[Clinical study of the cytokine panel in the diagnosis of ocular chronic graft-versus-host disease].

Objective: To investigate the association between cytokines and ocular chronic graft-versus-host disease (cGVHD) and identify specific biomarkers for ocular cGVHD to enhance clinical diagnosis, treatment, and evaluation. Methods: A mouse model of cGVHD was established to explore the correlation between cGVHD and serum cytokines. Based on the findings from the animal experiments and literature review, a panel of 16 cytokine combinations was identified. Enzyme-linked immunosorbent assay (ELISA) was used to compare the cytokine concentrations in the serum and tear samples from patients who underwent allogeneic hematopoietic stem cell transplantation from June 2017 to March 2022 at the Medical Center of Hematology, Xinqiao Hospital, Army Medical University. Results: ① Compared with the control group, mice with cGVHD exhibited elevated serum IL-1ß, IL-6, IL-8, IL-17, IFN-γ, CX3CL1, CXCL11, CXCL13, CCL11, and CCL19 concentrations (all P<0.05). ② Analysis of the cytokine profiles of the serum and tear samples revealed that compared with patients without ocular cGVHD, those with ocular cGVHD exhibited increased serum IL-8 [P=0.032, area under the curve (AUC) =0.678]; decreased serum IL-10 (P=0.030, AUC=0.701) ; elevated IL-8, IFN-γ, CXCL9, and CCL17 in tear samples; and lower IL-10 and CCL19 in tear samples (all P<0.05, all AUC>0.7). Moreover, cytokines in tear samples showed correlations with ocular surface parameters related to ocular cGVHD. Conclusions: Tear fluid demonstrates greater specificity and sensitivity as a biomarker for diagnosing ocular cGVHD than serum biomarkers. Among the identified cytokines in tear samples, IL-8, IL-10, IFN-γ, CXCL9, CCL17, and CCL19 serve as diagnostic biomarkers for ocular cGVHD post-transplantation, offering practical reference value for diagnosis.

[Evaluation of differences in quality of life in patients with chronic graft-versus-host disease].

Objective: To evaluate the status of, differences in, and factors influencing quality of life (QoL) in patients with chronic graft-versus-host disease (GVHD). Methods: From September 2021 to February 2023, a cross-sectional study of 140 patients with chronic GVHD was conducted at our center. Symptom burden was assessed by the Lee Symptomatology Scale (LSS), and QoL was assessed by the Medical Outcome Study 36-Item Short-Form Health Survey (SF-36) (version 1) and five-level EuroQoL five-dimensional questionnaire (EQ-5D-5L). Results: Data from 140 respondents, including 32 (22.9%) with mild chronic GVHD, 87 (62.1%) with moderate chronic GVHD, and 21 (15.0%) with severe chronic GVHD, were analyzed. Of the respondents, 61.4% were male, and the median transplantation age was 34 (15-68) years. The primary diagnoses were acute myeloid leukemia (50.0%), acute lymphoblastic leukemia (20.0%), and myelodysplastic syndrome (15.0%). The common chronic GVHD-affected organs included the skin in 74 patients (52.9%), the eyes in 57 patients (40.7%), and the liver in 50 patients (35.7%). Among the whole cohort, the eye (20.48±23.75), psychological (16.13±17.00), and oral (13.66±20.55) scores were highest in the LSS group. The physiological function (36.07±11.13), social function (36.10±10.68), and role-emotional functioning (38.36±11.88) scores were lowest in the SF-36 group. The EQ-5D index was 0.764. The total LSS scores for mild, moderate, and severe chronic GVHD were 6.51±6.15, 10.07±5.61, and 20.90±10.09, respectively. The SF-36 physical component scores (PCSs) were 43.12±6.38, 40.73±7.14, and 36.97±6.97, respectively, and the mental component scores (MCSs) were 43.00±8.47, 38.90±9.52, and 28.96±9.63, respectively. The EQ-5D values were 0.810±0.124, 0.762±0.179, and 0.702±0.198, respectively. The multivariate analysis showed that the overall symptom burden (ß=-0.517), oral symptom burden (ß=-0.456), National Institute of Health (NIH) criteria for the eyes (ß=-0.376), and nutrition-related symptom burden (ß=-0.211) were significantly negatively correlated with the PCS. The NIH score (ß=-0.260) was negatively correlated with the MCS score. Oral symptom burden (ß=-0.400), joint/fascia NIH criteria (ß=-0.332), number of involved systems (ß=-0.253), overall NIH criteria (ß=-0.205), and number of immunosuppressants taken (ß=-0.171) were significantly negatively correlated with the EQ-5D score (all P<0.05). Medium to strong correlations were found between the EQ-5D score and the SF-36 score (|r|=0.384-0.571, P<0.001). Conclusions: The QoL of patients with chronic GVHD is impaired, and the more severe the disease, the poorer the QoL. Overall symptom burden, severity of eyes, and oral symptom burden were the most important factors affecting QoL.

[Application and evaluation of artificial intelligence TPS-assisted cytologic screening system in urine exfoliative cytology].

