Objective To investigate the role of high-mobility group AT-hook 2(HMGA2)in osteogenic differentiation of adipose-derived mesenchymal stem cells(ADSCs)and the effect of Hmga2 knockdown for promoting bone defect repair.Methods Bioinformatics studies using the GEO database and Rstudio software identified HMGA2 as a key factor in adipogenic-osteogenic differentiation balance of ADSCs.The protein-protein interaction network of HMGA2 in osteogenic differentiation was mapped using String and visualized with Cytoscape to predict the downstream targets of HMGA2.Primary mouse ADSCs(mADSCs)were transfected with Hmga2 siRNA,and the changes in osteogenic differentiation of the cells were evaluated using alkaline phosphatase staining and Alizarin red S staining.The expressions of osteogenic markers Runt-related transcription factor 2(RUNX2),osteopontin(OPN),and osteocalcein(OCN)in the transfected cells were detected using RT-qPCR and Western blotting.In a mouse model of critical-sized calvarial defects,mADSCs with Hmga2-knockdown were transplanted into the defect,and bone repair was evaluated 6 weeks later using micro-CT scanning and histological staining.Results GEO database analysis showed that HMGA2 expression was upregulated during adipogenic differentiation of ADSCs.Protein-protein interaction network analysis suggested that the potential HMGA2 targets in osteogenic differentiation of ADSCs included SMAD7,CDH1,CDH2,SNAI1,SMAD9,IGF2BP3,and ALDH1A1.In mADSCs,Hmga2 knockdown significantly upregulated the expressions of RUNX2,OPN,and OCN and increased cellular alkaline phosphatase activity and calcium deposition.In a critical-sized calvarial defect model,transplantation of mADSCs with Hmga2 knockdown significantly promoted new bone formation.Conclusion HMGA2 is a crucial regulator of osteogenic differentiation in ADSCs,and Hmga2 knockdown significantly promotes osteogenic differentiation of ADSCs and accelerates ADSCs-mediated bone defect repair in mice.

Objective To investigate the role of high-mobility group AT-hook 2(HMGA2)in osteogenic differentiation of adipose-derived mesenchymal stem cells(ADSCs)and the effect of Hmga2 knockdown for promoting bone defect repair.Methods Bioinformatics studies using the GEO database and Rstudio software identified HMGA2 as a key factor in adipogenic-osteogenic differentiation balance of ADSCs.The protein-protein interaction network of HMGA2 in osteogenic differentiation was mapped using String and visualized with Cytoscape to predict the downstream targets of HMGA2.Primary mouse ADSCs(mADSCs)were transfected with Hmga2 siRNA,and the changes in osteogenic differentiation of the cells were evaluated using alkaline phosphatase staining and Alizarin red S staining.The expressions of osteogenic markers Runt-related transcription factor 2(RUNX2),osteopontin(OPN),and osteocalcein(OCN)in the transfected cells were detected using RT-qPCR and Western blotting.In a mouse model of critical-sized calvarial defects,mADSCs with Hmga2-knockdown were transplanted into the defect,and bone repair was evaluated 6 weeks later using micro-CT scanning and histological staining.Results GEO database analysis showed that HMGA2 expression was upregulated during adipogenic differentiation of ADSCs.Protein-protein interaction network analysis suggested that the potential HMGA2 targets in osteogenic differentiation of ADSCs included SMAD7,CDH1,CDH2,SNAI1,SMAD9,IGF2BP3,and ALDH1A1.In mADSCs,Hmga2 knockdown significantly upregulated the expressions of RUNX2,OPN,and OCN and increased cellular alkaline phosphatase activity and calcium deposition.In a critical-sized calvarial defect model,transplantation of mADSCs with Hmga2 knockdown significantly promoted new bone formation.Conclusion HMGA2 is a crucial regulator of osteogenic differentiation in ADSCs,and Hmga2 knockdown significantly promotes osteogenic differentiation of ADSCs and accelerates ADSCs-mediated bone defect repair in mice.

Objective:To investigate the clinicopathological factors affecting the long-term survival of patients with duodenal papillary carcinoma (DPC) after pancreaticoduodenectomy (PD).Methods:The clinicopathological and follow-up data of patients with DPC who underwent PD at the First Affiliated Hospital of Anhui Medical University and the Second Hospital of Anhui Medical University from Jan 2015 to Dec 2021 were retrospectively analyzed.Results:All 73 cases have been followed-up. The median follow-up time was 60 months. Multivariate analysis of COX proportional risk model showed that positive lymph node metastasis and tumor size over 2.5 cm were common independent risk factors for OS and DFS. Lymph node metastasis was confirmed pathologically in 20 patients. Multivariate analysis results of Logistic regression model showed that smoking, tumor breaking through the serous layer and tumor low differentiation were independent risk factors for lymph node metastasis.Conclusions:Poor prognosis was associated with tumors that were larger than 2.5 cm, and with lymph node metastases. Preoperative smoking history, tumor breaking through the serous layer and low tumor differentiation were the predictors of positive lymph node metastasis.

