Dendritic cells (DCs) serve as the primary antigen-presenting cells in autoimmune diseases, like rheumatoid arthritis (RA), and exhibit distinct signaling profiles due to antigenic diversity. Type II collagen (CII) has been recognized as an RA-specific antigen; however, little is known about CII-stimulated DCs, limiting the development of RA-specific therapeutic interventions. In this study, we show that CII-stimulated DCs display a preferential gene expression profile associated with migration, offering a new perspective for targeting DC migration in RA treatment. Then, saikosaponin D (SSD) was identified as a compound capable of blocking CII-induced DC migration and effectively ameliorating arthritis. Optineurin (OPTN) is further revealed as a potential SSD target, with Optn deletion impairing CII-pulsed DC migration without affecting maturation. Function analyses uncover that OPTN prevents the proteasomal transport and ubiquitin-dependent degradation of C-C chemokine receptor 7 (CCR7), a pivotal chemokine receptor in DC migration. Optn-deficient DCs exhibit reduced CCR7 expression, leading to slower migration in CII-surrounded environment, thus alleviating arthritis progression. Our findings underscore the significance of antigen-specific DC activation in RA and suggest OPTN is a crucial regulator of CII-specific DC migration. OPTN emerges as a promising drug target for RA, potentially offering significant value for the therapeutic management of RA.

COVID-19 is caused by a novel coronavirus-severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), which has being spreading around the world, posing a serious threat to human health and lives. Neutralizing antibodies and small molecule inhibitors for virus replication cycle are the main antiviral treatment for novel coronavirus recommended in China. To further promote the rational use of antiviral therapy in clinical practice, the National Center for Infectious Diseases (Beijing Ditan Hospital Capital Medical University and the First Affiliated Hospital, Zhejiang University School of Medicine) invited experts in fields of infectious diseases, respiratory and intensive care to develop an Expert Consensus on Antiviral Therapy of COVID-19 based on the Diagnosis and Treatment Guideline for COVID-19 ( trial version 10) and experiences in the diagnosis and treatment of COVID-19 in China. The consensus is concise, practical and highly operable, hopefully it would improve the understanding of antiviral therapy for clinicians and provide suggestions for standardized medication in treatment of COVID-19.

Objective To investigate the application value of double ovarian stimulations in the patients with low follicular output rate(FORT). Methods The data of 226 cases with low FORT at our hospital were ana-lyzed in this retrospective study. 67 patients received a subsequent luteal phase ovarian stimulation following regu-lar follicular phase stimulation(double stimulations group). The other 159 patients were performed fresh embryos transfer or whole embryos freezing(low FORT group),in which 60 patients who were not pregnant or had a pregnan-cy failure after fresh or freezing embryo transfer were served as control group and received conventional ovarian stimulation protocol in the next cycle. The clinical outcomes were compared among groups. Results The numbers of oocytes retrieved,metaphaseⅡoocytes,2PN fertilized oocytes,top-quality embryos in luteal phase stimulation were significantly higher than those in follicular phase stimulation(P < 0.05). Meanwhile,the parameters of IVF mentioned above along with cryopreserved embryos and the clinical pregnancy rate in double stimulations were sig-nificantly higher and the rate of abortion was significantly lower than low FORT group(P<0.05),which were simi-lar to control group(P > 0.05). Conclusions With the advantages of obtaining more available embryos in less time,the double stimulation could be served as an effective supplementary intervention for the patients with low FORT.

The pediatric reference intervals in clinical laboratory play an important role in diagnosis of illness,therapeutic monitoring,prediction of prognosis and health evaluation.Compared with establishing reference interval for adults,there are more challenges to establish pediatric reference intervals.Therefore,the procedure and key technologies of direct method and indirect method are stated based on the characteristics of children population and pediatric,by which to define,transfer and validate pediatric reference intervals.This study will provide systematically methodological ideas for clinical laboratories to establish pediatric reference intervals.

