Pancreatic neoplasm is one of the most commonly-appeared digestive tumors and has been well-recognized as the poor diseases which have the difficulties in diagnosis,treatment and prognosis estimation.Recently,the detection of circulating tumor cells (CTCs) has been a pretty highlight of the research on detecting tumor cells in peripheral blood,and furthermore,the clinical value in the diagnosis,treatment and prognosis prediction has already been verified through a large amount of samples analyses in various kinds of tumor diseases.This paper aims to review and conclude the techniques of CTCs enrichment,detection and clinical implications in pancreatic neoplasms.In addition,the existing papers have been summarized and prospect of application of CTCs is also presented.

Objective To investigate the role of autophagy in podocyte damage,and the intracellular mechanism of autophagy activation through passive Heymann nephritis (PHN) animal model.Methods Male Sprague-Dawley rats (n=40) were studied on day 0,2,4,7,and 21 after induction of PHN by injection of anti-Fx1A.Podocyte morphology and autophagosomes were observed by transmission electron microscopy.Podocyte numerical density was estimated by Weibel-Gomez =method.Cell apoptosis was detected by TUNEL assay and caspase-3 immunohistochemical staining.Expressions of autophagy markers and endoplasmic reticulum stress (ERS)-associated proteins were analyzed by Western blotting.Results (1) In PHN rats,immunohistochemical staining showed that C5b-9 deposited along glomerular basement membrane on day 4 to day 21.Small subepithelial electron -dense deposits and a part of foot process fusion were detected in the glomerulus of PHN rats on day 4 by transmission electron microscope,and podocyte damage was aggravated on day 21.Furthermore,compared with control,the urinary protein levels of PHN rats began to increase on day 3,and reached the top on day 21 [(50.6±6.0) mg/24 h].(2) The number of podocytes significantly decreased in PHN rats compared with control group on day 21(P ＜ 0.05).(3) In PHN rats,apoptotic podocytes were found by caspase-3 immunohistochemical staining and TUNEL assay on day 21.(4) The expression of autophagy marker LC3 Ⅱ was markedly increased on day 7 and 21,but down-regulated on day 21 compared with day 7.Moreover,accumulated autophagosomes in podocytes were detected on day 7 and 21 by transmission electron microscope.(5) The level of GRP78 was significantly increased on day 2 and 7 but reduced to baseline on day 21.At the same time,the downstream pathways (ATF6α,p-PERK and p-JNK) of unfolded protein response were also up-regulated in the early process of PHN and down-regulated later.Conclusions Autophagy is an important way to protect against immunemediated podocyte injury in membranous nephropathy.Autophagy activation is mainly related to endoplasmic reticulum stress induced by complement attack.This provides an important basis for a thorough understanding of the role of autophagy in the process of podocyte damage and the pathogenesis of membranous nephropathy.

Objective To describe the changes of thrombosed venous sinus on MRI after administration of contrast material and evaluate the sensitivity and specificity of thread-like enhancement around sinus to diagnose thrombosis in the corresponding sinus.Methods Patients with cerebral venous sinus thrombosis (CVST) admitted to our department from January 2005 to December 2014 and undergone a MRI scan with administration of contrast material were included in this study.The enhancement features of venous sinus were studied in the plane parallel to the interested sinus.The features of enhancement were classified as peripheral thread-like enhancement, partial enhancement and complete enhancement.The proportion of these three type of enhancement in thrombosed sinuses and normal sinuses were described and compared.The sensitivity and specificity of peripheral thread-like enhancement to diagnose thrombosis in corresponding sinus were calculated.The proportion of each type of enhancement was also described and compared in acute (≤ 7 d), subacute (8-30 d) and chronic (≥ 31 d) stage after onset of symptoms.Results Peripheral thread-like enhancement, partial enhancement and complete enhancement were all found in both thrombosed and normal sinuses.There was a significant difference of enhancement features between normal and thrombosed sinus in superior sagittal sinus (100％ (30/30) vs 60％ (27/45), x2 =13.789, P =0.001), left trans verse sinus, and right sigrnoid sinus.The sensitivity and specificity of peripheral thread-like enhancement to diagnose thrombosis in the corresponding sinus were 10.5％-44.4％ and 53.3％-76.7％ respectively.There was no significant difference of contrast features at different stage after onset.Conclusion The value of peripheral thread-like enhancement to diagnose CVST is limited because of low sensitivity and specificity.

