Rupatadine inhibits colorectal cancer cell proliferation through the PIP5K1A/Akt/CDK2 pathway.

BACKGROUND: Phosphatidylinositol-4-phosphate 5-kinase type 1 alpha (PIP5K1A) acts upstream of the Akt regulatory pathway and is abnormally expressed in many types of malignancies. However, the role and mechanism of PIP5K1A in colorectal cancer (CRC) have not yet been reported. In this study, we aimed to determine the association between PIP5K1A and progression of CRC and assess the efficacy and mechanism by which rupatadine targets PIP5K1A. METHODS: Firstly, expression and function of PIP5K1A in CRC were investigated by human colon cancer tissue chip analysis and cell proliferation assay. Next, rupatadine was screened by computational screening and cytotoxicity assay and interactions between PIP5K1A and rupatadine assessed by kinase activity detection assay and bio-layer interferometry analysis. Next, rupatadine's anti-tumor effect was evaluated by in vivo and in vitro pharmacodynamic assays. Finally, rupatadine's anti-tumor mechanism was explored by quantitative real-time reverse-transcription polymerase chain reaction, western blot, and immunofluorescence. RESULTS: We found that PIP5K1A exerts tumor-promoting effects as a proto-oncogene in CRC and aberrant PIP5K1A expression correlates with CRC malignancy. We also found that rupatadine down-regulates cyclin-dependent kinase 2 and cyclin D1 protein expression by inhibiting the PIP5K1A/Akt/GSK-3ß pathway, induces cell cycle arrest, and inhibits CRC cell proliferation in vitro and in vivo. CONCLUSIONS: PIP5K1A is a potential drug target for treating CRC. Rupatadine, which targets PIP5K1A, could serve as a new option for treating CRC, its therapeutic mechanism being related to regulation of the Akt/GSK-3ß signaling pathway.

Distinct roles of Kif6 and Kif9 in mammalian ciliary trafficking and motility.

Ciliary beat and intraflagellar transport depend on dynein and kinesin motors. The kinesin-9 family members Kif6 and Kif9 are implicated in motile cilia motilities across protists and mammals. How they function and whether they act redundantly, however, remain unclear. Here, we show that Kif6 and Kif9 play distinct roles in mammals. Kif6 forms puncta that move bidirectionally along axonemes, whereas Kif9 appears to oscillate regionally on the ciliary central apparatus. Consistently, only Kif6 displays microtubule-based motor activity in vitro, and its ciliary localization requires its ATPase activity. Kif6 deficiency in mice disrupts coordinated ciliary beat across ependymal tissues and impairs cerebrospinal fluid flow, resulting in severe hydrocephalus and high mortality. Kif9 deficiency causes mild hydrocephalus without obviously affecting the ciliary beat or the lifespan. Kif6-/- and Kif9-/- males are infertile but exhibit oligozoospermia with poor sperm motility and defective forward motion of sperms, respectively. These results suggest Kif6 as a motor for cargo transport and Kif9 as a central apparatus regulator.

Clinical analysis of laparoscopic treatment of chronic traumatic diaphragmatic hernia in 29 cases / 中华外科杂志

