Abstract: The differential expression and subcellular localization of single-cell proteins are closely related to the physiological state and pathological mechanisms of the body. The development of single-cell protein in situ imaging methods provides powerful tools for spatial single-cell proteomics research and single-cell protein profiling. This article summarizes the single-cell protein imaging methods developed in recent years, including the circulating immunofluorescence imaging methods based on ordered multi-round antibody incubation, mass spectrometry imaging based on metal element labeled antibodies, fluorescence imaging based on DNA-barcoded antibody, gene encoded fluorescence protein imaging and spectral imaging based on Raman spectroscopy or X-ray spectroscopy, with brief explanation of the imaging principles of these methods. It focuses on the multiple performance, imaging resolution and signal amplification performance of these methods, and analyzes their application characteristics in practical scientific research and clinical work, in the hope of providing some reference for the development of more revolutionary single-cell imaging methods, and promoting the development of biomedical and precision medicine.

Abdomen/diagnostic imaging* ; Artificial Intelligence ; Body Composition ; Magnetic Resonance Imaging ; Practice Guidelines as Topic

Objective:To explore the improvement rate of the cognitive function of computerized cognitive remediation therapy (CCRT) on patients with schizophrenia and the clinical effect of CCRT in patients with different levels of cognitive impairment.Methods:A random number table was used to divide 311 patients with schizophrenia into CCRT group ( n=196) and work and amusement therapy (WAT) group ( n=115). The independently developed CCRT and operational music and dance therapy were given for 12 weeks to two treatment groups respectively. All patients were assessed using the MATRICS Consensus Cognitive Battery (MCCB) before and after treatment. According to the total score of MCCB at baseline, the patient′s cognition function was divided into 4 levels: severe cognitive impairment, moderate cognitive impairment, mild cognitive impairment and normal cognitive function. According to the change of MCCB total score, the efficacy of the treatment was divided into 3 levels: no improvement (≤0 points), improvement (0-9.57 points), superior improvement (>9.57 points). The improvement rate of cognitive function between two treatment groups was compared. Results:In the CCRT group, there were 19 cases with superior improvement, 105 cases with improvement, and 46 cases with no improvement. In the WAT group, there were 7 cases with superior improvement, 39 cases with improvement, and 41 cases with no improvement. The improvement of cognitive function of CCRT group was better than that of WAT group, and the difference was statistically significant ( Z=2.978, P=0.003). The patients with serious cognitive impairment in the CCRT group had a higher improvement rate than those in the WAT group ( Z=1.860, P=0.032). The patients with moderate cognitive impairment in the CCRT group had a lower no improvement rate than those in the WAT ( Z=-1.817, P=0.035).The patients with mild cognitive impairment in the CCRT group had a lower no improvement rate ( Z=-3.294, P=0.001) and higher improvement rate and superior improvement rate ( Z=2.084, P=0.019; Z=1.969, P=0.025) than those in the WAT group. There was no statistically significant difference in improvement rate between patients with normal cognitive function in the CCRT group and in the WAT group ( P>0.05).The patients with improvement and superior improvement of cognition were combined as responder, and the two treatment groups were compared. The patients with mild cognitive impairment in the CCRT group had a higher improvement rate than those in the WAT group (77.2%（44/57） vs. 41.4%（12/29），χ2=10.853， P=0.001). However, for patients with serious and moderate cognitive impairment or with normal cognitive function at baseline, rates of improvement after treatment did not differ significantly between CCRT group and WAT group. According to Cohen′s d, the level of effect size in cognition improvement after CCRT treatment in patients with different cognitive dysfunction level was: mild cognitive impairment (0.59)>moderate cognitive impairment (0.48)>normal cognitive function (-0.12)>serious cognitive impairment (-0.24). Conclusions:Schizophrenic patients treated with CCRT had a higher improvement rate of cognitive function than those with WAT, and the improvement rate of cognitive function is higher in patients with mild cognitive impairment after CCRT treatment.

