Both cholinergic dysfunction and protein citrullination are the hallmarks of rheumatoid arthritis (RA), but the relationship between the two phenomena remains unclear. We explored whether and how cholinergic dysfunction accelerates protein citrullination and consequently drives the development of RA. Cholinergic function and protein citrullination levels in patients with RA and collagen-induced arthritis (CIA) mice were collected. In both neuron-macrophage coculture system and CIA mice, the effect of cholinergic dysfunction on protein citrullination and expression of peptidylarginine deiminases (PADs) was assessed by immunofluorescence. The key transcription factors for PAD4 expression were predicted and validated. Cholinergic dysfunction in the patients with RA and CIA mice negatively correlated with the degree of protein citrullination in synovial tissues. The cholinergic or alpha7 nicotinic acetylcholine receptor (α7nAChR) deactivation and activation resulted in the promotion and reduction of protein citrullination in vitro and in vivo, respectively. Especially, the activation deficiency of α7nAChR induced the earlier onset and aggravation of CIA. Furthermore, deactivation of α7nAChR increased the expression of PAD4 and specificity protein-3 (SP3) in vitro and in vivo. Our results suggest that cholinergic dysfunction-induced deficient α7nAChR activation, which induces the expression of SP3 and its downstream molecule PAD4, accelerating protein citrullination and the development of RA.

Objective:The purpose of this study was to investigate the evaluating value of modified critical care ultrasonic examination(M-CCUE) scheme for the etiological diagnosis of shock in ICU patients.Methods:The prospective study collected relevant clinical data of various shock patients admitted to the Department of Intensive Care Medicine, Henan Provincial People's Hospital from May 2020 to July 2021, including hemodynamic、blood indicators、organ/tissue perfusion and prognostic evaluation indicators.All selected patients completed the initial M-CCUE assessment within 30 minutes, were scored according to the M-CCUE score system and related data results were analyzed.Results:Ninety-three patients were included in this study,Two of them were not completed the M-CCUE assessment due to emergency treatment immediately after entering our department, and five were excluded due to inconsistent ultrasound judgments by the two physicians. In the end, a total of 86 patients were enrolled in the group. In patients applied with M-CCUE scheme,time to preliminary diagnosis and final diagnosis were (13.02±3.15)min and (67.70±20.20)min respectively, the accuracy of diagnosis was 83.7%. Among them, distributed shock accounted for 60.4%, hypovolemic shock accounted for 25.6%, cardiogenic shock and obstructive shock accounted for 3.5%, and mixed shock accounted for 7%; MCS is (13.27±4.91), M-CCUE scheme had the high sensitivity and specificity for the diagnosis of distributed shock (sensitivity 91.2%, specificity 93.9%), hypovolemic shock (sensitivity 96.0%, specificity 96.7%), cardiogenic shock (sensitivity 85.7%, specificity 98.7%) and obstructive shock (sensitivity 60.0%, specificity 100%); MCS has a good positive correlation with APACHEⅡ score ( r=0.861, P<0.001), and has no correlation with ICU cost ( r=0.012, P=0.915). There is no significant difference in MCS between the 28d death group and the recovery group ( P=0.391). Conclusions:For shock patients admitted to ICU with unknown etiology, the initial diagnosis of the cause of the M-CCUE program takes less time, has a higher correct diagnosis rate, sensitivity and specificity, and its quantitative evaluation results can predict the patient's criticality.

