Objective To study the diagnosis and treatment of cytomegalovirus (CMV) infection after liver transplantation. Methods The clinical data of 111 patients who received liver transplantation from November 2000 to December 2007 in our hospital were analyzed retrospectively. The recipients were diagnosed as having CMV infection by the predisposing factors, clinical symptoms and detection of CMV-PP65 and CMV-IgM in peripheral blood specimens in combination with chest X-ray. The treatment of CMV infection was administration of Ganciclovir. Results Five recipients were diagnosed as having CMV infection, with the incidence of 4.5%. Two were diagnosed as having CMV pneumonitis, with the incidence of 1.8% (40% of the recipients having CMV infection). Two were both improved. Three were diagnosed as having CMV active infection. Two of them were cured and one was improved. Conclusion The detection of CMV-PP65 is necessary for early diagnosis and guiding treatment of CMV infection. Ganciclovir can exert significant therapeutic effects on CMV infection.

Objective To evaluate the efficacy and accuracy of hammering reverse guide wire technique for safe placement of anterior column retrograde intramedullary screw in pelvic and acetabular surgery.Methods From September 2015 to March 2018,46 patients with pelvic or/and acetabular fracture involving the anterior column were treated with hammering reverse guide wire technique for safe placement of anterior column retrograde intramedullary screw at Department of Orthopaedics,Lishui Municipal Central Hospital.They were 28 men and 18 women,aged from 21 to 85 years (mean,55.6 years).There were 34 pelvic ring fractures,9 acetabular fractures and 3 combined pelvic ring and acetabular fractures.After the anterior lateral spine of pubic tuberosity was drilled by a guide pin and drill bit as the entry point,a reverse guide wire was knocked into the bone lightly by a hammer.For each retrograde intramedullary screwing into the acetabular anterior column,we recorded operation time,fluoroscopic frequency,and attempts to establish an acceptable screw pathway by the guide pin.The accuracy of screwing and the quality of fracture reduction were evaluated by imaging examination.For each patient,we recorded fracture union time and complications.Functional recovery of the pelvis and acetabulum was assessed by postoperative physical examination at the last follow-ups.Results The operation time of retrograde intramedullary screwing for the 46 patients averaged 28.9 minutes (from 16 to 55 minutes);the fluoroscopy frequency averaged 16.3 times (from 9 to 35 times);an acceptable screw pathway was established by the first attempt in 43 of the 46 patients (93.5％) and re-established after adjustment of the guide pin in the other 3.Forty patients were followed up for an average of 15.2 months(from 6 to 36 months).Postoperative CT scan and three-dimensional reconstruction showed that all the screws had been placed safely and accurately in the acetabular anterior column.Implant loosening and fracture displacement occurred in one case and lower limb thrombosis in another.No nail breakage,fracture nonunion,incision necrosis or infection,neurovascular injury or femoral head necrosis was observed.All fractures united after an average of 14.7 weeks (from 12 to 18 weeks).According to the Majeed scoring at the last follow-ups,the pelvic and acetabular function was evaluated as excellent in 29 cases,as good in 9,and as fair in 2,giving an excellent and good rate of 95.0％.Conclusion Hammering reverse guide wire technique is an effective method for safe placement of anterior column retrograde intramedullary screw in pelvic and acetabular surgery,because it can increase accuracy of screwing and reduce intraoperative radiation,operation time and incidence of complications though it is simple.

OBJECTIVE: To study the genetic variants of a child with Autism Spectrum Disorder (ASD) combined with epilepsy, and explore its possible pathogenic mechanism. METHODS: Clinical data of the child were collected and evaluated, whole-exome sequencing (WES) technology was used to explore the genetic variants sites of the child and his parents and candidate genes were filtered out. Sanger sequencing were performed to verify the variants identified by WES and PolyPhen2 was utilized to predict the function of these variants. qPCR was carry out to determine the expression of the variant gene. RESULTS: The proband carried a compound heterozygous mutation in the SIK3 gene (Chr11 q23.3, NM_025164.6), which contains a missense mutation c.1295A>G (p.N432S) inherited from the father and a deletion [c.2389_2391del(p.797del)] inherited from the mother. Both mutation sites are highly conservative, and PolyPhen2 predicted (c.1295A>G [p.N432S]) to be harmful. Compared to the mother, expression of SIK3in mRNA level in the peripheral blood of the proband and his father were both significantly decreased; compared to normal child, SIK3 expression in the peripheral blood of the proband and two other children with ASD were all decreased significantly too. In addition, studies on mice found that Sik3 gene has a marked higher level of expression in the brain. CONCLUSION The SIK3 gene variants may probably be associated with ASD. The detailed mechanism needs to be studied further, which may involve lipid metabolism dysfunction in the brain.
Animals ; Autism Spectrum Disorder/genetics* ; Epilepsy/genetics* ; Male ; Mice ; Mutation ; Mutation, Missense ; Protein Kinases ; Protein Serine-Threonine Kinases/genetics* ; Whole Exome Sequencing