Objective:To explore the improvement rate of the cognitive function of computerized cognitive remediation therapy (CCRT) on patients with schizophrenia and the clinical effect of CCRT in patients with different levels of cognitive impairment.Methods:A random number table was used to divide 311 patients with schizophrenia into CCRT group ( n=196) and work and amusement therapy (WAT) group ( n=115). The independently developed CCRT and operational music and dance therapy were given for 12 weeks to two treatment groups respectively. All patients were assessed using the MATRICS Consensus Cognitive Battery (MCCB) before and after treatment. According to the total score of MCCB at baseline, the patient′s cognition function was divided into 4 levels: severe cognitive impairment, moderate cognitive impairment, mild cognitive impairment and normal cognitive function. According to the change of MCCB total score, the efficacy of the treatment was divided into 3 levels: no improvement (≤0 points), improvement (0-9.57 points), superior improvement (>9.57 points). The improvement rate of cognitive function between two treatment groups was compared. Results:In the CCRT group, there were 19 cases with superior improvement, 105 cases with improvement, and 46 cases with no improvement. In the WAT group, there were 7 cases with superior improvement, 39 cases with improvement, and 41 cases with no improvement. The improvement of cognitive function of CCRT group was better than that of WAT group, and the difference was statistically significant ( Z=2.978, P=0.003). The patients with serious cognitive impairment in the CCRT group had a higher improvement rate than those in the WAT group ( Z=1.860, P=0.032). The patients with moderate cognitive impairment in the CCRT group had a lower no improvement rate than those in the WAT ( Z=-1.817, P=0.035).The patients with mild cognitive impairment in the CCRT group had a lower no improvement rate ( Z=-3.294, P=0.001) and higher improvement rate and superior improvement rate ( Z=2.084, P=0.019; Z=1.969, P=0.025) than those in the WAT group. There was no statistically significant difference in improvement rate between patients with normal cognitive function in the CCRT group and in the WAT group ( P>0.05).The patients with improvement and superior improvement of cognition were combined as responder, and the two treatment groups were compared. The patients with mild cognitive impairment in the CCRT group had a higher improvement rate than those in the WAT group (77.2%（44/57） vs. 41.4%（12/29），χ2=10.853， P=0.001). However, for patients with serious and moderate cognitive impairment or with normal cognitive function at baseline, rates of improvement after treatment did not differ significantly between CCRT group and WAT group. According to Cohen′s d, the level of effect size in cognition improvement after CCRT treatment in patients with different cognitive dysfunction level was: mild cognitive impairment (0.59)>moderate cognitive impairment (0.48)>normal cognitive function (-0.12)>serious cognitive impairment (-0.24). Conclusions:Schizophrenic patients treated with CCRT had a higher improvement rate of cognitive function than those with WAT, and the improvement rate of cognitive function is higher in patients with mild cognitive impairment after CCRT treatment.

Objective To evaluate the efficacy of one stage anterior debridement combined with posterior pedicle screw fixation in the treatment of cervical intervertebral space infection.Methods From June 2010 to June 2016,28 cases were fixed by anterior debridement combined with the posterior vertebral pedicle screws for the cervical intervertebral space infection,19 males and 9 females.The average age was 45-74 years (58±14.5 years old).21 cases (75％) were spontaneous infection,of which 6 cases were diabetes mellitus,15 cases were over 60 years old.The remaining 7 cases (25％) were intervertebral space infection after radiofrequency ablation of the cervical spine.All patients were excluded from tuberculosis and Brucella infection.All patients underwent hematological examination,with emphasis on WBC,ESP and CRP.All patients received JOA score before operation,applied antibiotic according to blood culture and drug sensitive test.All patients underwent one stage anterior debridement combined with posterior pedicle screw fixation,and the operative time and bleeding volume were recorded.After the operation,intravenous antibiotic therapy was continued,and the application of antibiotics was guided according to the results of ESP and CRP,and the time for the application of antibiotics was recorded.Follow up was performed at 3 months,6 months and 1 years after operation respectively.The JOA score and postoperative cervical lordosis Cobb angle were recorded.Results All operations were successfully completed in this group.The operation time was 130-225 min,with an average of 145.5±12.7 min.The intraoperative blood loss was 40-100 ml,with an average of 67±35.2 ml.The incision was healed in one stage.The time of application of antibiotics in 28 patients was 21-87 days,with an average of 30.8±8.7 days.The longest application time of antibiotics was 87 days,and no relapse was found during follow-up.The postoperative JOA score increased from 11.3± 1.2 to three months 14.9 ± 1.96 postoperatively and 6 months 15.1 ± 1.55 and 1 years 16.5±0.48 after operation.The JOA score was significantly higher than that before operation.No significant loss and change of the Cobb angle in the cervical spine surgery were found.All cases had good bone graft fusion at 1 years.Conclusion One stage anterior debridement combined with posterior pedicle screw fixation is a safe and effective method for the treatment of cervical vertebra instability and nerve function injury caused by cervical intervertebral space infection.It provides a new way for the treatment of cervical intervertebral space infection.

With the continuously exploration,in recent years,further understanding of anatomical characteristics of the cervical pedicle brings great breakthrough in cervical pedicle screw implantation.In addition,pedicle screw implantation in cervical spine is considered as a technique with high safety and reliability,which can be widely used in cervical trauma fracture,cervical instability,degenerative,inflammatory,benign or malignant tumor,deformity and other neck diseases.Because of the tremendous differences between upper cervical spine (C1,C2) and lower cervical spine (C3-7) in anatomical morphology,cervical pedicle screw implantation in C1 and C2 differs from in lower cervical spine.Due to the similar structure of C3-7,pedicle screw implantation methods are based on the same principle and sharing a few points in common.The pedicle screw technique can be classified in two groups according to the practice methods:navigation technology and manual placement of cervical pedicle screw.Navigation nailing is considered as reliable,easy handing,and with clear operative vision,however,with disadvantages as complex procedures,highly cost operation equipment,and risk in navigation draft.Therefore,manual placement of pedicle screw is more reasonable and practical comparing with the former.In this study,it analyzed anatomical characteristics of lower cervical pedicle and the measurement of pedicle structure,discussed technique of manual placement of pedicle screw in lower cervical spine and biomechanical study of pedicle screw,and summed up the comparison of the advantages and disadvantages of current representative manual placement technology.