Objective: To investigate the characteristics and prognostic value of peripheral blood T lymphocyte subsets in patients with severe influenza. Methods: This was a single-center cross-sectional study in influenza patients admitted to Peking Union Medical College Hospital from August 2017 to April 2018. Peripheral blood lymphocyte subsets were detected by flow cytometry in both patients and 108 healthy controls. Influenza patients were divided into mild group and severe group. Severe patients were further classified into alive and fatal subgroups. Results: A total of 42 influenza patients were recruited in this study, including 24 severe cases (6 deaths). The remaining 18 cases were mild. The peripheral blood lymphocyte counts and lymphocyte subset counts (B, NK, CD4⁺T, CD8⁺T) in either mild patients[795 (571,1 007), 43 (23,144), 70 (47,135), 330 (256,457), 226 (148,366) cells/μl respectively] or severe patients[661 (474,1 151),92 (52,139), 54 (34,134), 373 (235,555), 180 (105,310) cells/μl respectively] were both significantly lower than those of healthy controls [1 963 (1 603,2 394),179 (119,239), 356 (231,496), 663 (531,824), 481 (341,693) cells/μl respectively]. Meanwhile, the T cells and CD8⁺T counts in fatal patients [370 (260,537) cells/μl and 87 (74,105) cells/μl] were significantly lower than those in severe and alive patients [722 (390,990) cells/μl and 222 (154,404) cells/μl]. CD8⁺HLA-DR/CD8⁺and CD8⁺CD38⁺/CD8⁺T cell activating subgroups in mild cases[(53.7±19.2)% and 74.8% (64.1%,83.7%) respectively] were significantly higher than those in severe cases[(38.5±21.7)% and 53.3% (45.3%,67.2%) respectively].Moreover,CD8⁺HLA-DR/CD8⁺count in severe and alive group was higher than that in fatal group [(46.1±19.1)% vs. (18.2±14.6)%, P<0.01]. Logistic regression analysis showed that CD8⁺T cell count (OR=0.952, 95%CI 0.910-0.997, P=0.035) and CD8⁺HLA-DR/CD8⁺T (OR=0.916, 95%CI 0.850-0.987, P=0.022) were both negatively correlated with mortality.Peripheral blood lymphocyte counts in mild cases rapidly decreased within 1 day after diagnosis, and returned to the basic level one week later. Conclusions All peripheral blood lymphocyte subsets (T,B,NK) in patients with influenza are significantly reduced. These findings are consistent with the immunological characteristics of respiratory viral infections, in which peripheral lymphocytes (especially T cells) migrate to respiratory tract in the early stage and circulate to the peripheral blood after recovery. The activated CD8⁺T cell counts in peripheral blood are negatively correlated with the severity of disease, which could be considered as a prognostic indicator of severe influenza.

Objective: To evaluate the composite external fixation in the treatment of children with fracture of lower extremity metaphysis. Methods: A retrospective analysis was conducted of the 42 children with fracture of lower extremity metaphysis who had been admitted to Zhengda Shaoyang Orthopaedic Hospital between September 2016 and September 2018. They were 24 boys and 18 girls, aged from 3 to 14 years (mean, 8.3 years). Open injury occurred in 10 cases, with type Ⅰ in 2, type Ⅱ in 7 and type Ⅲ in one according to the Gustilo-Anderson classification, and closed injury in the other 32 ones. The fracture happened at distal femur in 12, at proximal tibia in 9 and at distal tibia in 21 cases. All the patients were fixated with composite external brackets. Fracture healing, functional recovery of the knee and ankle joints, and complications were recorded. Results: All the 42 patients were followed up for 12 to 18 months (mean, 15.8 months). All fractures healed well by the first intention with no malunion or no alignment change on the full length X-ray films of both lower limbs. Irritant growth within 1.5 cm was observed in 2 cases. No loosening occurred in the external fixation which was removed 3 to 5 months after surgery (mean, 3.8 months). Functional recovery of the knee and ankle joints was good at the last follow-up. For the patients with distal femoral metaphysis fracture, the knee function by the Merchan scoring was excellent in 3 cases, good in 7 cases, fair in one and poor in one; for the patients with proximal tibial metaphysis fracture, the knee function by the Merchan scoring was excellent in 3, good in 4 and fair in 2 cases; for the patients with distal tibial metaphysis fracture, the ankle function by the Kofoed scoring was excellent in 11, good in 7 and fair in 3 cases, giving an excellent and good rate of 83.3%. Of a total of 228 needle channels in the 42 patients, 58 were infected mildly or moderately, giving an infection rate of 25.4%. All the infections responded to active dressing change. Conclusion The composite external fixation brackets are a good choice for the treatment of children with fracture of lower extremity metaphysis, because they are easy in manipulation and stable in configuration, and can reduce the iatrogenic injury to the epiphyseal plate, spare cross-articular fixation and allow early functional exercise.

