Objective To investigate the causes of false-positive rifampicin resistant results in Xpert MTB/RIF (Xpert) test for samples with extremely low bacterial loads. Methods A total of 346 samples with extremely low bacterial loads and rifampicin-resistance results from Wuhan Pulmonary Hospital between June 2017 and March 2021 were collected. The samples were divided into probe-delayed and probe dropout groups based on amplification results. Mycobacterial culture and proportion method drug susceptibility testing were performed, and Xpert retesting was conducted for strains with discordant drug susceptibility results. Results Out of the 346 samples, 195 samples (56.36%) were positive in culture. Upon Xpert retesting, among the 64 Xpert-resistant but proportion method-sensitive strains, the proportions of samples in the delayed probe group with mutations in the probe D and probe E were 4.55%（1/22） and 13.33%（2/15）, respectively. In the probe dropout group, the proportions of samples with mutations in the probe A and probe E were 75.00% (9/12) and 80.00% (8/10), respectively. The false-positive rifampicin resistance rates in the delayed probe and probe dropout groups were 78.26% (36/46) and 3.36% (5/149), respectively. Conclusion The main reasons for false-positive rifampicin resistance results in the Xpert test for samples with extremely low bacterial loads were probe delay in the D and E probes, followed by low-level drug-resistant mutations in the A and E probes.

Objective To establish a trimethyltin chloride (TMT) -induced learning and memory impairment model in rats, and to investigate the protective effects and potential mechanisms of ferulic acid. Methods Specific pathogen-free male SD rats were randomly divided into control group, TMT intoxication group, fluoxetine group and 25, 50, 100 mg/kg ferulic acid group. The rats in the last five groups were injected with a dose of 8 mg/kg body weight TMT solution, and the rats in control group were injected with the same volume of 0.9% sodium chloride solution. After 24 hours of TMT injection, the rats in fluoxetine group were treated 10 mg/kg body weight of fluoxetine, the rats in the three ferulic acid groups were treated with ferulic acid at doses of 25, 50, and 100 mg/kg body weight, respectively. The rats in the control group and TMT intoxication group were treated with the same volume of 0.9% sodium chloride solution, once per day for continuous gavage for 28 days. Morris water maze experiment and light-dark box test were used to assess the learning and memory abilities of the rats. The mRNA and protein expressions of nuclear transcription factor-κB (NF-κB), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the rat hippocampus were detected by real-time quantitative polymerase chain reaction and Western blot. The levels of reactive oxygen species (ROS) and malondialdehyde (MDA) and the activities of superoxide dismutase (SOD) and catalase (CAT) in the rat hippocampus were detected by enzyme-linked immunosorbent assay. Results Compared with the control group, rats of TMT intoxication group on day four had prolonged escape latency (P<0.05), fewer platform crossing (P<0.05), shorter time spent in the target quadrant and shorter latency to enter the dark compartment (all P<0.05). The mRNA and protein relative expression of NF-κB, TNF-α and IL-1β increased (all P<0.05), ROS and MDA levels increased (all P<0.05), SOD and CAT activities decreased (all P<0.05) in the rat hippocampus of TMT intoxication group on day four compared with that of the control group. Except for the terms of escape latency and target quadrant period of the rats in the 25 mg/kg ferulic acid group, rats in three ferulic acid groups on day four had lower escape latency (all P<0.05), more platform crossing (all P<0.05), longer period in the target quadrant and longer latency to enter the dark compartment (all P<0.05), compared with TMT intoxication group. Except for the relative protein expression of TNF-α in the rats of 50 mg/kg ferulic acid group, the mRNA and protein expression of NF-κB, TNF-α and IL-1β decreased (all P<0.05), ROS and MDA levels were reduced (all P<0.05), and the activities of SOD and CAT increased (all P<0.05) in the hippocampus of rats of 50 and 100 mg/kg ferulic acid groups compared with TMT intoxication group. Conclusion Ferulic acid can reverse TMT-induced learning and memory impairment in rats, and its mechanism of action may be related to alleviating oxidative stress damage and excessive inflammatory response in rat hippocampus.