BACKGROUND:To date, it is stil unclear whether the intramuscular injection of heterogeneous umbilical cord mesenchymal stem cel s (UC-MSC) can cause cardiac ectopic pathological angiogenesis as wel as increase col agen synthesis to promote myocardial fibrosis. OBJECTIVE:To explore the effects of intramuscular injection of human UC-MSCs on myocardial micrangium and col agen expression in normal Wistar rats. METHODS:After 2 weeks of feeding, 60 male SPF Wistar rats were randomly assigned to receive intramuscular injection of PBS (normal group), DMEM (culture medium group), human UC-MSCs supernatant (supernatant group), 0.25×105, 1.0×105, 4.0×105 human UC-MSCs (low-, moderate-and high-dose groups), respectively (n=10 per group). Al the rats were subjected to second injection (same dose) at 4 weeks after first intramuscular injection. Then, the rats were kil ed under anesthesia at 4 weeks after second injection, to take heart tissues from the left ventricle for pathological observation, immunohistochemical examination and Masson staining. RESULTS AND CONCLUSION:No alteration of the response, activity, victualage, faeces, weight growth, and fur was found, and there was no death in rats during the experiment. Al the rats had no symptoms of molt, inflammation, skin ulcer, scleroma. Strong positive expression of CD34 for the micrangium in the myocardial tissue was observed, and positive expression of the col agen in the myocardial tissue observed by Masson staining. There were no significant differences in the microvessel density and col agen expression in the myocardium among the groups (F=0.110 and 0.585, P>0.05). To conclude, hUC-MSCs or its supernatant via intramuscular injection has no effect on the micrangium and col agen expression in normal rats.

Objective To investigate the distribution and changing resistance proifle ofSalmonella isolates in hospitals across China during the period from January 2005 to December 2014.Methods Seventeen general hospitals and two children’s hospitals were involved in this program. Antimicrobial susceptibility testing was carried out by means of a unified protocol using Kirby-Bauer method or MIC determination. The results were analyzed according to CLSI 2014 breakpoints.Results The proportion ofSalmonella isolates increased with time from 0.2% in 2005 to 0.7% in 2014. A total of 3 478Salmonella strains were collected from 19 hospitals. The proportion ofSalmonella typhimurium andSalmonella enteritidis was 27.4% and 24.4%, respectively. During the 10-year period, theSalmonella strains showed highest resistance rate to ampicillin (33.3%-64.8%), but low resistance to cefoperazone-sulbactam (0-5.3%) and ciprofloxacin (2.4%-14.3%).S. typhimurium showed higher resistance rate thanS. typhi,S. paratyphi andS. enteritidis. About 76.8% and 50.5% ofS. typhimurium were resistant to ampicillin and trimethoprim-sulfamethoxazole. The average prevalence of multi-drug resistantSalmonellawas 3.9% in the ten-year period, the highest (7.5%) was in 2005, the lowest (1.5%) in 2013.Conclusions During the period from 2004 to 2015, majority of theSalmonella isolates in hospitals across China wasS. typhimurium andS. enteritidis. Ampicillin and trimethoprim-sulfamethoxazole are no longer appropriate for empirical treatment ofS. typhimurium infection due to high resistance rate.Salmonella isolates are relatively more susceptible to third-generation cephalosporins and quinolones. Ongoing monitoring is necessary to identify multi-drug resistant strains ofSalmonella.

