Objective To investigate the effects of chronic starvation stress on the proliferation and migration of colorectal cancer cells, as well as the underlying mechanisms. Methods By using prolonged serum starvation to simulate chronic starvation stress in tumor cells, we established enduring serum-deprived models of SW480 and DLD-1 cells and observed cellular morphological change. Effects of prolonged serum starvation on SW480 and DLD-1 proliferative and migratory capabilities were assessed using CCK-8 and Transwell assays. Differential gene-expression analysis on SW480 cultured with 1% FBS or 10% FBS medium was followed by GO and KEGG pathway assessments. Migration-related protein interactions were explored using String database and Metascape software, leading to 16 genes being selected for RT-qPCR validation. Protein levels of ITGB1 and key molecules in the relevant pathways were measured. Mobility changes in SW480 were observed through Transwell assay after ITGB1 knockdown or STAT3 inhibition. Results Prolonged serum starvation significantly inhibited the proliferation of SW480 and DLD-1 cells, and DLD-1 mobility, while enhanced SW480 migration. Transcriptome analysis revealed that prolonged serum deprivation caused the upregulation of 3016 genes, among which 283 were involved in cell migration. Metascape analysis identified the correlations among potential core genes ITGB1, CD44, TNS1, STAT3, etc. Prolonged serum deprivation increased the mRNA levels of VTN, TNS1, VEGFA, STAT3, and ITGB1 while also increasing the protein levels of ITGB1 and MMP2 and the phosphorylation levels of JAK2 and STAT3. Mobility reduction in prolonged serum-starved SW480 cells was achieved through ITGB1 knockdown or a STAT3 inhibitor. Conclusion Colorectal cancer cells can endure chronic starvation stress which enhances migration capability by upregulating ITGB1 expression.

Objective To investigate the clinical manifestations of nodo-paranodopathy(NPP)with anti-neurofascin 186(NF186)antibody positive.Methods The clinical data of a NPP patient with cranial nerve damage caused by anti-NF186 antibody positive was retrospectively analyzed.Results The patient was a 70-year-old male with sudden speech disorder and dysphagia one month ago.Glucocorticoid therapy was discontinued after improvement.The patient's speech,swallowing,chewing,bristling,turning and head-up movements were laborious and progressively aggravated 5 days ago.The EMG examination of the limbs was normal,and the serum and CSF anti-NF186 antibody were positive.The curative effect of glucocorticoid treatment was not obvious,and the symptoms were significantly improved after plasma exchange treatment.Conclusions Anti-NF186 antibody-positive NPP has late onset age,severe illness and accompanied with cranial nerves damage.Conventional hormone therapy is not effective,but plasma exchange therapy is effective.

Objective To analyze the efficacy and adverse reactions of donepezil in the treatment of patients with a continuous disease spectrum of Alzheimer's disease(AD)with pharmacogenomics.Methods Seventy-two patients who took donepezil therapy at the time of initial molecular pa-thology diagnosis of AD continuous disease spectrum in Chinese PLA General Hospital from Jan-uary 2022 to January 2023 were recruited.Cells from the oral buccal mucosa were collected,and MassARRAY nucleic acid mass spectrometry was applied to detect the genotypes of CYP2D6,the gene encoding cytochrome P450 2D6 enzyme,and CHAT,the gene encoding acetylcholine trans-ferase.After 9 months of follow-up,drug efficacy was indirectly determined by neurological func-tion scales,caregiver evaluations,and drug prescribing behaviors,and thus,the 50 patients on donepezil alone were divide into effective group(n=28)and ineffective group(n=22).Seventy-two patients were divided into adverse reaction group(n=12)and no adverse reaction group(n=60).Multivariate logistic regression analysis was used to analyze the correlation between donepezil efficacy and pharmacogenomics.Results The frequencies of CHAT rs3793790 locus carrying G allele and rs2177370 locus carrying A allele were significantly higher in the effective group than the ineffective group(35.71％vs 9.09％,P=0.029;42.86％vs 9.09％,P=0.008).Multivariate lo-gistic regression analysis showed that donepezil was more effective in those who carrying rs3793790 G allele and/or rs2177370 A allele in the CHAT gene than those who carrying neither of the alleles(95％CI:1.20-34.47,P=0.030).There were no statistical differences in the CYP2D6 gene-adjusted activity score and whether or not carrying*10 between the patients with and without adverse reactions(P＞0.0 5).Conclusion In patients with a continuous spectrum of AD,donepezil efficacy is associated with CHAT gene polymorphisms,but there is no correlation between donepezil adverse reactions and CYP2D6 genotype.

