cancer cells possibly by inhibiting the PI3K/Akt signaling pathway.

[Objective]To explore the construction of the cultural confidence of the youth of the new era in traditional Chinese medicine(TCM)culture and provide value guidance for cultural confidence construction,based on the theory of historical initiative spirit.[Methods]Through literature survey,logical analysis and other methods,the study clarifies the spiritual force that the historical initiative spirit has exerted on the development of TCM since the founding of New China and explores the value focus of historical initiative spirit in cultivating young people's confidence in TCM in the new era.[Results]The historical initiative spirit is an important part of the spiritual character of the Communist Party of China,which injects inexhaustible spiritual impetus for the revival and development of Chinese medicine health care and Chinese medicine culture.Meanwhile,the rich spiritual essentials foster three dimensions of ideological guidance of young people on"strengthen cultural self-confidence""uphold the primacy of the people""adhere to the problem orientation".Through the exploration of cultivation path on"study cultural classics""cultivate TCM thinking mode""strengthen innovation and transformation""strive to forge ahead",it effectively enhances the confidence of young people in TCM culture in the new era.[Conclusion]The study on the confidence cultivation of TCM culture of young people,based on the theory of historical initiative spirit,is more theoretical and practical and the clear value guidance contributes to clearing direction,establishing ambition as well as strengthening responsibility for the confidence cultivation of TCM culture to the youth of the new era,so as to prosper the TCM culture and promote the building of a strong cultural country.

Objective To investigate the correlations of computed tomography (CT), clinical, and pathological features in patients with invasive lung adenocarcinoma positive and negative for spread through air spaces (STAS). Methods A total of 236 patients with invasive lung adenocarcinoma confirmed by surgery and pathology were selected, including 118 patients in STAS-positive group and 118 patients in STAS-negative group. The clinical data, CT signs, and pathological features of the two groups were collected and analyzed. Results There was a correlation between age and the occurrence of STAS. The age of the positive group was higher than that of the negative group. Smoking history and family history of tumor had no correlation with the occurrence of STAS. CT features signs such as nodule type and shape, tumor-lung interface, lobulation sign, spiculation sign, vacuole/cavity, air-bronchogram, pleural indentation sign, vascular changes, mean diameter of tumor, mean diameter of solid component, and the percentage of tumor solid components were significantly different between patients with and without STAS. The incidence of STAS in patients with solid nodules and partial solid nodules was significantly higher than that in patients with ground glass nodules. Multivariate analysis showed that the percentage of tumor solid components, air-bronchogram sign, lobulation sign, and tumor-lung interface were independent risk factors for predicting the occurrence of STAS. Conclusion The clinical data and CT signs of patients with invasive lung adenocarcinoma are related to the occurrence of STAS. CT signs such as the percentage of tumor solid components, air-bronchogram, lobulation sign, and tumor-lung interface are of great significance to STAS prediction. Our findings provide an important basis for selection of personalized clinical treatment plans.

Objective:To determine the effects of preperitoneal balloon (PPB) tamponade with different volumes of fluid on hemodynamically unstable pelvic fracture-associated arterial and venous hemorrhage in a swine model.Methods:A model of open-book pelvic fracture with injuries to external iliac vessels was established in 18 female 12-month old Bama miniature pigs. After the successful establishment of hemodynamically unstable pelvic fracture with vascular injury was confirmed by contrast agent imaging, the animals were randomized into 3 even groups ( n=6): a control group (group C) subjected to PPB tamponade with 0 mL fluid injected, group T1 subjected to PPB tamponade with 500-mL fluid injected, and group T2 subjected to PPB tamponade with 1,000-mL fluid injected. The 3 groups were compared in terms of 60-min survival rate, balloon pressure, peritoneal pressure, bladder pressure, 70-min survival rate, blood loss, and infusion volume. Results:There was no statistically significant difference in the basic hemodynamic or other experimental indicators among the 3 groups before experiment, indicating comparability ( P>0.05). The 60-min survival rate in group T2 was 100.0% (6/6), significantly higher than those in group C and group T1 [0.0% (0/6), 0.0% (0/6)] ( P<0.05). After fluid injection, the balloon pressure and preperitoneal pressure in group T2 were respectively (127.2±4.7) mmHg and (34.5±3.6) mmHg, significantly higher than those in group T1 [(78.7±3.8) mmHg and (13.7±2.8) mmHg] and in group C [0 mmHg and (9.0±1.4) mmHg], and the 2 indicators in group T1 were significantly higher than those in group C (all P<0.05). After fluid injection, there was no statistically significant difference among groups C, T1, and T2 in bladder pressure [(6.7±1.0) mmHg, (5.8±1.9) mmHg, and (6.0±1.1) mmHg] or in bleeding volume [(1,163.0±191.3) mL, (1,212.0±148.4) mL, and (975.0±133.2) mL] (all P≥ 0.05). The infusion volume in group T1 [(1,250.0±225.8) mL] was significantly larger than that in group C [(951.7±177.8) mL] ( P<0.05). No colorectal or bladder injuries were found by the anatomy of the experimental animals in 3 groups. Conclusions:PPB tamponade with 1,000-mL fluid injected in a swine model can efficiently control pelvic fracture-associated arterial and venous hemorrhage, and increase the 60-min survival rate with no colorectal or bladder injuries.

