Objective To compare the clinical effects and safety of surgical clipping and intravascular interventional therapy in treatment of intracranial wide-necked aneurysm.Methods The clinical data of 158 patients with intracranial wide-necked aneurysm from February 2010 to February 2013 were retrospectively analyzed,all patients were divided into two groups:surgical clipping group with 92 cases and intravascular interventional therapy group with 66 cases,the postoperative curative effects,treatment time,hospital stay,hospital expenses and postoperative complications between two groups were compared.Followed up for 10-46 months,the recurrence rate were compared.Results The good prognosis and defective rates between surgical clipping group and intravasular interventional therapy group had no significant difference [90.2％(83/92) vs.90.9％(60/66),9.8％(9/92) vs.9.1％ (6/66)] (x2 =0.298,P ＞ 0.05).The preoperative Hunt-Hess classification and CT Fisher classification between two groups had no significant difference (P ＞ 0.05).Six months after discharge,mRS score was used to evaluate the curative effect,the defective rates in same level patients between two kinds of treatment methods had no significantdifference (P ＞ 0.05).The treatment time,hospital stay in surgical clipping group were significantly longer than those in intravascular interventional therapy group [(4.03 ± 1.01) h vs.(1.61 ± 0.98) h,(15.90 ± 2.03) dvs.(13.20 ± 1.95) d],hospital expenses was significantly lower than that in intravascular intervention therapy group [61 829.4 ±320.6) yuan vs.(99 876.2 ±371.5) yuan] (P ＜0.05).The postoperative complications rate between two groups had no significant difference (P ＞ 0.05).Followed up for 31.3 (10-46) months,the recurrence rate in surgical clipping group was significantly lower than that in intravascular intervention therapy group [1.1％ (1/94) vs.8.8％ (6/68)] (P ＜ 0.05).Conclusion Surgical clipping and intravascular interventional therapy in treatment of intracranial wide-necked aneurysm has their own different characteristics,so patients' treatment methods should be based on their preoperative status (especially preoperative Hunt-Hess and Fisher classification) and patients' economic conditions.

Objective To discuss the clinical effects of using CT positioning keyhole approach to treat hy-pertensive intracerebral hemorrhage (HICH).Methods 85 cases of patients with hypertensive intracerebral hemor-rhage(HICH) were chosen and divided into two groups according to the operation methods:the observation group had 55 cases given CT positioning keyhole approach ,while the control group had 30 cases treated with traditional cranioto-my hematoma removal operation .All patients were supplemented by postoperative blood pressure control and nutrition -al support treatment .The average operation time ,hematoma disappearing time ,the length of hospital stay and re-bleed-ing rates and postoperative ability of daily life ( ADL) scores of the two groups were all carefully recorded and com-pared.Results The average operation time,hematoma disappearing time and hospital stay of the observation group were (66.5 ±12.8)min,(3.4 ±1.3)d,and (9.3 ±1.7)day which were all significantly lower than those of the con-trol group(193.5 ±23.7)min,(5.8 ±2.1)d and (15.2 ±3.8)d;T-test values of the two groups were 2.874,3.125 and 3.433 separately(P<0.05);there were 2 cases(3.6%) of postoperative hemorrhage in the observation group of while 6 cases(20.0%) in the control group,whose difference was statistically significant (χ2 =6.097,P<0.05);In the observation group 4 cases(7.3%) died after operation and also 4 cases(13.3%) died in the control group ,and the mortality of the two groups had no statistical significance (χ2 =0.836,P>0.05).6 months′follow-up after opera-tion,in the control group 2 cases were lost to follow-up while in the observation group 3 cases were lost to follow-up;Using ADL to evaluate the two groups of patients with survival and continuous follow-up,we found that the observation group′s postoperative quality of life was better than that of the control group′s(μ=3.325,P<0.05).Conclusion Using CT positioning keyhole approach has smaller trauma , shorter operation time and faster postoperative recovery and other characteristics,which is an effective method for the treatment of hypertensive intracerebral hemorrhage(HICH).

