Objective:To investigate the effects of paclitaxel combined with Ipatasertib on the proliferation,migration and epitheli-al-mesenchymal transition(EMT)of oral squamous cell carcinoma(OSCC)SCC-9 cells in vitro.Methods:SCC-9 cells were treated with paclitaxel and Ipatasertib repectively and in combination.CCK-8 test and EdU assay were used to detect cell proliferation ca-pacity.Cellular migration was detected by Transwell and scratch method.The protein expressions of E-cad,N-cad,Vimentin,AKT and NF-κB were detected by Western blot.Results:Paclitaxel of 0.5-32 μmol/L combined with Ipatasertib of 2.5 μmol/L(IC50)showed synergistic inhibitory effect on the proliferation of SCC-9 cells,the combination of paclitaxel and ipatasertib more significantly inhibited the migration,down-regulated the protein expression of AKT,NF-κB,N-cad and Vimentin,and up-regulated the protein expression of E-cad.Conclusion:The combination of paclitaxel and Ipatasertib may have synergistic inhibitory effects on the prolif-eration,migration and EMT of OSCC cells,the function may be ralated with the inhibition of PI3K/AKT signaling pathway.

Objective:To explore the characteristics and evolutionary features of cognitive impairment and clinical transformation in early-stage Parkinson′s disease (PD) patients.Methods:Based on the cohort of patients with primary unmedicated PD admitted to the Parkinson′s Specialized Outpatient Clinic of Affiliated Brain Hospital of Nanjing Medical University from November 2018 to July 2022, follow-up was conducted for PD patients who completed the baseline assessment and had a follow-up time of 1.5 years or more, and a total of 87 patients finally completed the follow-up and were included in the study. At follow-up, the 87 patients were divided into a cognitively impaired group ( n=36) and a cognitively normal group ( n=51) according to the norm proposed by Professor Jia Jianping and colleagues in 2011 for the Chinese elderly population. Differences in baseline clinical characteristics between the 2 groups were compared, and binary Logistic regression analysis was used to explore risk factors for cognitive impairment in PD patients. In addition, transformed grouping according to cognitive assessment results at baseline and follow-up was used to compare differences in patients′ baseline clinical characteristics among the 3 groups: a reversal group [Parkinson′s disease-mild cognitive impairment (PD-MCI), reverting to Parkinson′s disease-cognitively normal (PD-CN); n=15], a non-reversal group (persistent PD-MCI; n=24), and a stable group (stable PD-CN; n=36). Results:Cognitive reversal occurred at follow-up in 36.6% (15/41) of patients with cognitive impairment at baseline, and 21.7% (10/46) of patients with normal cognition at baseline had cognitive impairment at follow-up. At the end of the follow-up, the 87 patients with PD had higher Unified Parkinson′s Disease Rating Scale Ⅱ (UPDRS-II) scores [8 (6, 11)], Unified Parkinson′s Disease Rating Scale Ⅲ (UPDRS-Ⅲ) scores [23 (16, 30)], and Hoehn-Yahr stages [2.0 (1.5, 2.5)] than those at baseline [7(4, 10), 19(14, 25), 1.5(1.0, 2.0)]. The differences were statistically significant ( Z=-2.498, P=0.012; Z=-3.039, P=0.002; Z=-4.436, P<0.001). The cognitively impaired group had lower Montreal Cognitive Assessment scores [22.00(19.00, 23.75)] and fewer years of education [9.00(8.00, 11.75) years] but higher Parkinson′s Disease Non-Motor Symptoms Questionnaire (PD-NMSQ) scores [8.00(5.25, 12.00)] than the cognitively normal group [25.00(24.00, 27.00), 12.00(9.00, 15.00) years, 6.00(3.00, 8.00)], and the differences were statistically significant ( Z=-4.764, P<0.001; Z=-3.016, P=0.003; Z=-3.281, P=0.001). Multivariate Logistic regression showed that years of education ( OR=0.829, 95%CI 0.715-0.960, P=0.012) and PD-NMSQ scores ( OR=1.200, 95%CI 1.040-1.384, P=0.012) were independent predictors of cognitive impairment in patients with PD. There were statistically significant differences among the reversal, non-reversal, and stable groups in years of education ( F=5.366, P=0.010), PD-NMSQ scores ( H=10.795, P=0.005), and UPDRS-Ⅱ scores ( H=6.957, P=0.031). Pairwise comparisons showed lower PD-NMSQ scores [4.00(3.00, 7.00) vs 8.00(6.25, 12.75); Z=-2.989, P=0.003] and lower UPDRS-Ⅱ scores [6.00(3.00, 6.00) vs 7.00(6.00, 10.00); Z=-2.756, P=0.006] in the reversal group than in the non-reversal group, indicating better baseline quality of life in cognitive reversal patients. Conclusions:Low educational level and severe non-motor symptoms were risk factors predicting cognitive impairment in PD patients. Conversely, mild non-motor symptoms with high quality of life (lower UPDRS-Ⅱ scores) were important factors for cognitive reversal.