Objective:To investigate the correlation between the osseous structure of temporomandibular joint (TMJ) and three different status of anterior disc location, so that it could guide the clinical diagnosis further.Methods:Fifty-two patients [46 females and 6 males, with an age of (27.8±8.3) years] who treated with MRI and cone beam CT, were recruited from the Temporomandibular Joint Specialist Clinic, The First Affiliated Hospital of Xinjiang Medical University, between March 2018 to December 2021. According to the radiographic findings of the level of anterior disc displacement (ADD) in TMJ, patients were divided into three groups: normal articular disc position (NADP, n=28 TMJs), anterior disc displacement with reduction (ADDWR, n=28 TMJs), and anterior disc displacement without reduction (ADDWoR, n=28 TMJs). In the light of the reconstructed three-dimensional model, ten representative morphological parameters including condylar volume (CV), condylar superficial area (CSA), fossa volume (FV), fossa superficial area (FSA), the proportion of the condylar volume in the articular fossa (CV%), the proportion of the condylar superficial area in the articular fossa (CSA%), superior joint space (SJS), anterior joint space (AJS), posterior joint space (PJS), and medial joint space (MJS), were measured respectively under one-way analysis of variance (ANOVA), Kruskal-Wallis Htest and receiver operator characteristic curve(ROC curve) analyses. Results:CV and CSA values varied significantly in the pathological progression from normal location to irreversible anterior displacement in TMJ. For CV value, NADP group [(1 834.90±667.67) mm 3]>ADDWR group [(1 747.34±369.42) mm 3]>ADDWoR group [(1 256.29±418.27) mm 3] [ t=4.31, P(NADP-ADDWoR)<0.001; t=3.66, P(ADDWR-ADDWoR)<0.001], for CSA value, NADP group [(859.27±216.01) mm 2]>ADDWR group [(838.23±118.82) mm 2]>ADDWoR group [(669.14±150.26) mm 2] [ t=4.27, P(NADP-ADDWoR)<0.001; t=3.80, P(ADDWR-ADDWoR)<0.001]. The difference of SJS value in NADP group [(2.22±0.88) mm], ADDWR group [(1.94±0.64) mm] and ADDWoR group [(1.45±0.57) mm], was statistically significant [ t=4.11, P(NADP-ADDWoR)<0.001; t=2.63, P(ADDWR-ADDWoR)=0.010]. The results of MJS in NADP group [(5.03±1.41) mm], ADDWR group [(3.86±1.32) mm], and ADDWoR group [(4.91±1.65) mm] were significantly different [ t=3.00, P(NADP-ADDWR)=0.004; t=2.63, P(ADDWR-ADDWoR)=0.009]. As calculated by the ROC curve analysis, CV, CSA and SJS showed that (AUC CV=0.77, AUC CSA=0.76; AUC SJS=0.76) for the NADP and ADDWoR groups, and (AUC CV=0.80; AUC CSA=0.80; AUC SJS=0.72) for the ADDWR and ADDWoR groups. While the diagnostic accuracy of MJS for the comparison in NADP versus ADDWR and ADDWR versus ADDWoR was respectively AUC (NADP-ADDWR)=0.73, and AUC (ADDWR-ADDWoR)=0.69. Conclusions:CV, CSA, SJS, and MJS were significantly associated with the different disc displacement status, and the condyle in TMJ ADD exhibited three-dimensionally altered dimensions. They could be considered as promising biometric markers to diagnose the ADD status.

The gradually acidified tumor microenvironment plays a key role in the formation and advance of hepatocellular carcinoma. Under the regulation of acidic microenvironment, the differentiation and function of immune cells change to immunosuppression, which further leads to the occurrence of immune escape of hepatocellular carcinoma. In this paper, the formation of acidic microenvironment of hepatocellular carcinoma, the changes of various immune cells in acidic microenvironment and their effects on the occurrence and development of hepatocellular carcinoma, as well as their further mechanisms are reviewed in order to provide new ideas for the study of immunotherapy of hepatocellular carcinoma.

