Humans ; Aged ; Lung Diseases ; Pneumonia/drug therapy* ; Adrenal Cortex Hormones/therapeutic use* ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Administration, Inhalation ; Community-Acquired Infections/drug therapy*

Aim To explore the role of the ten-eleven translocation 2(TET2)/ubiquinol-cytochrome C reductase hinge protein(UQCRH)axis in the inhibition of vascular smooth muscle cell(VSMC)apoptosis by fibroblast growth fac-tor-2(FGF-2).Methods Cultured VSMCs were divided into control group,FGF-2 group,and FGF-2+fibroblast growth factor receptor(FGFR)pan-inhibitor LY2874455 group.VSMCs overexpressing TET2(OETET2)or UQCRH(OEUQCRH)were divided into control group,FGF-2 group,and OETET2+FGF-2 or OEUQCRH+FGF-2 group.Ho-echst33342 and PI staining were used to detect cell apoptosis,CCK-8 assay was employed to measure cell proliferation,and Western blot was used to examine the expression levels of apoptosis-related proteins pro-Caspase-3,cleaved Caspase-3,Bax,Bcl-2,as well as TET2 and UQCRH.The NCBI and methprimer websites were utilized for predicting and analyzing CpG island sites in the UQCRH gene promoter.Results FGF-2 could inhibit VSMC apoptosis,promote proliferation,downregulate apoptosis-related proteins cleaved Caspase-3,Bax,TET2,and UQCRH expression,and upregulate anti-ap-optotic protein Bcl-2 expression(compared with control group,P＜0.05).However,it did not affect pro-Caspase-3 ex-pression(compared with control group,P＞0.05).LY2874455 could counteract the effects of FGF-2(compared with FGF-2 group,P＜0.05).Overexpression of TET2 or UQCRH could reverse the anti-apoptotic and pro-proliferative effects of FGF-2 on VSMC,with upregulation of apoptosis-related protein expression and downregulation of anti-apoptotic protein expression(compared with FGF-2 group,P＜0.05).The UQCRH gene promoter region contained three CpG islands.Overexpression of TET2 could upregulate UQCRH expression in VSMC treated with FGF-2(compared with FGF-2 group,P＜0.05).Conclusion FGF-2,by inhibiting TET2 expression and UQCRH expression,reduces VSMC apoptosis and promotes its proliferation.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Bioluminescence is a widespread phenomenon in nature, and luminescent organisms can be found both on land and in the ocean. Among them, luciferase based bioluminescence systems have been widely studied, inspiring the exploration of genetic and epigenetic aspects and the development of a series of related assays for in vivo and in vitro studies. This paper summarizes the recent developments of luciferase based bioluminescence assays in terms of bioluminescence systems, types of luciferases, and the development and application of luciferase bioluminescence assays.

Objective:To construct a clinical predictive model of severe adenovirus pneumonia(SAP)in children using random forest and verify it.Methods:The clinical, laboratory and imaging data of 542 children with adenovirus pneumonia treated in Tianjin Children′s Hospital from January 2019 to January 2021 were analyzed retrospectively.The research object was randomly divided into training dataset and validation dataset(8∶2).The training dataset screened the predictors of SAP of pneumonia through random forest and established a prediction model, and the prediction model was expressed visually by the nomogram.In the validation dataset, the receiver operating characteristic curve(ROC)and sensitivity, specificity, error rate and confusion matrix were used to validate it.Results:A total of 439 children were in the training dataset, and 187 cases(42.60%)of the training data was divided as severe type.A total of 103 children were in validation dataset, and 44 cases(42.71%)of the validation dataset was divided as severe type.The percentage of monocytes(M%), PLT, AST, IL-6, the peak of body temperature, pulmonary inflammation of the consolidation and patchy shadowing were independent predictors of SAP in children.The area under the ROC curve of the training dataset and the validation dataset was 0.95(95% CI: 0.92~0.98)and 0.92(95% CI: 0.82~0.99), respectively.The accuracy, sensitivity, specificity, positive predictive value and negative predictive value of the training dataset were 0.994, 1.000, 0.987, 0.998, 1.000 and in validation dataset were 0.752, 0.990, 0.514, 0.945 and 0.857, respectively. Conclusion:The predictive model has good discriminant ability, and the early clinical and hematological indexes are helpful to improve the identification and screening of SAP in children.