Objective To investigate the distribution and antibiotic resistance proifle of clinicalEnterobacter isolates using the data from CHINET during the period from 2005 through 2014.Methods A total of 20 558 clinical strains ofEnterobacter spp. were collected from 2005 to 2014 in CHINET Antimicrobial Resistance Surveillance Program. Antimicrobial susceptibility testing was performed with Kirby-Bauer or minimum inhibitory concentration method. The results were analyzed according to CLSI 2014 breakpoints.ResultsEnterobacter cloacae andEnterobacter aerogenes accounted for 71.1% (14 617/20558) and 20.1% (4 129/20 558) of all theEnterobacterisolates, respectively. The proportion ofEnterobacter spp. increased with time from 3.5% in 2005 to 4.3% in 2014. The main source of the isolates was respiratory tract, accounting for 55.2% (11 358/20 558). More than 90% of theEnterobacterisolates were resistant to cefazolin and cefoxitin, but less than 30% of the strains were resistant to cefepime, piperacillin-tazobactam, cefoperazone-sulbactam, amikacin, gentamicin, ciprolfoxacin, meropenem, imipenem and ertapenem. TheEnterobacterisolates showed a trend of declining resistance to most antibiotics except ertapenem and meropenem. The resistance proifle ofEnterobacterisolates varied with departments where they were isolated. The strains from ICU and Department of Surgery were relatively more resistant to antibiotics. The prevalence of multi-drug resistant (MDR) strains was decreasing, but the prevalence of carbapenem-resistantEnterobacter (CRE, resistant to any of imipenem, meropenem or ertapenem) was increasing. The MDR and CRE strains were primarily isolated from ICU and Department of Surgery. At least 30% of the MDREnterobacter strains were resistant to any of the antimicrobial agents tested except meropenem, imipenem and ertapenem and at least 35% of the CRE strains were resistant to any of the antimicrobial agents tested except amikacin and ciprolfoxacin.Conclusions TheEnterobacter isolates in CHINET Antimicrobial Resistance Surveillance Program showed decreasing resistance to most of the antimicrobial agents tested since 2011, but the prevalence of CRE strains increased progressively. Effective measures should be carried out to prevent the spread of CRE strains in hospitals.

Objective To evaluate the changing pattern of antibiotic resistance inKlebsiella strains isolated from the patients in 19 hospitals across China based on the data from CHINET Antimicrobial Resistance Surveillance Program during the period from 2005 through 2014.Methods Kirby-Bauer disk diffusion and automated susceptibility testing methods were used to test the susceptibility ofKlebsiella isolates to the commonly used antibiotics. The results were interpreted according to the criteria of the Clinical and Laboratory Standards Institute (CLSI) Performance Standards for Antimicrobial Susceptibility Testing (CLSI-2014).Results A total of 61 406Klebsiella strains were identified between 2005 and 2014, includingK. pneumoniae (56 281 strains), K. oxytoca(4 779),Klebsiella pneumoniae subsp.Ozaenae (300) and otherKlebsiella species (46). Most (89.0%, 54 664/61 406) of theKlebsiella strains were isolated from inpatients, and 60.0% (36 835/61 406) were from respiratory tract speciems. About 16.7% (10 248/61 406) of the strains were isolated from pediatric patients aged 0-17 years and 83.3% (51 158/61 406) from adult patients. The prevalence ofKlebsiella spp. increased with time from 10.1% in 2005 to 14.3% in 2014. Based on the surveillance data during the 10-year period, we found a marked increase of resistance to imipenem (2.9% to 10.5%) and meropenem (2.8% to 13.4%) inKlebsiella spp. The prevalence of ESBLs-producing isolates inK. pneumoniae andK. oxytoca decreased from 39.0% in 2005 to 30.1% in 2014. The resistance to amikacin, ceftazidime, ciprolfoxacin, pipracillin-tazobactam and cefoperazone-sulbactam was on decline. The resistance rate to cefotaxime remained high about 49.5%. Carbapenem resistantance was identiifed in 5 796 (9.4%) of the isolates, including 5 492 strains ofK. pneumoniae and 280 strains ofK. oxytoca. Overall, 4 740 (7.8%) strains were identiifed as extensively-drug resistant (XDR), including 4 520 strains ofK. pneumoniae and 202 strains ofK. oxytoca. The carbapenem-resistant strains showed high (>60%) resistance rate to majority of the antimicrobial agents tested, but relatively low resistance to tigecycline (16.8%), amikacin (54.4%), and trimethoprim-sulfamethoxazole (55.5%).Conclusions During the 10-year period from 2005 through 2014, carbapenem resistance amongKlebsiella isolates has increased dramatically in the hospitals across China. The level of resistance to other antibiotics remains stable.

