Objective:To explore the efficacy and adverse reactions of nimotuzumab combined with induction chemotherapy (IC) based on albumin-bound paclitaxel plus cisplatin (TP regimen) for patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC).Methods:Clinical data were collected from 65 patients with LA-HNSCC (stages Ⅲ/Ⅳ A/Ⅳ B; excluding nasopharyngeal carcinoma) who received 2-3 cycles of IC followed by concurrent chemoradiotherapy (CRT) in the Second Hospital of Dalian Medical University from January 2018 to June 2022. Based on the IC regimen, these patients were categorized into a nimotuzumab combined with TP (Nimo-TP) group ( n = 34) and a TP group ( n = 31), and their short-term efficacy [i.e., the objective response rate (ORR)], survival outcomes [e.g., overall survival (OS), progression-free survival (PFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS)], and adverse reactions were compared. Additionally, factors affecting their survival outcomes were analyzed. Results:There were statistically significant differences in 1- and 2-year DMFS between both groups (90.4% vs. 69.5%, 90.4% vs. 66.0%, χ2=1.81, P < 0.05), so did the ORRs after IC and CRT of both groups (after IC: 67.6% vs. 41.9%, χ2=4.34, P = 0.037; after CRT: 88.2% vs. 67.7%, χ2=4.03, P = 0.045). However, there was no statistically significant difference in the 2-year OS, PFS, and LRFS between both groups ( P > 0.05). Multivariate analysis revealed that nimotuzumab combined with TP-based IC served as an independent prognostic factor for DMFS ( HR = 0.27, 95% CI: 0.07-0.97, P = 0.045), while complete/partial response after IC acted as an independent prognostic factor for both PFS and local relapse-free survival ( HR = 0.36, 95% CI: 0.17-0.76, P = 0.008; HR = 0.28, 95% CI: 0.11-0.69, P = 0.006). Notably, adding nimotuzumab did not aggravate the adverse reactions in the patients during IC and CRT( P > 0.05). Conclusions:Nimotuzumab combined with TP-based induction chemotherapy followed by CRT significantly improved the DMFS of LA-HNSCC patients, exhibiting high safety. However, such therapy failed to significantly improve their OS, PFS, and LRRFS, and, thus, further research is required.

Objective:To investigate the risk factors of positive peritoneal cytology (PPC) in patients with endometrial cancer and the impact of PPC on patients' prognosis.Methods:The clinicopathological data of 202 patients who underwent initial surgical treatment and were diagnosed with endometrial cancer by postoperative pathology at Qilu Hospital of Shandong University from January 2015 to December 2019 were retrospectively analyzed, and the peritoneal fluid of patients were sent intraoperatively for cytological liquid-based smear examination. Logistic regression was used to perform univariate and multivariate analyses of PPC in the whole group of patients and the early-stage patients; Univariate analysis of the progression-free survival in the whole group of patients and the early-stage patients was performed by Kaplan-Meier method and compared by log-rank method, and multivariate analysis of the progression-free survival in the whole group of patients and the early-stage patients was performed by Cox proportional hazards model.Results:Of 202 patients, 183 (90.6%) had negative peritoneal cytology (NPC) and 19 (9.4%) had PPC; 180 patients (89.1%) were stage Ⅰ-Ⅱ and 22 (10.9%) were stage Ⅲ-Ⅳ; 180 patients (89.1%) had early-stage endometrial cancer. Deep myometrial infiltration ( OR = 3.57, 95% CI 1.02-12.45, P = 0.046) and lymph node metastasis ( OR = 7.16, 95% CI 1.70-30.23, P = 0.007) were independent risk factors for PPC in patients with endometrial cancer; deep myometrial infiltration was an independent risk factor for PPC in patients with early-stage endometrial cancer ( OR = 6.22, 95% CI 1.22-31.73, P = 0.028). The 3-year PFS rates for the whole group of patients with PPC and NPC were 72.9% and 92.7%, and the difference was statistically significant ( P = 0.001); the 3-year PFS rates for early-stage patients with PPC and NPC were 82.5% and 96.2%, and the difference was statistically significant ( P = 0.002). PPC was an independent risk factor for PFS in the whole group of patients with endometrial cancer ( HR = 4.80, 95% CI 1.14-20.17, P=0.032); PPC was also an independent risk factor for PFS in patients with early-stage endometrial cancer ( HR = 8.85, 95% CI 1.96-39.93, P = 0.005). Conclusions:Deep myometrial infiltration is an independent risk factor for PPC, and PPC is an independent risk factor for PFS in patients with endometrial cancer. Routine cytological examination of peritoneal fluid is recommended in patients with endometrial cancer.

