Pancreatic cancer, a common digestive system tumor with high malignancy and a poor prognosis, has several treatment options. However, none of them are particularly effective because understanding the pathogenesis of pancreatic cancer remains a significant clinical challenge. Splicing isoforms mediate various biological phenotypes as an important means of regulating gene expression in eukaryotes, and their abnormalities can lead to a variety of diseases. Numb is an important cell fate determining protein whose alternative splicing has been linked to the development of various cancers. In pancreatic cancer, selective splicing of Numb can result in a variety of Numb protein subtypes, each with a different regulatory effect on the activation of various cancer-related signal pathways and tumor cell biology. This paper reviews the recent progress of Numb protein research in pancreatic cancer, with a focus on the regulatory role of its different isoforms in pathogenesis.

Objective:To investigate the possible mechanism of rubbing abdomen to regulate intestinal homeostasis in irritable bowel syndrome with constipation (IBS-C) mouse models.Methods:IBS-C mouse models of intestinal immune dysfunction were established using trinitrobenzene sulfonic acid (TNBS)-induced C57BL/J6 male mice. Thirty C57BL/J6 mice were randomly divided into three groups: the control group, the model group, and the mogul group. After 7 days of modeling, mice in the mogul group were given a mogul mechanical stimulation intervention once per day for 2 weeks, while mice in the control and model groups were not given any intervention. Changes in serum levels of interleukin-6 (IL-6) and IL-17A were detected by enzyme-linked immune sorbent assay (ELISA) and immunohistochemistry. The gene expression and protein levels of IL-17A and IL-23 were detected by quantitative real-time fluorescence PCR (qRT-PCR) and Western Blot, respectively. The morphological changes were observed by HE staining. The CD44 and CD62L expression changes were observed by immunofluorescence staining.Results:Compared with the model group, the levels of IL-6 and IL-17A in the serum of mice in the mogul group were decreased, and the expression of IL-6 and IL-7A in the tissues was down-regulated (all P<0.001). In addition, the gene expression and protein expression levels of IL-17A and IL-13 in the tissues of mice in the mogul group were decreased (all P<0.001). HE staining results showed that the mogul mechanical stimulation intervention could repair colonic tissues and reduce the inflammatory response. Immunofluorescence staining results showed that mogul mechanical stimulation intervention could downregulate the expression of CD44 but had no modulating effect on the expression of CD62L. Conclusions:Rubbing abdomen can improve intestinal homeostasis in IBS-C model mice by regulating changes in Th17 cell function.

Objective:To provide insight into the diagnosis for clinicians, the clinical characteristics, diagnosis and treatment history of 3 patients with 21-hydroxylase deficiency (21-OHD) and testicular adrenal rest tumors (TART) were analyzed.Methods:The clinical, laboratory and imaging data of 3 male patients with 21-OHD and TART, confirmed with CYP21 gene sequencing, from May 2010 to May 2021 in the First Medical Center of Chinese PLA General Hospital were analyzed retrospectively. The treatment strategy and clinical outcome were followed up.Results:All the 3 patients were first diagnosed with bilateral adrenal mass at the age of 27-42 years old. They were 145-162 cm tall. The levels of progesterone, 17-hydroxyprogesterone, and adrenocorticotropic hormone (ACTH) of the 3 patients were relatively high, and that of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) of the 3 patients were low. Testosterone level of 1 patient was significantly elevated, and that of the other 2 patients was below the lower limit of normal range. Testicular ultrasound showed heterogeneous hyperechoic masses in both testes. CT of the adrenal glands showed bilateral adrenal enlargement with mass. All 3 patients were treated with dexamethasone. After 4-96 months of follow-up, 17-hydroxyprogesterone level was kept above the median normal level. One of the patients got married and had a baby after treatment. The sizes of adrenal hyperplasia and testicular masses reduced to various degrees with the change of the testicular masses being proportional to that of adrenal hyperplasia.Conclusions:Patients with 21-OHD are prone to have TART, leading to the impaired testicular function. Early glucocorticold therapy is beneficial to the reduction of TART and restoration of testicular function.