Background/Aims: Data on the natural course of Chinese patients with ulcerative colitis (UC) was lacking. This study aimed to evaluate the natural history and prognosis of patients with UC in the past 15 years in China. Methods: This cohort study included patients with UC in a tertiary hospital in southern China from 2007 to 2021 (cohort I: 2007–2011, cohort II: 2012–2016, cohort III: 2017–2021). Patients’ clinical characteristics and natural history were analyzed retrospectively. Results: Of 1,139 included patients, 683 patients presented with proctitis or left-sided colitis at diagnosis and 38.5% of them (263/683) developed proximal disease extension. Fifty-eight percent of patients experienced relapse, chronic continuous and intermittent active course. Five patients (0.4%) developed colorectal tumors/dysplasia. The overall surgery rate was 8.6%, and the rates were 14.2%, 7.8%, and 8.0% in the 3 cohorts, respectively (P= 0.059). Average time from diagnosis to surgery decreased from cohorts I to III (144 months vs. 36 months, P< 0.001), so did the use of glucocorticoids (58.2% vs. 43.5%, P< 0.001) and immunosuppressants (14.1% vs. 13.4%, P= 0.016), and days of hospitalization (13 days vs. 9 days, P< 0.001). Biologics were used more frequently during the first year (0.8%, 2.1%, and 13.7% for cohorts I to III, respectively; P< 0.001). The rate of mucosal healing increased over time. Conclusions In Chinese UC patients, one-third of patients experienced proximal disease extension. The rates of malignancy and mortality were low. More biologics were used, while use of immunosuppressants and glucocorticoids were reduced over time. Early biologics use seemed to promote mucosal healing, but the rate of colectomy has not dramatically decreased.

Advances in novel drugs, therapies, and genetic techniques have revolutionized the diagnosis and treatment of cancers, substantially improving cancer patients' prognosis. Although rare tumors account for a non-negligible number, the practice of precision medicine and development of novel therapies are largely hampered by many obstacles. Their low incidence and drastic regional disparities result in the difficulty of informative evidence-based diagnosis and subtyping. Sample exhaustion due to difficulty in diagnosis also leads to a lack of recommended therapeutic strategies in clinical guidelines, insufficient biomarkers for prognosis/efficacy, and inability to identify potential novel therapies in clinical trials. Herein, by reviewing the epidemiological data of Chinese solid tumors and publications defining rare tumors in other areas, we proposed a definition of rare tumor in China, including 515 tumor types with incidences of less than 2.5/100 000 per year. We also summarized the current diagnosis process, treatment recommendations, and global developmental progress of targeted drugs and immunotherapy agents on the status quo. Lastly, we pinpointed the current recommendation chance for patients with rare tumors to be involved in a clinical trial by NCCN. With this informative report, we aimed to raise awareness on the importance of rare tumor investigations and guarantee a bright future for rare tumor patients.
Humans ; Neoplasms/pathology* ; Biomarkers ; Prognosis ; Oceans and Seas ; China/epidemiology*