Leptospirosis is a global natural zoonotic infectious disease.Research shows that short-chain fatty acids,metabolites of gut microbiota,are involved in host immune regulation and affect disease progression.This experiment was conducted to investigate the role of short-chain fatty acids in leptospirosis.The results showed that supplementation of short-chain fatty acid butyric acid could significantly improve the survival rate of leptospirosis in hamsters.In vitro experiments showed that butyric acid treatment inhibited the expression of Cat and Gsr genes in macrophages after infection with Leptospira,but enhanced the expression of NOX1 and NOX4 genes.At the same time,butyric acid treatment enhanced macrophage ROS levels after leptospirosis infection,and high levels of ROS enhanced the bactericidal function of macrophages.In vivo experiments al-so confirmed that butyric acid protects hamsters against acute leptospirosis by regulating ROS production.Collectively,the short-chain fatty acid butyric acid,a metabolite of gut microbiota,en-hances the bactericidal function of macrophages by regulating ROS expression,thereby protecting the host against leptospirosis.

Objective To compare the effectiveness and safety of ultramini percutaneous nephrolithotomy (UMP) and retrograde intrarenal surgery (RIRS) in treatment of moderate-sized (about 1-2 cm) renal lower caliceal calculi.Methods From March 2015 to December 2016,patients in our hospital scheduled for surgery due to renal lower caliceal calculi with the greatest diameter of 10-22 mm were prospectively analyzed.Patients were randomized into two groups according to the random number table.Group UMP's operational channel was only F14 and the nephroscope's diameter was 1 mm.200 μm holmium laser lithotripsy was used to break the stones which was rushed out by eddy cuurent.In Group RIRS,all patients needed placing a F6 double J stent preoperatively for two weeks.A flexible ureteroscope sheath required imbedding intraoperatively.The stones were smashed by 200 μm holmium laser lithotripsy through the WOLF flexible ureteroscope.The intraoperative and postoperative datas including stone-free status and the complications were compared.Results 100 patients were enrolled in the study 50 patients in Group UMP,28 were male and 22 were female,mean age was 43.4 ± 7.9 years old.Mean stone size was 14.5 ±3.0 mm(range 10-22 mm).Among them,18 cases were complicated with mild and moderate hydronephrosis.The other 50 cases were allocated to Group RIRS,including 31 males and 19 females.Their mean age was 44.5 ± 8.3 years old and mean stone size was 13.7 ± 3.1 mm (range 10-21 mm).Among them,16 cases were complicated with mild and moderate hydronephrosis.No statistically significant difference were seen between the two groups (P ＞ 0.05).After three months' follow-up,one-time stone free rate(SFR) of UMP group was 94.0％ (47/50),which was significantly more superior than the 72.0％ (36/50) of the RIRS group(P ＜ 0.05).The intraoperative decrease in hemoglobin were (7.8 ± 3.3) g/L vs.(3.1 ± 3.4) g/L,and operating time(26.5 ± 6.1) min vs.(43.3 ± 6.3) min.Significant differences were also seen between the two groups(P ＜0.05).There was more blood loss and less operating time in the group of UMP.The hospital stay,delayed hemorrhage and postoperative fever between the UMP and RIRS groups were (4.3±1.3)d vs.(3.24 ± 1.21)d,8.0％ (4/50)vs.0(0/50),16.0％ (8/50)vs.12.0％ (6/50) respectively.No significant differences were seen (P ＞ 0.05).Conclusions Both UMP and RIRS procedures are effective and safe in the treatment of moderate-sized renal lower caliceal calculi.Compared with RIRS,UMP may be more effective and has less operating time,however wtih more intraoperative blood loss.