Objective:To investigate the workflow, feasibility and advantages of respiratory navigator-guided stereotactic body radiation therapy (SBRT) of liver malignancies on the magnetic resonance linear accelerator (MR-linac).Methods:Clinical data of 10 patients with liver cancer treated with respiratory navigator-guided SBRT on the MR-linac from September to December 2021 were analyzed retrospectively. All patients underwent CT and MR simulated localization, and plain, enhanced and 4D CT scan, and T 1 3D MR and T 2 3D MR images were collected. The expiratory 4D CT was chosen to design the reference plan. The T 2 3D navigator MR image (end-exhalation) was collected before treatment, the target position was adjusted or the target shape was modified in combination with the real-time monitoring 2D MR image and appropriate online adaptive planning process was selected. Then, the ability of CT, T 2 3D and T 2 3D navigator MR images to display the tumor was evaluated by naked eye. The changes of target volume were calculated. Dosimetric differences between the adaptive and reference plans were compared. The efficacy and adverse reactions of patients were evaluated. Results:In the free breathing state, the T 2 3D navigator MR image was significantly better than T 2 3D MR image to clearly display the tumor and its boundary. The adaptive plans of adapt-to-position (ATP) and adapt-to-shape (ATS) adopted by 10 patients was 37 times and 22 times respectively. The tumor subsided significantly in 3 patients. The average target conformal index (CI) of the adaptive plans was no different from that of the reference plans, but the gradient index (GI) was higher ( P<0.05), especially in the ATS plans. Compared to the reference plans, the normal liver V 5 Gy, V 10 Gy and D mean were almost the same, but the average MU was increased with a significant difference in the ATP adaptive plans ( P<0.05). The average of MU, segments and normal liver D mean and V 10 Gy in the ATS adaptive plans were lower than those in the reference plans, and the liver V 5 Gy was slightly increased. Seven patients were evaluated after 1 month and 3 months. The local control of lesions was promising. Toxicities were mild and no grade 3 or higher toxicities were observed. Conclusion:Respiratory navigator on MR-linac improves the visual clarity of tumors and online MR images, and shows its advantages to guide the adaptive precision radiotherapy of liver tumors, especially in SBRT.

OBJECTIVE: Discuss the working ideas of the dynamic adjustment mechanism of medical device classification in the United States, and provide reference for the construction of medical device related mechanisms in China. METHODS: Collect and interpret the documents of regulatory background, procedures and orders of the dynamic adjustment mechanism of the medical device classification in the United States, and summarize the overall situation and specific cases of the medical device classification adjustment under this mechanism in recent years. RESULTS: The US work idea of the medical device classification dynamic adjustment mechanism is based on the latest valid scientific evidence, conducting risk analysis and identification, and determining the corresponding measures. CONCLUSIONS During the adjustment process, industry stakeholders have repeatedly discussed and achieved final agreement. Its procedures and working ideas can be used as a reference for China's work.
China ; United States ; United States Food and Drug Administration

Objective:To investigate the safety and mid-term efficacy of robotic versus laparoscopic total mesorectal excision surgery in rectal cancer.Methods:A total of 240 patients were diagnosed with rectal cancer at the Anorectal Department of Gansu Provincial Hospital from Aug 2015 to Mar 2021, 112 patients underwent laparoscopic total mesorectal excision (L-TME group) and 128 patients did robotic-assisted total mesorectal excision (R-TME group).Results:Compared to the R-TME group, the L-TME group had higher conversion rate (5.4% vs. 0.8%, χ2=4.417, P=0.036), higher incidence of complications (32.1% vs. 17.2%, χ2=7.290, P=0.007), higher circumferential resection margin involvement (7.1% vs. 1.6%, χ2=4.658, P=0.031), lower 3-year DFS and OS(74.1% vs. 85.2%, χ2=4.962, P=0.026) and (81.3% vs. 91.4%, χ2=5.494, P=0.019), lower 3-year DFS and OS in AJCC stage Ⅲ(52.5% vs. 76.1%, χ2=5.799, P=0.016) and (65.0% vs. 84.8%, χ2=4.787, P=0.029). Conclusion:R-TME can achieve better oncological outcomes and is more beneficial for RC patients compared with L-TME, especially for those with stage Ⅲ rectal cancers.