Objective: To explore the application of manual screening collaborated with the Artificial Intelligence TPS-Assisted Cytologic Screening System in urinary exfoliative cytology and its clinical values. Methods: A total of 3 033 urine exfoliated cytology samples were collected at the Henan People's Hospital, Capital Medical University, Beijing, China. Liquid-based thin-layer cytology was prepared. The slides were manually read under the microscope and digitally presented using a scanner. The intelligent identification and analysis were carried out using an artificial intelligence TPS assisted screening system. The Paris Report Classification System of Urinary Exfoliated Cytology 2022 was used as the evaluation standard. Atypical urothelial cells and even higher grade lesions were considered as positive when evaluating the recognition sensitivity, specificity, and diagnostic accuracy of artificial intelligence-assisted screening systems and human-machine collaborative cytologic screening methods in urine exfoliative cytology. Among the collected cases, there were also 1 100 pathological tissue controls. Results: The accuracy, sensitivity and specificity of the AI-assisted cytologic screening system were 77.18%, 90.79% and 69.49%; those of human-machine coordination method were 92.89%, 99.63% and 89.09%, respectively. Compared with the histopathological results, the accuracy, sensitivity and specificity of manual reading were 79.82%, 74.20% and 95.80%, respectively, while those of AI-assisted cytologic screening system were 93.45%, 93.73% and 92.66%, respectively. The accuracy, sensitivity and specificity of human-machine coordination method were 95.36%, 95.21% and 95.80%, respectively. Both cytological and histological controls showed that human-machine coordination review method had higher diagnostic accuracy and sensitivity, and lower false negative rates. Conclusions: The artificial intelligence TPS assisted cytologic screening system has achieved acceptable accuracy in urine exfoliation cytologic screening. The combination of manual screening and artificial intelligence TPS assisted screening system can effectively improve the sensitivity and accuracy of cytologic screening and reduce the risk of misdiagnosis.

[Clinical characteristics and risk factors for bronchoscopic airway mucus hypersecretion in childhood pneumonia infected by different pathogens].

Objective: To investigate the risk factors for airway mucus hypersecretion in childhood pneumonia infected by different pathogens. Method: A retrospective cohort included 968 children who were hospitalized for Mycoplasma pneumoniae pneumonia (MPP), respiratory syncytial virus (RSV) pneumonia, adenovirus pneumonia and underwent bronchoscopy in Respiratory Department of Children's Hospital of Chongqing Medical University from January 2019 to December 2021 was conducted. The children were divided into two groups distinguished by airway mucus secretion according to the airway mucus hypersecretion score which were scored according to the mucus secretion under the bronchoscope. The demographic characteristics, clinical characteristics, laboratory tests and disease severity of the two groups were compared. And the risk factors for the development of airway mucus hypersecretion in two groups were analyzed. Chi square test, Mann-Whithey U test and Fisher exact test were used to analyze the differences between the two groups, and multivariate Logistic regression was used to analyze the influencing factors. Result: There were 559 males and 409 females in the 968 children, with an age of 4.0 (1.4, 6.0) years. Among the 642 children with MPP, 185 cases were in the hypersecretion group and 457 cases were in the non-hypersecretion group. There were 41 cases in the hypersecretion group and 160 cases in the non-hypersecretion group of 201 children with RSV pneumonia. In the 125 children with adenovirus pneumonia, there were 39 cases in the hypersecretion group and 86 cases in the non-hypersecretion group. In these children, the age of children in the hypersecretion group was older than that in the non-hypersecretion group (6.0 (4.0, 7.0) vs. 5.0 (3.0, 7.0) years old, 1.5 (0.5, 3.6) vs. 0.8 (0.4, 1.6) years old, 2.0 (1.2, 4.5) vs. 1.3 (0.8, 2.0) years old, U=35 295.00, 2 492.00, 1 101.00, all P<0.05). Through multivariate Logistic regression analysis it found that increased risk of airway mucus hypersecretion was present in childhood MPP with increase in peripheral blood white blood cell count (OR=3.30, 95%CI 1.51-7.93, P=0.004) or increase in neutrophil ratio (OR=2.24, 95%CI 1.16-4.33, P=0.016) or decrease in lymphocyte count (OR=3.22, 95%CI 1.66-6.31, P<0.001) or decrease in serum albumin (OR=2.00, 95%CI 1.01-3.98, P=0.047). The risk of airway mucus hypersecretion was increased in children with RSV pneumonia combined with elevated peripheral blood eosinophils (OR=3.04, 95%CI 1.02-8.93, P=0.043). Meanwhile, airway mucus hypersecretion was associated with severe pneumonia (OR=2.46, 95%CI 1.03-6.15, P=0.047) in children with RSV pneumonia. Older age was associated with increased risk of airway mucus hypersecretion in children with adenovirus pneumonia (OR=1.02, 95%CI 1.00-1.04, P=0.026). In these children with occurrence of pulmonary rales, wheezes or sputum sounds (OR=3.65, 95%CI 1.22-12.64, P=0.028) had an increased risk of airway mucus hypersecretion. Neutrophils in bronchoalveolar lavage fluid (BALF) demonstrated higher ratio in hypersecretion group from children with MPP (0.65 (0.43, 0.81) vs. 0.59 (0.34, 0.76), U=24 507.00, P<0.01), while the proportion of macrophages in BALF was lower (0.10 (0.05, 0.20) vs. 0.12 (0.06, 0.24), U=33 043.00, P<0.05). Nucleated cell count and neutrophil ratio in BALF were higher in hypersecretion group of children with RSV pneumonia (1 210 (442, 2 100)×106 vs. 490 (210, 1 510)×106/L, 0.43 (0.26, 0.62) vs. 0.30 (0.13, 0.52), U=2 043.00, 2 064.00, all P<0.05). Conclusions: The increase in peripheral blood white blood cell count, neutrophil ratio and decrease in lymphocyte count, serum albumin in children with MPP is related to the development of airway mucus hypersecretion. In children with RSV pneumonia, the abnormal increase of eosinophils in peripheral blood has relationship with hypersecretion. The appearance of lung rale, wheezing, and sputum rale are associated with airway mucus hypersecretion in children with adenovirus pneumonia. In addition, local neutrophil infiltration in the respiratory tract is closely related to the occurrence of airway mucus hypersecretion caused by Mycoplasma pneumoniae and RSV infection.

Reengagement for Long-Term Smoking-Cessation In Military Personnel, Retirees, Family Members (TRICARE): A Randomized Trial.