Clinical researches including the Mayo Anesthesia Safety in Kids (MASK) study have found that children undergoing multiple anesthesia may have a higher risk of fine motor control difficulties. However, the underlying mechanisms remain elusive. Here, we report that erythropoietin receptor (EPOR), a microglial receptor associated with phagocytic activity, was significantly downregulated in the medial prefrontal cortex of young mice after multiple sevoflurane anesthesia exposure. Importantly, we found that the inhibited erythropoietin (EPO)/EPOR signaling axis led to microglial polarization, excessive excitatory synaptic pruning, and abnormal fine motor control skills in mice with multiple anesthesia exposure, and those above-mentioned situations were fully reversed by supplementing EPO-derived peptide ARA290 by intraperitoneal injection. Together, the microglial EPOR was identified as a key mediator regulating early synaptic development in this study, which impacted sevoflurane-induced fine motor dysfunction. Moreover, ARA290 might serve as a new treatment against neurotoxicity induced by general anesthesia in clinical practice by targeting the EPO/EPOR signaling pathway.
Animals ; Sevoflurane/toxicity* ; Microglia/drug effects* ; Anesthetics, Inhalation/adverse effects* ; Mice ; Mice, Inbred C57BL ; Receptors, Erythropoietin/metabolism* ; Neuronal Plasticity/drug effects* ; Male ; Prefrontal Cortex/drug effects* ; Erythropoietin/pharmacology* ; Signal Transduction/drug effects*

The clinical characteristics of the pneumonia includes hyperthermia, cough and pectoralgia, etc with simultaneous mixed signs of inflammatory infiltration, consolidation, cavity/air sac and abscess in pulmonary CT scan, and these signs change rapidly. Respiratory failure and septic shock frequently occur in severe such patients, resulting in refractory management and relatively long therapeutic course. The timely diagnosis, use of sensitive antibiotics, respiratory and nutritional support, etc comprehensive effective measures can elevate the rescue success rate with severe hematogenous staphylococcus aureus pneumonia.

Objective To explore the application values of GeneXpert MTB/RIF assay (Xpert assay) for rifampicin resistance and multidrug resistant tuberculosis (MDR-TB).Discordance of Xpert and L-J proportion DST of rifampicin was analyzed.Methods Specimens of 1 300patients from January 2014to June 2016in our hospital were collected for solid culture, Xpert assay and L-J proportion drug susceptibility test (DST).Rifampicin resistance detected by Xpert assay was compared with L-J proportion method as a gold standard.Sequencing of rpoB gene and determination of minimum inhibition concentration were accomplished on the discordant MTB strains between Xpert and L-J proportion DST.Results Compared with the DST, the sensitivity, specificity, positive and negative predictive value of Xpert assay for rifampicin resistance were 99.31％, 97.82％, 92.88％and 99.80％, respectively.Among 1 300culture-positive specimens, mutations were detected from 309specimens by Xpert assay, which included 125initial treatment and 184retreatment patients.Among309specimens with rpoB gene mutations, mutations detected by probes E, D and B were common, and the rates were 65.70％, 14.56％and 10.68％, respectively.Totally 239patients were MDR-TB[77.35％ (239/309) ], of which 94initial treatment patients[75.20％ (94/125) ]and 145retreatment patients[78.80％ (145/184) ]were MDR-TB.Among 22strains which were detected rpoB gene mutations by Xpert, but sensitive by L-J proportion DST, 6strains had no mutation in rpoB gene rifampicin resistance determining region (RRDR);16strains had mutations, which were mainly located in L511Pcodon (8strains) and L533Pcodon (4strains).Among 2strains which had no rpoB gene mutation by Xpert, but were resistant by L-J proportion DST, 1strain had no mutation in rpoB gene RRDR region;1strain had mutation which was located in E546G codon outside RRDR region.Conclusion Xpert assay can be used to rapidly detect rifampicin resistance and to screen MDR-TB.Mutations in codon 511and 533are related to low-level resistance to rifampicin.