Objective Doppler ultrasonography was used to screen the incidence of central venous catheter (CVC) thrombosis in severe patients to observe the incidences of catheter-related thrombosis (CRT) at subclavian (SC) and internal jugular (IJ) venous insertion sites, and to analyze the factors affecting the thrombosis. Methods One hundred and twenty three adult patients with IJ or SC CVC admitted to the Department of Intensive Care Unit (ICU) of Zhongnan Hospital of Wuhan University from May to December 2015 were enrolled to be the research objects, they were divided into an IJCVC group (35 cases) and a SCCVC group (88 cases) according to different catheterization sites; they were divided into an operation group (85 cases) and a non-operation group (38 cases) according to whether operation was performed or not; and they were also divided into an anticoagulation group (25 cases) and a non-anticoagulation group (98 cases) according to whether anticoagulation therapy was used or not. Doppler ultrasonography was performed every day to observe the incidences of CRT during ICU stay. Results One hundred and twenty-three patients were included in this study. CRT was detected in 11 (8.9%) patients, with an incidence of 22.1 per 1 000 catheter-days. All the 11 cases with CRT were presented within 3 days after the insertion, with 9 cases (81.8%) on the first day and 2 cases (18.2%) on the third day. The incidence of CRT in SCCVC group was significantly lower than that in IJCVC group [5.7% (5/88) vs. 17.1% (6/35), P < 0.05], with the rates of 12.6 and 59.4 per 1 000 catheter-days, respectively. There were no statistical significant differences in the incidences of CRT between operation group and non-operation group [11.8% (10/85) vs. 2.6% (1/38)], and between anticoagulation group and non-anticoagulation group [8.0% (1/25) vs. 9.2% (2/98), both P > 0.05]. Conclusions The incidence of CRT at IJCVC site is estimated to be 3-times higher than that at SCCVC site, anticoagulants or surgical operation may have impacts on the incidence of CRT, although there were no statistically significant differences. The CRT usually occurs within 3 days after the catheter insertion. Frequent bedside ultrasonography in the first 3 days after catheterization can confirm the diagnosis and guide clinical treatment.

Objective To report the efficacy of closed pry reduction and cross Kirschner wiring in the treatment of refractory flexion-type fracture of supracondylar humerus in children.Methods A retrospective analysis was done of 19 children who had been treated for refractory flexion-type fracture of supracondylar humerus by closed pry reduction and cross Kirschner wiring at Department of Orthopaedics,Shaoyang Orthopaedic Hospital from March 2015 to March 2017.They were 9 boys and 10 girls,aged from 2 to 12 years (mean,6.37 years);10 left and 9 right sides were involved.According to the severity of fracture displacement,11 cases had rotational displacement with their broken ends obviously inserted into one another,and 8 cases complete displacement with no contact of the broken ends.All the fractures were closed,treated with closed reduction by leverage and cross fixation with Kirschner wire.Postoperative complications were recorded and the elbow function was evaluated by the Flynn assessment system at the last follow-up.Results The operation time for the 19 patients ranged from 15 to 60 minutes,with an average of 30 minutes.The patients were followed up for 12 to 24 months (average,18.0 months).All the fractures united after 2 to 4 months (average,2.8 Months).At the last follow-up,according to the Flynn system,the elbow function was evaluated as excellent in 10 cases,good in 7,and fair in 2.No ossifying myositis,cubitus varus or iatrogenic injury to the ulnar nerve was observed in any patient.Nails had to be removed in one case due to implant loosening after pin-hole infection.Conclusion Closed reduction and Kirschner wire cross fixation is an ideal surgical treatment for refractory flexion-type supracondylar fracture of humerus in children,because its intraoperative closed pry reduction can reduce the rate of incision.