INTRODUCTION: We sought to determine what type of treatment reengagement after smoking relapse would increase long-term cessation. AIMS AND METHODS: Participants were military personnel, retirees, and family members (TRICARE beneficiaries) recruited across the United States from August 2015 through June 2020. At baseline, consented participants (n = 614) received a validated, four-session, telephonic tobacco-cessation intervention with free nicotine replacement therapy. At the 3-month follow-up, 264 participants who failed to quit or relapsed were offered the opportunity to reengage in cessation. Of these, 134 were randomized into three reengagement conditions: (1) repeat initial intervention ("recycle"), (2) Smoking reduction with eventual cessation goal ("rate reduction"), or (3) Choose #1 or #2 ("choice"). Prolonged abstinence and 7-day point prevalence abstinence were measured at 12 months. RESULTS: Despite being in a clinical trial advertised as having the opportunity for reengagement, only 51% (134 of the 264) of participants who still smoked at 3-month follow-up were willing to reengage. Overall, participants randomized to recycle had higher prolonged cessation rates at 12 months than rate reduction conditions (OR = 16.43, 95% CI: 2.52 to 107.09, Bonferroni adjusted p = .011). When participants who randomly received recycle or rate reduction were pooled, respectively, with participants who chose recycle or rate reduction in the Choice group, recycle had higher prolonged cessation rates at 12 months than rate reduction (OR = 6.50, 95% CI: 1.49 to 28.42, p = .013). CONCLUSIONS: Our findings suggest service members and their family members who fail to quit smoking but are willing to reengage in a cessation program are more likely to benefit from repeating the same treatment. IMPLICATIONS: Finding methods that are both successful and acceptable to reengage people who smoke who want to quit can have a significant impact on improving the health of the public by reducing the portion of the population who smoke. This study suggests that repeating established cessation programs will result in more people ready to quit successfully achieving their goal.

[Long-term outcome of EVAHEART I implantable ventricular assist device for the treatment of end stage heart failure: clinical 3-year follow-up results of 15 cases].

Objective: To evaluate the long-term efficacy and safety of the implantable ventricular assist system EVAHEART I in clinical use. Methods: Fifteen consecutive patients with end-stage heart failure who received left ventricular assist device therapy in Fuwai Hospital from January 2018 to December 2021 were enrolled in this study, their clinical data were retrospectively analyzed. Cardiac function, liver and kidney function, New York Heart Association (NYHA) classification, 6-minute walk distance and quality of life were evaluated before implantation and at 1, 6, 12, 24 and 36 months after device implantation. Drive cable infection, hemolysis, cerebrovascular events, mechanical failure, abnormally high-power consumption and abnormal pump flow were recorded during follow up. Results: All 15 patients were male, mean average age was (43.0±7.5) years, including 11 cases of dilated cardiomyopathy, 2 cases of ischemic cardiomyopathy, and 2 cases of valvular heart disease. All patients were hemodynamically stable on more than one intravenous vasoactive drugs, and 3 patients were supported by preoperative intra aortic balloon pump (IABP). Compared with before device implantation, left ventricular end-diastolic dimension (LVEDD) was significantly decreased ((80.93±6.69) mm vs. (63.73±6.31) mm, P<0.05), brain natriuretic peptide (BNP), total bilirubin and creatinine were also significantly decreased ((3 544.85±1 723.77) ng/L vs. (770.80±406.39) ng/L; (21.28±10.51) µmol/L vs. (17.39±7.68) µmol/L; (95.82±34.88) µmol/L vs. (77.32±43.81) µmol/L; P<0.05) at 1 week after device implantation. All patients in this group were in NYHA class Ⅳ before implantation, and 9 patients could recover to NYHA class Ⅲ, 3 to class Ⅱ, and 3 to class Ⅰ at 1 month after operation. All patients recovered to class Ⅰ-Ⅱ at 6 months after operation. The 6-minute walk distance, total quality of life and visual analogue scale were significantly increased and improved at 1 month after implantation compared with those before operation (P<0.05). All patients were implanted with EVAHEART I at speeds between 1 700-1 950 rpm, flow rates between 3.2-4.5 L/min, power consumption of 3-9 W. The 1-year, 2-year, and 3-year survival rates were 100%, 87%, and 80%, respectively. Three patients died of multiple organ failure at 412, 610, and 872 d after surgery, respectively. During long-term device carrying, 3 patients developed drive cable infection on 170, 220, and 475 d after surgery, respectively, and were cured by dressing change. One patient underwent heart transplantation at 155 d after surgery due to bacteremia. Three patients developed transient ischemic attack and 1 patient developed hemorrhagic stroke events, all cured without sequelae. Conclusion: EVAHEART I implantable left heart assist system can effectively treat critically ill patients with end-stage heart failure, can be carried for long-term life and significantly improve the survival rate, with clear clinical efficacy.

[Gasless submental approach endoscopic removal of thyroglossal cyst].

Objective: To explore the safety and feasibility of gasless submental approach endoscopic removal of thyroglossal cyst. Methods: This work prospectively included the clinical data of 13 patients who underwent the gasless submental approach endoscopic removal of thyroglossal cyst at the Department of Otolaryngology, the First Affiliated Hospital of Chongqing Medical University from August 2021 to February 2022. The operative time, bleeding volumes, postoperative complications, subjective pain levels, satisfaction with incisional scars, neck and facial deformities, and recurrences were prospectively evaluated by visual analogue scale(VAS) score. Results: All of 13 patients were successfully treated using this new technique. The patients had a median age of 38 years, ranging from 24 to 59 years, comprising of 3 males and 10 females. The length of the submental incision was about 3 cm and the median of operation time was 135 minutes. Postoperative complications were minimal. The median volume of blood loss was 10 ml. Surgical site swelling existed in 1 case and dysphagia for more than 1 week occurred in 2 cases. Patients were discharged from the hospital with a median of 3 days after surgery. On a VAS of 0-10 scores, the pain had a median of 2 on the first day after surgery, and the satisfaction with incision scars and neck and facial deformities showed a median of 8 at 6 months after surgery. There were no recurrences during the follow-up period of 9-15 months. Conclusion: Gasless submental approach endoscopic removal of thyroglossal cyst may be a reliable new surgical method that is safe and has cosmetic advantages.