Objective: To examine the safety and effectiveness of laparoscopic individualized surgical treatment for chronic traumatic diaphragmatic hernia (CTDH). Methods: The clinical data and follow-up data of 29 CTDH cases admitted to the Qilu Hospital of Shandong University or the First Affiliated Hospital of Shandong First Medical University from June 2015 to January 2023 were retrospectively analyzed. There were 21 males and 8 females, aged (49.4±17.8) years (range: 19 to 79 years). The main clinical manifestations were symptoms of the digestive system and respiratory system, and only 4 cases were asymptomatic. All patients received laparoscopic treatment (conversion to open surgery was not excluded). Intraoperative exploration (location of the hernia, contents of the hernia, diameter of the hernia ring), surgical conditions (surgical repair plan, operation time, blood loss, postoperative complications) and postoperative follow-up were analyzed and discussed. Results: Laparoscopic repair was successfully completed in 27 cases, including simple suture in 6 cases, suture and patch repair in 17 cases, the anterior abdominal wall muscle flap reversal suture and patch repair of in 3 cases, and patch bridge repair in 1 case. The operation time was (112.8±44.7) minutes (range: 60 to 200 minutes). The amount of bleeding (M(IQR)) was 35 (58) ml (range: 10 to 300 ml). The other 2 patients were converted to laparotomy. Except for one patient with transverse colon strangulation necrosis who died of aggravated pulmonary infection after surgery, the remaining 28 patients were discharged successfully. The follow-up time was 36 (24) months (range: 1 to 60 months). During the follow-up period, only two patients had occasional left upper abdominal discomfort. Twenty-seven patients with left diaphragmatic hernia had no recurrence, and the symptoms of 1 patient with right diaphragmatic hernia were relieved. Conclusion: Customized laparoscopic surgical repair for CTDH according to the location and size of the diaphragmatic defect can achieve good surgical results.

Application of task-based learning in the teaching of standardized residency training of non-dermatology and venereology / 中华医学教育探索杂志

Objective:To evaluate the effect of the task-based learning (TBL) teaching mode on improving the knowledge of clinical skin diseases for non-dermatology and venereology residents.Methods:Sixty internal medicine physicians who had undergone standardized residency training in the Department of Dermatology and Venereology of Affiliated Zhongshan Hospital of Dalian University from January 2017 to December 2019 were selected as the research subjects, and they were randomized to experimental group and control group in average. The experimental group adopted the TBL teaching mode, and the control group adopted the traditional teacher-student internship model for the residency training. After one month of regular rotation, we observed the theoretical assessment and clinical case consultation of the two groups. The questionnaire was set for evaluating the satisfaction of physicians on the effectiveness of the residency training. SPSS 19.0 was performed for t test. Results:The average theoretical scores of the experimental group were (82.80±4.31) points, and those of the control group were (77.20±4.41) points. The average scores of the clinical case diagnosis and treatment in the experimental group were (54.73±2.65) points, and those of the control group were (44.13±4.26) points, and the experimental group scored significantly higher than the control group ( P<0.001). The average scores of the satisfaction survey questionnaire in experimental group were (78.13±2.87) points, and those of the control group were (63.73±4.32) points. The experimental group scored significantly higher than the control group ( P<0.001). Conclusion:The TBL teaching mode can promote non-dermatology and venereology professional physicians to have a certain theoretical basis of dermatology and venereology and the ability to solve practical problems.

An epidemiological investigation on the pathogenic factors of knee osteoarthritis in Uygur, Kazakh and Han populations in pastoral areas of northern Xinjiang Uygur Autonomous Region, China / 中国组织工程研究

BACKGROUND:The living standard of farmers and herdsmen in Xinjiang Uygur Autonomous Region, China is significantly lower than that of urban residents in general. Meanwhile, the shortage of doctors and medicines and lack of medical knowledge are the main reasons for local farmers and herdsmen to suffer from knee osteoarthritis. Most of the farmers and herdsmen are not aware of or prevent knee osteoarthritis in the early days to remove pathogenic factors, which results in a serious condition at the time of their medical treatment. OBJECTIVE: To investigate the main pathogenic factors of knee osteoarthritis in Uygur, Kazakh and Han populations in pastoral areas of northern Xinjiang Uygur Autonomous Region, China.METHODS:The permanent residents of Uygur, Kazakh and Han ethnic groups in northern Xinjiang, China who met the criteria were selected by the method of stratified, multistage and cluster random sampling during June 2012 to October 2014. The investigation of knee osteoarthritis was conducted among al the residents who meet the inclusion criteria using the method of home scene closed questionnaire. X-ray lateral plain film examination of the knee joint was performed among the patients presenting with the symptoms of knee osteoarthritis. The database was established. The multi-factor and unconditional Logistic regression analysis was conducted among the 40 variables using SPSS 20.0 software. RESULTS AND CONCLUSION:The 3 402 of 3 540 questionnaires were valid. The Logistic regression analysis suggest that the common pathogenic factors in Han, Uygur and Kazakh ethnic groups are associated with older ages, female gender, high body mass and drink alcohol. Smoking, history of internal disease, high education level, standing position, climbing, trauma, family history, fried food, housing conditions and amenorrhea, different nationalities, churchgoing of ethnic minorities are also the major risk factors. Among the three ethnic groups, the prevalence of female patients in Uygur and Kazak ethnic groups is significantly higher than that of Chinese Han nationality. The morbidity is different among these three nationalities. The dietary preferences cannot be determined as the related influencing factor of knee osteoarthritis. Whether the means of transportation, residence climate and environment, the number of pregnancies and deliveries, drinking tea or not, the type of tea are related to knee osteoarthritis remains unclear.

