To explore the impact of an airway stepwise management strategy in the treatment of hospital acquired pneumonia (HAP) in the ultra elderly critically ill patients.

Objective:To analyze the genus, drug resistance/virulence and phylogenetic characteristics of Brucella strains isolated from brucellosis surveillance sentinels in Henan Province from 2013 to 2022, and provide baseline data for the surveillance, early warning and outbreak tracing of brucellosis. Methods:Blood samples were collected from patients with Brucella infection for strain isolation, culture and species identification, drug susceptibility test, whole genome sequencing, splicing and assembly, functional/virulence/resistance gene prediction analysis and phylogenetic tree drawing based on single nucleotide polymorphism (SNP). Results:In 36 brucellosis patients, the majority were men (86.11%, 31/36), young adults aged 18-50 (88.89%, 32/36) and farmers/herdsmen (72.22%, 26/36). A total of 36 strains of Brucella melitensis were isolated, and average 1 305 functional proteins of 21 categories were predicted by strain genome; all the strains carried four main virulence factors (pmm, VirB group, BtpA/BtpB, BvrS/BvrR). The drug sensitivity rate was 100.00% to six types of antibiotics including levofloxacin, rifampicin, doxycycline, streptomycin, tetracycline and gentamicin, they showed different resistances to three antibiotics including compound trimethoprim-sulfamethoxazole, ciprofloxacin and ampicillin. The strains carried four types of resistance genes and two clusters of resistance genes, with four combinations of genotypes, the resistance mechanisms included antibiotic degradation/modification enzymes, resistant nodular cell differentiation (RND) efflux pumps, 16S/23S ribosomal rRNA binding site mutations, etc. The number of SNP differed in the genomes of 36 Brucellamelitensis strains ranged from 0 to 454 and phylogenetic tree was divided into three major branches, with relative branch distances between 0.000 0 and 0.498 6 for each strain. Conclusions:Human Brucellamelitensis strains isolated from surveillance sentinels in Henan from 2013 to 2022 carried multiple virulence and antibiotic resistance genes and had different drug resistance phenotypes. Single nucleotide polymorphism analysis and phylogenetic tree analysis showed significant differences in phylogenetic relationships among different strains.

Messenger RNA(mRNA) CCT6A can encode chaperone proteins and plays an important role in malignant tumors such as colorectal cancer, lung cancer and breast cancer. CCT6A is highly expressed in malignant tumors, which can be used as a biomarker to assess patients' prognosis, and promote malignant biological behaviors such as tumor proliferation and metastasis by regulating transforming growth factor β signals, cell cycles, and other pathways. CCT6A can also modulate immune cell infiltration in the tumor microenvironment and may be a potential target for tumor immunotherapy. The paper reviews the expression and function of CCT6A in malignancies.

Objective:To explore the clinical phenotype and gene characteristics of a case of TSC2/PKD1 adjacency gene syndrome, so as to improve the clinical understanding of the disease.Methods:A case of TSC2/PKD1 adjacency gene syndrome diagnosed in the Department of Neurology of the Children′s Hospital Affiliated to Zhengzhou University was analyzed retrospectively. The clinical data, laboratory examination, imaging characteristics and gene variation characteristics of the child were summarized.Results:The patient was a 17 months old girl, with the main complaint of "intermittent convulsion with 17 months of underdevelopment". The clinical manifestations were epileptic seizures, which were in the form of a series of spastic seizures, absence seizures, focal seizures, and depigmentation spots can be seen in the trunk and neck. Cranial magnetic resonance imaging showed multiple patchy signals in the cortex and subcortical areas of the bilateral cerebral hemispheres, multiple small nodular shadows under the ependyma of the bilateral lateral ventricles, the heart color Doppler ultrasound showed patent foramen ovale and pericardial effusion, and the abdomen color Doppler ultrasound showed polycystic kidney. Ophthalmic color Doppler ultrasound showed that there were localized small swelling lesions around the optic disc of the left eye. The whole exon gene sequencing of the pedigree showed the proband had partial deletion of TSC2 gene (NM_000548) at chromosome position chr16: 2125799-2185690. The real-time quantitative detection system verified that exons 23-42 were deleted, and all exons of PKD1 gene were deleted (NM_001009944), and multiple ligation dependent probe amplification verified that exons 1-46 were deleted, and no downstream gene deletion was found. The overall deletion size was about 60 kb. Both of the girl's father and mother had normal phenotypes and were wild-type.Conclusions:TSC2/PKD1 adjacency gene syndrome is relatively rare. It can have clinical manifestations of tuberous sclerosis/autosomal dominant polycystic kidney disease. Most of the nervous system and kidney are seriously affected, and the prognosis is poor. TSC2/PKD1 gene deletion and variation is the genetic cause of the TSC2/PKD1 adjacency gene syndrome.