Objective To assess the disorders of glucose metabolism and insulin resistance in patients with rheumatoid arthritis (RA) and its relationship with disease activity.Methods One hundred and twenty-three RA patients along with 98 age and sex matched controls were studied.Seventy-five g oral glucose tolerance test was performed.The homeostasis model assessment of insulin resistance (HOMA-IR) and beta cell function (HOMA-β) were evaluated.Disease activity score (DAS28) was used to assess disease activity.According to their DAS28 values,patients were divided into high disease activity group and low to moderate disease activity group.Glucose tolerance and HOMA-IR were compared between the two groups.Parameters that reflects disease activity,such as CRP and ESR,as well as disease activity scores were compared between patients with T2DM or prediabetes and patients with normal glucose tolerance.The data was analyzed by t test,Pearson correlation analysis and chi-square test.Results The prevalence of T2DM [20.3％(25/123) vs 5.1％ (5/98),x2=10.774,P＜0.01] and prediabetes [39.0％ (48/123) vs 7.1％ (7/98),x2=29.657,P＜0.01] increased in RA patients compared to controls.RA patients had higher HOMA-IR (2.5±1.5 vs 0.8±0.4; t=5.185,P＜0.01) and lower HOMA-β (83±69 vs 192±85; t=3.768,P＜0.01) compared to controls.ESR [(55±30) mm/1 h vs (37±26) mm/1 h; t=3.159,P＜0.01],CRP [(40±23) mg/L vs (19±10) mg/L; t=3.628,P＜0.01] and DAS28 score (5.6±1.3 vs 4.8±1.2; t=2.923,P＜0.01) were higher in RA patients with T2DM or prediabetes than in RA patients with normal glucose tolerance.In RA patients,the HOMA-IR was significantly positively correlated with DAS28 (r=0.39,P＜0.01),ESR (r=0.54,P＜0.01)and CRP (r=0.20,P＜0.05).The HOMA-IR value and fasting insulin levels were higher in high disease activity patients (DAS28＞ 5.5) than in low-to-moderate disease activity patients (DAS28 ≤5.5) although fasting plasma glucose level did not differ significantly in these two groups.Conclusion The prevalence of T2DM and prediabetes increases in RA patients comparing to controls.RA patients have insulin resistance that is associated with disease activity and systemic inflammation.

Objective To determine the effect of rapamycin on sublytic C5b-9-induced podocyte adhesion damage,and whether autophagy is involved in this progression.Methods Sublytic complement C5b-9 stimulation was used in vitro.Autophagosomes were viewed using electron microscopy.Western blotting was used to measure the change of autophagy-related markers.Attachment assay was used to assess the adhesion of podocyte.Confocal microscopy was used to explore the expression patterns of cytoskeletal protein F-actin.Flow cytometry was used to measure the level of adhesion-associated protein integrin α3.Results (1) For ensuring sublytic complement injury,the maximal amounts of anti-podocyte antiserum and 160×-diluted normal human serum were used without inducing cell lysis (defined as ＞ 5％ LDH release).(2) Sublytic C5b-9 promoted autophagy in podocyte in vitro.The proautophagic effect of sublytic C5b-9 manifested in the form of accumulated autophagosomes and enhanced expression of LC3-lⅡ.(3) Inhibition of autophagy by 3-methyadenine enhanced the effect of sublytic C5b-9-induced podocyte injury,including serious cytoskeleton damage and markedly reduced adhesion of podocyte.(4) Rapamycin treatment significantly improved the above lesions.(5) Rapamycin enhanced autophagy induced by sublytic C5b-9 in podocyte.Conclusions In summary,rapamycin can improve sublytic CSb-9-induced podocyte adhesion damage by appropriate autophagy activation.These findings provide important information for the development of appropriate protocols for the application of mTOR (mammalian target of rapamycin) inhibitors in podocytopathy.