Objective To preliminary investigate the clinical efficacy of whole brain simultaneous integrated boost intensity-modulated radiotherapy ( SIB-IMRT ) in patients diagnosed with brain metastases ( BM) . Methods Fifty-two cases of BM admitted to our hospital from January 2016 to December 2017 were equally recruited and randomly divided into the observation and control groups. Patients in the observation group were treated with SIB-IMRT, and those in the control group received conventional whole brain radiotherapy (WBRT).The clinical efficacy and prognosis were statistically compared between two groups. Results The ORR in the observation group was 77％, significantly higher than 27％ in the control group (P=0. 00).The median survival in the observation group was 384 d,significantly longer compared with 211 d in the control group (P=0. 00).All patients in both groups successfully completed corresponding treatment. Acute adverse reactions were mainly 1-2 grade reactions. Conclusions SIB-IMRT is an efficacious and safe treatment of BM,which yields tolerable adverse events and deserves application in clinical practice.

OBJECTIVE: To comprehend clinical features and patient's physician visit patterns at onset of immunoglobulin G4 related disease (IgG4RD). METHODS: In the study, 100 patients with IgG4RD who received treatments in the Department of Rheumatology and Immunology of Peking University People's Hospital from Apr. 1st, 2017 to Apr. 1st, 2018 were investigated, including gender, age, height, body weight, age of onset, physician visit history, primary history and how did the disease affected their life, etc. RESULTS: In this 100 IgG4RD cohort (57 males and 43 females), the male/female ratio was 1:0.75, the mean age of onset was (51.51±12.9) years, and the median duration was 49 months (ranging from 4 to 231 months). The onset age of males was significantly older than that of females (P<0.01). The manifestations showed that up to 69% patients had submaxillay glands lesion, 59% patients had lacrimal glands lesion, 28% patients had pancreas involvement and 28% patients had parotid glands involvement. The females had more lacrimal glands involvement (P<0.05). 62% patients were complicated with anaphylactic disease. The primary physician visit departments concentrated upon general surgery department (19/100), oral and maxillofacial surgery department (17/100), rheumatology and immunology department (16/100), ophthalmology department (15/100) and gastroenterology department (10/100). The departments where the confirmed diagnose was made concentrated upon rheumatology department (67/100),oral and maxillofacial surgery department (16/100) and gastroenterology department (7/100). The mean diagnosis duration after 2010 was (16.96±2.163) months, significantly shorter than that before 2010, which was (113.3±11.01) months. Before the definite diagnose was made, 43% patients underwent surgeries and 12% patients had more than one time surgeries. The patients whose first-visit department was a surgery department were more likely to undergo surgeries (P<0.01). 18% patients (18/100) stated that the disease had affected their work. CONCLUSION In this cohort of the IgG4RD patients, female is common and has earlier onset age than male. The major manifestations of IgG4RD are salivary glands, lacrimal glands and pancreas involvement. The common chief complains are salivary glands and lacrimal glands enlargement. Accompanied by anaphylactic disease is a marked manifestation of this disease. Delayed diagnoses are not rare, though this situation has been improved since 2010, and more attention still should be paid to the disease.
Adult ; Age of Onset ; Aged ; China ; Cross-Sectional Studies ; Delayed Diagnosis ; Female ; Hospitals, Public ; Humans ; Immunoglobulin G/analysis* ; Immunoglobulin G4-Related Disease/therapy* ; Lacrimal Apparatus/pathology* ; Male ; Middle Aged ; Referral and Consultation ; Salivary Glands/pathology*

Objective To design a worksheet generation software for satisfy the two CHEMCLIN ? 600 instruments (CC 600) and laboratory information system(LIS) data transmission needs in Daxing Hospital of Capital Medical University ,ensure consis‐tency and uniqueness of the test sample number .Methods Microsoft Visual Studio 2010 and DotNetBar for Windows Forms were used to develop a work table generation software .Results Work table generation software had good interface ,and the CC 600 sys‐tem interaction had the advantage of simple operation ,generation of working table was operating normally ,and data transmission with laboratory information system was correct .Conclusion The worksheet generation software solves CC 600 linking problem be‐tween different test batches ,gives full play to the detection performance of the two instruments ,clinical application effect is good .