Objective:To evaluate the accuracy of measuring the siae of atrial septal defect(ASD) by transthoracic echocardiography(TTE) on " compression of right superior pulmonary vein sheath during operation" (compression-size) using multi-layer perceptron.Methods:From January 2016 to January 2019, 460 cases of ASD with soft margin, thin growth or central type with atrial septal tumor in the First Hospital Affiliated of Air Force Medical University were analyzed retrospectively. The age was (34.32±18.84)years, 129 males and 331 females. Preoperative TTE and intraoperative TTE were performed to measure the size of ASD and compression-size. With the final occluder size selected as the dependent variable, the preoperative and intraoperative ultrasound measurements were used as covariates, and all patients were randomly divided into training set, test set and verification set according to the proportion of 5∶2∶3, which were imported into multi-layer perceptron. Gradient descent method was used to optimize and adjust the weight, and 10 operations were carried out respectively, and the average value was calculated to evaluate the two ultrasound methods for blocking.Results:The mean values of ASD were (15.26±5.33)mm for preoperative, (23.83±6.39)mm for compression-size intraoperative TTE, and (25.14±6.55)mm for the occluder, respectively. The difference was statistically significant (χ 2=850.450, P<0.001). There were significant differences between the pairwise ( P<0.001). Ten times of multi-layer perceptron were used to obtain a training model for predicting the size of the occluder based on preoperative transthoracic ultrasound and TTE measurement after right upper pulmonary vein sheath compression. The average relative error of the model obtained by preoperative ultrasound measurement in the validation set was (16.55±0.02)%, and that of the model obtained by intraoperative ultrasound measurement in the validation set was (4.81±0.01)%. The difference between the two methods was statistically significant ( t=16.185, P<0.001). Conclusions:It is more accurate to measure the ASD size for selection of occluder by the use of the right superior pulmonary vein sheath compression and TTE, especially for ASD patients with soft margin, thin growth or atrial septal tumor.

The outbreak of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 has rapidly spread globally. Cancer patients are at a higher risk of being infected with the coronavirus and are more likely to develop severe complications, as compared to the general population. The increasing spread of COVID-19 presents challenges for the clinical care of patients with gynecological malignancies. Concerted efforts should be put into managing gynecological malignancies in an orderly manner by strictly implementing the measures that are specifically developed for controlling the spread of COVID-19. We have drafted Recommendations on Management of Gynecological Malignancies during the COVID-19 Pandemic based on our experience on controlling COVID-19 pandemic in China. We recommend that patients with gynecological malignancies should be managed in hierarchical and individualized manners in combination with local conditions related to COVID-19. Medical care decision should be balanced between controlling COVID-19 pandemic spread and timely diagnosis and treatment for gynecologic oncology patients.

Cervical cancer is one of the most common gynecological malignancies, seriously threatening women's health. As early as 1878, Freund first used hysterectomy to treat cervical cancer. In 1898, Wertheim first proposed radical surgery for cervical cancer. With the continuous development of diagnosis and treatment technology, the etiology of cervical cancer has become increasingly clear. The various screening measures have been applied in early detection, early diagnosis and early treatment of cervical cancer. In recent years, the increasing promotion of human papillomavirus (HPV) vaccine has brought a new hope in the prevention and control of cervical cancer.

Macrophages play critical roles in renal fibrosis. However, macrophages exhibit ontogenic and functional heterogeneities, and which population of macrophages contributes to renal fibrosis and the underlying mechanisms remain unclear. In this study, we genetically targeted Notch signaling by disrupting the transcription factor recombination signal binding protein-Jκ (RBP-J), to reveal its role in regulation of macrophages during the unilateral ureteral obstruction (UUO)-induced murine renal fibrosis. Myeloid-specific disruption of RBP-J attenuated renal fibrosis with reduced extracellular matrix deposition and myofibroblast activation, as well as attenuated epithelial-mesenchymal transition, likely owing to the reduced expression of TGF-β. Meanwhile, RBP-J deletion significantly hampered macrophage infiltration and activation in fibrotic kidney, although their proliferation appeared unaltered. By using macrophage clearance experiment, we found that kidney resident macrophages made negligible contribution, but bone marrow (BM)-derived macrophages played a major role in renal fibrogenesis. Further mechanistic analyses showed that Notch blockade reduced monocyte emigration from BM by down-regulating CCR2 expression. Finally, we found that myeloid-specific Notch activation aggravated renal fibrosis, which was mediated by CCR2 macrophages infiltration. In summary, our data have unveiled that myeloid-specific targeting of Notch could ameliorate renal fibrosis by regulating BM-derived macrophages recruitment and activation, providing a novel strategy for intervention of this disease.