OBJECTIVE:To systematically evaluate the relationship of multi-drug resistance gene MDR1 C3435T gene polymor-phism with therapeutic efficacy of proton pump inhibitors (PPIs)-based triple therapy for Helicobacter pylori eradication. METH-ODS:Retrieved from PubMed,EMBbase,CBM,CJFD,Wanfang database and VIP,clinical studies about MDR1 C3435T gene polymorphism and PPIs-based triple therapy for the eradication of H. pylori infection were collected. Meta-analysis was performed by using Rev Man 5.3 statistical software after data extraction and quality evaluation by using STREGA statement. RESULTS:A to-tal of 7 studies were included,involving 1019 patients. The results of MDR1 C3435T genotyping in patients were classified as wild homozygote genotype(CC),mutant heterozygous genotype(CT)and mutant homozygote genotype(TT). The results of Me-ta-analysis showed that there was no statistical significance in the eradication rate of H. pylori among CC,CT and TT groups of MDR1 C3435T gene polymorphism [CC vs. CT:OR=0.99,95%CI(0.69,1.42) ,P=0.95;CC vs.TT:OR=1.44,95%CI(0.66, 3.15),P=0.36;CT vs.TT:OR=1.54,95%CI(0.86,2.73),P=0.14]. Subgroup analysis showed the eradication rate of H. pylori in CT genotype group was higher than that in TT genotype group among Asian population [OR=2.35,95%CI(1.53,3.62),P<0.001]. CONCLUSIONS:MDR1 C3435T gene polymorphism basically do not affect therapeutic efficacy of PPIs-based triple thera-py for H. pylori eradication. For Asian population,gene detection is useful for the treatment.

Objective To evaluate the optimum ratio of medicine dosage for dexmedetomidine mixed with sufentanil used for patient?controlled intravenous analgesia ( PCIA) after Nuss procedure in pedi?atric patients with pectus excavatum. Methods Sixty pediatric patients diagnosed with pectus excavatum, aged 5-12 yr, weighing 18-50 kg, of ASA physical statusⅠorⅡ, scheduled for elective Nuss procedure under general anesthesia, were randomly divided into 3 equal groups using a random number table:different ratios of medicine dosage while dexmedetomidine was added to sufentanil groups ( SD1-3 groups) . Postopera?tive analgesia was as follows: group SD1 received sufentanil 1 μg∕kg + dexmedetomidine 2 μg∕kg; group SD2 received sufentanil 1 μg∕kg + dexmedetomidine 3 μg∕kg; group SD3 received sufentanil 1 μg∕kg +dexmedetomidine 4 μg∕kg. A mixture of tropisetron 0?1 mg∕kg and dexamethasone 0?1 mg∕kg ( in 100 ml of normal saline) was added in each group. The PCA pump was programmed to deliver 0?5 ml with a lockout interval of 15 min and background infusion at 2 ml∕h. The PCA pump was connected immediately after the end of operation, and sufentanil with a dosage of 0?1μg∕kg was used as a rescue analgesic within 48 h post?operatively. The VAS score was maintained below 4. The requirement for rescue analgesics was recorded. The Ramsay sedation scores was recorded at 4, 8, 12, 24 and 48 h postoperatively, and the occurrence of adverse reactions such as nausea and vomiting, bradycardia, over?sedation, respiratory depression, agitation and shivering was recorded within 48 h after surgery. Results No pediatric patients developed nausea and vomiting, respiratory depression, bradycardia, over?sedation, and shivering. No pediatric patients required rescue analgesics in SD2 and SD3 groups. Compared with group SD1 , the requirement for rescue analgesics and incidence of agitation were significantly decreased, and Ramsay sedation scores were increased at 4 and 8 h after operation in SD2 and SD3 groups. Ramsay sedation scores were significantly higher at 4 h after oper?ation in SD3 group than in SD2 group. Conclusion Dexmedetomidine 3 μg∕kg mixed with sufentanil 1μg∕kg is the optimum ratio of medicine dosage when used for PCIA after Nuss procedure in pediatric patients with pectus excavatum.

Objective To investigate the characteristics and the frequencies of B cell subsets in peripheral blood of rheumatoid arthritis (RA) patients,and to study the correlation between B cell subsets and clinical indices and influence of different therapies on B cell subsets to deeply understand the pathogenesis of RA.Methods Peripheral blood witched memory B cells,non-switched memory B cells,naive B cells,and double negative B cells of 141 patients and 33 healthy controls were measured by flow cytometry.Patients were divided into three groups based on their therapeutic regimen,including tumor necrosis factor-or (TNF-α) inhibitors combined with disease modifying antirheumatic drugs (DMARDs),DMARDs only and patients without any therapy.The relevance between B cells subsets and clinical manifestations,lab test results exemption were assessed as well as the influence of different therapies.All data were were analyzed by Statistical product and service solutions (SPSS) 23.0 statistical analysis for unpaired t test,analysis of variance and Spearman's correlations analysis.Results ① New-onset RA patients with less than 12 weeks disease duration and never accepted any drugs had a significantly lower frequency of peripheral blood memory B cells,including non-switched memory B cells [(8 ±4)％ vs (13 ±4)％,P＜0.05,t =3.3)] and switched memory B cells [(18±10)％ vs (23±7)％,P＜0.05,t=2.2)],than healthy individuals.② There was a negative association between non-switched memory B cells and disease activity score in 28 joints (r=-0.23,P＜0.05).③ Negative association between non-switched memory B cells and erythrocyte sedimentation rate (ESR),lgG was found,while therewas no association between pre-switched B cells and other laboratory test results.④ Non-switched memory B cells and switched memory B cells increased after TNF-α arntagonist or DMARDs therapy.Conclusion The results of this study suggest that B cell abnormalities in new-onset RA patients with short disease duration are reduced non-switched memory B cells and switched memory B cells.A negative correlation has been found between non-switched memory B cells and ESR and lgG.B cells subsets frequency are changed by TNF-α antagonist and DMARDs,which suggests that changes of B cell subsets may contribute to the occurrence and development of RA.