OBJECTIVETo study the role of p16 gene mutation status as detected by fluorescence in-situ hybridization (FISH) and p16 protein expression as detected by immunohistochemistry in differential diagnosis of malignant mesothelioma and benign mesothelial hyperplasia.

METHODSp16 gene mutation status and protein expression were detected by FISH and immunohistochemistry respectively in 55 cases of pleural malignant mesothelioma and 30 cases of benign mesothelial hyperplasia.

RESULTSFISH study showed that the rate of p16 deletion in malignant mesothelioma (81.8%,45/55) was higher than that in benign mesothelial hyperplasia (3.3%,1/30). The difference was statistically significant (P<0.05). Immunohistochemical study showed that the rate of p16 protein expression in malignant mesothelioma (23.6%) was lower than that in benign mesothelial hyperplasia (76.7%). The difference was also statistically significant. The sensitivity and specificity of FISH in distinguishing between mesothelioma and reactive mesothelial hyperplasia were higher than those of immunohistochemistry.

CONCLUSIONSIn contrast to reactive mesothelial hyperplasia, p16 gene is deleted and p16 protein is not expressed in malignant mesothelioma. The sensitivity and specificity of FISH are higher than those of immunohistochemistry in the distinction.

Cyclin-Dependent Kinase Inhibitor p16 ; metabolism ; Diagnosis, Differential ; Epithelium ; pathology ; Genes, p16 ; Humans ; Hyperplasia ; diagnosis ; genetics ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Mesothelioma ; diagnosis ; genetics ; metabolism ; Mutation ; Pleura ; pathology ; Pleural Neoplasms ; diagnosis ; genetics ; metabolism ; Sensitivity and Specificity

Objective To verify and monitor the performance of accuracy, precision and comparability of 26 clinical biochemical analytes (29 methods) in the six centers involved in multi-centers reference intervals research, and to ensure the reliability of theirmeasurement results.Methods During the period of the systems evaluating, two levels of commercial quality control materials and fresh frozen human serum reference materials were applied to verify the performance of inter-laboratory precision and accuracy of analysis systems. During the period of samples testing, the commercial quality control materials were measured whenever samples were analysed, the fresh frozen serum reference materials were measured once a month.The coefficient of variations (CVs), bias and total errors were calculated to assess the precision, accuracy and comparability.Results Verification of precision and accuracy: ( 1 ) the ranges of CVs of 29 methods in the six laboratory laboratories were 0.4%-6.0%, the CVs of all 29 methods met the criterion . (2) The overall average bias of the analysis systems of 21 analytes (24 methods) ranged from -5.15%( ALT) to 4.46% ( Ur ) .Among 24 methods the overall average bias of TP, Glu-GOD, Ur, Cl, Ca exceeded the acceptable range.The quality assessment during the period of samples testing:(1) The overall average bias ranged from -1.95%(Ca) to 2.92%(Ur), median 1.26%, they all met the requirements of relevant standards.( 2 ) When commercial control materials were tested, the requirements of CVs were fulfilled for most methods in the six laboratories,and the CVs of TP, Alb, Cl, Ca exceeded the acceptable range.The overall average TE of all methods met the quality specification for the C-N controls material.For the C-P control material, only the overall average TE of TP (5.05%) exceeded thearceptable range while the other methods met the requirement in criterion.Conclusions The performance of precision and accuracy of the analysis systems used in the six laboratories passed the verification.During the period of sample testing, the performance of precision and accuracy of the most methods in the 6 laboratories met the requirements of quality specifications, and the overall performance was good.Because of the limitation of current technology the performance of some methods didn't fulfill the requirement of specifications, and need to be improved.