Objective:To investigate the clinical and electrophysiological characteristics of ANCA-associated vasculitic neuropathy (VN) and analyze the predictors of treatment outcomes.Methods:Retrospective case series. In all, 652 consecutive patients with ANCA-associated vasculitis were admitted to the First Medical Center of the Chinese PLA General Hospital between January 2006 and December 2022. Peripheral neuropathy occurred in 91 patients. Patients were excluded if other known causes of neuropathy were present. Sixty-one patients were eventually enrolled, including 17 with eosinophilic granulomatosis with polyangiitis (EGPA), 11 with granulomatosis polyangiitis (GPA), and 33 with microscopic polyangiitis (MPA). Their clinical data were collected and clinical characteristics, VN manifestations, electrophysiological findings (including interside amplitude ratio [IAR]), and treatment outcomes were compared among the three subsets of AAV. Then, factors influencing the treatment outcomes were analyzed using multivariable logistic regression analysis.Results:Peripheral neuropathy occurred in 62.1%(18/29) of EGPA, 8.3%(15/180) of GPA, and 13.1%(58/443) of MPA patients. The age at onset and examination was higher in patients with MPA than those with EGPA or GPA ( P<0.01). The occurrence of VN was later in patients with GPA than those with EGPA ( P<0.01), and the GPA group had fewer affected nerves than the other two groups ( P<0.016). The abnormal IARs of motor nerves in lower limbs were more detected in the EGPA than the MPA group ( P<0.01). Logistic regression analysis suggested that higher Birmingham vasculitis activity score-version 3 (BVAS-V3) ( OR=6.85, 95% CI 1.33-35.30) was associated with better treatment outcomes of VN. However, central nervous system involvement was a risk factor for poor treatment outcomes ( OR=0.13, 95% CI 0.02-0.89). Conclusions:The clinical and electrophysiological characteristics of VN were slightly different among subsets of AAV. Patients with GPA often presented with polyneuropathy and had fewer nerves affected; mononeuritis multiplex was more common in EGPA than GPA and MPA. Higher BVAS-V3 and central nervous system involvement might predict the treatment outcome of VN.

Objective To explore the safety of minimally invasive esophagectomy (MIE) with three-field lymphadenectomy (3-FL) for esophageal squamous cell carcinoma (ESCC) by comparing the short-term outcomes between the 3-FL and the two-field lymphadenectomy (2-FL) in MIE. Methods The clinical data of patients with ESCC who underwent minimally invasive McKeown esophagectomy in our hospital from July 2015 to March 2022 were collected retrospectively. Patients were divided into a 3-FL group and a 2-FL group according to lymph node dissection method. And the clinical outcomes and postoperative complications were compared between the two groups. Results A total of 257 patients with ESCC were included in this study. There were 211 males and 46 females with an average age of 62.2±8.1 years. There were 109 patients in the 3-FL group and 148 patients in the 2-FL group. The operation time of the 3-FL group was about 20 minutes longer than that of the 2-FL group (P<0.001). There was no statistical difference between the two groups in the intraoperatve blood loss (P=0.376). More lymph nodes (P<0.001) and also more positive lymph nodes (P=0.003) were obtained in the 3-FL group than in the 2-FL group, and there was a statistical difference in the pathological N stage between the two groups (P<0.001). But there was no statistical difference in the incidence of anastomotic leak (P=0.667), chyle leak (P=0.421), recurrent laryngeal nerve injury (P=0.081), pulmonary complications (P=0.601), pneumonia (P=0.061), cardiac complications (P=0.383), overall complications (P=0.147) or Clavien-Dindo grading (P=0.152) between the two groups. Conclusion MIE 3-FL can improve the efficiency of lymph node dissection and the accuracy of tumor lymph node staging, but it does not increase the postoperative complications, which is worthy of clinical application.