Allografts ; COVID-19 ; China/epidemiology* ; Disease Outbreaks ; Humans ; Kidney Transplantation/adverse effects* ; SARS-CoV-2

Objective:To evaluate the performance of the European Evidence-based Guidelines on Pancreatic Cystic Neoplasms (EEGPCN)(2018) and International Association of Pancreatology(IAP) Guideline(Version 2017) in predicting high grade dysplasia/invasive carcinoma-intraductal papillary mucinous neoplasm(HGD/INV-IPMN).Methods:A retrospective analysis of 363 patients,who underwent surgical resection in Changhai Hospital affiliated to Navy Medical University from January 2012 to December 2018 and were pathologically identified as (intraductal papillary mucinous neoplasm, IPMN),was performed. The patients,including 230 males and 133 females,aging (61.7±10.1) years(range:19 to 83 years). The proportion of HGD/INV-IPMN who met with the absolute indication(AI) of EEGPCN and high risk stigma(HRS) of IAP were compared. The binary Logistic regression analysis was used to find the independent risk factors of HGD/INV-IPMN.Eight combinations of risk factors derived from relative indication/worrisome feature or risk factors in this study,were made to evaluate the diagnostic efficacy. The area under curve(AUC) of receiver operating characteristics was used to evaluate the the cutoff value of risk factors(①CA19-9≥37 U/ml,②diameter of main pancreatic duct 5.0-9.9 mm,③enhancing mural nodule<5 mm,④(acute) pancreatiti,⑤ acyst diameter ≥40 mm,⑤ bcyst diameter ≥30 mm, ⑥thickened or enhancing cyst walls,⑦neutrophile granulocyte to lymphocyte ratio(NLR)≥2, ⑧cyst located in head, uncinate or neck,⑨carcinoembryonic antigen(CEA) ≥5 μg/L) number for predicting HGD/INV-IPMN.The accuracy,sensitivity,specificity,positive predictive value,negative predictive value,true positive,true negative,false positive,false negative,positive likelihood ratio,negative likelihood ratio,Youden index and F1 score were calculated. Results:Ninety-two patients(49.5%) of 186 ones who met AI and 85 patients(48.3%) of 176 ones who met HRS were respectively confirmed as HGD/INV-IPMN. In those patients who were not met AI,tumor location,thickened/enhancing cyst wall,CA19-9 elevated,NLR≥2 and CEA elevated were significantly ( P<0.05) correlated with HGD/INV-IPMN. And tumor location(head/uncinate/neck vs. body/tail, OR=3.284,95% CI:1.268-8.503, P=0.014),thickened/enhancement cyst wall (with vs.without, OR=2.713,95% CI:1.177-6.252, P=0.019),CA19-9(≥37 U/L vs.<37 U/L, OR=5.086,95% CI:2.05-12.62, P<0.01) and NLR(≥2 vs.<2, OR=2.380,95% CI:1.043-5.434, P=0.039) were the independent risk factors of HGD/INV-IPMN. Patients with ≥4 risk factors of 9 in combination Ⅷ(①②③④⑤ b⑥⑦⑧⑨) were diagnosed as HGD/INV-IPMN with the moderate accuracy(71.0%),moderate sensitivity (62.0%) and moderate specificity (73.0%). Patients with ≥4 risk factors of 9 in Combination Ⅶ(①②③④⑤ a⑥⑦⑧⑨) were diagnosed as HGD/INV-IPMN with the highest specificity(83.0%) and patients with ≥3 risk factors of 8 in combination Ⅵ(①②③④⑤ b⑥⑧⑨) were diagnosed as HGD/INV-IPMN with the highest sensitivity(74.0%). The AUC for diagnosis of HGD/INV-IPMN in combination Ⅵ,Ⅶ and Ⅷ were 0.72,0.75 and 0.75,respectively. Older patients and younger patients could respectively refer to combination Ⅶ and combination Ⅵ to improve the management of IPMN. Conclusions:Patients who meet AI of EEGPCN should undertake resection, otherwise the method we explored is recommended. The method of improvement for diagnosis of HGD/INV-IPMN is relatively applicable and efficient for decision-making of surgery, especially for younger patients with decreasing of missed diagnosis and elder patients with decreasing of misdiagnosis.

