Objective: To investigate the efficacy and safety of ⁹⁹Technetium-methylenediphosphonate injection (⁹⁹Tc-MDP) in the treatment of thyroid associated ophthalmopathy (TAO). Methods: The trail was conducted in Affiliated Zhongshan Hospital of Dalian University. Patients were recruited from October 2016 to October 2018. Fifty patients with active moderate to severe TAO were randomly assigned to receive ⁹⁹Tc-MDP (n = 25) or methylprednisolone administered intravenously (n = 25), the final completion of treatment and follow-up were 21 and 20 cases, respectively. In ⁹⁹Tc-MDP group, 30 sets of ⁹⁹Tc-MDP were applied to each course of treatment for 10 d, with a course interval of 20 d, a total of 3 courses of treatment. Patients in methylprednisolone group were given a pulse regimen, once every week for a total of 12 infusions, altogether 4.5 g in 12 weeks. The clinical activity score (CAS) and exophthalmos were assessed in a patient at weeks 12 and 24, respectively. A response was defined as a reduction of 2 points or more in CAS and reduction of 2 mm or more in exophthalmos. Safety was assessed according to the incidence of adverse events at week 12. Results: At week 12 treatment, no significant difference was observed in CAS and exophthalmos between the two groups [CAS: (2.48 ± 0.60) , (2.20 ± 0.62) points, exophthalmos: (2.57 ± 1.02), (2.20 ± 1.09) mm, P > 0.05]. Adverse events in ⁹⁹Tc-MDP group was significantly lower than that in methylprednisolone group [4.8%(1/21) vs 40.0%(8/20), P < 0.05]. At week 24, the reduction in the CAS in ⁹⁹Tc-MDP group was significantly greater than that in methylprednisolone group [CAS: (3.86 ± 0.67), (3.05 ± 0.59) points, P < 0.05]. The difference in exophthalmos of patients between the two groups was not statistically significant [(3.17 ± 0.60), (2.88 ± 0.57) mm, P > 0.05]. The difference in total effective rate of patients between the two groups was not statistically significant (P > 0.05). Conclusion ⁹⁹Tc-MDP regimen could provide similar benefit to methylprednisolone pulse therapy for those patients with TAO, but with longer reduction in CAS and less adverse events.

CircRNA(circular RNA) is a new class of covalently closed circular non-coding RNAs, with the function of the microRNA sponge, regulation of gene expression, and other functions. Studies have confirmed that circRNAs are involved in the occurrence and progression of a variety of tumors, and can be used as biomarkers and therapeutic targets for tumor diagnosis and prognosis evaluation. In this paper, the expression and mechanism of circRNA in head and neck squamous cell carcinoma are reviewed.

Objective To evaluate the clinical efficacy and safety of continuous renal replacement therapy (CRRT) in patients with severe acute pancreatitis (SAP) receiving percutaneous drainage (PCD). Methods Clinical data of SAP patients receiving PCD admitted to department of hepatobiliary surgery of the First Affiliated Hospital of Xi'an Jiaotong University from November 11th 2015 to May 13th 2018 were retrospectively analyzed. The patients were divided into CRRT group and control group according to whether or not receiving CRRT. Demographic data, relevant variables before and after PCD, complication and outcome were all compared. Results A total of 75 patients were included in the study, 30 were treated with application of CRRT and 45 without CRRT. ① There was no significant difference in gender, age, body mass index (BMI), medical history (smoking, drinking), complications (cardiovascular disease, chronic lung disease, diabetes, chronic renal insufficiency), etiology (gallstone, alcohol abuse, hyperlipidemia and others), or white blood cell count (WBC), C-reactive protein (CRP), serum procalcitonin (PCT), fluid resuscitation, mechanical ventilation, vasoactive agent or intra-abdominal pressure within 48 hours after admission between the two groups. However, acute physiology and chronic health evaluationⅡ(APACHEⅡ) score within 48 hours after admission of CRRT group was significantly higher than that of control group (18.3±4.5 vs. 12.8±6.2, P < 0.05). ② There was no significant difference in WBC, PCT, APACHEⅡ score or computed tomography severity index (CTSI) before PCD between the two groups. There was no significant difference in the position or times of PCD procedure between the two groups, but the time interval of PCD in the CRRT group was significantly longer than that in the control group (days: 19.4±5.4 vs. 12.8±2.2, P < 0.05). Meanwhile, there was no significant difference in drainage of fluid properties, incidence of abdominal bleeding, infection, gastrointestinal fistula, endoscopic removal of necrotic tissue, laparotomy for removal of necrotic tissue or the time from PCD to endoscopy or laparotomy between two groups. However, the length of intensive care unit (ICU) stay and the length of hospital stay in the CRRT group were significantly longer than those in the control group (days: 23.2±8.5 vs. 15.3±12.1, 51.2±21.2 vs. 31.2±14.0, both P < 0.01). ③ Kaplan-Meier survival analysis showed that there was no significant differences in 1-year or 3-year cumulative survival rates between the two groups (χ21 = 0.097, P1 = 0.755; χ22 = 0.013, P2 = 0.908). Conclusions CRRT is safe and feasible in the treatment of SAP patients receiving PCD procedure. It does not increase the risk of bleeding and may delay the time interval of PCD intervention. However, it may prolong the length of ICU stay and the length of hospital stay. It should be worthy of much attention for clinicians.