[Long term results of central hole type posterior chamber intraocular lens in the correction of moderate to high myopia].

Objective: To evaluate the long-term safety,effectiveness,predictability and stability of ICL V4c implantation for moderate to high myopia. Methods: In this retrospective case series study, 95 eyes from 50 patients with moderate to severe myopia who were treated in 2015 underwent central hole type posterior chamber intraocular lens (ICL V4c) implantation at Eye & ENT Hospital of Fudan University. The patients were followed up for a period of five years, during which we assessed various parameters including uncorrected visual acuity (UDVA), corrected visual acuity (CDVA), refractive error, axial length, intraocular pressure, endothelial cell density (ECD), vault, and complications. We used the paired t-test and repeated measures one-way ANOVA in SPSS statistical software to analyze the data. Results: The mean spherical equivalent refraction (SE) decreased significantly from (-12.16±3.04) D preoperatively to (-0.19±0.55) D at one month and (-1.14±0.84) D at five years postoperatively. The safety indices (postoperative CDVA/preoperative CDVA) were 1.24±0.27 and 1.13±0.27, respectively, and the efficacy indices (postoperative UDVA/preoperative CDVA) were 1.14±0.25 and 0.87±0.26 at one month and five years postoperatively. At one month after surgery, 80.00% of the eyes were within ±0.50 D of the expected correction, and 96.84% were within ±1.00 D. There was no significant difference in IOP between preoperative and postoperative measurements. The rate of ECD was 3.87%, and the vault decreased by 106.32 µm at five years postoperatively. Conclusion: ICL V4c implantation is safe and effective with good predictability and stability for long term.

[Research progress in the treatment of refractory temporal lobe epilepsy based on stereotactic-electroencephalogram].

Temporal lobe epilepsy, with a variety of etiological, symptomatic, electrophysiological characteristics, has the highest incidence among all focal epilepsy, and a high rate of progression to refractory epilepsy. Surgery is an effective treatment, but traditional methods are usually difficult to accurately locate the epileptogenic zone, which may be resolved by stereotactic-electroencephalogram(SEEG) technique. Radiofrequency thermocoagulation and MRI-guided laser interstitial thermal therapy based on SEEG provide a new accurate and minimally invasive choice for refractory epilepsy patients with high surgical risk and difficulty.

[Multidisciplinary regenerative treatment and mechanisms for rescuing a severe calciphylaxis patient with human amnion-derived mesenchymal stem cells].

Calciphylaxis is a rare disease with severe pain and high-mortality due to cutaneous ischemic necrosis and infection that currently lacks proved effective therapies. The occurrence of calciphylaxis in end stage kidney disease (ESKD) patients is known as calcific uremic arteriolopathy (CUA), which is characterized histologically by dermal microvessel calcification, intimal fibroplasia and microthrombosis. Here we innovatively treated a severe CUA patient with human amnion-derived mesenchymal stem cells (hAMSCs). A 34-year-old uremic woman was presented with progressive, painful malodorous ulcers in buttocks and mummified lower limbs. Skin pathological features supported the diagnosis of calciphylaxis. The patient was refractory to conventional multidisciplinary symptomatic therapies. With the approval of our hospital ethics committee, she was treated with hAMSCs including intravenous and local intramuscular injection, and external application of hAMSC culture supernatant to the wound area. During 15-month follow-up, the patient had regeneration of skin and soft tissues, with improved blood biochemical, inflammatory, mineral and bone metabolic indices and immunoregulation effects. After 15-month hAMSC treatment, the score of pain visual analog scale (VAS) decreased from 10 to 0, Bates-Jensen wound assessment tool (BWAT) score decreased from 65 to 13, and wound-quality of life (Wound-QoL) questionnaire score decreased from 68 to 0. We propose that hAMSC treatment is promising for CUA patients. The therapy is potentially involved in the multiple beneficial effects of inhibiting vascular calcification, stimulating angiogenesis and myogenesis, modulating adverse inflammatory and immunologic responses, promoting re-epithelialization and restoring skin integrity.

[Effect and mechanism of siRNA targeting α-enolase gene combined with paclitaxel on proliferation, invasion and apoptosis of hepatocellular carcinoma cell].