Objective:To study whether aspirin has inhibitory effect on microglia activation induced by Poly-IC and its mechanism.Methods:Microglia cell line BV2 were cultured in vitro to establish a Poly-IC stimulation-induced microglia cell immune activation model. The experiment groups were divided into control group (no treatment), model group (Poly-IC 10 μg/ml), high dose aspirin group (1 mmol/L aspirin), low dose aspirin group (0.1 mmol/L aspirin), high dose aspirin pretreatment group (Poly-IC 10 μg/ml + 1 mmol/L aspirin) and low dose aspirin pretreatment group (Poly-IC 10 μg/ml + 0.1 mmol/L aspirin). The phagocytosis ability of microglia cells, reactive oxygen species (ROS) and Iba1 protein expression were detected by using immunofluorescence method. The expression of the inflammatory cytokines Il-1β, Il-6, Il-10, TNF-α and cox-2 mRNA in microglia cells were detected by real-time quantitative PCR (RT-qPCR).Results:Compared with the control group, the morphology of microglia cells in model group changed significantly, and the phagocytosis ability and production of reactive oxygen species (ROS) increased. At the meantime, the expression of Iba1 protein was strongly decreased. In the model group, The mRNA expressions of IL-1β(20.55±1.92), IL-6 (63.98±7.83), TNF-α (16.84±3.19), COX-2 (6.78±0.42) were higher than IL-1β(1.01±0.14), IL-6 (0.95±0.17), TNF-α (1.22±0.38), COX-2 (0.87±0.11) in the control group. (Il-1β ( t=26.14), Il-6 ( t=10.22), TNF-α ( t=17.06) and COX-2 ( t=37.07), all P<0.01). In the aspirin pretreatment group, the phagocytic ability of microglia cells was inhibited compared with the model group, and the production of reactive oxygen species (ROS) reduced. The expression of Iba1 protein was also partly recovered. Meanwhile, the effect of the high aspirin dose pretreatment group on pro-inflammatory factors IL-1β(9.95±0.52), IL-6 (39.64±6.89), TNF-α(1.57±0.42), COX-2 (2.47±0.14)were lower than those in the model group significantly.(IL-1β: t=14.18, IL-6: t=3.69, TNF-α: t=16.68, COX-2: t=27.03, all P<0.01). Conclusion:Aspirin has an inhibitory effect on microglial activation induced by Poly-IC, which may be related with inhibiting the expression of inflammatory factors.

BACKGROUND: The screening of periprosthetic joint infection (PJI) in patients with inflammatory diseases before revision arthroplasty remains uncertain. Serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), plasma fibrinogen (FIB), monocyte/lymphocyte ratio, and neutrophil/lymphocyte ratio (NLR) can help screening PJI, but their values in patients with inflammatory diseases have not been determined. METHODS: Patients with inflammatory diseases who underwent revision hip or knee arthroplasty at West China Hospital, Sichuan University, from January 2008 to September 2020 were divided into infected and non-infected groups based on the 2013 International Consensus Meeting criteria. Sensitivity and specificity of the tested biomarkers for diagnosing infection were determined based on receiver operating characteristic (ROC) curves, and optimal cutoffs were determined based on the Youden index. The diagnostic ability of these biomarkers was re-assessed after combining them with each other. RESULTS: A total of 62 patients with inflammatory diseases were studied; of them 30 were infected. The area under the ROC curve was 0.813 for CRP, 0.638 for ESR, 0.795 for FIB, and 0.656 for NLR. The optimal predictive cutoff of CRP was 14.04 mg/L with a sensitivity of 86.2% and a specificity of 68.7%, while FIB had a sensitivity of 72.4% and a specificity of 81.2% with the optimal predictive cutoff of 4.04 g/L. The combinations of CRP with FIB produced a sensitivity of 86.2% and specificity of 78.1%. CONCLUSION: CRP with a slightly higher predictive cutoff and FIB are useful for screening PJI in patients with inflammatory diseases, and the combination of CRP and FIB may further improve the diagnostic values. TRIAL REGISTRATION ChiCTR.org.cn, ChiCTR2000039989.
Humans ; C-Reactive Protein/analysis* ; Prosthesis-Related Infections/diagnosis* ; Fibrinogen ; Arthroplasty, Replacement, Hip ; Arthritis, Infectious/surgery* ; Blood Sedimentation ; Sensitivity and Specificity ; Biomarkers ; Retrospective Studies

Chaperone-mediated autophagy (CMA) is a lysosome-dependent selective degradation pathway implicated in the pathogenesis of cancer and neurodegenerative diseases. However, the mechanisms that regulate CMA are not fully understood. Here, using unbiased drug screening approaches, we discover Metformin, a drug that is commonly the first medication prescribed for type 2 diabetes, can induce CMA. We delineate the mechanism of CMA induction by Metformin to be via activation of TAK1-IKKα/β signaling that leads to phosphorylation of Ser85 of the key mediator of CMA, Hsc70, and its activation. Notably, we find that amyloid-beta precursor protein (APP) is a CMA substrate and that it binds to Hsc70 in an IKKα/β-dependent manner. The inhibition of CMA-mediated degradation of APP enhances its cytotoxicity. Importantly, we find that in the APP/PS1 mouse model of Alzheimer's disease (AD), activation of CMA by Hsc70 overexpression or Metformin potently reduces the accumulated brain Aβ plaque levels and reverses the molecular and behavioral AD phenotypes. Our study elucidates a novel mechanism of CMA regulation via Metformin-TAK1-IKKα/β-Hsc70 signaling and suggests Metformin as a new activator of CMA for diseases, such as AD, where such therapeutic intervention could be beneficial.