Objective To evaluate the efficacy and safety of oXiris hemofilter for septic shock patients. Methods Clinical data of septic shock patients receiving continuous renal replacement therapy (CRRT) with oXiris hemofilter in department of surgical intensive care unit (SICU) of the First Affiliated Hospital of Xi'an Jiaotong University from March 1st, 2018 to July 20th, 2019 were retrospectively analyzed. The heart rate (HR), mean arterial pressure (MAP), oxygenation index (PaO2/FiO2), lactate (Lac), platelet count (PLT), serum procalcitonin (PCT), interleukin-6 (IL-6) and C-reactive protein (CRP), noradrenaline (NE) dosage, acute physiology and chronic health evaluation Ⅱ(APACHEⅡ) and sequential organ failure score (SOFA) were compared before and after oXiris treatment and the prognosis were also analyzed. Results Six patients with septic shock were included [5 males, the average age was (56.3±11.8) years old]. A total of 13 oXiris hemofilter sets were performed during treatment. Compared with before treatment, the HR, IL-6 and CRP levels were significantly decreased after treatment [HR (bpm): 93.8±9.7 vs. 133.5± 18.3, IL-6 (ng/L): 509.2±169.6 vs. 3739.8±618.2, CRP (mg/L): 169.1±148.3 vs. 277.8±68.7, all P < 0.05], MAP, PaO2/FiO2 and PLT were significantly increased [MAP (mmHg, 1 mmHg = 0.133 kPa): 73.3±2.2 vs. 63.3±1.6, PaO2/FiO2 (mmHg): 166.8±40.4 vs. 95.1±56.2, PLT (×109/L): 73.3±27.5 vs. 41.2±21.4, all P < 0.05]; meanwhile, NE dosage, APACHEⅡ and SOFA scores were significantly decreased [NE (μg·kg-1·min-1): 0.4±0.3 vs. 1.2±0.7, APACHEⅡ:18.8±6.9 vs. 30.0±7.3, SOFA: 11.7±4.2 vs. 17.3±2.1, all P < 0.05]. Although Lac and PCT decreased after treatment, there was no significant difference [Lac (mmol/L): 3.5±2.1 vs. 6.1±3.2, PCT (μg/L): 37.7±48.3 vs. 85.1±32.8, both P > 0.05]. At the end, 3 of the 6 patients survived and the others were discharged again medical advice. The length of SICU stay was 3 to 23 days, with an average of (13.0±8.5) days. No adverse events occurred during the treatment. Conclusion oXiris hemofilter can effectively remove inflammatory mediators in circulation, significantly improve hemodynamic status and severity, and may be considered as a safe and reliable treatment modality for septic shock patients.