Objective: To investigate the effect of siRNA targeting inhibition of α-enolase (ENO1) combined with paclitaxel on the proliferation, invasion and apoptosis of hepatocellular carcinoma SK-HEP-1 cell and its mechanism. Methods: siRNA-ENO1 (siRNA-ENO1 group) and siRNA-negative control (siRNA-NC group) were transfected into SK-HEP-1 cells in vitro, the untransfected SK-HEP-1 cells were used as the control group, and the transfection effect was detected by real-time fluorescent quantitative polymerase chain reaction and western blotting. After SK-HEP-1 cells were treated with 0, 2.5, 5, 10, 20 and 40 µg/L paclitaxel for 48 hours, the cell survival rate was measured by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) method and the semi inhibitory concentration of paclitaxel was calculated. SK-HEP-1 cells transfected with siRNA-ENO1 or siRNA-NC were treated with 10 µg/L paclitaxel as paclitaxel+ siRNA-ENO1 group and paclitaxel+ siRNA-NC group. The proliferation, clonogenesis, invasion and apoptosis of siRNA-NC group, siRNA-ENO1 group, paclitaxel+ siRNA-ENO1 group and paclitaxel+ siRNA-NC group were detected by MTT, clonogenesis, Transwell chamber and flow cytometry respectively. The expression levels of the phosphorylation of phosphatidylinositol-3-kinase (p-PI3K), p-protein kinase B (Akt) and proliferating cell nuclear antigen (PCNA), matrix metalloproteinase 9 (MMP-9) and B lymphocytoma-2 gene (Bcl-2) were detected by western blotting. Results: Compared with the control group (1.00±0.00 and 0.69±0.04, respectively), the expression levels of ENO1 mRNA and protein (0.25±0.03 and 0.23±0.02, respectively) in siRNA-ENO1 group decreased significantly (P<0.05), but there were no significant differences in the expression levels of ENO1 mRNA and protein in siRNA-NC group (P>0.05). Compared without treatment group [(100.00±0.00)%, P<0.05], the survival rates of SK-HEP-1 cells treated with 2.5, 5, 10, 20 and 40 µg/L paclitaxel [(88.65±6.46)%, (72.36±6.08)%, (60.48±4.23)%, (38.52±3.56)% and (20.75±2.32)%, respectively] decreased significantly (P<0.05), and the semi inhibitory concentration of paclitaxel was 13.26 µg/L. The cell survival rate and clone formation rate of siRNA-ENO1 group [(68.86±5.12)% and (18.12±2.25)%, respectively] were lower than those of siRNA-NC group [(100.00±0.00)% and (29.65±3.06)%, respectively, P<0.05]. The cell survival rate and clone formation rate of the paclitaxel+ siRNA-ENO1 group [(43.28±2.64)% and (8.72±0.52)%, respectively] were significantly different from those of the paclitaxel+ siRNA-NC group [(61.75±5.06)% and (13.48±2.16)%, respectively, P<0.05] and siRNA-ENO1 groups [(68.86±5.12)% and (18.12±2.25)%, respectively, P<0.05]. Cell invasion number in paclitaxel+ siRNA-ENO1 group (23.64±2.12) was lower than that in siRNA-ENO1 group and paclitaxel+ siRNA-NC group (42.16±2.75 and 37.35±2.42, respectively, P<0.05). The apoptosis rates of paclitaxel+ siRNA-NC group and siRNA-ENO1 group [(17.49±1.35)% and (15.29±1.50)%, respectively] were higher than that of siRNA-NC group [(7.21±0.70)%, P<0.05]. The apoptosis rate in the paclitaxel+ siRNA-ENO1 group [(24.59±2.40)%] was higher than those in the paclitaxel+ siRNA-NC group and siRNA-ENO1 group [(17.49±1.35)% and (15.29±1.50)%, respectively, P<0.05]. The expression levels of ENO1, PI3K/Akt signaling pathway related proteins including p-PI3K and p-Akt and the expression levels of PCNA, MMP-9 and Bcl-2 in siRNA-ENO1 group and paclitaxel+ siRNA-NC group were lower than those in siRNA-NC group (P<0.05). The expression levels of ENO1, p-PI3K, p-Akt, PCNA, MMP-9 and Bcl-2 in paclitaxel+ siRNA-ENO1 group were lower than those in siRNA-ENO1 group or paclitaxel+ siRNA-NC group (P<0.05). Conclusion: siRNA targeting inhibition of ENO1 expression can enhance the inhibitory effect of paclitaxel on proliferation, invasion and apoptosis of SK-HEP-1 cells, and its mechanism may be related to the inhibition of PI3K/AKT signaling pathway.

Synergistic effects ofα-Fe2O3nanoparticles and Fe-doping on gas-sensing performance of NiO nanowires and interface mechanism.

High surface area nickel oxide nanowires (NiO NWs), Fe-doped NiO NWs andα-Fe2O3/Fe-doped NiO NWs were synthesized with nanocasting pathway, and then the morphology, microstructure and components of all samples were characterized with XRD, TEM, EDS, UV-vis spectra and nitrogen adsorption-desorption isotherms. Owing to the uniform mesoporous template, all samples with the same diameter exhibit the similar mesoporous-structures. The loadedα-Fe2O3nanoparticles should exist in mesoporous channels between Fe-doped NiO NWs to form heterogeneous contact at the interface of n-typeα-Fe2O3nanoparticles and p-type NiO NWs. The gas-sensing results indicate that Fe-dopant andα-Fe2O3-loading both improve the gas-sensing performance of NiO NWs sensors.α-Fe2O3/Fe-doped NiO NWs sensors presented the highest response to 100 ppm ethanol gas (55.264) compared with Fe-doped NiO NWs (24.617) and NiO NWs sensors (3.189). The donor Fe-dopant increases the ground state resistance and the absorbed oxygen content in air.α-Fe2O3nanoparticles in electron depletion region result in the increasing resistance in ethanol gas and decreasing resistance in air. In this way,α-Fe2O3/Fe-doped NiO NWs sensor presents the excellent gas-sensing performance due to the formation of heterogeneous contact at the interface.

[Efficacy and safety of infliximab in the treatment of pediatirc Crohn's disease].

