Predictive value of serum glycoprotein non-metastatic melanoma protein B in patients with non-small cell lung cancer accompanied by epidermal growth factor receptor amplification with mutation / 中国医科大学学报

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.

Research on BHLHE40 targets HMGA2 to reduce the sensitivity of thyroid cancer cells to cisplatin through activating the oxidative phosphorylation pathway / 国际肿瘤学杂志

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.

Clinical features of patients with syndrome of intracranial hypotension complicated by bilateral chronic subdural hematoma / 中华神经医学杂志

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.

Artemisia capillaris Thunb. decoction exerts a protective effect on rats with severe acute pancreatitis by regulating the lncRNA PVT1/miRNA-30a-5p signaling pathway / 临床肝胆病杂志

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.

Clinical significance and change curve of ADH in central diabetes insipidus after neurosurgical operation / 吉林大学学报(医学版)

Objective To study the change curve of ADH in central diabetes insipidus after neurosurgical operation,and analyse the clinical significance of differentiating the types of central diabetes insipidus through the change curve.Methods The serum level of ADH was observed in 158 central diabetes insipidus patients undergone neurosurgical operation.The change curve of ADH in different types of central diabetes insipidus were painted,including transient,continuous and triphasic diabetes insipidus.Results The serum concentrations of ADH in transient and triphasic diabetes insipidus decreased after operation,and arrived the low point(41.7% and 63.6% of the preoperative serum concentration of ADH) after 2 d. The serum concentration of ADH in transient diabetes insipidus recovered to the preoperative level after 10 d.The serum concentration of ADH in triphasic diabetes insipidus arrived the peak after 7 d,then descended.The serum concentration of ADH in continuous diabetes insipidus fell in postoperative 1 d,and arrived the low point(33.3% of the preoperative serum level of ADH) after 7 d.The serum concentration of ADH in continuous diabetes insipidus postoperative 2 weeks was lower than preoperation.Conclusion Though the concentration change curve of ADH,the transient diabetes insipidus can be distinguished from continuous and triphasic diabetes insipidus.The correct differential diagnosis and seemly treatment are beneficial for patients' prognosis.

Assessment of general and trace elements in CSF of patients with spinal cord injury / 中国康复理论与实践

@#Objective To analyze general and trace elements in cerebral spinal fluid (CSF)of patients with spinal cord injury (SCI). Methods To assess contents of general and trace elements (K, Na, Ca, Mg, Zn, Mn, Fe, Cu) in CSF of six SCI patients using ICP-AES. Results Compared with normal value, contents of Ca and Zn were significantly decreased (P<0.01), Fe and Mn were significantly increased (P<0.01), but no significant differences for Na, Mg, K and Cu in CSF of SCI patients. Conclusion The excitation of central nerve system in SCI patients may be higher than normal people indeed.

Progress of clinical pharmacological study on rifabutin / 中国临床药理学与治疗学

Rifabutin(RBT) is a rifamycin derivative,like rifampicin(RIF),registered for the prophylaxis and treatment of mycobacterium avium complex (MAC)in patients with AIDS by FDA in 1992.Subsequently,the drug was approved by many other countries.But now,it is used not only in the prophlaxis and treatment of mycobacterium avium complex but also in the treatment of pulmonary tuberculosis and Helicobacter pylori.For its high lipophilic characteristic and weak inducing properties compare to other rifamycin derivative,it can be applied in treatment with many diseases successfully,especially when combine with other antibiotics,and can solve the problem of traditional antibiotics resistance and increase the clinical safety of combined medical treatment.This paper just shows the progress of clinical pharmacological study and related aspects on rifabutin in order to instruct prescription.