Objective To evaluate the clinical value of free glycoprotein non-metastatic melanoma protein B(GPNMB)as a drug resis-tance and prognostic marker for non-small cell lung cancer(NSCLC)patients with epidermal growth factor receptor(EGFR)amplifica-tion accompanied by mutations.Methods Fifty-five cases of NSCLC patients with EGFR amplification associated with mutations who received treatment from March 2018 to September 2019 were included as the observation group.All patients received an EGFR-tyrosine kinase inhibitor(EGFR-TKI)as the first-line treatment;67 blood samples from the physical examination center during the same period were randomly included as healthy control.We compared the expression levels of free GPNMB between the two groups,explored the correlation between GPNMB expression and the clinicopathological information in the observation group;and combined the clinical efficacy to evaluate its value as a drug resistance marker.Through follow-up,the progress free survival(PFS)of patients was statistically analyzed,and through multivariate Cox regression analysis,independent risk factors affecting the survival in the observation group were explored.Results Compared with that in the control group,the expression level of free GPNMB in the observation group was signi-ficantly up-regulated.The expression level of free GPNMB in the observation group is significantly related to the clinical efficacy of EGFR-TKI(P = 0.016).Patients with high GPNMB expression have significantly stronger drug resistance,and patients with high GPNMB expression have significantly shorter PFS duration(P = 0.032).A high free GPNMB expression(HR = 4.029,95%CI:1.942-8.358,P＜0.001)is also an independent risk factor affecting patient survival.Conclusion The expression level of free GPNMB in patients with EGFR amplification accompanied by mutant NSCLC is significantly up-regulated,and its high expression is significantly related to the enhancement of the patient's drug resistance.High GPNMB expression is significantly related to the poor prognosis of patients and is an independent risk factor affecting patient survival.

Objective:To study the clinical value of lung ultrasound score (LUSsc) within 2 h after birth for pulmonary surfactant (PS) use in preterm infants with respiratory distress syndrome (RDS).Methods:From July 2019 to May 2021, preterm infants with RDS hospitalized in our hospital and received pulmonary ultrasound within 2 h after birth were prospectively enrolled. 12-area LUSsc was calculated. The infants were assigned into <32 weeks group and 32-36 weeks group according to gestational age (GA). Simple random sampling was carried out in each group with 1/5 as the validation set and the other 4/5 as the training set. The infants were also assigned into PS group and non-PS group according to PS usage within 24 h after birth. Receiver operator characteristic (ROC) curve of LUSsc predicting PS usage was drawn and validated.Results:A total of 857 RDS infants were enrolled, including 313 in <32 weeks group and 544 in 32-36 weeks group. For <32 weeks group, area under curve (AUC) of LUSsc>8.5 predicting PS use was 0.779 (95% CI 0.722-0.837), with 76.4% sensitivity and 81.4% specificity. The accuracy of using LUSsc>8.5 as cut-off predicting actual clinical PS application was 82.3% (Kappa value 0.692, P<0.05, McNemar's test P>0.05).For 32-36 weeks group, AUC of LUSsc>9.5 predicting PS use was 0.785 (95% CI 0.723-0.848), with 71.1% sensitivity and 81.7% specificity. The accuracy of using LUSsc>9.5 as cut-off predicting actual clinical PS application was 92.6% (Kappa value 0.772, P<0.05, McNemar's test P>0.05). Conclusions:LUSsc within 2 h after birth is independent predictor of PS use in preterm infants with RDS. For <32 weeks group, LUSsc>8.5 suggests PS application and for 32-36 weeks group the cut-off is LUSsc>9.5.