Objective: To analyze the efficacy and safety of the biological agent infliximab (IFX) in the treatment of pediatric Crohn's disease. Methods: A total of 86 children with Crohn's disease who had received IFX in three hospitals (Ruijin Hospital, Ruijin Hospital North and Shanghai Children's Hospital) in Shanghai from January 2007 to December 2017 were included in this retrospective study. The efficacy of IFX was assessed by comparing clinical and laboratory data before and after IFX treatment. Student t test, Mann-Whitney U test or chi-square test were used to analyze the data of the two groups. Logistic reggression analysis were used to analyze the effects of variables such as age, clinical characteristics, disease behavior and combined medications on the efficacy and safety of IFX. Results: Among the 86 children with Crohn's disease in the study, 50 were males and 36 females. The IFX treatment was initiated at 12.0 (7.1, 13.6) years of age, and the follow-up period was 94.1 (47.8, 185.5) weeks. Efficacy analysis showed that in the induction remission phase, the clinical response rate was 97% (79/81) and the remission rate was 74% (60/81). In the maintenance remission phase, the clinical response rate was 75% (51/68) and the remission rate was 68% (46/68). After 34 weeks of treatment with IFX, pediatric Crohn's disease activity index (PCDAI) (5 (0, 10) vs. 36 (26, 45)), C-reactive protein (3 (1, 8) vs. 8 (3, 31) mg/L), erythrocyte sedimentation rate (10 (6, 10) vs. 35 (20, 50) mm/1 h), platelet ( (327±107)×109 vs. (438±159) ×109/L), albumin ((37±6) vs. (30±6) g/L), hemoglobin ((116±16) vs. (103±18) g/L), change of body weight (-0.5±1.2 vs. -1.0±0.9), anemia (29% (20/68) vs. 75% (51/68)), and perianal disease (13/21 vs. 0) were significantly improved (all P<0.05). By the end of 34 weeks of IFX treatment, 25% (17/68) of children experienced secondary loss of response to IFX. Logistic reggression analysis showed that PCDAI>30 was positively correlated with secondary loss of response (OR=3.823, 95%CI 1.015-15.328, P=0.048), and combined with azathioprine was conducive to maintaining efficacy of IFX (OR=0.440, 95%CI 0.106-1.033, P=0.044). The IFX-related adverse events included infusion reactions in 17% (15/86) and infections in 42% (36/86) of children. Analysis showed that age<6 years was a risk factor for infusion reactions (χ2=6.556, P=0.010), and combined use of steroids (χ2=5.230, P=0.022) may increase the incidence of infection. Conclusions: IFX is effective in the treatment of pediatric Crohn's disease with favorable safety. Reducing secondary loss of response to IFX is an urgent issue that need to be addressed. At the same time, it is necessary to pay close attention to the adverse events during IFX treatment.

Propofol alleviates intestinal ischemia/reperfusion injury in rats through p38 MAPK/NF-κB signaling pathway.

OBJECTIVE: The aim of this study was to investigate the influences of propofol on intestinal ischemia/reperfusion (I/R) injury in rats through the p38 mitogen-activated protein kinase (MAPK)/nuclear factor-kappa B (NF-κB) signaling pathway. MATERIALS AND METHODS: The models of intestinal I/R injury were first successfully established. All rats were randomly divided into 4 groups, namely, S group, I/R group, P group and P + S group. Pathological-morphological changes, injury score and wet-to-dry weight ratio of intestinal tissues as well as oxidative stress indexes in each group of rats were detected. Enzyme-linked immunosorbent assay (ELISA) was applied to measure the levels of inflammatory factors such as creatine kinase-MB (CK-MB), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in each group of rats. Furthermore, Western blotting (WB) assay was applied to determine the protein expression levels of p38 MAPK and NF-κB in different groups. RESULTS: Intestinal tissue injury was the severest in I/R group, with the infiltration of massive inflammatory cells and oozing of blood (Figure 1A, I/R). Compared with those in I/R group, the infiltration of inflammatory cells and damage to intestinal villi were notably relieved in P group and P + S group, revealing that the intestinal mucosal injury was remarkably repaired in P group and P + S group (Figure 1A, P). Moreover, the intestinal tissue injury score was evidently higher in I/R group, P group and P + S group than that in S group (p<0.05). However, it was markedly lower in P group and P + S group than that in I/R group (p<0.05). I/R group, P group and P + S group exhibited significantly increased wet-to-dry weight ratio of intestinal tissues in comparison with S group (p<0.05). However, P group and P + S group exhibited distinctly lower wet-to-dry weight ratio of intestinal tissues than I/R group (p<0.05). The content of malondialdehyde (MDA) was reduced prominently, while that of superoxide dismutase (SOD) was elevated significantly in P group and P + S group in contrast with those in I/R group (p<0.05). On the contrary, P + S group displayed remarkably lower MDA content and higher SOD content than P group (p<0.05). The levels of CK-MB, TNF-α and IL-6 in the blood rose markedly in I/R group compared with those in S group (p<0.05). However, they declined evidently in P group and P + S group in contrast with those in I/R group (p<0.05). Besides, the protein expression level of phosphorylated p38 MAPK was significantly higher in I/R group, P group and P + S group than that in S group (p<0.05). However, no significant difference was observed in the protein expression of total p38 MAPK among the four groups (p>0.05). However, the protein expression level of phosphorylated p38 MAPK was distinctly down-regulated in P group and P + S group in comparison with that in I/R group (p<0.05). Finally, I/R group, P group and P + S group had a prominently higher protein expression level of NF-κB than S group (p<0.05). However, P group and P + S group exerted a significantly lower protein expression level of NF-κB than I/R group (p<0.05). CONCLUSIONS: Propofol decreases the release of inflammatory factors and alleviates intestinal edema by inhibiting the p38 MAPK/NF-κB signaling pathway, thereby mitigating and treating the intestinal I/R injury in rats.

Circ-0079593 promotes proliferation and migration of melanoma cells by sponging microRNA-433 and elevating EGFR expression.