Objective To study the effect of enhanced MK gene expression in hepatic carcinoma cells.Methods The recombinant plasmid pIRES2-EGFP-MK was transfected into SMMC 7721 cells.The mRNA and protein expression levels of MK gene in these cells were determined by real-time PCR,Western blotting and flow cytometry.The intracellular DNR accumulation of these cells was measured by flow cytometry.To investigate the effect of MK gene mediated multidrug resistance,MTT assay was employed to determine the cellular sensitivity of different chemotherapeutic drugs in MK-overexpressed SMMC 7721 cells.Results The mRNA and protein expression levels of MK gene significantly increased after the recombinant plasmid pIRES2-EGFP-MK transfected into SMMC 7721 cells,suggesting that the recombinant plasmid pIRES2-EGFP-MK can enhance the transcription of MK effectively.The DNR accumulation of MK transfected cells decreased significantly (4.06 ± 0.88,P ＜ 0.05),and IC50 of MK transfected cells to ADM/5-FU increased significantly (15 ± 3,27 ± 4,P ＜ 0.05).Conclusions After the recombinant plasmid pIRES2-EGFP-MK transfected into hepatic carcinoma cells,expression of midkine increased,enhancing the resistance of hepatic carcinoma cells to chemotherapeutic drugs.

Objective To explore the role of NT-proBNP in the differentiation of acute pulmonary embolism (APE) from congestive heart failure (CHF) in patients with acute dyspnea.Methods Consecutive 260 patients aged ≥ 60 years complaining of acute dyspnea were collected between June 2010 and October 2015.The patients were divided into two groups of APE and CHF according to their diagnosis standards.The levels of NT-proBNP between the two groups were compared using t test,and receiver operating characteristic curve (ROC curve) was made to show the value of NT-proBNP in differentiation of APE from CHF.Results Patients in APE group had significantly lower median levels of NT-proBNP as compared with patients in CHF group [(2 478.8±1 473.9)ng/L vs.(5 955.4±3 180.1)ng/L,t =-12.020,P ＜ 0.01].The ROC curve of APE existence against serum levels of NT-proBNP showed an optimal cut-point of NT-proBNP of 1 518 ng/L,with specificity up to 98.8％,and the area under the ROC curve for NT-proBNP was 0.877.Conclusions NT-proBNP as a simple and bedside approach to identify APE versus CHF patients with acute dyspnea can help clinicians identify APE early and reduce the rates of misdiagnosis and missed diagnosis of APE.But the confirmative diagnosis of APE is still based on spiral CT angiography.

Auditory neuropathy spectrum disorder (ANSD) represents a variety of sensorineural deafness conditions characterized by abnormal inner hair cells and/or auditory nerve function, but with the preservation of outer hair cell function. ANSD represents up to 15％ of individuals with hearing impairments. Through mutation screening, bioinformatic analysis and expression studies, we have previously identified several apoptosis-inducing factor (AIF) mitochondria-associated 1 (AIFM1) variants in ANSD families and in some other sporadic cases. Here, to elucidate the pathogenic mechanisms underlying each AIFM1 variant, we generated AIF-null cells using the clustered regularly interspersed short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system and constructed AIF-wild type (WT) and AIF-mutant (mut) (p.T260A, p.R422W, and p.R451Q) stable transfection cell lines. We then analyzed AIF structure, coenzyme-binding affinity, apoptosis, and other aspects. Results revealed that these variants resulted in impaired dimerization, compromising AIF function. The reduction reaction of AIF variants had proceeded slower than that of AIF-WT. The average levels of AIF dimerization in AIF variant cells were only 34.5％?49.7％ of that of AIF-WT cells, resulting in caspase-independent apoptosis. The average percentage of apoptotic cells in the variants was 12.3％?17.9％, which was significantly higher than that (6.9％?7.4％) in controls. However, nicotinamide adenine dinucleotide (NADH) treatment promoted the reduction of apoptosis by rescuing AIF dimerization in AIF variant cells. Our findings show that the impairment of AIF dimerization by AIFM1 variants causes apoptosis contributing to ANSD, and introduce NADH as a potential drug for ANSD treatment. Our results help elucidate the mechanisms of ANSD and may lead to the provision of novel therapies.