Objective:To explore whether BHLHE40 can affect the sensitivity of thyroid cancer (TC) cells to cisplatin by activating oxidative phosphorylation (OXPHOS) pathway by targeting high mobility group A2 (HMGA2) .Methods:The mRNA expression of HMGA2 and its upstream transcription factor BHLHE40 in TC tissues was analyzed by TCGA-THCA and hTFtarget online databases. The si-HMGA2, oe-HMGA2, oe-BHLHE40, negative control si-NC and oe-NC were transfected into TC cells (K1 and SW579) by liposome transfection method. The mRNA expression levels of BHLHE40 and HMGA2 in TC cells (SW579, FTC-133, and K1) and normal thyroid cells (Nthy ori3-1) were detected by real-time quantitative PCR (qRT-PCR). The cell viability was detected by MTT assay, the half inhibitory concentration (IC 50) value of cisplatin was calculated by CCK-8 assay, the apoptosis level was detected by flow cytometry, and the expression of OXPHOS complex was detected by Western blotting. Seahorse XFe 96 was used to analyze the oxygen consumption rate of the TC cells. Dual-luciferase assay and chromatin immunoprecipitation (ChIP) assay were used to analyze the binding relationship between BHLHE40 and HMGA2. Results:TCGA database results showed that the mRNA expression levels of HMGA2 and BHLHE40 in TC tissues (10.57±2.58, 13.89±1.13) were higher than those in normal thyroid tissues (4.82±1.69, 12.28±1.01), with statistically significant differences ( t=16.69, P<0.001; t=10.43, P<0.001). The results of qRT-PCR showed that the relative mRNA expression levels of HMGA2 in normal thyroid cells (Nthy ori3-1) and TC cells (SW579, FTC-133, and K1) were 1.00±0.13, 2.94±0.23, 4.71±0.41 and 6.29±0.49, while those of BHLHE40 were 1.00±0.12, 2.60±0.23, 3.39±0.35 and 6.18±0.51 respectively, both with statistically significant differences ( F=130.50, P<0.001; F=125.20, P<0.001). Further pairwise comparison showed that mRNA expression levels of HMGA2 and BHLHE40 in TC cells were significantly higher than those in normal thyroid cells (all P<0.001). According to MTT experimental results, si-HMGA2 treatment significantly reduced the cell viability of K1 cells compared to the si-NC group (all P<0.05). In addition, compared to the oe-NC group, oe-HMGA2 treatment significantly increased the cell viability of SW579 cells (all P<0.05). Compared to the oe-NC+DMSO group, the oe-HMGA2+DMSO group showed enhanced cell viability of SW579 cells, while the OXPHOS pathway inhibitor Gboxin was able to reverse the effect of overexpressing HMGA2 on cell viability (all P<0.05). The results of flow cytometry and CCK-8 experiments showed that compared to the si-NC group (apoptosis level: 6.19%±0.28%; cisplatin IC 50 value: 17.47 μmol/L), knocking down HMGA2 could increase the apoptosis level (11.96%±0.32%; t=19.17, P<0.001) and cisplatin sensitivity (IC 50 value: 1.49 μmol/L) of K1 cells. In addition, compared to the oe-NC group (apoptosis level: 9.98%±0.32%; cisplatin IC 50 value: 8.17 μmol/L), overexpressing HMGA2 significantly decreased the apoptosis level (4.32%±0.25%; t=19.65, P<0.001) and cisplatin sensitivity (IC 50 value: 34.95 μmol/L) of SW579 cells. The results of dual-luciferase assay showed that compared with the si-NC group, knocking down the expression of BHLHE40 in human kidney epithelial 293T cells significantly reduced the luciferase activity of wild-type HMGA2 (0.31±0.02 vs. 1.00±0.11; t=10.69, P=0.004). However, there was no significant effect on the luciferase activity of mutant-type HMGA2 (1.06±0.11 vs. 1.00±0.07; t=0.80, P=0.470). ChIP results showed that the mRNA expression level of HMGA2 in K1 cells was significantly increased in the anti-BHLHE40 group (6.57±0.62) compared with the IgG group (1.00±0.10; t=15.36, P<0.001). Compared to the oe-NC+DMSO group, the oe-HMGA2+DMSO group showed decreased apoptosis level ( P<0.05) and cisplatin sensitivity of SW579 cells, with a significant increase in the expression of OXPHOS complexes Ⅰ-Ⅴ and cellular oxygen consumption rates (all P<0.05). The effect of overexpressing HMGA2 was reversed by treatment with oe-HMGA2+Gboxin (all P<0.05). The recovery experiment showed that compared to the oe-NC+si-NC group, overexpression of BHLHE40 in SW579 cells increased cell viability and the expression of OXPHOS complexes Ⅰ-Ⅴ, while decreasing apoptosis levels and increasing cellular oxygen consumption rates and cisplatin IC 50 values (all P<0.05). However, simultaneous knockdown of HMGA2 reversed the effect of overexpressing BHLHE40 (all P<0.05) . Conclusion:BHLHE40 can activate the OXPHOS pathway by targeting and regulating the expression of HMGA2, thereby affecting the sensitivity of TC cells to cisplatin.