Objective:To explore the effect of cholesterol on the expression of genes for matrix synthesis and degradation of human meniscal fibrochondrocytes and its mechanism.Methods:Meniscal tissue was taken from patients undergoing arthroscopic surgery to extract fibrochondrocytes. The cells were divided into a control group in which the normal cells were not processed, a positive control group in which interleukin-1 β was used to create a degeneration model, and 2 treatment groups which were subjected to treatment with 15 and 30 μg/mL cholesterol respectively. Safranin O staining, β-galactosidase staining and enzymic kits were used to detect the morphology and total cholesterol (TCH) content of meniscal fibrochondrocytes in the 4 groups. Immunofluorescence and western blot were used to detect the protein expression of type Ⅰcollagen precursor α1 (COL1A1) and type Ⅱ collagen precursor α1 (COL2A1). RT-qPCR was used to detect the mRNA expression of COL1A1, COL2A1, matrix metalloproteinase (MMP) 3, MMP9, MMP13, and genes related to cholesterol efflux pathways [like liver X receptor α (LXR α), ATP binding cassette transporter A1 (ABCA1) and ABCG1]. Results:There was no significant difference between the control and the positive control groups in the TCH content in human meniscal fibrochondrocytes ( P>0.05). The treatments with 15 and 30 μg/mL cholesterol resulted in significantly increased TCH contents in human meniscal fibrochondrocytes in the treatment groups ( P<0.05). Compared with the control group, the mRNA expression of LXR α, ABCA1 and ABCG1 was significantly decreased in the treatment groups ( P<0.05), and the meniscal fibrochondrocytes in the positive group and the treatment groups presented with a lower density, chaotic distribution and obvious signs of degradation. Compared with the control groups, the mRNA expression of matrix synthesis genes (COL1A1 and COL2A1) in the meniscal fibrochondrocytes was significantly inhibited while the mRNA expression of matrix degradation metalloenzymes (MMP3, MMP9 and MMP13) was significantly promoted ( P<0.05). Conclusion:Cholesterol may inhibit the cholesterol efflux pathways of meniscal fibrochondrocytes, and thus cause accumulation of cholesterol in the meniscal fibrochondrocytes, eventually leading to degeneration of meniscus.