Objective:To examine the clinical value of rapid detection of drug-resistant bacteria by immunochromatography and the effects of rapid detection on the prognosis of patients with severe intra-abdominal infection complicated by carbapenem-resistant Enterobacteriaceae (CRE) bloodstream infection.Methods:This was a retrospective cohort study. We analyzed clinical data of 73 patients with severe abdominal infections with sepsis or septic shock complicated by CRE bloodstream infection admitted to the general surgery department of Jinling Hospital between February 2022 and February 2023. Patients were divided into a colloidal gold immunochromatographic assay (GICA) group (17 patients) and conventional testing group (56 patients) based on whether a GICA for CRE had been performed on the patients' first blood culture sample during the diagnosis and treatment process. There were no statistically significant differences between the GICA and conventional testing groups in age ([55.9±17.3] vs. [47.6±16.4] years), sex ([16 men vs. one woman ] vs. [41 men vs. 15 women]), median Charlson comorbidity index (3.0[2.0,4.0] vs. 3.0[2.0, 4.8]), septic shock (10 vs. 39), or acute kidney injury (8 vs. 40) (all P>0.05). Both groups routinely underwent traditional bacterial identification and drug susceptibility testing. Additionally, patients in the GICA group were tested directly for positive blood cultures using a GICA carbapenemase test kit. The main outcomes were mortality rates on Days 28 and 90 after the first identification of CRE bloodstream infection in both groups. We also compared the microbial clearance rate, duration of hospitalization and intensive care unit stay, and time from onset of CRE bloodstream infection to initiation of targeted and appropriate antibiotics between the two groups. Results:The rate of microbial clearance of bloodstream infection was significantly greater in the GICA group than in the conventional testing group (15/17 vs. 34/56 [60.7%], χ 2=4.476, P=0.034), whereas the 28-day mortality tended to be lower in the GICA than conventional testing group [5/17 vs. 44.6% [25/56], χ 2=1.250, P=0.264). The 90-day mortality (8/17 vs. 53.6% [30/56], χ 2=0.222, P=0.638), median duration of hospitalization (37.0 [18.0, 46.5] days vs. 45.5 [32.2, 64.8] days, Z=-1.867, P=0.062), and median duration of intensive care unit stay (18.0 [6.5, 35.0] days vs. 32.0 [5.0, 51.8] days, Z=-1.251, P=0.209). The median time between the onset of bloodstream infection and administration of antibiotics was 49.0 (38.0, 69.0) hours in the GICA group, which is significantly shorter than the 163.0 (111.8, 190.0) hours in the conventional testing group ( Z=-5.731, P<0.001). The median time between the onset of bloodstream infection and administration of appropriate antibiotics was 40.0 (34.0, 80.0) hours in the GICA group, which is shorter than in the conventional testing group (68.0 [38.2, 118.8]) hours; however, this difference is not statistically significant ( Z=-1.686, P=0.093). Conclusions:GICA can provide information on carbapenemase- producing pathogens faster than traditional drug sensitivity testing, enabling early administration of the optimal antibiotics. The strategy of 'carbapenemase detection first' for managing bacterial infection has the potential to improve prognosis of patients and reduce mortality rate.

