Adult ; Aged ; Bone Screws ; Female ; Femoral Neck Fractures ; surgery ; Fracture Fixation, Intramedullary ; Humans ; Internal Fixators ; Male ; Middle Aged

With the development of molecular pathology,many types of epidermal growth factor receptor (EGFR) mutations have been identified.The efficacy of EGFR tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer (NSCLC) patients with different types of EGFR mutations,especially in patients with single rare mutations or complex mutations (co-occurrence of two or more different mutations),has not been fully understood.This study aimed to examine the efficacy of EGFR-TKIs in NSCLC patients with different types of EGFR mutations.Clinical data of 809 NSCLC patients who harbored different types of EGFR mutations and treated from January 2012 to October 2016 at Renmin Hospital and Zhongnan Hospital,Wuhan,were retrospectively reviewed.The clinical characteristics of these patients and the efficacy of EGFR-TKIs were analyzed.Among these patients,377 patients had only the EGFR del-19 mutation,362 patients the EGFR L858R mutation in exon 21,33 patients single rare mutations and 37 patients complex mutations.Among these 809 patients,239 patients were treated with EGFR-TKIs.In all the 239 patients,the disease control rate (DCR) was 93.7％ with two patients (0.2％) achieving complete response (CR),the median progression free survival (PFS) was 13.0 months (95％ confidence interval [CI],11.6-14.4 months),and the median overall survival (OS) was 55.0 months (95％ CI,26.3-83.7 months).Subgroup analysis revealed that the DCR in patients harboring single rare or complex mutations of EGFR was significantly lower than in those with del-19 or L858R mutation (P＜0.001).Patients with classic mutations (del-19 and/or L858R mutations) demonstrated longer PFS (P＜0.001) and OS (P=0.017) than those with uncommon mutations (single rare and/or complex mutations).Furthermore,the patients with single rare mutations had shorter median OS than in those with other mutations.Multivariate Cox regression analysis identified that the type of EGFR mutations was an independent risk factor for PFS (hazard ratio [HR]=0.308,95％ CI,0.191-0.494,P＜0.001) and OS (HR=0.221,95％ CI,0.101-0.480,P＜0.001).The results suggest that the single rare or complex EGFR mutations confer inferior efficacy of EGFR-TKIs treatment to the classic mutations.The prognosis of the single rare EGFR mutations is depressing.EGFR-TKIs may be not a good choice for NSCLC patients with single rare mutations of EGFR.Further studies in these patients with uncommon mutations (especially for the patients with single rare mutations) are needed to determine a better precision treatment.

inal event.

OBJECTIVETo seek differentially expressed serum proteins in recovered SARS patients complicating avascular necrosis of femoral head (AVNFH).

METHODS2-DE and MALDI-TOF MS were used to study the comparative serum proteomics among female SARS AVNFH group, female SARS non-AVNFH group and female healthy group. ELISA method was used to detect serum amyloid P component in individual serum; specificity and sensitivity of serum amyloid P component were analyzed.

RESULTSAverage protein points on 2-DE of 3 groups were 632 +/- 28, 671 +/- 55, 688 +/- 42 respectively, and the matching rate of protein points was ranged from 85% to 95%; eighteen differentially expressed proteins were discovered including transthyretin, serpin peptidase inhibitor, alpha-1-antitrypsin precursor, serum amyloid P components, etc. Compared to healthy group and SARS non-AVNFH group, transthyretin, C4B3, fibrinogen gamma, apolipoprotein L, apolipoprotein A-IV precursor, albumin and prealbumin showed lower expression, inversely serpin peptidase inhibitor, alpha-1-antitrypsin precursor and serum amyloid P components showed higher expression in serum in the SARS AVNFH necrosis group. The serum amyloid P component in 3 groups were 0.54 +/- 0.30 ng/ml, 0.83 +/- 0.39 ng/ml, 1.21 +/- 0.29 ng/ml respectively. The areas under the ROC curve on serum amyloid P component was 0.854, the specificity was 77.8% and the sensitivity was 85.2%.

CONCLUSIONThere were differentially expressed serum proteins in three groups. Serum amyloid P components might be one of the potential biomarkers in serum of recovered SARS patients complicating avascular necrosis of femoral head.

Adult ; Blood Proteins ; analysis ; Case-Control Studies ; Electrophoresis, Gel, Two-Dimensional ; Female ; Femur Head Necrosis ; blood ; etiology ; Humans ; Proteomics ; Severe Acute Respiratory Syndrome ; blood ; complications ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

OBJECTIVETo define the criteria of selective thoracic fusion in adolescent idiopathic scoliosis patients.

METHODSBy reviewing the roentgenograms of adolescent idiopathic scoliosis patients undergoing selective thoracic fusion, the curve type, Cobb angle, apical rotation and translation, trunk shift, and thoracolumbar kyphosis were measured and analyzed.

