Objective To study the role of ubiquitin-conjugating enzyme 9(UBC9)in the pyroptosis of homocysteine-induced macrophages mediated by small ubiquitin-like modifier(SUMO)modification.Methods First,the effects of homocysteine at different concentrations(0 μmol/L,50 μ.mol/L,100 μmol/L,150 μmol/L and 200 μmol/L)on the viability and pyrodeath of mouse macrophages(RAW264.7)were detected by CCK-8 and Western blot.Western blot was used to detect the expression levels of UBC9,SUMO-1,and the inflammatory cytokine IL-1β in different groups of cells.qRT-PCR was used to detect the mRNA expression of UBC9 before and after RNA interference and the expression of UBC9,pyrogen-related protein,and SUMO-1 after RNA interference.Results After stimulation with 100 μmol/L homocysteine,the effect of macrophage activity was minimal,and NLRP3 and Caspase-1 were the proteins with the most obvious increase in expression(P＜0.05).Compared with the Control group,the Hcy group's expression of IL-1β and SUMO-1 was increased(P＜0.01).Compared with the Control group,the Hcy group's UBC9 protein and mRNA levels were increased(P＜0.05).The expression of NLRP3,Caspase-1,IL-1β,UBC9,and SUMO-1 was decreased in the si-UBC9+Hcy group compared with the si-NC+Hcy group(P＜0.01).Conclusions Homocysteine induces pyroptosis in macrophages,and its mechanism of action is related to the up-regulation of UBC9 to induce SUMO modification.

Anaplastic lymphoma kinase (ALK) fusions represent the second most common oncogenic driver mutation in non-small cell lung cancer (NSCLC). As the new class of 3rd generation of ALK tyrosine kinase inhibitor (TKI), lorlatinib has shown robust potency and brain-penetrant clinical activity against a wide spectrum of multiple resistance mutations within the ALK domain detected during crizotinib and 2nd generation ALK TKI treatment. Lorlatinib is generally well-tolerated with unique adverse drug reaction/adverse event, including hyperlipidemia and central nervous system effects, which are mostly mild to moderate severity and manageable through dosage modifications and/or standard medical intervention. For advanced NSCLC with ALK positivity, patients should be evaluated for baseline characteristics and pre-existing medication, informed of the potential toxicities, and periodically monitored to balance benefits and risks. Moreover, a multidisciplinary group of experts is essential to establish a comprehensive diagnostic and therapeutic strategy.
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Aminopyridines ; Carcinoma, Non-Small-Cell Lung/pathology* ; China ; Consensus ; Drug Resistance, Neoplasm/genetics* ; Drug-Related Side Effects and Adverse Reactions/drug therapy* ; Humans ; Lactams ; Lactams, Macrocyclic/adverse effects* ; Lung Neoplasms/pathology* ; Protein Kinase Inhibitors/adverse effects* ; Protein-Tyrosine Kinases/genetics* ; Pyrazoles

Objective:To analyze the clinical characteristics of adult Chinese patients with syncope.Methods:This is a cross-sectional survey study. Patients with preliminary diagnosis of syncope in the Emergency Department, Geriatrics and Cardiology Outpatient Department, or Syncope Unit of 37 hospitals in 19 provinces, autonomous regions and the Hong Kong Special Administrative Region from June 2018 to March 2021 were included in this study. The clinical features of these patients with syncope were analyzed.Results:A total of 4 950 consecutive patients with syncope were included in this study. The age was (56.3±16.8)years, and 2 604 cases (52.6%) were male. The most common type of syncope was neurally mediated syncope (2 345 (47.4%)), followed by cardiac syncope (1 085 (21.9%)), orthostatic hypotensive syncope (311 (6.3%)), and unexplained syncope accounted for nearly one third (1 155 (23.3%)). Predisposing syncope was more common in patients under 65 years of age(2 066(72.4%) vs. 786(27.6%),χ 2=136.5, P<0.001). Presyncope was more common in patients with neurally mediated syncope (1 972(79.0%) vs.1 908(73.9%), χ 2=17.756, P<0.001). Premonitory symptoms were more common in women(1 837(80.0%) vs. 1 863(73.0%),χ 2=33.432, P<0.001). Presyncope syndrome was more common in patients under 65 years of age (2 482(77.8%) vs. 1 218(73.4%),χ 2=17.523, P=0.001). Cyanosis was more common in ≥65 years old patients (271(18.2%) vs. 369(12.7%), χ 2=23.235, P<0.001). Urinary incontinence was more common in old patients aged ≥65 years(252(15.2%) vs. 345(10.8%), χ 2=19.313, P<0.001). Family history was more common in patients with cardiogenic syncope compared with other types of syncope (264(24.3%) vs. 754(19.5%), χ 2=11.899, P=0.001). Hypertention(1 480(30.5%)), coronary heart disease(1 057(21.4%)), atrial flutter and atrial fibrillation(359(7.2%)), second degree atrioventricular block(236(4.8%)) were common complications of syncope. The proportion of patients with coronary heart disease was significantly higher in cardiac syncope than that of other types of syncope(417(38.4%) vs. 640(16.6%), χ 2=241.376, P<0.001). Other common complications included cerebrovascular diseases (551 (11.1%)) and diabetes mellitus (632(12.8%)). Conclusions:Neurally mediated syncope is the most common syncope in adult Chinese population. Patients with predisposing conditions and premonitory conditions are younger. Presyncope is more common in women. The proportion of family history and coronary heart disease is higher in patients with cardiogenic syncope.