Objective:To evaluate the performance of the European Evidence-based Guidelines on Pancreatic Cystic Neoplasms (EEGPCN)(2018) and International Association of Pancreatology(IAP) Guideline(Version 2017) in predicting high grade dysplasia/invasive carcinoma-intraductal papillary mucinous neoplasm(HGD/INV-IPMN).Methods:A retrospective analysis of 363 patients,who underwent surgical resection in Changhai Hospital affiliated to Navy Medical University from January 2012 to December 2018 and were pathologically identified as (intraductal papillary mucinous neoplasm, IPMN),was performed. The patients,including 230 males and 133 females,aging (61.7±10.1) years(range:19 to 83 years). The proportion of HGD/INV-IPMN who met with the absolute indication(AI) of EEGPCN and high risk stigma(HRS) of IAP were compared. The binary Logistic regression analysis was used to find the independent risk factors of HGD/INV-IPMN.Eight combinations of risk factors derived from relative indication/worrisome feature or risk factors in this study,were made to evaluate the diagnostic efficacy. The area under curve(AUC) of receiver operating characteristics was used to evaluate the the cutoff value of risk factors(①CA19-9≥37 U/ml,②diameter of main pancreatic duct 5.0-9.9 mm,③enhancing mural nodule<5 mm,④(acute) pancreatiti,⑤ acyst diameter ≥40 mm,⑤ bcyst diameter ≥30 mm, ⑥thickened or enhancing cyst walls,⑦neutrophile granulocyte to lymphocyte ratio(NLR)≥2, ⑧cyst located in head, uncinate or neck,⑨carcinoembryonic antigen(CEA) ≥5 μg/L) number for predicting HGD/INV-IPMN.The accuracy,sensitivity,specificity,positive predictive value,negative predictive value,true positive,true negative,false positive,false negative,positive likelihood ratio,negative likelihood ratio,Youden index and F1 score were calculated. Results:Ninety-two patients(49.5%) of 186 ones who met AI and 85 patients(48.3%) of 176 ones who met HRS were respectively confirmed as HGD/INV-IPMN. In those patients who were not met AI,tumor location,thickened/enhancing cyst wall,CA19-9 elevated,NLR≥2 and CEA elevated were significantly ( P<0.05) correlated with HGD/INV-IPMN. And tumor location(head/uncinate/neck vs. body/tail, OR=3.284,95% CI:1.268-8.503, P=0.014),thickened/enhancement cyst wall (with vs.without, OR=2.713,95% CI:1.177-6.252, P=0.019),CA19-9(≥37 U/L vs.<37 U/L, OR=5.086,95% CI:2.05-12.62, P<0.01) and NLR(≥2 vs.<2, OR=2.380,95% CI:1.043-5.434, P=0.039) were the independent risk factors of HGD/INV-IPMN. Patients with ≥4 risk factors of 9 in combination Ⅷ(①②③④⑤ b⑥⑦⑧⑨) were diagnosed as HGD/INV-IPMN with the moderate accuracy(71.0%),moderate sensitivity (62.0%) and moderate specificity (73.0%). Patients with ≥4 risk factors of 9 in Combination Ⅶ(①②③④⑤ a⑥⑦⑧⑨) were diagnosed as HGD/INV-IPMN with the highest specificity(83.0%) and patients with ≥3 risk factors of 8 in combination Ⅵ(①②③④⑤ b⑥⑧⑨) were diagnosed as HGD/INV-IPMN with the highest sensitivity(74.0%). The AUC for diagnosis of HGD/INV-IPMN in combination Ⅵ,Ⅶ and Ⅷ were 0.72,0.75 and 0.75,respectively. Older patients and younger patients could respectively refer to combination Ⅶ and combination Ⅵ to improve the management of IPMN. Conclusions:Patients who meet AI of EEGPCN should undertake resection, otherwise the method we explored is recommended. The method of improvement for diagnosis of HGD/INV-IPMN is relatively applicable and efficient for decision-making of surgery, especially for younger patients with decreasing of missed diagnosis and elder patients with decreasing of misdiagnosis.