RESULTSThere were 12 King type II patients (PUMC type: IIb1 9, IIc3 3). The coronal Cobb angle of thoracic curve before and after surgery were 54.0 degrees and 19.0 degrees respectively, and the average correction rate was 62.7%. The coronal Cobb angle of lumbar curve before and after surgery were 34.6 degrees and 12.5 degrees respectively, and the average spontaneous correction rate was 64.7%. At the final follow-up, the coronal Cobb angle of thoracic and lumbar curve was 18.8 degrees and 15.9 degrees respectively. There was no significant change in the coronal Cobb angle, apical vertebral translation and rotation compared with that after surgery. 1 patient had 12 degrees of thoracolumbar kyphosis after surgery, no progression was noted at the final follow-up. There was no trunk decompensation or deterioration of the lumbar curve. In this group, 3.5 levels were saved compared with fusing both the thoracic and lumbar curves.

CONCLUSIONSelective thoracic fusion can be safely and effectively performed in patients with a moderate and flexible lumbar curves, which can save more mobile segments to maintain a good coronal and sagittal balance.

Adolescent ; Female ; Follow-Up Studies ; Humans ; Male ; Retrospective Studies ; Scoliosis ; surgery ; Spinal Fusion ; methods ; Thoracic Vertebrae ; pathology ; surgery ; Treatment Outcome

OBJECTIVETo evaluate the effect of preoperative transarterial chemoembolization (TACE) on hepatocellular carcinoma located in caudate lobe.

METHODSTotally 29 cases of caudate lobe hepatocellular carcinoma admitted from January 2001 to December 2010 were analyzed retrospectively. Among the 29 patients, 23 were male and the other 6 were female. The median age was 52 years. According to receiving preoperative TACE or not, the 29 cases were divided into two groups: preoperative TACE plus surgery (group A, n = 11) and surgery only (group B, n = 18). The surgical results and long-term survival were compared between two groups.

RESULTSAfter TACE, the diameter of the tumour reduced by over 33.3% in 3 patients, 10.0% to 33.3% in 6 patients, and less than 10.0% in 2 patients. The duration of surgery and intraoperative blood loss in group A were (298 ± 39) minutes and (1031 ± 310) ml, respectively. The duration of surgery and intraoperative blood loss in group B were (281 ± 54) minutes and (868 ± 403) ml, respectively. No significant difference was found in terms of these two groups (t = 1.006, P = 0.324; t = 1.223, P = 0.232). In addition, 6 cases in group A developed complications and 4 cases in group B did so. Only one patient died because of postoperative complication, and this patient belonged to group A. No significant difference was found between two groups (χ(2) = 0.028, P = 0.868; χ(2) = 0.633, P = 0.426). The 5-year survival rate was 56.8% in group A and 34.9% in group B. The difference did not reach significant difference (P = 0.132).

CONCLUSIONSFor hepatocellular carcinoma located in caudate lobe, preoperative TACE does not significantly increase the surgical difficulty and impair the safety. In addition, preoperative TACE has the tendency to provide benefit to long-term survival.

Carcinoma, Hepatocellular ; surgery ; Chemoembolization, Therapeutic ; Hepatectomy ; Humans ; Liver Neoplasms ; surgery ; Retrospective Studies

OBJECTIVE: To explore the efficacy of venetoclax (VEN) plus azacitidine (AZA) in patients with FLT3-ITD mutated relapsed/refractory acute myeloid leukemia (FLT3-ITD^mut R/R AML) and analyze the molecular genetic characteristics of the patients. METHODS: Clinical baseline characteristics and follow-up data of 16 R/R AML patients treatd with VEN plus AZA in the hematology department of Shenzhen Second People's Hospital from November 2018 to April 2021 were collected. Leukemia related genes were detected by next-generation sequencing(NGS) or PCR. The relationship between the efficacy of VEN plus AZA and molecular genetics characteristics of patients with FLT3-ITD^mut R/R AML were analyzed. RESULTS: 14.3% (1/7) of the patients in FLT3-ITD^mut group and 22.2% (2/9) of the patients in FLT3-ITD^wt group achieved complete remission (CR)/CR with incomplete blood count recovery (CRi), respectively, with no significant difference (P=0.69). There was no significant difference in overall response rate (ORR) (CR/CRi+PR) between FLT3-ITD^mut group and FLT3-ITD^wt group [42.9%(3/7) vs 44.4%(4/9), P=0.95], too. The median overall survival (OS) time of FLT3-ITD^mut patients was significantly shorter than that of FLT3-ITD^wt patients (130 vs 300 days, respectively) (P =0.02). Co-existing mutations of FLT3-ITD and IDH1 were detected in one patient who achieved CR. Co-existing mutations of FLT3-ITD and SF3B1 were found in one patient who achieved PR. Three FLT3-ITD^mut R/R AML patients accompanied with NPM1 mutation had no response to VEN plus AZA. CONCLUSION VEN plus AZA showed a certain effect on patients with FLT3-ITD^mut R/R AML. To improve OS of the patients, bridging transplantation is need. IDH1 and SF3B1 mutations might predict that patients with FLT3-ITD^mut R/R AML have treatment response to VEN plus AZA, while the combination of NPM1 mutation may indicate poor response.
Humans ; Nucleophosmin ; Prognosis ; Leukemia, Myeloid, Acute/genetics* ; Mutation ; Azacitidine/therapeutic use* ; fms-Like Tyrosine Kinase 3/genetics*