Study on relativity of hypoxic pulmonary hypertension with levels of endothelin-1 and vascular endothelial growth factor in plasma of pulmonary artery and carotid artery / 中国应用生理学杂志

<p><b>AIM</b>To study the effects of endothelin-1 (ET-1) and vascular endothelial growth factor (VEGF) on the mechanism of hypoxic pulmonary hypertension (HPH).</p><p><b>METHODS</b>We studied 4 groups of age-controlled male rats, i.e., normal control for 2 weeks group (N2), normal control for 3 weeks group (N3), exposed to hypoxia for 2 weeks group (H2) and for 3 weeks group (H3). Chronic HPH rat models were established by chronic hypobaric hypoxia [(10.0% +/- 0.5% O2] for 2 and 3 weeks, respectively. The rats were anesthetized and fixed, and the levels of mean pulmonary artery pressure (mPAP) and carotid arterial pressure (CAP) were measured using catheters by a microcomputer via transducers. The weight ratio of right ventricle (RV) and left ventricle and septum (LV + S) [RV/ (LV+S)] were determined. The contents of ET-1 in plasma of pulmonary artery and carotid artery and in homogenates of lung and systemic arteries were determined by radioimmunoassay, and the contents of VEGF in serum of pulmonary artery and carotid artery were determined by ABC-ELISA.</p><p><b>RESULTS</b>HPH rat models were established successfully. Compared with control groups, the values of ET-1 were both enhanced in carotid artery and pulmonary artery plasma in model groups (P < 0.01). In the HPH groups, the level of pulmonary artery plasma ET-1 was significantly lower than that of carotid artery plasma, but just the reverse was ET-1 in control rats. The levels of ET-1 in homogenates of lungs from HPH models were significantly higher than those in homogenates of lungs from control groups (P < 0.01), and markedly higher than those in homogenates of systemic arteries from HPH rats (P < 0.01) SThe values of VEGF in serum of pulmonary artery from H3 group were significantly higher than those from control groups and H2 group (P < 0.01). In serum of carotid artery, the values of VEGF from the HPH models were higher than those from the control groups (P < 0.01).</p><p><b>CONCLUSION</b>ET-1 and VEGF play important roles in the pathogenesis of HPH. The result that ET-1 concentration around pulmonary arteries was significantly higher than that around systemic arteries may be one of the mechanisms accounting for the different reaction of them to hypoxia.</p>

CT Manifestations and Differential Diagnosis for Mass-like Hepatic Lesion / 实用放射学杂志

Objective To evaluate the role of CT in manifestations and differential diagnosis of mass-like hepatic lesion. Methods 310 cases of mass-like hepatic lesion, including hepatocellular carcinoma, metastasis, hemangioma, abscess, cyst, hydatidosis were included. The CT findings including mass location, number, edge and the degree of contrast-enhancement were analyzed. Results On CT, mass-like lesions manifested single or multiple lesions with low density, with sharp edge or without, with contrastenhancement in various degrees or without. In our study, there were characteristic CT manifestations for hepatocellular carcinoma, metastasis tumor, hemangioma, abscess, cyst and hydatidosis. Conclusion The diagnosis and differential diagnosis can be made correctly with CT manifestations in most of mass-like hepatic lesions.