OBJECTIVE: Identifying novel strategies to prevent particulate matter (PM)-induced lung injury is crucial for the reduction of the morbidity of chronic respiratory diseases. The combined intervention represented by herbal formulae for simultaneously targeting multiple pathological processes can provide a more beneficial effect than the single intervention. The aim of this paper is therefore to design a safe and effective medicinal and edible Chinese herbs (MECHs) formula against PM-induced lung injury. METHODS: PM-induced oxidative stress, inflammatory response and apoptosis A549 cell model were used to screen anti-oxidant, anti-inflammatory and anti-apoptotic MECHs, respectively. A network pharmacology method was utilized to rationally design a novel herbal formula. Ultra performance liquid chromatography-mass spectrometer was utilized to assess the quality control of MECHs formula. The excretion of magnetic iron oxide nanospheres of the MECHs formula was estimated in zebrafish. The MECH formula against PM-induced lung injury was investigated with mice experiments. RESULTS: Five selected herbs were rationally designed to form a new MECH formula, including Citri Exocarpium Rubrum (Juhong), Lablab Semen Album (Baibiandou), Atractylodis Macrocephalae Rhizoma (Baizhu), Mori Folium (Sangye) and Polygonati Odorati Rhizoma (Yuzhu). The formula effectively promoted the magnetic iron oxide nanospheres excretion in zebrafish. The mid/high dose formula significantly prevented PM-induced lung damage in mice by enhancing the activity of SOD and GSH-Px, reducing the MDA and ROS level and attenuating the upregulation of pro-inflammatory cytokine (IL-6, IL-8, IL-1β and TNF-α), down regulating the protein expression of NF-κB, STAT3 and Caspase-3. CONCLUSION Our findings suggest that the effective MECHs formula will become a novel strategy for preventing PM-induced lung injury and provide a paradigm for the development of functional foods using MECHs.

Objective:To explore the clinical features of patients with syndrome of intracranial hypotension (SIH) complicated by bilateral chronic subdural hematoma (CSDH).Methods:A case-control study was conducted; 16 patients with SIH complicated with bilateral CSDH (SIH group) and 32 patients with bilateral CSDH (non-SIH group) admitted to Department of Neurology and Neurosurgery, Shanghai Tenth People's Hospital Affiliated to Tongji University from January 2016 to October 2020 were selected. The differences of demographic characteristics, initial symptoms, medical history and CT image features between the two groups were compared.Results:(1) In 16 patients from the SIH group, 13 (81.3%) complained of typical postural headache symptoms, 3 (18.6%) showed fake subarachnoid hemorrhage on CT, 80.0% (12/15) showed dural diffuse enhancement on MRI, and 33.3% (5/15) showed signs of brain droop. Spinal MRI showed 27.3% patients (3/11) had signs of intracranial cerebrospinal fluid leakage. Of the 10 patients underwent bilateral trepanation and drainage, 6 experienced postoperative deterioration (4 received multiple additional surgeries including decompressive craniectomy, and 1 severe patient died in hospital after giving up treatment due to malignant tumor). (2) SIH group had significantly younger age, and significantly lower percentages of patients with limb weakness symptoms, hypertension, head trauma histories and increased hematoma pressure during trepanation and drainage, significantly lower age-adjusted comorbidities index, significantly decreased total and differential thickness of bilateral hematoma on CT, significantly shorter disease course, and statistically higher proportion of patients with postural headache and hematoma uniform density than non-SIH group ( P<0.05). Conclusion:According to age, initial symptoms and CT features, bilateral CSDH patients caused by SIH can be identified to a certain extent, and cranial and spinal MRI is recommended for definitive diagnosis of SIH.

ObjectiveTo investigate the protective effect and mechanism of Artemisia capillaris Thunb. decoction (YCHT), a classic heat-clearing and cholagogic traditional Chinese medicine (TCM) prescription, on rats with severe acute pancreatitis (SAP) induced by sodium taurocholate. MethodsA total of 30 Sprague-Dawley rats were randomly divided into sham-operation (SO) group, SAP model group, and YCHT (4.0 g/kg) treatment group, with 10 rats in each group. At 24 hours after successful modeling, pancreatic tissue and plasma samples were collected for analysis. HE staining was used to observe pathological injury of the pancreas; ELISA was used to measure the plasma levels of amylase, tumor necrosis factor-α (TNFα), and interleukin-1β (IL-1β); immunofluorescent staining was used to measure the fluorescence intensity of LC-3 protein, and TUNEL was used to measure cell apoptosis. Western blot was used to measure the protein expression of LC-3, Beclin-1, X-linked inhibitor of apoptosis protein (XIAP), caspase-3, and nuclear factor-kappa B (NF-κB) in the pancreas, and quantitative real-time PCR was used to measure the expression levels of lncRNA PVT1 and miRNA-30a-5p. A one-way analysis of variance and the Tukey’s test were used to analyze the differences between multiple independent samples. ResultsYCHT significantly alleviated the pathological injury of the pancreas of SAP rats, such as edema, necrosis, hemorrhage, and inflammatory cell infiltration. Compared with the SO group, the SAP group had significant increases in the plasma levels of amylase and the inflammatory factors TNFα and IL-1β, and there were significant reductions in the plasma levels of amylase, TNFα, and IL-1β after YCHT treatment (all P＜0.05). Compared with the SO group, the SAP group had significant increases in LC-3II/LC-3I ratio and the protein expression of Beclin-1, XIAP, caspase-3, and NF-κB, and compared with the SAP group, the YCHT group had significant reductions in LC-3II/LC-3I ratio and the protein expression of Beclin-1, XIAP, and NF-κB (all P＜0.05). Compared with the SO group, the SAP group had a significant increase in the expression of lncRNA PVT1 and a significant reduction in the expression of miRNA-30a-5p in the pancreas (both P＜0.05), and compared with the SAP group, the YCHT group had a significant reduction in the expression of lncRNA PVT1 and a significant increase in the expression of miRNA-30a-5p (both P＜0.05). ConclusionCell autophagy and apoptosis mediated by lncRNA PVT1/miRNA-30a-5p may be a drug target for YCHT treatment of SAP, which provides experimental and theoretical bases for further development of the TCM prescription YCHT for the treatment of SAP.