Objective:To investigate the clinical phenotypes, imaging features and pathogenic variants of ANO10 gene related autosomal recessive spinocerebellar ataxia-10 (SCAR10).Methods:A cohort of 30 probands of autosomal recessive cerebellar ataxia pedigrees from China-Japan Friendship Hospital from 2018 to 2020 were collected. Friedreich ataxia and other causes of acquired ataxia were excluded, then probands were detected by whole-exome sequencing (WES), and potential pathogenic variants were confirmed by Sanger sequencing and validated in all family members. Clinical phenotypes and auxiliary examinations of the patients were analyzed in detail.Results:A pedigree of SCAR10 caused by ANO10 gene mutations was identified through WES. The 40-year-old male proband of this pedigree carried compound heterozygous mutations: c.1219-2A>C and c.1163-2A>G of the ANO10 gene, both of which were novel mutations, and Sanger sequencing revealed these two mutations were respectively inherited from his healthy parents. Bioinformatic analysis predicted these two mutations were pathogenic. The proband exhibited progressive unsteady walk, dysarthria, mild cognitive impairment. His plasma total coenzyme Q 10 was decreased (0.76 μg/ml). Brain magnetic resonance imaging showed remarkable cerebellar atrophy. Conclusions:Through WES, a SCAR10 patient caused by novel compound heterozygous mutations of ANO10 gene was identified, which is rare in China. The main clinical manifestation was progressive cerebellar ataxia and cognitive decline, and brain image showed remarkable cerebellar atrophy.

BACKGROUNDAs a time-dependent antibiotic, the time of cefazedone concentration exceeds the minimum inhibitory concentration (MIC) is the key pharmacokinetic-pharmacodynamic (PK-PD) variable associated with the killing of pathogens. The purpose of the study was to evaluate the clinical regimen rationality of intravenous cefazedone sodium in the treatment of community-acquired pneumonia (CAP) by PK/PD study.

METHODSTen patients with mild to moderate CAP were enrolled to receive intravenous cefazedone sodium (2 g q12 h) for 7-14 days. Blood samples were collected in any day during day 5-7. Sputum specimens were collected before treatment for bacteria isolated, and susceptibility to cefazedone determined. PK-PD analysis was performed using the noncompartmental analysis of Phoenix WinNolin software (version 6.1, Pharsight Corporation, CA, USA). The maximal time above MIC (ƒT > MIC) was calculated, and its correlation with clinical efficacy was analyzed.

RESULTSAll 10 patients completed the study and 8 of them were cured. Six strains were isolated from patients before treatment (one for each patient) and all susceptible to cefazedone. Five patients of six in culture positive group were cured. All pathogens were cleared at the end of therapy. The MICs were between 0.25 and 1 mg/L. The main PK parameters were C max 175.22 ± 36.28 mg/L; T½ 1.52 ± 0.23 h; AUC (0-∞) 280.51 ± 68.17 mg·L -1·h -1 ; CL 7.37 ± 1.84 L/h; Vd 16.06 ± 4.42 L. The average ƒT > MIC was 55.45 ± 8.12%.

CONCLUSIONSIntravenous injection of cefazodone sodium with 2 g q12 h dosage regimen is used in the treatment of CAP caused by sensitive bacteria, either ƒT > MIC or clinical efficacy shows that such dosing regimen is reasonable.

Administration, Intravenous ; Adolescent ; Adult ; Aged ; Anti-Bacterial Agents ; administration & dosage ; pharmacokinetics ; therapeutic use ; Cefazolin ; administration & dosage ; analogs & derivatives ; pharmacokinetics ; therapeutic use ; Community-Acquired Infections ; drug therapy ; metabolism ; Female ; Humans ; Male ; Microbial Sensitivity Tests ; Middle Aged ; Young Adult