AIM: To compare the changes of exotropia deviation in children with basic type of intermittent exotropia before and after monocular occlusion test.METHODS: Prospective clinical study. A total of 258 children with basic type of intermittent exotropia who underwent strabismus correction in our hospital from July 2021 to September 2022 were selected, including 122 males and 136 females, aged from 5 to 12 years, with an average age of 8.0±3.1 years. The exotropia deviation was measured at distance(6 m)and near(33 cm)fixation by prism alternating occlusion method, and the exotropia deviation was checked again after covering the non-dominant eyes of children for 40 min.RESULTS: Before and after the monocular occlusion test, the exotropia deviation at distance(6 m)fixation was 28.23△±10.79△ and 29.79△±10.85△, respectively(t=-0.903, P=0.368), while the exotropia deviation at near(33 cm)fixation was 33.14△±8.89△ and 36.90△±10.76△, respectively(t=-2.377, P=0.019).CONCLUSIONS: Monocular occlusion test has a great impact on the exotropia deviation at near(33 cm)fixation in children with basic type of intermittent exotropia before surgery. It can expose the maximum exotropia deviation, reduce the rate of undercorrection after strabismus surgery, and provide a reliable surgical plan.

Objective To investigate the signal abnormality of conus medullaris in patients with overactive bladder(OAB)and un-deractive bladder(UAB)by MRI diffusion tensor imaging(DTI). Methods From May,2021 to April,2023,23 patients with lower urinary tract dysfunction without trauma and supraspi-nal lesions were enrolled(case group).All patients underwent imaging urodynamics and pelvic floor electromy-ography.Based on the bladder contraction during the filling phase of urodynamics,the patients were divided into UAB group and OAB group.Eight healthy subjects were included as the control group.All participants under-went T10 to L5 spinal segment MRI scans and DTI scans.The position of conus medullaris was determined by comparing the DTI sequences with the MRI scans.The fractional anisotropy(FA),apparent diffusion coefficient(ADC),and relative anisotropy(RA)of the conus medullaris intermediate segment were compared. Results Twelve cases were in UAB group,and eleven in OAB goup.Abnormalities were found in the pelvic floor elec-tromyography in the case group.There was significant difference in sacral reflex arc nerve conduction testing be-tween UAB and OAB groups(P = 0.036).Compared with the control group,ADC increased(t = 2.185,P = 0.037)in the case group;FA decreased(t = 3.439,P = 0.005)and ADC increased(t = 4.582,P<0.001)in UAB group. Conclusion DTI is helpful to find the potential lesion of spinal cord in patients with lower urinary tract dysfunction.FA and ADC are valuable indicators for the diagnosis of conus medullaris injury.

Objective To investigate the clinical application of three-dimensional intracavitary/free-hand interstitial brachytherapy technique in radical radiotherapy for cervical cancer. Methods A retrospective study was conducted on the clinical data of patients with cervical cancer who underwent radical radiotherapy using CT-guided three-dimensional intracavitary/free-hand interstitial brachytherapy technique in The Affiliated Cancer Hospital of Nanjing Medical University from April 2019 to September 2021. The short-term efficacy and adverse reactions were analyzed, and the independent predictors affecting short-term efficacy were evaluated by logistic risk regression model. Results A total of 182 patients were included, and all patients successfully completed the treatment. Clinical efficacy assessment performed 3 months after treatment revealed an overall response rate of 90.65%; the incidence of grade 3 and 4 adverse reactions in the lower gastrointestinal tract was 4.4% during treatment. After reclassifying stage IIIC patients according to the International Federation of Gynecology and Obstetrics (FIGO) 2009 staging system and including factors affecting the stage, it was found that the tumor volume before brachytherapy was the main factor affecting the clinical efficacy of patients at this stage (P = 0.004). Conclusion As a key method in radical radiotherapy for cervical cancer, three-dimensional intracavitary/free-hand interstitial brachytherapy technique is safe and effective and can be quickly popularized in primary hospitals beyond regional cancer centers for cervical cancer brachytherapy.