Objective:To construct a prediction model for the prognosis of breast cancer patients with long non-coding RNA expression characteristics.Methods:To construct a long non-coding RNA(LncRNA) model for predicting the prognosis of breast cancer patients.Methods Analyzing LncRNA expression profiles and clinical characteristics of 1 081 breast cancer patients in the cancer genome atlas (TCGA) database.Performing differential expression analysis and univariate analysis on 112 paired breast cancer and normal breast tissues′ transcriptome sequencing data in the TCGA database, and screened for differentially expressed (DELncRNAs) that significantly correlated with the prognosis of BRCA (To reduce batch effects, sequencing data has been normalized using the DESeq function). One thousand eighty-one breast cancer patients were randomly divided into two groups: training set (541) and validation set (540). Performing Cox proportional hazard regression using DELncRNAs and establishing a multi-LncRNA prognosis model in the training set, followed by proportional hazards assumption test(PH assumption test). Patients were divided into high-risk and low-risk groups based on calculated risk score.Kaplan-Meier method was used for survival analysis, and 540 patients′ data were used for validation.To evaluate the prognostic value of the model in patients with squamous cell carcinoma of the lung and hepatocarcinoma in TCGA database.Gene Set Enrichment Analysis (GSEA) was used to analyze the specific mechanism of lncrna affecting the survival of patients.Results:There were 2815 differentially expressed genes screened by transcriptome sequencing, 91 of which were significantly related to the prognosis of breast cancer patients ( P<0.05). Based on the Cox regression analysis of 91 delncrna expression data from 541 breast cancer patients in training set, a Cox proportional risk regression model was constructed based on 5 LncRNA (training set AUC=0.746, validation set AUC=0.650): AC004551.1, MTOR-AS1, KCNAB1-AS2, FAM230G and LINC01283, and PH assumption test( P=0.388). K-M survival analysis showed that the survival time of high-risk group was significantly worse than that of low-risk group (median survival time: 7.049 and 12.21 years, HR 0.367, 95% CI0.228-0.597, P<0.001), and the survival time of high-risk group was significantly shorter than that of low-risk group (median survival time: 7.57 and 10.85 years, HR 0.412, 95% CI0.214-0.793, P<0.001). Similar prediction results were also obtained in other cancer species of TCGA: lung squamous cell carcinoma ( HR 0.604, 95% CI0.383-0.951, P=0.007) and liver cell carcinoma ( HR 0.551, 95% CI0.307-0.987, P=0.011). GSEA results suggested that the expression patterns of the above five LncRNA were related to the cell cycle regulation of tumor cells. Conclusion:The prognostic model constructed based on expression profile of AC004551.1, MTOR-AS1, KCNAB1-AS2, FAM230G and LINC01283 can be used to predict the prognosis of breast cancer patients, which is helpful to further guide clinical treatment.

Nonalcoholic fatty liver disease (NAFLD), especially nonalcoholic steatohepatitis (NASH), is a common hepatic manifestation of metabolic syndrome. However, there are no effective therapy to treat this devastating disease. Accumulating evidence suggests that the generation of elastin-derived peptides (EDPs) and the inhibition of adiponectin receptors (AdipoR)1/2 plays essential roles in hepatic lipid metabolism and liver fibrosis. We recently reported that the AdipoR1/2 dual agonist JT003 significantly degraded the extracellular matrix (ECM) and ameliorated liver fibrosis. However, the degradation of the ECM lead to the generation of EDPs, which could further alter liver homeostasis negatively. Thus, in this study, we successfully combined AdipoR1/2 agonist JT003 with V14, which acted as an inhibitor of EDPs-EBP interaction to overcome the defect of ECM degradation. We found that combination of JT003 and V14 possessed excellent synergistic benefits on ameliorating NASH and liver fibrosis than either alone since they compensate the shortage of each other. These effects are induced by the enhancement of the mitochondrial antioxidant capacity, mitophagy, and mitochondrial biogenesis via AMPK pathway. Furthermore, specific suppression of AMPK could block the effects of the combination of JT003 and V14 on reduced oxidative stress, increased mitophagy and mitochondrial biogenesis. These positive results suggested that this administration of combination of AdipoR1/2 dual agonist and inhibitor of EDPs-EBP interaction can be recommended alternatively for an effective and promising therapeutic strategy for the treatment of NAFLD and NASH related fibrosis.

BACKGROUNDDry eye is a multifactorial disease of the tears and the ocular surface. This study aimed to investigate the clinical efficacy of a non-steroidal anti-inflammatory drug, pranoprofen, in the treatment of dry eye.

METHODSIt is a prospective, multi-center, randomized, controlled, parallel group study. One hundred and fifteen patients with mild to moderate dry eye disease (55-60 in each treatment group) participated in this multi-center study. Patients were randomly administered with eyedrops containing 0.1% pranoprofen (PRA) plus 0.1% sodium hyaluronate (SH) or SH only, three times daily for 28 days, followed by a 1-week after treatment observation. Dry eye symptom score (DESS), fluorescein corneal staining (FLCS), tear break-up time (TBUT), and Shirmer 1 tear test (ST1, without anesthesia) were evaluated or conducted before treatment and at each study visit. Conjunctival impression cytology was taken from the patients treated with PRA plus SH before and after treatment and real-time polymerase chain reaction (RT-PCR) was performed to detect the changes of human leukocyte antigen DR (HLA-DR) and intercellular adhesion molecule 1 (ICAM-1).

RESULTSPatients treated with PRA plus SH showed gradual improvements of DESS, FLCS, and TBUT. Between-group comparisons of FLCS and TBUT have statistically significant differences from day 14. Good tolerance with no severe adverse events was found in both groups. Patients treated with PRA plus SH had a reduced expression level of HLA-DR and were statistically different after 28 days of therapy.

CONCLUSIONSThe application of PRA at a dose of 0.1% was well tolerated and benefited to the patients with mild to moderate dry eye disease. The underlying mechanism of its efficacy may be associated with the reduction of inflammatory factors of conjunctival epithelial cells.