Objective:To evaluate the efficacy and safety of vedolizumab (VDZ) in the treatment of active ulcerative colitis (UC).Methods:From November 1, 2020 to October 30, 2022, at the Department of Gastroenterology, the Sixth Affiliated Hospital of Sun Yat-sen University, 81 UC patients who received VDZ treatment and completed a 14-week follow-up were retrospectively selected. The clinical data of patients, including age, disease duration, disease activity of UC were collected. The VDZ efficacy evaluation included primary and secondary efficacy indicators. The primary efficacy indicator was the clinical remission rate after 14 weeks of VDZ treatment, and the secondary efficacy indicators included the clinical response rate, steroids-free remission rate, endoscopic remission rate after 14 weeks of treatment as well as the clinical response rate, clinical remission rate, steroids-free remission rate, secondary loss of response rate after 52 weeks of treatment. The adverse reactions during the treatment were recored. Taking clinical remission after 14 weeks of treatment as the dependent variable, univariate analysis was performed to identify the risk factors affecting clinical remission of VDZ. Binary logistic regression analysis was used for multivariate analysis to determine the independent risk factors of VDZ-included clinical remission. Chi-square test and Wilcoxon signed-rank test were used for statistical analysis.Results:Among the 81 UC patients, the age was 40.0 years old (29.0 years old, 53.5 years old) and the disease duration was 42.5 months (22.5 months, 94.7 months). The proportion of patients with mild active UC was 21.0% (17/81), the proportion of patients with moderate active UC was 64.2% (52/81), and the proportion of patients with severe active UC was 14.8% (12/81). After 14 weeks of treatment, the total Mayo score decreased from baseline level of 7.0 (6.0, 9.0) to 1.0 (0.0, 3.0), and the difference was statistically significant ( Z=-6.87, P<0.001). The clinical response rate was 84.0% (68/81) and the clinical remission rate was 69.1% (56/81) after 14 weeks of treatment. Of the 17 patients treated with combination of corticosteroid therapy, 10 achieved steroid-free remission, and the endoscopic remission rate was 34.8% (23/66). Of the 43 patients followed up to 52 weeks, the total Mayo score of UC patients decreased from baseline level of 7.0 (6.0, 9.0) to 0.0 (0.0, 1.0) after 52 weeks of treatment, and the difference was statistically significant ( Z=-3.25, P<0.001). The clinical response rate was 69.8% (30/43), and the clinical remission rate was 65.1% (28/43). Of the 13 patients treated with combination of corticosteroid therapy, 10 patients achieved steroid-free remission. The secondary loss of response rate was 15.2%(5/33) .The result of the univariate analysis showed that previous use of glucocorticoids was a risk factor of clinical remission after 14 weeks of VDZ treatment ( χ2=5.88, P=0.015). The result of multivariate logistic regression analysis showed that previous use of glucocorticoids was an independent risk factor of clinical remission after 14 weeks of VDZ treatment ( OR=3.429, 95% confidence interval 1.235 to 9.517, P=0.014). During the follow-up period, 12.3% (10/81) of patients developed Clostridium difficile infections, except for 1 case stopped VDZ treatment because the clinical response was not reached, remaining 9 cases continued VDZ treatment after received anti- Clostridium difficile treatment. Conclusion:VDZ has good clinical efficacy and safety in the treatment of Chinese UC patients, and patients with no history of glucocorticoid use may be more likely to achieve clinical remission after 14 weeks of treatment.

Objective:To investigate the diagnostic value of bronchial arteriography CT (BA-ACT) combined with bronchoscopy (BS) in bronchial Dieulafoy′s disease (BDD), and the role of bronchial artery embolization (BAE) in the treatment of BDD.Methods:Retrospective analysis was made on the clinical data of 5 patients suspected of being BDD treated by BS in Guangzhou First People′s Hospital or Guangzhou Thoracic Hospital from January 2008 to January 2018 due to hemoptysis. Bronchial arteriography (BAG) and BA-ACT were performed during the operation of interventional embolization. BAG rotary acquisition data were post-processed according to BS findings, and BA-ACT reconstruction images of the diseased bronchi and bronchial arteries were obtained. BS reexamination and clinical follow-up observation were carried out after embolization to analyze the effect of embolization.Results:There were one BDD lesion for the five patients respectively, and the BAG lacked characteristic manifestations. Bronchoscopy revealed BDD foci to present as papillary (case 1-case 3), nodular (case 4), or lirellate (case 5) subbronchial submucosal protrusion lesions. On the BA-ACT reconstruction plot, the BDD lesions of papillary, nodular and carination manifested correspondingly as a bronchial artery branches locally " pointed arch" shaped (cases 1-case 4) or " bead-like" (case 5) fold and protruding toward the bronchial lumen. The BDD lesions of the cases 1-case 4 retraction and disappearance after one BAE were observed by BS examination, and no hemoptysis recurrence during the follow-up period (54-91 months). The ridge like BDD lesion of the case 5 remained unchanged after BAE, and hemoptysis recurred at 71 months after the first BAE; the uncollapsed foci were supplied by two collateral vessels that confirmed by second BAG and BA-ACT, and no hemoptysis for 71 months followed up after second BAE.Conclusions:BA-ACT combined with BS enables a locative and qualitative diagnosis of BDD, and BAE is a very effective treatment method for BDD.