Objective:To examine the clinical value of rapid detection of drug-resistant bacteria by immunochromatography and the effects of rapid detection on the prognosis of patients with severe intra-abdominal infection complicated by carbapenem-resistant Enterobacteriaceae (CRE) bloodstream infection.Methods:This was a retrospective cohort study. We analyzed clinical data of 73 patients with severe abdominal infections with sepsis or septic shock complicated by CRE bloodstream infection admitted to the general surgery department of Jinling Hospital between February 2022 and February 2023. Patients were divided into a colloidal gold immunochromatographic assay (GICA) group (17 patients) and conventional testing group (56 patients) based on whether a GICA for CRE had been performed on the patients' first blood culture sample during the diagnosis and treatment process. There were no statistically significant differences between the GICA and conventional testing groups in age ([55.9±17.3] vs. [47.6±16.4] years), sex ([16 men vs. one woman ] vs. [41 men vs. 15 women]), median Charlson comorbidity index (3.0[2.0,4.0] vs. 3.0[2.0, 4.8]), septic shock (10 vs. 39), or acute kidney injury (8 vs. 40) (all P>0.05). Both groups routinely underwent traditional bacterial identification and drug susceptibility testing. Additionally, patients in the GICA group were tested directly for positive blood cultures using a GICA carbapenemase test kit. The main outcomes were mortality rates on Days 28 and 90 after the first identification of CRE bloodstream infection in both groups. We also compared the microbial clearance rate, duration of hospitalization and intensive care unit stay, and time from onset of CRE bloodstream infection to initiation of targeted and appropriate antibiotics between the two groups. Results:The rate of microbial clearance of bloodstream infection was significantly greater in the GICA group than in the conventional testing group (15/17 vs. 34/56 [60.7%], χ 2=4.476, P=0.034), whereas the 28-day mortality tended to be lower in the GICA than conventional testing group [5/17 vs. 44.6% [25/56], χ 2=1.250, P=0.264). The 90-day mortality (8/17 vs. 53.6% [30/56], χ 2=0.222, P=0.638), median duration of hospitalization (37.0 [18.0, 46.5] days vs. 45.5 [32.2, 64.8] days, Z=-1.867, P=0.062), and median duration of intensive care unit stay (18.0 [6.5, 35.0] days vs. 32.0 [5.0, 51.8] days, Z=-1.251, P=0.209). The median time between the onset of bloodstream infection and administration of antibiotics was 49.0 (38.0, 69.0) hours in the GICA group, which is significantly shorter than the 163.0 (111.8, 190.0) hours in the conventional testing group ( Z=-5.731, P<0.001). The median time between the onset of bloodstream infection and administration of appropriate antibiotics was 40.0 (34.0, 80.0) hours in the GICA group, which is shorter than in the conventional testing group (68.0 [38.2, 118.8]) hours; however, this difference is not statistically significant ( Z=-1.686, P=0.093). Conclusions:GICA can provide information on carbapenemase- producing pathogens faster than traditional drug sensitivity testing, enabling early administration of the optimal antibiotics. The strategy of 'carbapenemase detection first' for managing bacterial infection has the potential to improve prognosis of patients and reduce mortality rate.

The spread of coronavirus disease 2019 (COVID-19) throughout the world has resulted in stressful healthcare burdens and global health crises. Developing an effective measure to protect people from infection is an urgent need. The blockage of interaction between angiotensin-converting enzyme 2 (ACE2) and S protein is considered an essential target for anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) drugs. A full-length ACE2 protein could be a potential drug to block early entry of SARS-CoV-2 into host cells. In this study, a therapeutic strategy was developed by using extracellular vesicles (EVs) with decoy receptor ACE2 for neutralization of SARS-CoV-2. The EVs embedded with engineered ACE2 (EVs-ACE2) were prepared; the EVs-ACE2 were derived from an engineered cell line with stable ACE2 expression. The potential effect of the EVs-ACE2 on anti-SARS-CoV-2 was demonstrated by both in vitro and in vivo neutralization experiments using the pseudovirus with the S protein (S-pseudovirus). EVs-ACE2 can inhibit the infection of S-pseudovirus in various cells, and importantly, the mice treated with intranasal administration of EVs-ACE2 can suppress the entry of S-pseudovirus into the mucosal epithelium. Therefore, the intranasal EVs-ACE2 could be a preventive medicine to protect from SARS-CoV-2 infection. This EVs-based strategy offers a potential route to COVID-19 drug development.

The heparin polysaccharide nanoparticles block the interaction between heparan sulfate/S protein and inhibit the infection of both wild-type SARS-CoV-2 pseudovirus and the mutated strains through pulmonary delivery.Image 1.

[This corrects the article DOI: 10.1016/j.apsb.2021.09.004.].