Objective:To investigate the effects of paclitaxel combined with Ipatasertib on the proliferation,migration and epitheli-al-mesenchymal transition(EMT)of oral squamous cell carcinoma(OSCC)SCC-9 cells in vitro.Methods:SCC-9 cells were treated with paclitaxel and Ipatasertib repectively and in combination.CCK-8 test and EdU assay were used to detect cell proliferation ca-pacity.Cellular migration was detected by Transwell and scratch method.The protein expressions of E-cad,N-cad,Vimentin,AKT and NF-κB were detected by Western blot.Results:Paclitaxel of 0.5-32 μmol/L combined with Ipatasertib of 2.5 μmol/L(IC50)showed synergistic inhibitory effect on the proliferation of SCC-9 cells,the combination of paclitaxel and ipatasertib more significantly inhibited the migration,down-regulated the protein expression of AKT,NF-κB,N-cad and Vimentin,and up-regulated the protein expression of E-cad.Conclusion:The combination of paclitaxel and Ipatasertib may have synergistic inhibitory effects on the prolif-eration,migration and EMT of OSCC cells,the function may be ralated with the inhibition of PI3K/AKT signaling pathway.

Objective:To explore the characteristics and evolutionary features of cognitive impairment and clinical transformation in early-stage Parkinson′s disease (PD) patients.Methods:Based on the cohort of patients with primary unmedicated PD admitted to the Parkinson′s Specialized Outpatient Clinic of Affiliated Brain Hospital of Nanjing Medical University from November 2018 to July 2022, follow-up was conducted for PD patients who completed the baseline assessment and had a follow-up time of 1.5 years or more, and a total of 87 patients finally completed the follow-up and were included in the study. At follow-up, the 87 patients were divided into a cognitively impaired group ( n=36) and a cognitively normal group ( n=51) according to the norm proposed by Professor Jia Jianping and colleagues in 2011 for the Chinese elderly population. Differences in baseline clinical characteristics between the 2 groups were compared, and binary Logistic regression analysis was used to explore risk factors for cognitive impairment in PD patients. In addition, transformed grouping according to cognitive assessment results at baseline and follow-up was used to compare differences in patients′ baseline clinical characteristics among the 3 groups: a reversal group [Parkinson′s disease-mild cognitive impairment (PD-MCI), reverting to Parkinson′s disease-cognitively normal (PD-CN); n=15], a non-reversal group (persistent PD-MCI; n=24), and a stable group (stable PD-CN; n=36). Results:Cognitive reversal occurred at follow-up in 36.6% (15/41) of patients with cognitive impairment at baseline, and 21.7% (10/46) of patients with normal cognition at baseline had cognitive impairment at follow-up. At the end of the follow-up, the 87 patients with PD had higher Unified Parkinson′s Disease Rating Scale Ⅱ (UPDRS-II) scores [8 (6, 11)], Unified Parkinson′s Disease Rating Scale Ⅲ (UPDRS-Ⅲ) scores [23 (16, 30)], and Hoehn-Yahr stages [2.0 (1.5, 2.5)] than those at baseline [7(4, 10), 19(14, 25), 1.5(1.0, 2.0)]. The differences were statistically significant ( Z=-2.498, P=0.012; Z=-3.039, P=0.002; Z=-4.436, P<0.001). The cognitively impaired group had lower Montreal Cognitive Assessment scores [22.00(19.00, 23.75)] and fewer years of education [9.00(8.00, 11.75) years] but higher Parkinson′s Disease Non-Motor Symptoms Questionnaire (PD-NMSQ) scores [8.00(5.25, 12.00)] than the cognitively normal group [25.00(24.00, 27.00), 12.00(9.00, 15.00) years, 6.00(3.00, 8.00)], and the differences were statistically significant ( Z=-4.764, P<0.001; Z=-3.016, P=0.003; Z=-3.281, P=0.001). Multivariate Logistic regression showed that years of education ( OR=0.829, 95%CI 0.715-0.960, P=0.012) and PD-NMSQ scores ( OR=1.200, 95%CI 1.040-1.384, P=0.012) were independent predictors of cognitive impairment in patients with PD. There were statistically significant differences among