Objective:To study the angiographic anatomy of the lateral costal artery (LCA) and its effect on hemoptysis.Methods:The CT data of angiography and angiographic-CT in 303 patients with hemoptysis in Guangzhou First People′s Hospital were analyzed retrospectively. The origin and travel of the lateral costal artery and the blood supply of the LCA involved in the pulmonary lesion were analyzed.Results:In 303 patients with hemoptysis, 30 LCA were detected in 24 cases, including 12 on the left and 18 on the right, 18 on one side and 6 on both sides. All of them were the first branch of the first segment of the internal thoracic artery (ITA). The level of LCA originating from ITA was located in 1(3.3%) branch above clavicle, 27(90.0%) branches behind clavicle and 2(6.7%) branches below clavicle. LCA entered into the chest behind the first anterior rib, and walked along inner surface of the thorax from the anterior and superior direction to the outer and posterior direction, between the rib-intercostal medial muscle and pleura (i.e., anatomical intrathoracic fascia), and mostly terminated at the axillary midline plane. 28 LCA in 23 patients which can be used for morphological analysis, roughly manifested as follow three shapes: ⑴ 13(46.4%) of them were arc-shaped. The developed LCA was longer and showed shallow or deep arc-shaped curve; ⑵ High flat shape, total 11 LCA (39.3%), the LCA were relatively shorter, position higher and more gentle; ⑶ 4(14.3%) were straight and oblique. The developed LCA was relatively long, and the angle between LCA and ITA was linear. 11 vessels (36.67%) of 10 patients participated in the blood supply of pulmonary lesions, among which 2, 5, 1, 2 and 1 vessels were responsible for the first, second, third, fourth and fifth hemoptysis respectively.Conclusions:The LCA is a relatively common blood vessel and it can be well shown by angiography and angiographic CT. It is of great clinical significance to understand LCA.

P1B-ATPases are a group of proteins that can transport heavy metal ions across membranes by hydrolyzing ATP and they are a subclass of the P-type ATPase family. It was found that P1B-ATPases are mainly responsible for the active transport of heavy metal ions in plants and play an important role in the regulation of heavy metal homeostasis in plants. In this paper, we dissusses the mechanism of P1B-ATPases from the structure and classification of P1B-ATPases, and review the current research progress in the function of P1B-ATPases, in order to provide reference for future research and application of P1B-ATPases in improving crop quality and ecological environment management.
Adenosine Triphosphatases/metabolism* ; Biological Transport ; Metals, Heavy ; Plants/enzymology*

Objective:To investigate the application value of obliquus externus abdominis pedicle flap graft technique in repair of giant abdominal incisional hernia.Methods:The retrospective and descriptive study was conducted. The clinical data of 14 patients with giant abdominal incisional hernia who were admitted to Affiliated Hangzhou First People′s Hospital of Zhejiang University School of Medicine from June 2015 to June 2018 were collected. There were 5 males and 9 females, aged (67±10)years, with a range from 45 to 80 years. All the 14 patients underwent repair of abdominal wall defect and functional reconstruction with obliquus externus abdominis pedicle flap graft technique. Observation indicators: (1) surgical situations; (2) postoperative situations; (3) hernia-related quality of life; (4) follow-up. Follow-up using outpatient examination was performed at postoperative 1 and 12 months, and once a year thereafter to detect the recurrence of incisional hernia or abdominal bulging up to June 2019. Measurement data with normal distribution were represented as Mean± SD, and comparison within groups was analyzed using the paired sample t test. Measurement data with skewed distribution were described as M (range). Count data were described as absolute numbers or percentages. Results:(1) Surgical situations: all the 14 patients underwent repair of abdominal wall defect and functional reconstruction with unilateral obliquus externus abdominis pedicle flap graft technique successfully, and reinforced repair with mesh. All the meshes were standard polypropylene meshes which were placed in the retro muscular or preperitoneal space. The operation time, volume of intraoperative bleeding, mesh size of the 14 patients were (153±34)minutes, (119±59)mL, (450±156)cm 2, respectively. (2) Postoperative situations: the duration of hospital stay of the 14 patients were (14±3)days. Of the 14 patients, 1 had type Ⅲ seroma and was cured after conservative treatment. There were no complications such as ischaemia and necrosis of external oblique muscle flap, incision dehiscence, infection of operation site, intestinal obstruction or intestinal fistula observed in the 14 patients. (3) Hernia-related quality of life: the score of hernia-related quality of life of the 14 patients before operation and at postoperative 12 months were 38±8 and 77±15 respectively, showing a significant difference ( t=12.729, P<0.05). (4) Follow-up: 14 patients were followed up for 12-48 months, with a median follow-up of 16 month. During the follow-up, none of the 14 patients had recurrence of incisional hernia or abdominal wall bulging. Conclusion:Obliquus externus abdominis pedicle flap graft technique can be used for repair of giant abdominal incisional hernia, which will lead to less surgical complications and improve hernia-related quality of life of patients.