Objective To ascertain the specific activities of nigericin on inhibiting human epithelial ovarian cancer(EOC)cells,and to investigate the possible molecular mechanism of nigericin on cell migration and invasion.Methods Cell viability under different treatments of nigericin(0.312 5,0.625,1.25,2.5,5,10,20,40,80 μmol/L)on EOC A2780 and SKOV3 cell lines was examined by CCK-8 assay,with DMSO as a control.The human epithelial ovarian cancer cell lines A2780 and SKOV3 were treated with 5,10 or 20 μmol/L nigericin or with DMSO as a control.Transwell chambers was used to observe the impact of nigericin on migration and invasion of EOC cells.Western blot was used to detect the expressions of epithelial cell marker(E-cadherin),mesenchymal cell marker(Vimentin)and the epithelial-mesenchymal transition(EMT)-related transcription factors Slug,Snail,and Twist,as well as the expressions of proteins related to Wnt/β-catenin signaling pathway such as Gsk-3β,p-Gsk-3β and β-catenin under different concentration treatment of nigericin.Results CCK-8 assay showed that nigericin exhibited strong cytotoxicity on A2780 [ IC 50(16.19 ± 0.26)μmol/L,95％CI 1.077-1.341)] and SKOV3 [ IC50(11.87 ±0.21)μmol/L,95％CI 1.003-1.146] cell lines.Transwell chamber assay revealed that nigericin at different concentration(5,10,20 μmol/L)induced a remarkable reduction in the number of cells migrating through the membrane relative to the vehicle-treated controls in A2780 and SKOV3 cells [(121±9),(92±7),(59±5)/HP and(120.4±2.6),(91.8±5.5),(80.0±4.0)/HP,all P <0.05]; the invasive ability of A2780 and SKOV3 cells also inhibited [(61.2±3.7),(43.2±4.3),(23.6±2.1)/HP and(85.2±7.0),(65.2±4.6),(45.6±4.4)/HP,all P< 0.05].Western blot revealed that the increased expression of E-cadherin and decreased expression of Vimentin,Slug,Snail,Twist,p-Gsk-3β,β-catenin in EOC cells with the nigericin treatment at different concentration(5,10 and 20 μmol/L)showed concentration dependence(P < 0.05).Conclusion Nigericin may induce EMT by activating Wnt-β-catenin signaling pathway to promote the migration and invasion of EOC cells.

Obesity and exogenous hormone exposure are the well-established endometrial cancer risk factors, which are associated with chronic inflammation. Some evidences have shown that inflammation is potentially related to the increased risk of endometrial neoplasms. Aspirin is one of the most studied non-steroidal anti-inflammatory drugs, which can benefit the endometrial cancer patients with obesity. Although aspirin-related bleeding has to be considered prior to therapy, in most cases, the benefits of low-dose aspirin therapy substantially will exceed the risk. Aspirin and other non-steroidal anti-inflammatory drugs are expected to become effective new methods for the treatment of the tumors. This paper reviews the progress of aspirin in endometrial neoplasms.

[Summary] A more conservative approach for endometrial cancer ( EC ) is desirable in women who have requirement to preserve fertility, without compromising their survival .In this article, we tried to formulate clinical recommendations of preserving fertility based on suggestions of European Society of Gynaecological Oncology ( ESGO) in 2015 and relevant research progress .

Objective To explore the expression levels of microRNA(miR)-34a in hippocampus of temporal lobe epilepsy rats and the effect of miR-34a on its target signaling pathway Notch1.Methods Rats were divided randomly into experiment group (n=40) and control group (n=40) by adopting random number table method.The status epilepticus model and the temporal lobe epilepsy model were induced by using lithium-pilocarpine for experiment group.The control group rats received an injection of an equal amount of 9 g/L saline as instead of pilocarpine.Racine grading was performed at 24 hours,day 3,day 7,day 15,and 1 month after modeling to evaluate the behavior.Real-time fluorescent quantitative polymerase chain reaction was used to test the mRNA expressions of miR-34a and Notch1.Western blot was performed to explore the protein expression of Notch1.Results The expression levels of miR-34a at post-status epilepticus in 24 hours,day 3,day 7,day 15 were 2.55±0.29,2.11±0.17,1.68±0.49 and 1.84±0.42,respectively,which showed statistically significant difference compared with the control group (1.00±0.00) (t=-1.55,-1.11,-0.68,-0.84,all P<0.05).The expression levels of Notch1 mRNA at post-status epilepticus in 24 hours,day 3,day 7,day 15,1 month were 1.44±0.31,1.27±0.13,1.52±0.28,0.91±0.33,and 0.80±0.09 respectively.There were significant differences at 24 hours,day 7 in Notch1 mRNA expression (t=-0.44,-0.52,all P<0.05) compared with the control group(1.00±0.00).The expression level of Notch1 mRNA on day 15 was significantly lower than 24 hours and day 7 (t=-0.54,-0.62,all P<0.05),and the expression in 1 month was significantly lower than in 24 hours,or day 3 and day 7 (t=-0.64,-0.46,-0.72,all P<0.05).The expression levels of Notch1 protein at post-status epilepticus 24 hours,day 3,day 7,day 15,1 month were 0.78±0.09,0.57±0.13,0.55±0.16,0.42±0.13,and 0.33±0.09,respectively.There was significantly up-regulated at 24 hours of Notch1 protein expression compared with control group (0.51±0.15)(t=-0.20,P<0.05);and the expression level at day 15 were significantly lower than 24 hours (t=-0.26,P<0.05),while the expression in 1 month was significantly lower than in 24 hours and on day 3 (t=-0.36,-0.24,all P<0.05).Conclusion miR-34a is significantly up-regulated in the post-status epilepticus rat hippocampus,and it may contribute to temporal lobe epilepsy by activating Notch1 signaling pathway.