Objective:To confirm the reuse of mismatched regenerated motor axons of brachial plexus and explore the effect of target organs on their regeneration in a rat model.Methods:This study was carried out between January 2021 and December 2021 at the research laboratory of the Department of Microsurgery, Orthopaedic Trauma and Hand Surgery, the First Affiliated Hospital of Sun Yat-sen University. Animals were randomly assigned into 2 groups, as a regeneration group (RGen) with 5 subgroups and a reuse group (RUs) with 3 subgroups. There were 6 rats per subgroup with 42 rats in total. It was observed that in the groups of RGen1-4, after the transection and suture of the musculocutaneous nerve, the motor axons of the proximal end could accurately grow into the distal corresponding endoneural tube. It was also observed that in the mismatched regenerated group, motor axons were the axons that grew into the endoneurial tube of the lateral forearm cutaneous nerve (LFCN), and other non-target organ contacts were made to the regenerated nerves after mismatch. It was specifically further divided into RGen1, the group without an organ for nerve to make contact with; RGen2, the group with skin as the target organ with nerves contact by neurorrhaphy; RGen3, the group with skin as the target organ with originally reserved natural nerve contact; RGen4, the group with muscle as the target organ with nerves contact by neurorrhaphy and RGen5, a control group. After 8 weeks, the positive area (PA), mean density (MD) and integral optical density (IOD) were measured, with AChE and ChAT fluorescence staining of the medial branch of LFCN, to evaluate the regenerated nerves after mismatch. Of the RUs group, firstly, the innervating branches of the flexor carpi radialis (FCR) were dissected and exposed, then further assigned according to initially innervated FCR (RUs1), contacted with regenerated nerves after mismatch (RUs2) and denervated (RUs3), respectively. After 8 weeks, compound muscle action potential (CMAP) and wet weight ratio of FCR were taken. Masson staining of FCR was also performed to evaluate muscle reinnervation by the regenerated nerves after mismatch. Data analysis with One-Way ANOVA and Bonferroni 0.05 indicated a statistically significant difference.Results:In the RGen groups, after AChE staining, the PA, MD and IOD of RGen3 and RGen4 were higher than that of RGen1 and RGen5, and PA of RGen4 were higher than that of RGen2, with a statistically significant difference ( P<0.05). After ChAT staining, the values of PA and IOD of RGen3 and RGen4 were higher than that of RGen1 and RGen5, and PA of RGen4 were higher than that of RGen2, with a statistically significant difference ( P<0.05). In the RUs, electrophysiological assessment showed that no CMAP was observed in RUs3, there was no significant difference in Latency of RUs1 and RUs2. The difference was statistically significant ( P<0.05). Wet weight rate of muscle of RUs1 (98.91%±3.86%) was higher than that of RUs3 (86.67%±4.68%) with a statistically significant difference ( P<0.01), but no significant difference when compared with RU2 (92.74%±3.88%). Masson staining showed that the CVF value of RUs2 (8.61%±1.16%) was significantly higher than that of RUs1 (3.17%±0.76%), and statistic significantly lower than that of RUs3 (16.44%±2.26%)( P<0.01). Conclusion:Target organ contact can promote the regenerated nerves after mismatched regeneration, and the muscle target organs exhibit greater facilitation than the cutaneous target organs. Besides, regenerated nerves after mismatch can establish effective innervation with muscle target organs, comfirming their effective reuse.