the reversal, non-reversal, and stable groups in years of education ( F=5.366, P=0.010), PD-NMSQ scores ( H=10.795, P=0.005), and UPDRS-Ⅱ scores ( H=6.957, P=0.031). Pairwise comparisons showed lower PD-NMSQ scores [4.00(3.00, 7.00) vs 8.00(6.25, 12.75); Z=-2.989, P=0.003] and lower UPDRS-Ⅱ scores [6.00(3.00, 6.00) vs 7.00(6.00, 10.00); Z=-2.756, P=0.006] in the reversal group than in the non-reversal group, indicating better baseline quality of life in cognitive reversal patients. Conclusions:Low educational level and severe non-motor symptoms were risk factors predicting cognitive impairment in PD patients. Conversely, mild non-motor symptoms with high quality of life (lower UPDRS-Ⅱ scores) were important factors for cognitive reversal.

Objective:To explore the clinical value of a trinity strategy for the treatment of multiple orthopedic trauma.Methods:A retrospective case series study was conducted to analyze the clinical data of 1 267 patients with multiple orthopedic trauma admitted to Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine and the First Affiliated Hospital of Navy Medical University from June 2013 to May 2023, including 862 males and 405 females, aged 18-93 years [(55.2±19.8)years]. Associated injuries included hemorrhagic shock in 632 patients, traumatic wet lung in 274, cranial injuries in 135, abdominal and pelvic bleeding in 116, pneumothorax in 89, urinary injury in 13, and vesical rupture in 8. All the patients were treated with the trinity strategy and the treatment process was divided into the phases of first aid, remodeling, and rehabilitation. The first aid phase focused on stabilizing symptoms and saving lives; the remodeling phase centered on restoring the anatomical structure and alignment; the rehabilitation phase aimed for functional recovery through the integration of both Western and traditional Chinese medicine. The all-cause mortality within 30 days after surgery and fracture healing time were calculated; the excellent and good rates of Constant-Murley shoulder score, Mayo elbow score, Gartland-Werley wrist score, Harris hip score, Hospital for Special Surgery (HSS) knee score and the American Orthopedic Foot & Ankle Society (AOFAS) ankle-hindfoot score at the last follow-up and the overall excellent and good rate of all joint function scores were measured. The short form health survey (SF-36) scores were collected preoperatively and at 6 months postoperatively, including 8 aspects such as physical functioning, physical role, bodily pain, general health, vitality, social functioning, emotional role, and mental health. The incidence of postoperative complications was recorded.Results:All the patients were followed up for 6-18 months [(10.2±4.2)months]. The mortality rate during the acute phase (within 30 days after surgery) was 2.37% with 12 deaths due to hemorrhagic shock, 10 due to traumatic brain injury, 6 due to multiple organ dysfunction syndrome (MODS), and 2 due to pulmonary infection. The average fracture healing time averaged 3.8-18 months [(11.5±4.2)months], with 89.49% of the patients having bone union within 12 months after surgery, 8.93% having bone union within 18 months after surgery, and 1.58% undergoing reoperation. For the patients with internal fixation failure and nonunion, the average healing time was extended to (10.2±2.2)months and (13.7±3.3)months respectively. At the last follow-up, the excellent and good rates of Constant-Murley shoulder score, Mayo elbow score, Gartland-Werley wrist score, Harris hip score, HSS knee score, and AOFAS ankle-hindfoot score were 83.93%, 90.24%, 94.12%, 85.57%, 88.46%, and 92.31% respectively, with an overall excellent and good rate of 89.11%. At 6 months after surgery, the SF-36 scores of all the patients in the eight dimensions,including the physical functioning, physical role, bodily pain, general health, vitality, social functioning, emotional role, and mental health were (74.4±8.6)points, (44.7±14.4)points, (77.4±10.9)points, (68.4±18.2)points, (72.5±16.0)points, (76.8±8.7)points, (49.9±17.6)points, and (72.8±17.9)points, significantly improved compared with those before operation [(63.4±12.7)points, (30.9±17.4)points, (56.4±18.0)points, (55.4±24.7)points, (53.5±21.0)points, (55.8±24.3)points, (36.9±24.0)points, (58.8±21.6)points] ( P<0.01). Complications of different degrees occurred in 214 patients (16.89%), including lung infections in 118 patients (9.31%), lower extremity deep vein thrombosis in 50(3.95%), pressure injuries in 26(2.05%), internal fixation failure in 12(0.95%), and nonunion in 8(0.63%). Conclusions:The trinity strategy provides whole-process management, personalized treatment, and overall rehabilitation for multiple orthopedic trauma. It can decrease mortality, shorten fracture healing time, improve joint function and quality of life, and reduce the incidence of complications.

Objective:To explore the application effect of Jiankuai psychosomatic active therapy in the elderly perioperative patients.Methods:From March 2018 to December 2019, 387 elderly patients in the urology department of the First People′s Hospital of Lianyungang City, Jiangsu Province were selected. According to the patients in two medical groups in the same ward, 193 patients in one medical group were divided into the experimental group and 194 patients in two medical groups as the control group. The experimental group was intervened by routine perioperative nursing combined with simple and fast psychosomatic active therapy, while the control group was only intervened by routine perioperative nursing. Self rating Anxiety Scale (SAS), Rosenberg Self-confidence Scale and General Self-efficacy Scale (GSEs) were used as the evaluation indexes before and after the implementation of the two groups.Results:The SAS score of the experimental group was 31.13 ± 3.64 and that of the control group was 48.45 ± 7.72 on the 7th day after operation. The difference between the two groups was statistically significant ( t value was 16.36, P < 0.05). The effective rate of self-confidence was 98.4% (190/193) and 94.8% (183/193) in the experimental group and 86.6% (168/194) and 85.1% (165/194) in the control group on the first day and the seventh day after operation, respectively. The difference between the two groups was statistically significant ( Z values were - 3.27 and 14.66, all P < 0.05). The GSEs score of the patients in the experimental group was 26.79 ± 2.17 and that of the control group was 16.86 ± 1.90. The difference between the two groups was statistically significant ( t value was 10.19, P < 0.05). Conclusions:The application of Jiankuai psychosomatic active therapy can effectively reduce the tension and anxiety of the elderly patients during the perioperative period, increase their self-confidence and self-efficacy, effectively improve the communication efficiency between doctors and patients, and promote rehabilitation.

Lung cancer is the one of the malignant tumor of the highest morbidity and mortality over the world, and non-small cell lung cancer (NSCLC) makes up about 80%. Nowadays, molecular targeted therapy has been the first-line treatment for NSCLC. Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are increasingly used in the clinical treatment, but the EGFR-TKIs acquired resistance becomes the bottleneck of continuation of EGFR-TKIs therapy. Epithelial-mesenchymal transition (EMT) is a biological phenomenon in which epithelial cells are transformed into mesenchymal cells. EMT promoted metastasis, invasion of lung cancer and conferred characteristic of stem cell on cancer cells. Meanwhile, EMT is one of an important cause of EGFR-TKIs resistance in NSCLC. The recent studies have found that resistant cells restored the sensitivity to EGFR-TKIs by reversing EMT which suggested that the target of EMT may contribute to inhibit or even reverse the resistance of EGFR-TKIs. Here we make a review about research progress of EMT in EGFR-TKIs resistance in NSCLC.
.