Early detection and treatment of high-risk adenomas and colorectal cancer (CRC) can reduce mortality of this disease.CRC screening is aimed at minimizing its harm and colonoscopy is presently the gold standard for it.However,colonoscopy needs bowel preparation and is invasive with high risk of intestinal perforation,causing a bad compliance,which is unfavorable to its popularization and application.Recently,non-invasive detection methods for CRC have gone through a rapid development.Tests based on CRC-related biomarkers in fecal and blood samples provide new options for non-invasive CRC screening.However,detection methods for these biomarkers still need further research and improvement because of the complex composition of feces and blood.In the two aspects of fecal tests and blood tests,the progress of recent studies on non-invasive screening methods for CRC was reviewed in this article.

Objective The NDRG4 gene methylation in stool is a candidate biomarker for non?invasive diagnosis of colorectal cancer. However, the traditional methods for methylation detection could not be well applied to stool samples due to the low sensitivity and low specificity. The aim of this study was to develop a highly sensitive and specific method for quantifying the methylated NDRG4 gene in stools. Methods Forty one stool samples were collected from 12 colorectal cancer patients, 4 adenoma patients and 25 nor?mal persons. The invasive reaction was combined with real?time PCR and the relative quantification was performed by 2-ΔCT method to develop the highly sensitive and specific methylated DNA detection method, which was used for detecting NDRG4 methylation levels in 41 of stool samples. Results The sensitivity of the method was as low as 10 copies of methylated NDRG4 gene fragments. The specificity was high enough to distinguish 0.01% of methylated fragments from un?methylated fragments and 105 copies of unmethylated NDRG4 fragments gave noamplification signals. The detection results from 41 of stool samples showed that detection rate of the NDRG4 gene in stool from adenoma and colorectal cancer groups had a significant difference comparing to that from the normal group. Conclusion The 2-ΔCT method could accurately quantify the methylation levels of the NDRG4 gene in stool samples, and provide an efficient tool for non?invasive colorectal cancer detection.

A method for the real-time polymerase chain reaction ( PCR ) coupled with high specific invader assay to detect single nucleotide polymorphism ( SNP) was established. To reduce the background signal, the amount of flap endonuclease 1 ( FEN1 enzyme ) and wild-type detection probe was optimized. Under the optimum conditions including 0. 05 μmo/L invasive oligonucleotide probe, 0. 125 μmol/L wild-type detection probe, 0. 5 μmol/L mutation detection probe, 0. 25 μmol/L each fluorescence resonance energy transfer (FRET) probe and 1. 5 U FEN1, the background signal of wild-type sample and mutation sample was dramatically decreased and the background interference to the detecting results was thus eliminated. A total of 21 cases of aldehyde dehydrogenase-2*2 ( ALDH2*2 ) , 19 cases of cytochrome p450 2 C19*2 ( CYP2 C19*2 ) and 19 cases of CYP2C19*3 were analyzed with the established method, and the genotypes of ALDH2*2 were 10 cases of GG homozygote, 8 cases of GA heterozygote and 3 cases of AA homozygote; the genotypes of CYP2C19*2 were 9 cases of GG homozygote, 8 cases of GA heterozygote and 2 cases of AA homozygote;and the genotypes of CYP2C19*3 were 18 cases of GG homozygote and 1 case of GA heterozygote. These results were consistent with those by pyrosequencing. The established method was specific, simple, short time-consuming and low cost, and could be used for the detection of SNP genotyping with non-polluting in single closed tube.

Objective To investigate the emergency treatment measures of spontaneous frontotemporal intracerebral hematoma.Methods Retrospectively analyzed the rescue process and surgical experiences of 27 patients with spontaneous frontotemporal intracerebral hematoma combined with subarachnoid hemorrhage or ventricular hemorrhage.Twenty-three cases underwent surgery;4 cases with cerebral hernia under general anesthesia underwent craniotomy hematoma clearance,aneurysm clip and decompressive craniectomy;7 cases with previous history of hypertension,considered with hypertensive intracerebral hemorrhage,was performed with craniotomy hematoma clearance and decompressive craniectomy in the emergency under general anesthesia; 12 cases of middle cerebral artery aneurysms bleeding,chosen craniotomy hematoma clearance and aneurysm clip;4 cases found nothing by digital subtraction angiography (DSA) or CT angiography (CTA),were given conservative treatment,one of them was found arteriovenous malformations after 1 month,which was treated by γ-ray.Results After the surgery,2 cases died due to severe cerebral infarction,25 cases were followed up for 6 months,according to the Glasgow outcome scale(GOS) classification:17 cases with good prognosis,7 cases with poor prognosis,1 case with vegetative state.Conclusions Cerebral hernia formation in patients with spontaneous frontotemporal intracerebral hematoma should relieve cerebral hernia and mass effect as soon as possible,early surgery to save lives.Which of them without brain hernia,after diagnosis by CTA or DSA,choice suitable treatment.Sufficient preoperative evaluation,suitable surgical timing and good microsurgical techniques can improve the prognosis.