Objective:To explore the expression of GATA3 in breast cancer tissues and its correlation with pathological types of tumors and prognosis.Methods:The paraffin samples of breast cancer tissues and paraffin samples of normal para-cancerous tissues from 100 breast cancer patients who underwent surgical excision in Luanzhou People′s Hospital of Hebei Province from June 2014 to June 2017 were retrospectively analyzed. The expression of GATA3 in breast cancer tissues and normal para-cancerous tissues was detected by immunohistochemistry. And its significance in prognosis evaluation was analyzed. The survival rates of patients with different GATA3 expression were analyzed by Kaplan-Meier survival curves.Results:The positive expression rate of GATA3 in breast cancer tissues was significantly lower than that in normal para-cancerous tissues: 61.00% (61/100) vs. 86.00% (86/100), and there was statistical difference ( χ2 = 16.044, P<0.01). The positive expression rate of GATA3 was related with histological grading, lymph node metastasis, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER-2), P<0.05, and not related with age, TNM staging or tumor long diameter ( P>0.05). Multivariate Logistic regression analysis result showed that histological grading at gradeⅢ, positive HER-2 and lymph node metastasis were independent risk factors of GATA3 positive expression of breast cancer tissues in patients with breast cancer ( OR = 1.747, 2.699 and 1.730; 95% CI 1.107 to 2.758, 1.035 to 7.039 and 1.139 to 2.626; P<0.05). The 3-year survival rate in GATA3 positive patients was significantly higher than that in GATA3 negative patients: 86.89% (53/61) vs. 66.67% (26/39), and there was statistical difference ( P<0.05). Conclusions:The positive expression rate of GATA3 in breast cancer tissues is significantly lower than that in normal para-cancerous tissues. The expression level of GATA3 is related to pathological types of breast cancer, histological grading, lymph node metastasis, ER, PR and HER-2. The expression level of GATA3 is of certain significance in evaluating prognosis of patients.

Objective To compare the clinical efficacy of posterior pedicle screw fixation through Wiltse paraspinal approach and posterior traditional open approach in the treatment of thoracolumbar fracture and dislocation.Methods A retrospective case control study was performed based on the clinical data of 40 patients with thoracolumbar fracture and dislocation admitted between January 2013 and January 2016.All the surgeries were performed through posterior midline incision,and they were divided into two groups according to different approaches.Patients in Group A received pedicle screw fixation through Wiltse paraspinal approach while Group B received fixed pedicle screw through open surgery.Group A was composed of 12 males and 8 females,aged 21-60 years [(41.5 ±9.6)years].Group B was composed of 13 males and 7 females,aged 18-58 years [(39.1 ± 13.1) years].The same surgical procedures were adopted in spinal decompression,reduction,and the spinal vertebral interbody bone graft and fusion surgery in the two groups.Operation duration,intraoperative blood loss,postoperative drainage volume,visual analogue scale (VAS),spinal canal patency at the last follow-up,percentage of postoperative injury of vertebral height recovery,and Cobb angle were compared.CT and MRI were used to evaluate postoperative paravertebral muscle atrophy,and American spinal injury association (ASIA) impairment scale was used to evaluate neurological function assessment.Results All patients were followed up for 9-33 months,with (19.3 ± 5.6) months for Group A and (22.5 ± 4.9) months for Group B (P ＞ 0.05).The operation duration was (240.5 ± 38.3) min in Group A and (258.5 ± 43.7) min in Group B (P ＞ 0.05).The intraoperative blood loss was (525.0 ± 168.2) ml in Group A,less than (770.0 ± 269.2) ml in Group B (P ＜ 0.05).Postoperative drainage volume was (190.1 ± 78.9) ml in Group A,less than (281.7 ± 122.3) ml in Group B (P ＜ 0.05).VAS score 24 hours after operation and at the last follow-up in Group A was (6.4 ± 1.0) points and (1.6 ± 0.5) points,respectively,better than those in Group B [(7.8 ± 0.7) points and (2.2 ± 0.4) points] (P ＜ 0.05).No significant differences were observed in terms of spinal canal patency at the last follow-up,percentage of postoperative injury of vertebral height recovery,and Cobb angle [Group A:(85.3 ± 3.7) ％,(85.5 ± 2.7) ％,and (4.7 ± 1.2)°;GroupB:(85.8±1.8)％,(88.8 ±1.3)％,and (5.3 ±1.5)°] (P＞0.05).In terms of MRI evaluation score of postoperative paravertebral muscle atrophy,Group A reported better results than Group B [(2.1 ± 0.6) points vs.(1.2 ± 0.6) points] (P ＜ 0.05).At the last follow-up,there were 7,5,6,1 and 1 patients in Group A,while 6,6,5,2 and 1 patients in Group B at ASIA grades A,B,C,D and E (P ＞ 0.05).Within the same group,significant difference was observed between the preoperative data and that at the last follow-up in terms of postoperative VAS score,spinal canal patency,percentage of injury of vertebral height,Cobb angle,and ASIA impairment scale (P ＜ 0.05).Conclusion For thoracolumbar fracture and dislocation,compared with traditional open approach,posterior pedicle screw fixation through Wiltse paraspinal approach can effectively restore the vertebral body height and spinal canal patency and can reduce the intraoperative bleeding,postoperative drainage,postoperative back pain,and paravertebral lesion.