OBJECTIVE: The aim of this study was to analyze the biological effects of circ-0079593 and its potential mechanism in the progression of melanoma. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was carried out to detect circ-0079593 expression in melanoma tissue samples and cell lines, and the relationship between circ-0079593 expression and prognosis of patients with melanoma was analyzed based on collected clinical information. Then, the melanoma cell line stably overexpressing circ-0079593 was constructed using lentiviral stable transfection technique, and then, Cell Counting Kit-8 (CCK-8) and transwell assays were carried out to detect the proliferation rate, migration, as well as invasion abilities of melanoma cells, respectively. In addition, the potential binding targets of circ-0079593 were searched through bioinformatics analysis, and the results were verified by Dual-Luciferase assay. RESULTS: It was found that, in comparison with the normal control group, circ-0079593 showed a significantly high expression in melanoma tissues and cell lines, which predicted a poor prognosis of melanoma patients. In vitro experiments showed that the overexpression of circ-0079593 remarkably enhanced proliferation rate, as well as invasion ability of melanoma cells. Moreover, bioinformatics data analysis revealed that there exist binding sites of microRNA-433 both in circ-0079593 and EGFR. Meanwhile, the results of the Luciferase assay confirmed that circ-0079593 probably bound to microRNA-433, as an endogenous competitive RNA (ceRNA), to regulate EGFR expression. At last, cell reverse experiments demonstrated that the overexpression of microRNA-433 could attenuate the capacity of melanoma cells to proliferate and migrate, while simultaneous overexpression of circ-0079593 partially restored those cell functions. CONCLUSIONS: In melanoma, circ-0079593 may serve as a cancer-promoting gene to accelerate the rates of cell proliferation and migration, which may exert its effects by elevating EGFR expression by binding to microRNA-433.

Sevoflurane ameliorates adriamycin-induced myocardial injury in rats through the PI3K/Akt/GSK-3ß pathway.

OBJECTIVE: The aim of this study was to explore the effects of sevoflurane (SEV) pretreatment on Adriamycin (ADR)-induced myocardial injury through the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/glycogen synthase kinase-3ß (GSK-3ß) pathway. MATERIALS AND METHODS: A total of 24 rats weighing 200-250 g were divided into four groups, including: control group (C group), ADR injection group (ADR group), SEV pretreatment group (ADR + SEV group) and inhibitor group (ADR + SEV + LY group). H9c2 cells were cultured in vitro and were divided into control group (C group), ADR treatment group (ADR group), and SEV pretreatment group (ADR + SEV group) and inhibitor group (ADR + SEV + LY group) as well. Next, the content of aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and creatine kinase (CK) in the serum was detected via Enzyme-Linked Immunosorbent Assay (ELISA). Hematoxylin-eosin (HE) staining assay was performed to determine the severity of myocardial injury. Meanwhile, the apoptosis rate of cells was detected through terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) assay. Additionally, Western blotting (WB) was employed to measure the protein expression levels of phosphorylated (p)-GSK-3ß, p-PI3K, Akt and p-Akt. RESULTS: Compared with C group, ADR significantly increased the content of AST, LDH and CK in the serum (p<0.01), reduced protein expression levels of p-GSK-3ß, p-PI3K and p-Akt (p<0.01), increased apoptosis rate (p<0.01), and induced myocardial injury. SEV pretreatment significantly alleviated the effect of ADR, manifested as significantly lowered content of AST, LDH and CK in the serum (p<0.01), distinctly elevated protein expression levels of p-GSK-3ß, p-PI3K and p-Akt (p<0.01), notably reduced apoptosis rate (p<0.01), and relieved myocardial injury. LY294002 remarkably inhibited the protective effect of SEV against myocardial injury (p<0.01) CONCLUSIONS: SEV is able to prominently ameliorate ADR-induced myocardial injury by regulating the phosphorylation level of the PI3K/Akt/GSK-3ß signaling pathway.

Effect of CTCs and INHBA level on the effect and prognosis of different treatment methods for patients with early breast cancer.

OBJECTIVE: We aimed at investigating the changes in the number of circulating tumor cells (CTCs) in patients with early breast cancer (BCa) before and after different treatments, and the influence of INHBA expression on patients' therapy efficacy and prognosis prediction was also evaluated. PATIENTS AND METHODS: Treatment plans were formulated based on patient's condition and willingness. 160 patients with early BCa were divided into trastuzumab adjuvant group (80 cases) and surgery group (80 cases). The correlation between the number of CTCs and Inhibin, beta A (INHBA) level was assessed by Spearman correlation analysis. The cumulative survival curve was depicted using Kaplan-Meier method to evaluate the prognosis of patients in different groups. RESULTS: The number of detected CTCs and INHBA expression in the two groups were both reduced as compared with those before chemotherapy. After 3 months of treatment, CTCs and INHBA level in the surgical group were detected lower than those in the trastuzumab group. The number of CTCs was positively correlated with INHBA level. The overall survival rate of patients in the surgery group was remarkably higher than those in the adjuvant trastuzumab group. CONCLUSIONS: The CTCs in the peripheral blood of patients with early BCa showed a great relevance to INHBA expression, which may thus serve as predictors of treatment effect and prognosis of BCa patients in early stage. Meanwhile, we demonstrate that surgery should be the first choice for early BCa patients after chemotherapy.

Protective effect of dexmedetomidine against renal injury in diabetic nephropathy rats through inhibiting NF-κB pathway.