Objective    To evaluate the safety and application value of three-dimensional reconstruction for localization of pulmonary nodules in thoracoscopic lung wedge resection. Methods    The clinical data of 96 patients undergoing thoracoscopic lung wedge resection in our hospital from January 2019 to August 2020 were retrospectively reviewed and analyzed, including 30 males and 66 females with an average age of 57.62±12.13 years. The patients were divided into two groups, including a three-dimensional reconstruction guided group (n=45) and a CT guided Hook-wire group (n=51). The perioperative data of the two groups were compared. Results    All operations were performed successfully. There was no statistically significant difference between the two groups in the failure rate of localization (4.44% vs. 5.88%, P=0.633), operation time [15 (12, 19) min vs. 15 (13, 17) min, P=0.956], blood loss [16 (10, 20) mL vs. 15 (10, 19) mL, P=0.348], chest tube placement time [2 (2, 2) d vs. 2 (2, 2) d, P=0.841], resection margin width [2 (2, 2) cm vs. 2 (2, 2) cm, P=0.272] or TNM stage (P=0.158). The complications of CT guided Hook-wire group included pneumothorax in 2 patients, hemothorax in 2 patients and dislodgement in 4 patients. There was no complication related to puncture localization in the three-dimensional reconstruction guided group. Conclusion    Based on three-dimensional reconstruction, the pulmonary nodule is accurately located. The complication rate is low, and it has good clinical application value.

Objective ToexplorethevalueofspectralCTimaginginmultiGparameterquantitativeanalysisoflungcancerwithdifferent pathologicaltypes.Methods SpectralCTimagesof72patientswithlungcancerprovedbypathologywereanalyzed,includingadenocarcinoma (ADC)in44cases,squamouscellcarcinoma(SQCC)in23casesandsmallcelllungcancer(SCLC)in5cases.Theslopeof40－100keVspectralattenuationcurve(λH),effectiveatomicnumber(EffectiveGZ),Calciumconcentration,hydroxyapatite(HAP)concentration, normalizediodineconcentration(NIC)and Waterconcentration were measuredandcomparedrespectively.The O n eG W a y analysisof variance (ANOVA ) was used and a value of P＜0.05 was considered statistically significant.Results (1 )O n plain C T ,there were statisticallysignificantdifferencesinEffectiveGZandλHamongthreeGdiseasegroups(F＝3.423,P＝0.04,F＝3.476,P＝0.038,respectively). (2)IncontrastGenhancedarterialphase,theWaterconcentrationandλHshowedstatisticallysignificantdifferencesamongthreegroups (F＝6.303,P＝0.003,F＝5.833,P＝0.005,respectively).(3)Invenousphase,thedifferenceinNICandλH wasstatisticallysignificant amongthegroups(F＝3.974,P＝0.023,F＝6.766,P＝0.002,respectively).(4)Apairwisecomparisonshowedtherewerestatistically significantdifferencesinallquantitativeparametersofspectralCTbetweenADCandSQCCgroups.ROCcurveanalysisshowedthat thosequantitativeparametersinvenousphaseappearedtohavehighdiagnosticefficiencyindifferentiatingADCfromSQCC,especiallyfor theλHinVP,withaAUCof0.754,sensitivityof79.5%,specificityof69.6%andthresholdvalueof1.78.Conclusion CTSpectral multiGparameterimagingprovidesanewsupplementarymethodforpreoperativediagnosisofADCandSQCC,andλHinvenousphase hasthehighestvalueindifferentiatingADCfromSQCC.