OBJECTIVES: To study the effect and mechanism of low-level laser irradiation (LLLI) on lipopolysaccharide (LPS)-induced inflammatory injury of human periodontal ligament fibroblasts (hPDLFs). METHODS: hPDLFs were inoculated into well plates and randomly divided into the normal group, LPS group, and LPS+LLLI group. The cells in the normal group were cultured in conventional medium. The hPDLFs in the LPS and LPS+LLLI groups were cultured in RPMI1640 medium containing 1 mg·L RESULTS: Compared with the normal group, the LPS group showed increased apoptosis rate of hPDLFs and intracellular free Ca CONCLUSIONS LLLI has a protective effect on the inflammatory injury of hPDLFs induced by LPS, and the effect is most obvious when the irradiation intensity is 4 J·cm
Cells, Cultured ; Fibroblasts ; Humans ; Interleukin-1beta ; Lasers ; Lipopolysaccharides ; Periodontal Ligament ; Tumor Necrosis Factor-alpha

By collecting and analyzing the explanation/conception, acupoint name, acupoint location, indications, acupuncture and moxibustion techniques and contraindications of
Acupuncture ; Acupuncture Points ; Acupuncture Therapy ; Humans ; Meridians ; Moxibustion

Objective:To study the cause of 1 PICC catheter rupture, and discuss the nursing interventions.Methods:Comprehensive analysis was carried out on the review of the use and maintenance of PICC catheter, patient's life style and catheter quality test.Results:The main reasons of PICC catheter rupture were the pinch-off syndrome and catheter plug caused by gaming disorders and non-canonical maintenance of PICC outhospital.Conclusions:With the growing of video game players, gaming disorder may be one acquired factor of PICC catheter rupture. To reduce the occurrence of PICC catheter rupture, prompt identification of and timely intervention to gaming disorder and intensified outhospital care are paramount. The predictive diagnostic tests of catheter ectopia based on clinical syndromes, physical signs and catheter state, are helpful for the early recognition and treatment of PICC catheter rupture, followed by the risk reduction of pulmonary embolism.

Objective To study the diagnostic value of Japan narrow band imaging expert team ( JNET) classification for differentiating pathological type of colorectal lesions. Methods A total of 418 colorectal lesions were retrospectively diagnosed by magnifying endoscopy with narrow band imaging ( ME-NBI) using JNET classification by two inexperienced doctors after a short time of training in JNET classification. Then lesions were diagnosed with Sano classification by the two doctors. Diagnostic results were compared with histologic findings as a golden standard. Results The sensitivity, specificity, and accuracy of JNET classification and Sano classification for neoplastic lesion differentiation were 98. 2％ VS 98. 5％, 77. 8％ VS 66. 7％, and 96. 9％ VS 96. 4％, respectively ( all P>0. 05 ) . These indicators for diagnosing cancerous lesions, including high grade intraepithelial neoplasia, intramucosal carcinoma and submucosal carcinoma, were 66. 7％ VS 80. 2％ ( P=0. 023) , 87. 6％ VS 79. 5％ ( P=0. 006) , and 82. 1％ VS 79. 7％( P=0. 379 ) , respectively, and those for predicting submucosal deep invasive cancers were 34. 8％ VS 39. 1％, 100. 0％ VS 99. 0％, and 96. 4％ VS 96. 3％, respectively ( all P>0. 05) . The diagnostic accuracy of JNET classification for differentiating neoplastic lesions were 95. 2％ in those with diameter <10 mm, 97. 0％ in 10～<20 mm, and 97. 8％ in ≥20 mm (P=0. 483), this finding were 95. 2％, 85. 1％ and 72. 1％ for cancer, respectively ( P<0. 0001 ) , and 100％, 96. 3％, and 94. 4％ for submucosal deep invasive cancer, respectively (P=0. 026). Shape and location of colorectal lesions showed no significant effect on the diagnostic efficacy of JNET classification. Conclusion JNET classification is valuable for doctors without experience of ME-NBI in diagnosing colorectal lesions and the efficiency is slightly superior to Sano classification. However, the accuracy of diagnosis for cancer with diameter ≥20 mm need to be improved.