Objective To investigate the effects and mechanisms of Omega-3 polyunsaturated fatty acid (ω-3 PUFA) supplementation on spatial learning and memory capacity,neuronal apoptosis,microglia activation,neuroinflammatory response and nuclear factor-κB (NF-κB) pathway in cognitive impairment model rats.Methods Cognitive impairment model rats were induced by intraperitoneal injection of D-galactose.Thirty-six Wistar rats were randomly divided into three groups:control group (Con),Cognitive impairment group (AD) and ω-3 PUFA supplementation group (AD+ω-3).The spatial learning and memory capacity of experimental rats were examined by the Morris water maze (MWM).Apoptotic neurons were determined by Nissl staining.The microglia activation relatived protein (Iba-1) expressions was determined by immunohistochemistry staining and western blot,respectively.While,the serum levels of tumor necrosis factor-α (TNF-α),interleukin (IL)-1 and IL-6 were tested by enzyme linked immunosorbent assay (ELISA).In addition,the protein expression of NF-κB related indexes including NF-κB p65,p-IκB and TLR4 were tested using western blot.Results Compared with the Con group,the escape latency increased and the distance percentage in target quadrant decreased;neurons apoptosis,microglia activation and neuroinflammatory factors significantly increased in the other two groups (P=0.00).Compared with the AD group,the escape latency was remarkably shorter (2 d:41.35±2.34vs.58.07±3.27,P=0.03;3 d:35.07±2.45 vs.44.39±3.21,P=0.02;4d:28.12±2.43vs.35.63±2.20,P=0.01;5 d:23.74±1.06 vs.29.76±1.15,P=0.03),and the distance percentage in target quadrant increased significantly [(48.26±4.02)％ vs.(34.14±3.49)％,P =0.01] after ω-3 PUFA supplementation.The incidence of neurons apoptosis significantly decreased in AD + ω-3 group [(29.93 ±3.05) ％ vs.(47.58±4.14)％,P=0.01].ω-3 PUFA supplementation inhibited the protein expression of microglia,and meanwhile inhibed the expression of microglia-induced neuroinflammatory factors [TNF-α:(85.27±9.77vs.156.13±14.53) pg/ml,P=0.00;IL-1:(41.23±5.38vs.75.04±9.27) pg/ml,P=0.01;IL-6:(47.58±4.23 vs.97.47±9.09) pg/ml,P=0.00].Compared with AD group,the protein expression of NF-κB pathway significantly decreased in AD+ω-3 group.Conclusion ω-3 PUFA supplementation can inhibited microglia activation,decrease microglia-mediated neuroinflammatory response,reduce neuron apoptosis and markedly improve spatial learning and memory capacity in cognitive impairment rats,possibly mediated by inhibiting NF-κB pathway.

Objective To investigate the common opportunistic infections and the characteristics of peripheral lymphocyte subsets in patients with systemic lupus erythematosus (SLE). Methods From December 2013 to December 2016, peripheral lymphocyte subsets were consecutively detected by flow cytometry in treated SLE patients with or without opportunistic infections(OIs).The lymphocyte subsets in healthy donors were used as normal control group. Results A total of 145 treated SLE patients were enrolled including 108 with OIs and 37 without OIs.The common OIs were cytomegalovirus(CMV)diseases (66/108), Pneumocystis jirovecii pneumonia (PJP, 16/108), other fungal infections (16/108), Epstein-Barr virus (EBV, 15/108) and tuberculosis (14/108). Compared with treated SLE without OIs, total lymphocyte, CD4+T,and CD8+T lymphocyte counts were significantly reduced in SLE with OIs[1 260(780,1 810)cells/μl vs. 565(399,1 043)cells/μl,P<0.001; 485(280,811)cells/μl vs. 173(95,327)cells/μl,P<0.001; 464 (339,764)cells/μl vs.265(158,424)cells/μl,P=0.003,respectively].Conclusions The common OIs in treated SLE patients were CMV diseases,PJP,other fungi,EBV and tuberculosis.OIs are prone to develop in SLE patients with severe lymphocytopenia,especially CD4+T cell depletion.