Objective:To analyze the dynamic changes and possible influencing factors of anti-2019 novel Coronavirus (2019-nCoV) neutralizing antibody in confirmed Coronavirus Disease 2019 (COVID-19) cases.Methods:Microneutralization was used to test the anti-2019-nCoV neutralizing antibody. Excel 2007 and SPSS 22.0 were used for data processing and analysis.Results:There were 420 serum samples collected from 155 confirmed COVID-19 cases. These serum samples contained acute phase serum, convalescent phase serum and serum from cases recovered for about six months. The sampling time was 0-221 days after the onset of COVID-19. The geometric mean titer (GMT) of anti-2019-nCoV neutralizing antibody was 1∶13 at 1 week, and 1∶31 at 2 week. The titers of anti-2019-nCoV neutralizing antibody of individual cases were still<1∶4 on the 15 th day. The GMT was all over 1: 52 (13×4) at 6-32 week. Taking 1: 64 as the cut-off point, the serum anti-2019-nCoV neutralizing antibody positive rates was 30.56% in acute phase serum samples (0-14 d, 0-2 w), 82.31% in convalescent phase serum samples (36-63 d, 6-9 w) and 86.52% in serum samples from cases recovered for about six months (183-210 d, 27-30 w). Statistical analysis showed that there was no significant difference in anti-2019-nCoV neutralizing antibody levels at the other weeks except 1-2 week ( χ2=9.270, P=0.931), there was no statistically differences in gender, age and occupation of the cases, and also between the normal and mild cases ( P>0.05). Conclusions:The serum anti-2019-nCoV neutralizing antibody level is only statistically correlated with the disease progression of COVID-19, and maintain the protective level from 3 to 30 week.

Objective:To investigate the efficacy and the safety of intravascular therapy for cerebrovascular ischemic tandem stenosis.Methods:Clinical data of 35 patients with symptomatic anterior circulation and posterior circulation tandem stenosis who received intravascular therapy for two sites of stenosis at the same time at Department of Neurosurgery of Peking University First Hospital from January 2013 to December 2018 were analyzed retrospectively. There were 27 males and 8 females,aged (65.6±9.4)years (range:47 to 81 years).There were 14 cases of anterior circulation tandem stenosis and 21 of posterior circulation tandem stenosis.The medical records were collected with emphasis on postoperative symptoms,imaging manifestations and modified Rankin scale(mRS) scores.Results:Sixty-eight stents were implants in to 35 patients,including 49 extracranial implants and 19 intracranial implants.The surgical success rate was 100%.The perioperative death rate was 0,and 1 patient(1/35,2.9%) had cerebral hemorrhage.All patients were followed up for 18 months.During 3 to 12 months after the intervention,1 case(1/35,2.9%) had stent restenosis,and 4 cases(4/35,11.4%) had persisted symptoms such as dizziness and weakness in limbs.All patients′mRS scores were ≤2. No new stroke occurred. During 12 to 18 months after the intervention,3 cases had in-stent restenosis,increasing the rate to 11.4% (4/35). The mRS scores of 32 patients(32/35,91.4%) were ≤2.Conclusion:Intravascular therapy for patients with symptomatic tandem stenosis is a feasible and safe procedure with good short-term outcomes.

Objective:To investigate the strategy and the clinical effect of single stage treatment for intracranial or extracranial artery stenosis with intracranial aneurysm.Methods:The clinical data of 15 patients with intracranial aneurysms and extracranial or intracranial artery stenosis treated by one-stage endovascular therapy at Department of Neurosurgery of Peking University First Hospital from April 2013 to September 2018 were analyzed,respectively.There were 6 males and 9 females,aged (63.9±9.1)years (range:43 to 79 years).Fifteen arterial stenosis were found, including 8 in anterior circulatiion and 7 in posterior circulation, and the stenosis rates ranged from 75% to 95%. There were 17 aneurysms, among which 11 in the anterior circulation and 6 in the posterior.The maximal diameter was (5.3±1.2)mm (range:3 to 7 mm).All patients were treated with stenting and embolization at one stage. The operation choices, perioperative and postoperative symptoms,imaging data and complications were recorded.Results:Stents were successfully implanted into arterial stenosis of 15 cases, reducing the stenosis rates to less than 30%.Among the 17 aneurysms,10 cases were treated by coil embolization alone,7 cases by stenting and coil embolization. Eventually all the 17 aneurysms reached complete embolization.One patient had mild symptoms of the cerebral infarction during the perioperative period,and the rest had not shown surgical complications.The follow-up time was (43.8±8.2)months (range:24 to 85 months). All the patients underwent digital subtraction angiography 6 to 12 months after operation.Among them,2 cases had asymptomatic in-stent restenosis,and no recurrence was found in aneurysms.Up to the last follow-up,no patients had showed new symptoms or signs of intracranial hemorrhage or ischemic stroke.Conclusions:For patients suffered from both stenosis and aneurysms,individualized treatment should be made based on the location and severity of the vascular stenosis and aneurysms.With careful preoperative evaluation and surgical planning,the single stage endovascular treatment for intracranial or extracranial artery stenosis combined with intracranial aneurysm is safe,feasible and effective for selected patients.