Adult ; Benzopyrans ; therapeutic use ; Dry Eye Syndromes ; drug therapy ; Humans ; Middle Aged ; Ophthalmic Solutions ; therapeutic use ; Propionates ; therapeutic use

In clinical application, a microneedle system that continuously delivers drugs is of great value for the delivery of some vaccines and hormone drugs. In this study, a controlled-release chitosan-based microneedle array (PVA/CS-MN) was designed, combining microneedle patches with drugs for controlled-release of drugs. Here we report the optimization of the preparation process of PVA/CS-MN. The appearance, morphology, mechanical properties, dissolution and swelling properties, and in vitro penetration properties of the MN arrays were characterized. The PVA/CS-MN prepared by the optimal process showed good morphology and mechanical properties. PVA/CS-MN can smoothly open microchannels on the skin and achieve controllable dissolution and swelling functions. Ascorbic acid (l-ascorbic acid) was used as a model drug to prepare a Vc-PVA/CS-MN. In vitro transdermal diffusion experiments showed that the Vc-PVA/CS-MN released about 57% of the drug within 1 h. About 66.7% of the drug was slowly released within 12 h, and a total of 92% of the drug was released after 7 days. The controllable sustained-release properties and excellent drug delivery efficiency of PVA/CS-MN provide a new option for sustained transdermal drug delivery.
Ascorbic Acid ; Chitosan ; Delayed-Action Preparations ; Drug Delivery Systems ; Hormones ; Vaccines

SARS-CoV-2 can cause multiple organ injuries in some susceptible people in a short time, which seriously threatens the health and safety of people, and intensive care and multiple extracorporeal organ support are important means of treatment. Although many experts’ consensus and clinical guidelines have been published, a series of clinical problemsstill exist during the treatment procedure, and no consensushas not been reached until now. Therefore,in this paper wemake some reflections and explorations to provide experience and help for clinicians.

Objective: To evaluate the efficacy and safety of oXiris hemofilter for septic shock patients. Methods: Clinical data of septic shock patients receiving continuous renal replacement therapy (CRRT) with oXiris hemofilter in department of surgical intensive care unit (SICU) of the First Affiliated Hospital of Xi'an Jiaotong University from March 1st, 2018 to July 20th, 2019 were retrospectively analyzed. The heart rate (HR), mean arterial pressure (MAP), oxygenation index (PaO₂/FiO₂), lactate (Lac), platelet count (PLT), serum procalcitonin (PCT), interleukin-6 (IL-6) and C-reactive protein (CRP), noradrenaline (NE) dosage, acute physiology and chronic health evaluationⅡ(APACHEⅡ) and sequential organ failure score (SOFA) were compared before and after oXiris treatment and the prognosis were also analyzed. Results: Six patients with septic shock were included [5 males, the average age was (56.3±11.8) years old]. A total of 13 oXiris hemofilter sets were performed during treatment. Compared with before treatment, the HR, IL-6 and CRP levels were significantly decreased after treatment [HR (bpm): 93.8±9.7 vs. 133.5±18.3, IL-6 (ng/L): 509.2±169.6 vs. 3 739.8±618.2, CRP (mg/L): 169.1±148.3 vs. 277.8±68.7, all P < 0.05], MAP, PaO₂/FiO₂ and PLT were significantly increased [MAP (mmHg, 1 mmHg = 0.133 kPa): 73.3±2.2 vs. 63.3±1.6, PaO₂/FiO₂ (mmHg): 166.8±40.4 vs. 95.1±56.2, PLT (×10⁹/L): 73.3±27.5 vs. 41.2±21.4, all P < 0.05]; meanwhile, NE dosage, APACHEⅡ and SOFA scores were significantly decreased [NE (μg·kg^-1·min^-1): 0.4±0.3 vs. 1.2±0.7, APACHEⅡ: 18.8±6.9 vs. 30.0±7.3, SOFA: 11.7±4.2 vs. 17.3±2.1, all P < 0.05]. Although Lac and PCT decreased after treatment, there was no significant difference [Lac (mmol/L): 3.5±2.1 vs. 6.1±3.2, PCT (μg/L): 37.7±48.3 vs. 85.1±32.8, both P > 0.05]. At the end, 3 of the 6 patients survived and the others were discharged again medical advice. The length of SICU stay was 3 to 23 days, with an average of (13.0±8.5) days. No adverse events occurred during the treatment. Conclusion oXiris hemofilter can effectively remove inflammatory mediators in circulation, significantly improve hemodynamic status and severity, and may be considered as a safe and reliable treatment modality for septic shock patients.