Objective To observe the therapeutic effects and adverse effect of different lipid-lowering regimens in Atherosclerosis renal artery stenosis (ARAS) rat model and select the optimal treatment.Methods 90 Wister rats were randomly divided into sham operation group (group F) and operation group.The operation group was divided into normal feed group (group N) and high-fat feed group (group T).We established the rat model in operatino group by narrowing the renal artery with acupuncture needle and 8 weeks of high-fat feeding.According to the different lipid-lowing therapeutic schedules,the T group rats were randomly divided into five groups:the blank group (T0 group),the Xuezhikang group (T1 group),the rosuvastatin group (T2 group),the regular dose of rosuvastatin combined with Xuezhikang (T3 group),the low dose of rosuvastatin combined with Xuezhikang (T4 group).Mter 6 weeks of intervention,the serum lipids [total cholesterol (TC),triglyceride (TG),high density lipoprotein-cholesterol (HDL-C),low density lipoproteincholesterol (LDL-C)],liver function [alanine aminotransferase (ALT),aspartate aminotransferase (AST)],kidney function [blood urea nitrogen (BUN),serum creatinine (Scr)] and pathological changes of aorta and kidney were detected before and after treatment.Results (1) The blood pressure,BUN and Scr were significantly increased in N group and T group compared with F group (P ＜ 0.05).TC,TG,LDL-C were significantly increased (P ＜ 0.05) and HDL-C were significantly decreased (P ＜ 0.05) in T group compared with N,T group.According to the pathological section,the aorta in T group had visible atherosclerosis change,the renal tubules were atrophied and decreased.All above,the rat model of ARAS was successfully established.(2) After 6 weeks of drug intervention,compared with prior treatment,TC,TG,LDL-C,BUN and Scr were significant decrease (P ＜ 0.05),while HDL-C was significantly increased (P ＜ 0.05) in all treatment groups,and the most remarkable change was in T3,T4 group,T3 group was better than T4 group but with no significant difference between T3 and T4 group (P ＞ 0.05).We found that ALT and AST were significantly increased in T2 and T3 group (P ＜ 0.05) after treatment.Compared with T0 group,pathological lesions of aorta and kidney were reduced best in T3 and T4 group.Conclusions Low dose of rosuvastatin combined with Xuezhikang can achieve ideal lipid-lowing effects.At the same time,it has a protective effect on kidney,and has little damage to liver function.

Objective To explore the ultrasonographic imaging characteristics of placenta increta and clinical data, and analyze the reasons for failure to make an accurate diagnosis. Methods By means of a retrospective analysis of 27 patients with placenta increta confirmed by operation and pathologic examination from January 2014 to May 2017 in the General Hospital of the People's Liberation Army (also Hospital 301 for short), the reasons for missed diagnosis and misdiagnosis are comprehensively summarized. Results The ultrasound examination in all the 27 cases (5 cases of first pregnancy, 17 cases of scar, 5 cases of maternal) illustrated the poorly-defined boundary between placenta and uterus mesometrium, the loss of retroplacental space, multiple lacunae echo areas, and the incomplete high-echo area of the serous membrane of placenta and bladder (involving the bladder); despite 3 normal placenta, the rest 24 were all diagnosed as placenta previa before operation, of which 20 belonged to central placenta previa and the other 4 belonged to marginal placenta previa. Twenty liveborn infants were delivered in the study, 13 of them went through abdominal hysterectomy after cesarean section surgery, 8 of them only received cesarean section surgery; 2 of them went through vaginal hysterectomy, 1 received cesarean section surgery after interventional embolization, 1 Uterine rupture in utero before got to the hospital, with the rest 2 received interventional embolization clamp scraping as a consequence of deadly induced labor or stillbirth. Postoperative placenta increta types demonstrated adhensive implantation, penetrating implantation, and implantation into muscular but not membrane layer in 3, 2, and 22 cases respectively. In terms of implanting position, only 3 patients (3/17) with cicatricial uterus did't undergo the implantation into the scar area mainly in the left wall, left anterior wall and posterior wall, as for patients with non-scar uterus, posterior wall implantation was the main mode presented in 6 cases (6/10). Fifteen of all the involved 27 cases were identified while 12 cases failed to be distinguished. The deep reasons of misdiagnosis were placental location (placenta adheres to the posterior wall), fetal head shelter, or small placental placement, gestational age, larger range of placenta implantation, emergency ultrasound only pay attention to the emergency situation and ignore the exist at the same time, experience of inspectors with placenta increta and so on. Conclusions Although there are some limitations in prenatal ultrasound diagnosis of placenta, it is still an important method for the diagnosis and prenatal dynamic monitoring of the condition before the placenta implantation.