Objective:To investigate the efficacy and the safety of intravascular therapy for cerebrovascular ischemic tandem stenosis.Methods:Clinical data of 35 patients with symptomatic anterior circulation and posterior circulation tandem stenosis who received intravascular therapy for two sites of stenosis at the same time at Department of Neurosurgery of Peking University First Hospital from January 2013 to December 2018 were analyzed retrospectively. There were 27 males and 8 females,aged (65.6±9.4)years (range:47 to 81 years).There were 14 cases of anterior circulation tandem stenosis and 21 of posterior circulation tandem stenosis.The medical records were collected with emphasis on postoperative symptoms,imaging manifestations and modified Rankin scale(mRS) scores.Results:Sixty-eight stents were implants in to 35 patients,including 49 extracranial implants and 19 intracranial implants.The surgical success rate was 100%.The perioperative death rate was 0,and 1 patient(1/35,2.9%) had cerebral hemorrhage.All patients were followed up for 18 months.During 3 to 12 months after the intervention,1 case(1/35,2.9%) had stent restenosis,and 4 cases(4/35,11.4%) had persisted symptoms such as dizziness and weakness in limbs.All patients′mRS scores were ≤2. No new stroke occurred. During 12 to 18 months after the intervention,3 cases had in-stent restenosis,increasing the rate to 11.4% (4/35). The mRS scores of 32 patients(32/35,91.4%) were ≤2.Conclusion:Intravascular therapy for patients with symptomatic tandem stenosis is a feasible and safe procedure with good short-term outcomes.

Objective:To investigate the strategy and the clinical effect of single stage treatment for intracranial or extracranial artery stenosis with intracranial aneurysm.Methods:The clinical data of 15 patients with intracranial aneurysms and extracranial or intracranial artery stenosis treated by one-stage endovascular therapy at Department of Neurosurgery of Peking University First Hospital from April 2013 to September 2018 were analyzed,respectively.There were 6 males and 9 females,aged (63.9±9.1)years (range:43 to 79 years).Fifteen arterial stenosis were found, including 8 in anterior circulatiion and 7 in posterior circulation, and the stenosis rates ranged from 75% to 95%. There were 17 aneurysms, among which 11 in the anterior circulation and 6 in the posterior.The maximal diameter was (5.3±1.2)mm (range:3 to 7 mm).All patients were treated with stenting and embolization at one stage. The operation choices, perioperative and postoperative symptoms,imaging data and complications were recorded.Results:Stents were successfully implanted into arterial stenosis of 15 cases, reducing the stenosis rates to less than 30%.Among the 17 aneurysms,10 cases were treated by coil embolization alone,7 cases by stenting and coil embolization. Eventually all the 17 aneurysms reached complete embolization.One patient had mild symptoms of the cerebral infarction during the perioperative period,and the rest had not shown surgical complications.The follow-up time was (43.8±8.2)months (range:24 to 85 months). All the patients underwent digital subtraction angiography 6 to 12 months after operation.Among them,2 cases had asymptomatic in-stent restenosis,and no recurrence was found in aneurysms.Up to the last follow-up,no patients had showed new symptoms or signs of intracranial hemorrhage or ischemic stroke.Conclusions:For patients suffered from both stenosis and aneurysms,individualized treatment should be made based on the location and severity of the vascular stenosis and aneurysms.With careful preoperative evaluation and surgical planning,the single stage endovascular treatment for intracranial or extracranial artery stenosis combined with intracranial aneurysm is safe,feasible and effective for selected patients.