Animals ; Antineoplastic Agents ; administration & dosage ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; genetics ; metabolism ; physiopathology ; Drug Resistance, Neoplasm ; Epithelial-Mesenchymal Transition ; drug effects ; ErbB Receptors ; antagonists & inhibitors ; genetics ; metabolism ; Humans ; Lung Neoplasms ; drug therapy ; genetics ; metabolism ; physiopathology ; Protein Kinase Inhibitors ; administration & dosage

Objective To explore the effect of ultrasound-guided stellate ganglion block (SGB) in the incidence of postoperative headache, nausea and vomiting in conventional thyroidectomy. Methods Ninety patients undergoing conventional thyroidectomy were randomly allocated to three groups with 30 patients in each group. In group L, SGB was performed with 5 ml 0.5% lidocaine; in group N, SGB was performed with 5 ml 0.9% sodium chloride; and in group C, no prior block was performed. Postoperatively, during the 48 h after surgery, every episode of postoperative headache and postoperative nausea and vomiting was recorded and a safety assessment was performed. In group L and group N, the hemodynamic status of the vertebral artery and carotid artery was recorded before and after the SGB was performed. In group C, the hemodynamic status of the vertebral artery and carotid artery was recorded before and after the neck was in the full extension position. Results One patient of group N and one patient of group C was discharged. During the 48 h after surgery, headache occured in 5 patients (16.7%) of group L, 8 patients (27.6%) of group N, and 17 patients (58.6%) of group C, and the headache rate in group C was significantly higher than that in group L (P=0.0007). The headache mostly occurred at 2 h and 4 h after operation. During the 48 h after surgery, nausea and vomiting occured in 8 patients (26.7%) of group L, 11 patients (37.9%) of group N, and 20 patients (60.9%) of group C, and the nausea and vomiting rate in group C was significantly higher than that in group L (P=0.0017) and group N (P=0.0343). The nausea and vomiting mostly occurred at 2 h and 4 h after operation.In group L and group N, and the inner diameters of the vertebral and carotid arteries after SGB were wider than those before SGB (P<0.05). In group C, the inner diameters of the vertebral and carotid arteries after the neck extension position were narrower than prostration position (P<0.05). No side effects were observed during or after SGB. Conclusions Preoperative SGB performed with 5 ml 0.5%lidocaine is an effective technique for reducing postoperative headache and nausea and vomiting after thyroidectomy.

Objective To investigate the effect of bisphosphonate medication (zoledronic acid,aclasta) on spinal fusion for osteoporotic patients through radiographic,clinical,and biological assessments.Methods A total of 79 patients with osteoporosis who were candidates for single-level posterior lumbar interbody fusion was randomly assigned to the experimental group (zoledronic acid injection,5mg,on the third day after surgery) or the control group (the same amount of saline injection,on the third day after surgery).Functional radiography and CT scans were used to evaluate fusion status.Bridging bone formation was graded into 3 categories:Grade A (bridging bone through bilateral vertebral),Grade B (bridging bone through a unilateral vertebral),or Grade C (incomplete bony bridging).The incidence of vertebral compression fractures occurring after surgery was assessed by means of MR imaging.A solid fusion was defined as less than 5° of angular motion in flexion-extension radiographs and the presence of Grade A or B bridging bone.Bone metabolic markers (β-C-terminal telopeptide of type Ⅰ collagen,β-CTX; and N-terminal propeptide of type Ⅰ collagen,PINP) were measured to investigate the biological effects of zoledronic acid on spinal fusion.Bone mineral density of femoral neck was measured by the dual X-ray absorptiometry.Clinical outcome was evaluated by means of the Oswestry Disability Index (ODI).Results Grade A or B bridging bone was more frequently observed in the experimental group at 3,6,and 9 months postoperatively (all P ＜ 0.05,respectively,Mann-Whitney U-test).At 12-months postoperative follow-up,bridging bone and solid fusion were not significantly different.No vertebral fractures were observed in the experimental group,whereas 6 patients in the control group showed vertebral compression fractures(P ＜ 0.05,Mann-Whitney U-test).Biochemical analysis of bone turnover demonstrated that zoledronic acid inhibited bone resorption from the early phase of the fusion process and also suppressed bone formation.Poor clinical results in the control group were demonstrated by ODI.Conclusions Osteoporosis patients undergoing spinal fusion who take bisphosphonates throughout the postoperative period was recommended.