OBJECTIVE: To explore the stability of recombinant human serum albumin and interferon alpha 2b fusion protein for injection. METHODS: According to the testing methods of Ch.P, influencing factors test [high temperature test at (42±2)℃, strong light test at (4 500±500)lx and humidity test at RH of 90%], accelerated test (37 and 25 ℃)and long-term test were carried out according to the technical guidelines of biological stability study. RESULTS: The results of influencing factors test, accelerated test and long-term test showed that temperature had influence on the purity of products. The protein purity decreased with the increase of temperature. Humidity also had influence on the moisture content of products, with little influence on other indicators. Long term stability investigation found that the sample was relatively stable within 24 months and the examined indexes accorded with the quality standard. CONCLUSION: This recombinant protein can be stored at 2-8 ℃ for 24 months.

Objective:To determine the inhibitory effect of Rupixiao ( RPX) granule on mammary gland hyperplasia ( HMG) in rabbits and explore the possible mechanism to provide reference for clinical medication. Methods:Rabbit model of mammary hyperpla-sia was established by estradiol benzoate and progesterone. Xiaoyao pills and tamoxifen were used as the positive control, and the RPX granule group was respectively at low, medium and high dose (0. 525,1. 05,2. 1 g·kg-1). Each group was with intragastric adminis-tration for 30 days. The levels of E2 , PROG, FSH, LH and PRL in serum and the expression of VEGF in the homogenate tissue were determined by an Elisa method. The breast tissue of rabbits in each group was withdrawn to observe the structure changes after Hema-toxylin-eosin staining ( HE) . Results:Ovarian preservation-benzoic acid, estradiol combined with progesterone could be used to estab-lish mammary gland hyperplasia in rabbits. RPX granule could significantly decrease the serum levels of E2 and PRL (P<0. 01)and increase that of PROG (P<0. 01 or P<0. 001). The results of pathological section showed that the breast structure in RPX granule high dose group could be restored to the level of the blank control group, which showed its therapeutic effect on HMG was better than that of tamoxifen and Xiaoyao pills. The expression of VEGF in each treatment group significantly decreased compared with that in the model group by the Elisa reagent (P<0. 001). Conclusion:RPX granule has good efficacy in HMG rabbits. The inhibitory effects of RPX granule on HMG in rabbits maybe related to the inhibition of VEGF in rabbit breast tissues, and the inhibition of RPX granule was similar to that of tamoxifen and Xiaoyao pills.