Cell Differentiation ; Humans ; Hyperthermia, Induced ; Stem Cells

Objective To investigate the correlation between the features of multimodal magnetic resonance imaging (MRI) and the expression of human epidermal growth factor receptor-2 (HER-2) in ductal carcinoma in situ (DCIS). Methods A total of 53 patients with DCIS confirmed by surgery and pathology in Dezhou Second People’s Hospital from September 2018 to June 2021 were analyzed retrospectively. The patients were divided into HER-2 positive group (29 cases) and HER-2 negative group (24 cases). MRI features were compared between the two groups. Results There were significant differences in the internal enhancement characteristics, microvascular sign, and time-intensity curve type between the two groups (P < 0.05). There were no significant differences in lesion morphology, non-mass-like enhancement pattern, and apparent diffusion coefficient value (P > 0.05). The HER-2 positive group showed clumped enhancement (65.5%), type Ⅱ (48.1%) andtype Ⅲ (29.6%) time-intensity curves, and microvascular sign (89.7%). The HER-2 negative group showed clusteredring enhancement (50.0%), type Ⅱ (45.8%) and type I (54.2%) time-intensity curves, and microvascular sign (54.2%). A combination of clumped enhancement, microvascular sign, and type Ⅲ time-intensity curve showed 100% specificity and 100% positive predictive value for the diagnosis of HER-2 positive DCIS. Conclusion Clumped enhancement, microvascular sign, and type Ⅱ or Ⅲ time-intensity curve on MRI can largely reflect the expression of HER-2 in DCIS. The three can be used in combination to improve the diagnostic efficiency of HER-2 positive DCIS.

Objective:To explore the diagnostic process and outcomes of patients with aplastic anemia (AA) who received outpatient treatment in a real-world setting.Methods:The diagnostic processes, treatment regimens, and outcomes of 176 patients with AA treated in outpatient centers from January 2018 to December 2019 were reviewed.Results:The median interval from the onset of symptoms to the first visit was 7 (5-120) months. Complaints during the first visit included bleeding (52.3% ) , anemia (51.7% ) , and infection (6.8% ) . For diagnosis, 168 patients (95.5% ) underwent bone marrow aspiration; however, only 22 of them (17.1% ) consented aspiration in multiple sites (sternum) . The completion rate of bone marrow biopsy was 85.1% (143/168) ; flow immunophenotype and karyotype analyses were performed on 59.5% (100/168) and 58.9% (99/168) of AA patients, respectively, and the culture of clonal forming units by bone marrow mononuclear cells was performed on 26.8% (45/168) of AA patients. The most preferred regimen was cyclosporine combined with androgen and levamisole (43.8% , 77 patients) , followed by cyclosporine combined with androgen (25.6% , 45 patients) . Cyclosporine alone was administered in 24 patients (13.6% ) and androgen alone in 16 patients (9.1% ) . Furthermore, 14 patients (7.9% ) did not consent to any drugs or only chose traditional Chinese medicine. The patients were divided according to the frequencies of follow-up: regular follow-up group (≥4 times/year, n=130) and irregular group (<4 times/year, n=46) . The former had a higher 6-month remission rate (52.5% vs 28.0% , P=0.005) , a greater high-quality remission rate in 12 months (40.7% vs 16.7% , P=0.027) , and a lower relapse rate in 24 months (4.4% vs 36.4% , P=0.001) . Conclusion:In real-world settings, bone marrow aspiration in multiple sites should be addressed in outpatient treatment for AA diagnostic work-up, including PNH clone screening, flow immunophenotype, chromosome karyotype analysis, and culture of clonal forming units. Patients with AA who follow regular visits were more likely to achieve high-quality remission and a lower relapse rate. Visits at least four times per year are recommended for AA patients undergoing outpatient treatment.

Objective:To explore the efficacy and safety of ibrutinib treatment for relapsed/refractory (R/R) primary autoimmune hemolytic anemia (AIHA) .Methods:Two cases of primary AIHA with relapse events were refractory to glucocorticoid, anti-CD20 monoclonal antibody, immunosuppressive drugs, and splenectomy (case 1 only) . Ibrutinib treatment was administered at an initial dose of 280 mg/d (420 mg/d for case 1 from the 3rd to 8th week) .Results:Both patients achieved transfusion independence and HGB>20 g/L above baseline after 2 weeks (partial response) . For case 1, HGB concentration restored to 113 g/L but with incomplete hemolysis recovery after 10 weeks; HGB reached the level of 118 g/L, also with incomplete hemolysis recovery, after 6 weeks in case 2. They all acquired complete response with incomplete hemolysis recovery (CRi) . The responses sustained 14 weeks and 10 weeks after follow-up at 16 weeks and 12 weeks, respectively. During the treatment, hematologic and nonhematologic toxicity is mild and acceptable.Conclusion:Ibrutinib alone is effective for the 2 R/R primary AIHA cases. We need further clinical trial to identify its efficacy and safety.