Objective To investigate the effect of erythroid differentiation associated gene(EDAG)on hematopoietic stem/progenitor cells(HSPCs)under chronic inflammation.Methods In this study,EDAG-/-and wild type(WT)mice were divided into the experiment group and control group.An infectious chronic inflammation model was established via multiple intraperitoneal injections of Listeria monocytogenes(LM),while a sterile chronic inflammation model was generated via multiple intraperitoneal injections of polyinosinic-polycytidylic acid[Poly(I∶C)].The effect of EDAG on HSPCs was explored under chronic inflammation conditions.Results In the LM repeated infection model,EDAG deletion led to a decrease in HSPCs and long-term hematopoietic stem cells(LT-HSCs)in mice as well as a significant bias towards myeloid differentiation in peripheral blood.Similarly,EDAG knockout also resulted in reduced numbers of HSPCs and decreased colony-forming ability in aseptic chronic inflammation models.Conclusion EDAG deficiency accelerates HSPC depletion in young mice under chronic inflammation,indicating strong protection of EDAG against HSPC damage induced by chronic inflammation.

Objective:To investigate the clinicopathological features and prognostic factors of breast cancer patients with low expression of human epidermal growth factor receptor 2 (human epidermal growth factor receptor-2, HER-2).Methods:Retrospective analysis was made on the clinical data of 823 cases of breast cancer with HER-2 non positive treated by surgery in the First Affiliated Hospital of Bengbu Medical College from January 1, 2013 to December 31, 2016. Collect general clinical indicators (age, site of onset, menstrual status, etc.), pathological features (tumor TNM staging, histological grading, pathological type, axillary lymph node status, Ki-67 index, and expression of HER-2, ER, PR), treatment plans (endocrine therapy, radiotherapy, and chemotherapy plans), survival status (pathological diagnosis time, surgery time, recurrence or metastasis time, and death time). To compare the clinicopathological characteristics of HER-2 non positive breast cancer patients with different hormone receptor status, and analyze the influencing factors of DFS and overall survival. Non normally distributed econometric data are represented by M( Q1, Q3), and Wilcoxon rank sum test is used for comparison between the two groups; Count data is represented as an example (%), and χ 2 test is used for inter group comparison; Use Kaplan Meier method to plot survival curves, and analyze the differences in disease-free survival rate and overall survival rate among different subgroups through Log rank test; Use univariate and multivariate Cox proportional risk models to analyze the influencing factors of prognosis. P<0.05 indicates a statistically significant difference. Results:Among 823 HER-2 non positive breast cancer patients, 657 (79.83%) were hormone receptor positive and 166 (20.17%) were negative; 287 cases (34.87%) had zero expression of HER-2, and 536 cases (65.13%) had low expression. Compared with the hormone receptor negative group, the hormone receptor positive group had a higher proportion of HER-2 low expression (68.49% (450/657) compared to 51.81% (86/166), χ 2=16.25, P<0.001), and a lower proportion of Ki-67>30% (32.57% (214/657) compared to 72.29% (120/166), χ 2=86.69, P<0.001). In the hormone receptor positive group, compared with the HER-2 zero expression subgroup, the HER-2 low expression subgroup had a lower proportion of patients with onset age ≥ 40 years old ( P=0.026), a higher proportion of premenopausal women ( P=0.045), a later pathological stage ( P=0.042), and a lower positive rate of axillary lymph nodes ( P=0.023). Multivariate analysis showed that primary tumor size stage T3-T4, Ki-67 > 30% and HER-2 zero expression were risk factors for 10-year DFS and total survival of hormone receptor positive HER-2 non positive breast cancer patients (10-year DFS: HR values were 2.840, 2.010, 2.652, 95% CI: 2.265－4.010, 1.563－2.471, 1.983－3.441, all P=0.001; Overall survival: HR values were 1.923, 1.954, 95% CI: 1.332－2.642, 1.774－2.531, with P values of 0.041 and 0.012, respectively; Primary tumor size stage T3-T4 and HER-2 zero expression are risk factors for 10-year DFS in hormone receptor negative HER-2 non positive breast cancer patients ( HR values are 2.096 1.885, 95% CI: 1.687－3.000, 1.452－2.774, P values are 0.026 and 0.005, respectively). Regional lymph node stage N1-N3 is a risk factor for 10-year overall survival ( HR=1.982, 95% CI: 1.230－2.710, P=0.001). Conclusions:Low HER2 expression in HR Positive patients with breast cancer is more common than in TNBC.There is heterogeneity between the clinicopathological features of patients with zero expression of HER-2 and low expression of HER-2. The survival prognosis of patients with breast cancer with low expression of HER-2 is better than that of patients with zero expression of HER-2, and the expression of HER2 has a significant effect on survival and prognosis.