Objective To construct four types of glucagon-like peptide-1 (GLP-1) and human serum albumin (HSA) fusion proteins that can be realeased at different rate in vivo by introducing protease cleavage sites between these two moieties.The therapeutic effect and release rate are studied to achieve balanced pharmacokinetics ( PK) and pharmacody-namics ( PD) of GLP-1 and HSA fusion proteins.Methods The gene with different polypeptide joint of GLP-1 and HSA fusion proteins were synthesized by overlap extension PCR amplification, cloned into expression vector pPIC9 and transformed into Pichia pastoris GS115.Then, fusion proteins were obtained by protein purification after being induced by methanol.The preliminary PK and PD of the fusion proteins were studied after purification.Results The fusion protein Gly2-GLP-1-GGGGG-HSA showed no release while Gly2-GLP-1-VTR-HSA, Gly2-GLP-1-SARSVRA-HSA, and Gly2-GLP-1-GRSRVTRSV-HSA showed a slow, medium and fast release rate, respectively, after incubation with furin.In vitro biological activity test results dispalyed that each type of fusion protein promoted insulin secretion of MIN6 cells.In vivo PK test indicated the half-life size of fusion proteins was the largest in Gly2-GLP-1-GGGGG-HSA, followed by Gly2-GLP-1-VTR-HSA, Gly2-GLP-1-SARSVRA-HSA, and Gly2-GLP-1-GRSRVTRSV-HSA.In vivo PD test exhibited hypoglycemic activity that was the highest in Gly2-GLP-1-VTR-HSA, followed by Gly2-GLP-1-SARSVRA-HSA, Gly2-GLP-1-GRSRVTRSV-HSA, and Gly2-GLP-1-GGGGG-HSA.Conclusion GLP-1 can be released from fusion proteins with full activity after the introduction of protease cleavage sites.Releasable fusion proteins at an appropriate release rate have the most balanced PK and PD.

Objective To explore the application of central venous catheter(CVT) in hemodialysis.Methods The clinical data of 2 206 cases of CVT patients were analyzed retrospectively,and the catheter puncture site,the catheter indwelling time,4 weeks of blood flow rate and the incidence of catheter related infections,and so on were observed.Results Internal jugular vein in 2 033 cases,the femoral vein in 173 cases.Internal jugular vein indwelling catheter time was (40.6 ±32.7) d,the femoral vein catheter indwelling time was (22.4 ± 16.3) d,and the difference was statistically significant (P＜ 0.05).Blood flow patency rate in four weeks was of 96.4％ (1 959/2 033) indwelling catheter in internal jugular vein,which was significantly higher than that of the femoral vein in 83.2％ (144/173),and the difference was statistically significant (P ＜ 0.05).Femoral vein catheter related infection rate was 11.0％ (19/173),significantly higher than that of internal jugular vein in 3.6％ (73/2 033),the difference was statistically significant (P ＜ 0.05).Conclusion Application of CVT for hemodialysis is convenient and reliable,with low infection rate,fewer complications,operation technology level is the key to success.

OBJECTlVE To study the anti-HBV activity of prepared recombinant human serum aIbu-min-interferon α-2b fusion protein(HSA-IFNα-2b) in vitro. METHODS HepG2 ceIIs were infected with recombinant adenovirus with green fIuorescence protein and 1.6-foId HBV DNA(AdGFP-HBV). The ex-pression of HBV antigens,HBsAg and HBeAg in cuIture medium was detected by ELISA assay. The tox-icity of HSA-IFNα-2b on HepG2 ceIIs was evaIuated by mTT assay.The reIative expression of HBV RNA in ceIIs and the absoIute quantity of HBV DNA in cuIture supernatant were determined by quantitative PCR assay. The activity of HBV enhancer Ⅰ was detected by DuaI-Reporter gene assay. RESULTS HBV couId repIicate and express in HepG2 ceIIs after infection with AdGFP-HBV. The expression of HBsAg and HBeAg in cuIture serum of HepG2 ceIIs infected with AdGFP-HBV decreased by 51.32%(P﹤0.01)and 50.26%(P﹤0.01),respectiveIy,when HSA-IFNα-2b 500 kU·L-1 was added. The same concentration of HSA-IFNα-2b didn't inhibit the proIiferation of HepG2 ceIIs,but inhibited HBsAg in a concentration-dependent manner. The regression formuIa between HBsAg inhibitory rate(Y)and con-centration of HSA-IFNα-2b(X)was Y=21.11 IgX+11.91(r 2 = 0.954),IC50 = 63.76 kU·L-1 . HBV RNA in ceIIs and HBV DNA in the cuIture serum decreased by 52.83%(P﹤0.01)and 53.07%(P﹤0.01), respectiveIy,when HSA-IFNα-2b 500 kU·L-1 was added. The activity of enhancer Ⅰ decreased by 40.04%(P﹤0.01)when HSA-IFNα-2b 500 kU·L-1 was added. CONCLUSlON The ceII modeI of HBV repIication for evaIuating anti-HBV agents is successfuIIy estabIished. HSA-IFNα-2b exhibits noticeabIe anti-HBV effect invitro.