Objective To investigate the effect of Liensinine on lipopolysaccharide ( LPS)-induced acute lung injury (ALI) in mice. Methods BALB/c mice were randomly divided into six group: control group, LPS group, LPS+Liensinine (2 mg/kg, 4 mg/kg, 8 mg/kg) groups, and dexamethasone group. Acute lung injury in mice was induced by nasal instillation of LPS. After 12 h, the pathological changes of lung tissue were observed. The levels of TNF-α, IL-6 and IL-1β in bronchoalveolar lavage fluid (BALF) were detected by ELISA. The number of neutrophils in BALF was detected using Wright-Giemsa staining. Total protein content was detected by BCA protein quantification assay. The pulmonary capillary permeability was examined with Evans blue. The MPO activity, MDA content, SOD activity, and GSH content in lung homogenate supernatant were detected by spectrophotometry. The content of ROS in lung tissue was detected by flow cytometry. Results The LPS group showed inflammatory cell infiltration, thickening of bronchial alveolar wall and pulmonary congestion in the lung tissue, while Liensinine improved the lung injury. In the LPS group, the contents of TNF- α, IL-6 and IL-1β in BALF were significantly increased, the number of neutrophils and the content of total protein were significantly increased, pulmonary capillary permeability, MPO activity and MDA content were increased, SOD activity and GSH content were decreased, the content of ROS was increased; while the Liensinine group reduced the contents of TNF-α, IL-6, IL-1β in BALF, reduced the number of neutrophils and total protein content, decreased the pulmonary capillary permeability, attenuated MPO activity and MDA contents and increased SOD activity and GSH content, and reduced ROS content in the LPS-challenged lung tissue. Conclusions Liensinine protects mice from LPS-induced acute lung injury by its anti-inflammatory and anti-oxidative activities.

Objective: To analyze the clinical effect of the endoscopic holistic rhinoplasty in order to improve its clinical application and safety. Methods: The patients with external nasal deformities and complained nasal congestion were assessed before operation and undergoing endoscopic holistic rhinoplasty from January 2015 to June 2017. Therefore, the internal nasal plasty and external nasal plasty were performed simultaneously, so as to correct the abnormalities of internal and external nasal structures, restore nasal ventilation function, and achieve the purpose of external nose cosmetology. The nasal congestion, visual analog scale, rhinomanometry and acoustic rhinometry and patient satisfaction were used to assess the efficacy. SPSS 21.0 was used for statistical analysis. Paired sample t test was used for preoperative and postoperative comparison, and P<0.05 was taken as statistically significant difference. Results: All the patients were followed up from one month to one year without complications. Postoperative nasal obstruction VAS score (1.63±0.76) was significantly lower than preoperative(6.35±0.65) (t=6.315, P<0.001). The minimum nasal cross-sectional area was (0.38±0.29) cm² preoperatively and (0.52±0.14) cm² postoperatively, which was significantly higher than that before the operation (t=9.732, P<0.001). Postoperative nasal volume (9.21±3.23) cm³ was significantly higher than preoperative (6.44 ± 1.04) cm³ (t=9.559, P<0.001), and postoperative nasal resistance (0.26 ± 0.07) kPa·s/L was lower than preoperative (0.65±0.21) kPa·s/L(t=7.524, P<0.001). The postoperative satisfaction survey result were very satisfactory in 41 cases (78.85%), accounted satisfaction in 11 cases (21.15%). Conclusions The application of the endoscopic holistic rhinoplasty has a good clinical effect and a high degree of satisfaction.

Objective: To investigation the situation of cold chain on vaccine in parts of Zhejiang Province and to provide recommendations for the management. Methods: From October to December, 2016, we each selected an immunization clinic in Cangnan County of Wenzhou, Yongkang City of Jinhua, Jianggan District of Hangzhou. Temperature recorder and vaccine viral monitor (VVM) labels were used to monitor the cold chain during all the storage and transportation process. In Jianggan District, we use optical density sensor to detected 20 VVM labels every time when the vaccine was stock in and out. Results: In total, 54 958 records were collected by temperature recording devices in all the three immunization clinic. 275 records exceeded the temperature limit required for store and transportation, of which 270 (98.2%) were above 8 ℃ and 5 (1.9%) were under 2 ℃. Excessive temperature exposure mainly occurred during the transportation (38.2%, n=105), followed by storage process in CDCs at different levels (26.2%, n=72), stock in and out (20.7%, n=50) and storage in the refrigerators in immunization clinics (14.9%, n=41). The average optical density difference between VVM labels and the reference circular decreased from 0.404 to 0.344 when the vaccines were delivered from the Zhejiang provincial CDC to immunization clinics. The color of VVMs did not significantly changed before use. Conclusions The potential risk of vaccine cold chain in the monitoring sites is over-temperature. The weak links of cold chain management include the transportation, storage process, and stock in and out.