OBJECTIVE: The aim of this study was to investigate the protective effect of dexmedetomidine (Dex) against renal injury in diabetic nephropathy (DN) rats by inhibiting the nuclear factor-κB (NF-κB) pathway. MATERIALS AND METHODS: A total of 36 Sprague-Dawley rats were randomly divided into three groups, including: normal group (n=12), model group (n=12) and Dex group (n=12). The rats underwent no treatment in normal group. In model group, the diabetes model was successfully established, and normal saline was intraperitoneally injected after operation. In Dex group, the diabetes model was established as well, and Dex was intraperitoneally injected after operation. After intervention for 2 weeks, the samples were taken for use. Blood urea nitrogen (BUN) and serum creatinine (Cr) were detected using a full-automatic biochemical analyzer. The expression of Caspase-3 was detected via immunohistochemistry. Western blotting was conducted to detect the protein expression of NF-κB. The apoptosis was detected via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. In addition, the levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were determined via enzyme-linked immunosorbent assay (ELISA). RESULTS: The levels of BUN and Cr were significantly higher in model group and Dex group than those in normal group (p<0.05). However, they were significantly lower in Dex group than those in the model group (p<0.05). Immunohistochemistry results showed that the mean optical density of Caspase-3 positive expression increase remarkably in model group and Dex group when compared with normal group (p<0.05). However, it significantly declined in Dex group when compared with the model group (p<0.05). The results of Western blotting revealed that model group and Dex group exhibited evidently higher relative protein expression of NF-κB than normal group (p<0.05). However, Dex group displayed notably lower relative protein expression of NF-κB than model group (p<0.05). TUNEL assay demonstrated that the apoptosis rate increased significantly in the model group and Dex group when compared with normal group (p<0.05). However, it remarkably declined in Dex group in comparison with the model group (p<0.05). Finally, ELISA assay indicated that model group and Dex group had markedly higher levels of IL-6 and TNF-α than normal group (p<0.05). However, the levels of IL-6 and TNF-α were significantly lower in Dex group than model group (p<0.05). CONCLUSIONS: Dex inhibits inflammation and apoptosis by suppressing the NF-κB signaling pathway, thereby exerting a protective effect against renal injury in DN rats.

[Clinical analysis of 67 cases of pure red cell aplastic anemia].

Objective: To investigate secondary factors, laboratory features, treatment options, and prognosis of pure red cell aplastic anemia (PRCA) . Methods: This was a multicenter retrospective clinical study. Patients aged above 18 years newly diagnosed with PRCA between June 1, 2010, and June 1, 2019, were recruited as the main study object. A comparative analysis of remission rate and overall survival rate was made according to different treatment schemes adopted by patients and different drug reduction rates. Results: A total of 67 patients with PRCA were included in this study and the secondary PRCA group accounted for 44.8% (30/67) . The most common secondary factors were thymoma (n=10) and T-cell large lymphocytic leukemia (T-LGLL) (n=6) . The overall response rate of PRCA was 85.7% and the 3-year overall survival rate of PRCA was (74.3±7.5) %. The remission rate of cyclosporine A alone was slightly higher than that of oral glucocorticoid alone or combined with glucocorticoid[90.0% (36/40) vs 75.0% (12/16) , P=0.147]. After patients applied with cyclosporine A treatment reached CR/PR and remained stable for 3-6 months, the dose of cyclosporine A was reduced by 25 mg each time. The cyclosporine A reduction interval of a 25 mg/d reduction in more than 1 month significantly prolonged the median disease-free survival compared with a 25 mg/d reduction in less than 1 month [not reached vs 15 (95% CI 7-23) months, P<0.001]. There were 62.5% (10/16) of patients who responded to the initial or incremental treatment regimen after relapse. Conclusion: PRCA has features of various secondary factors, high overall survival rate, and high remission rate. Treatment with cyclosporine A alone is preferred, and cyclosporine A should be slowly tapered to reduce the risk of later relapse after it takes effect and patients reach a steady state.

Effects of gene polymorphism and serum levels of IL-2 and IL-6 on endometriosis.

OBJECTIVE: EMT is closely related to gene polymorphism and the expression level of immune-related substances in patients. Therefore, the aim of this study was to investigate the relationship between single nucleotide polymorphism (SNP), as well as serum levels of interleukin 2 (IL-2) and interleukin 6 (IL-6) in patients with endometriosis (EMT) and disease susceptibility. PATIENTS AND METHODS: Peripheral blood of EMT patients and healthy people were collected, respectively. Genomic deoxyribonucleic acid (DNA) was extracted and sequenced to obtain gene polymorphisms of IL-2 rs11575812 (T>C), rs2069772 (A>G), rs2069762 (T>G), and IL-6 rs1800795 (C>G). Meanwhile, the serum levels of IL-2 and IL-6 were determined by the relative kits. RESULTS: For IL-2 rs11575812 allele (C>G), the odds ratio (OR) was 0.49, the 95% confidence interval (CI) was 0.37-0.66, and the p-value was 0. For IL-2 rs2069772 allele (C>G), the OR was 0.97, the 95% CI was 0.73-1.27, and the p-value was 0.83. For IL-2 rs2069762 allele (T>G), the OR was 1.73, the 95% CI was 1.31-2.29, and the p-value was 0. For IL-6 rs1800795 allele (C>G), the OR was 1.26, the 95% CI was 0.96-1.66, and the p-value was 0.09. CC genotype (p=0.000) and TT genotype (p=0.040) of IL-2 rs11575812 (T>C), AG genotype (p=0.000) of IL-2 rs2069772 (A>G), and GT genotype (p=0.000) of rs2069762 (T>G) were remarkably associated with the serum level of IL-2 in patients with EMT. Similarly, the CG genotype (p=0.000) of IL-6 rs1800795 (C>G) was significantly correlated with the serum level of IL-6 in patients with EMT. IL-2 haplotype CAG (p=0.005), CAT (p=0.001), CGG (p=0.047), TAG (p=0.000), and TGG (p=0.000) were significantly different from other haplotypes. Furthermore, there was a significant correlation between the serum levels of IL-2 and IL-6 (r=0.63, p<0.001). CONCLUSIONS: IL-2 rs11575812 (T>C) TT genotype, rs2069772 (A>G) AG genotype and rs2069762 (T>G) GG genotype increases the risk of EMT, which are related to the serum levels of IL-2 and IL-6.