Carboxylesterase 1 (CE1) is an important serine hydrolase in mammals, which involved in the hydrolysis of a variety of compounds (endogenous substrates like cholesterol and xenobiotic compounds like ester-contain drugs and pesticides). This study aimed to design and develop the fluorescent probe substrates for human carboxylesterase 1 (hCE1), on the basis of the structural features of hCE1 preferred substrates. Four carboxylic esters deriving from BODIPY-8-carboxylic acid were designed and synthesized. After then, reaction phenotyping assays and chemical inhibition assays were used to evaluate the selectivity of these four ester derivatives towards hCE1. Our results clearly demonstrated that the substrate specificity of these ester substrates towards hCE1 would be improved with the decrease of the alcohol group on BODIPY-8-carboxylesters, while BODIPY-8-carboxylesters with small alcohol groups including methyl (BCM) and ethyl (BCE) esters could serve as the ideal probe substrates for hCE1. Given that BCM exhibit rapid hydrolytic rate in hCE1, we further investigate the enzymatic kinetics of this fluorescent probe substrate in both human liver microsomes (HLM) and recombinant hCE1, as well as to explore its potential application in high-throughput screening of hCE1 inhibitors by using HLM as enzyme source. The results showed that the kinetic behaviors and the affinity of BCM in HLM is much closed to those in recombinant hCE1, implying that hCE1 played the key roles in BCM hydrolysis in HLM. Furthermore, the inhibition study demonstrated that BCM could be used for rapid screening and characterization of hCE1 inhibitors, by using HLM to replace recombinant hCE1 as enzyme source.

ObjectiveTo study the plasma pharmacokinetics and tissue distribution of five representative components in Wujiwan， and to illustrate the difference of metabolism and tissue distribution before and after compatibility. MethodHealthy male SD rats were divided into four groups， including Wujiwan group（A group， 62.96 g·L^-1）， Coptidis Rhizoma group（B group， 38.4 g·L^-1）， processed Euodiae Fructus group（C group， 5.88 g·L^-1） and fried Paeoniae Radix Alba group（D group， 18.68 g·L^-1）， with 65 rats in each group， and were administered the drugs according to the clinical dose of decoction pieces converted into the dose of the extracts. Then plasma， liver， small intestine and brain were taken at pharmacokinetic set time in each group after administration. Ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry was developed for the quantitative analysis of five representative components［berberine（Ber）， palmatine（Pal）， evodiamine（Evo）， rutecarpine（Rut） and paeoniflorin（Pae）］ in Wujiwan， their concentrations in plasma， liver， small intestine and brain were detected at different time， plasma samples were processed by protein precipitation， and tissue samples were pretreated by protein precipitation plus liquid-liquid extraction. Non-atrioventricular model was used to calculate the pharmacokinetic parameters of each component， and the parameters of each group were compared. ResultPharmacokinetic results of A group showed that area under the curve（AUC_0-t） of the five representative components were ranked as follows：Ber and Pal were small intestine>liver>blood， Evo and Rut were liver>small intestine>plasma， Pae was small intestine>plasma， which was not detected in the liver， no other components were detected in brain except for Ber. In comparison with plasma and other tissues， peak concentration（C_max） of Ber， Pal， Evo， and Rut were the highest and time to peak（t_max） were the lowest in the liver of A group. In plasma， the AUC_0-t and C_max of Evo and Rut were increased in A group compared with C group， t_max of Pea was elevated and its C_max was decreased in A group compared with D group. In the liver， compared with B-D groups， C_max values of 5 representative components except Pae were elevated， AUC_0-t of Pae was decreased and AUC_0-t of Evo and Rut were increased in the A group. In the small intestine， half-life（t_1/2） of each representative components in A group was elevated and t_max was decreased， and C_max of each representative ingredient except Pal was decreased， AUC_0-t values of Ber and Pal were increased， whereas the AUC_0-t values of Evo and Rut were decreased. ConclusionThe small intestine， as the effector organ， is the most distributed， followed by the liver. The pharmacokinetic parameters of the representative components in Wujiwan are changed before and after compatibility， which is more favorable to the exertion of its pharmacodynamic effects.

Humans ; Severe Acute Respiratory Syndrome ; diagnosis ; therapy