Objective:To observe the structural and functional changes of each nucleus group in generalized anxiety disorder(GAD) rat models before and after the massage therapy, and to explore the central regulating mechanism of the massage therapy in GAD.Methods:60 Wistar male rats were randomly divided into blank group, model group and abdominal rubbing group, 20 rats for each group. GAD rat models were established by chronic emotional stress, and the models were evaluated by the elevated cross maze experiment. In the abdominal rubbing group, the GAD rats were treated with abdominal rubbing once a day for 10 min for 14 days. In the control group, the GAD rats were only bound to the experimental platform once a day for 10 min for 14 days. Horseradish peroxidase (HRP) retrograde tracking marker method was used to detect the changes of the structure of each nuclear cluster in the affective loop of the GAD rats in each group. The liquid-mass spectrometry quantitative analysis was used to determine the relative concentrations of N-acetyl aspartate (NAA), glutamic acid, choline and creatine in nuclear cluster of the GAD rats in each group.Results:Compared with the blank group, the HRP labeled cells in the rats of model group were less expressed and the activity of the emotional circuit in the brain was weak. The NAA/creatine ratio in the left hippocampal tissue of the rats in the model group was significantly increased than that of the blank group(0.94±0.08 vs 0.79±0.10, P<0.05), the glutamic acid/creatine ratio in the right hippocampal tissue was significantly decreased (0.95±0.10 vs 1.12±0.13, P<0.01), and the NAA/creatine andglutamic and acid/creatineratios in the left cortical tissue were all significantly decreased (1.04±0.05 vs 1.41±0.23, and 1.21±0.04 vs 1.57±0.11, all P<0.01). Compared with the model group, the hippocampal tissues of the GAD rats in the abdominal rubbing group had a large number of HRP aggregation and spread to the surrounding tissues, the NAA/creatine and glutamic acid/creatine ratios in the left hippocampal tissue of the abdominal rubbing group were significantly decreased (0.74±0.21 vs 0.94±0.09 and 0.92±0.20 vs 1.21±0.12, all P<0.01). The differences between the model group and the abdominal rubbing group in the ratio of glutamic acid/creatine in the right hippocampal tissue (1.01±0.23 vs 0.95±0.10), the ratio of NAA/creatine in the left cortical tissue (1.12±0.09 vs 1.04±0.05), and the ratio of glutamic acid/creatine in the left cortical tissue (1.22±0.12 vs 1.21±0.04) were not statistically significant ( P>0.05). Conclusions:Abdominal rubbing can effectively enhance the activity of affective loop and improve the relative concentration of neuron metabolites in hippocampal and cortical tissues in the affective loop, suggesting that the mechanism of GAD treatment by abdominal rubbing may be closely related to the structure and function of regulating affective loop.