Air dispersal of multi-drug-resistant organisms including meticillin-resistant Staphylococcus aureus, carbapenem-resistant Acinetobacter baumannii and carbapenemase-producing Enterobacterales in general wards: surveillance culture of air grilles.

BACKGROUND: The environmental surveillance of air grilles in clinical areas has not been systematically analysed. METHODS: Samples were collected from frequently touched items (N = 529), air supply (N = 295) and exhaust (N = 184) grilles in six medical and 11 surgical wards for the cultures of multi-drug-resistant organisms (MDROs): meticillin-resistant Staphylococcus aureus (MRSA), carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenemase-producing Enterobacterales (CPE), and isolates were selected for whole-genome sequencing (WGS). The contamination rates were correlated with the colonization pressures of the respective MDROs. RESULTS: From 3rd October to 21st November 2023, 9.8% (99/1008) of the samples tested positive, with MRSA (24.2%, 24/99), CRAB (59.6%, 59/99) and CPE (2.0%, 2/99), being the only detected MDROs. The contamination rate in air exhaust grilles (26.6%, 49/184) was significantly higher than in air supply grilles (5.8%, 17/295; P<0.001). The contamination rate of air exhaust grilles with any MDRO in acute medical wards (73.7%, 14/19) was significantly higher than in surgical wards (12.5%, 4/32; P<0.001). However, there was no difference in the contamination rate of air exhaust grilles between those located inside and outside the cohort cubicles for MDROs (27.1%, 13/48 vs 28.8%, 30/104; P=0.823). Nevertheless, the weekly CRAB colonization pressure showed a significant correlation with the overall environmental contamination rate (r = 0.878; 95% confidence interval (CI): 0.136-0.986; P=0.004), as well as with the contamination rate in air supply grilles (r = 0.960; 95% CI: 0.375-0.999; P<0.001) and air exhaust grilles (r = 0.850; 95% CI: 0.401-0.980; P=0.008). WGS demonstrated clonal relatedness of isolates collected from patients and air exhaust grilles. CONCLUSIONS: Air grilles may serve as MDRO reservoirs. Cohort nursing in open cubicles may not completely prevent MDRO transmission through air dispersal, prompting the consideration of future hospital design.

[A dry-reagent assay to rapidly detect Mycobacterium tuberculosis using loop-mediated isothermal amplification].

A molecular diagnostic assay which could be stored at room temperature was developed to rapidly detect Mycobacterium tuberculosis (MTB) based on loop-mediated isothermal amplification (LAMP) technology and dry-reagent process. LAMP uses 4 or 6 primers and Bst DNA polymerase to amplify DNA at a constant temperature. The results showed that the LAMP assay could detect the amplification of IS6110 target gene within 20 min using real-time fluorescence signal detection. The sensitive of LAMP assay was similar to the PCR technology while the precision of PCR was better than LAMP (coefficient of variation, LAMP 18.9%, PCR 3.4%), meaning LAMP was more suitable for qualitative detection. The LAMP assay did not amplify DNA of other 10 types of pathogens, including Neisseria meningitidis, Haemophilus influenzae, Staphylococcus aureus, Streptococcus pneumoniae, Rubivirus, mumps virus, adenovirus (type 3), adenovirus (type 7), respiratory syncytial virus B and parainfluenza virus type 2, indicating a good specificity. Furthermore, a dry-reagent assay was developed using air-drying and freeze-drying process. The performance of dried reagents did not change after 10 days storage at 50 ℃, meaning the dried reagents could be stored at room temperature (25 ℃) for more than six months. The dry-reagent LAMP assay also successfully amplified MTB DNA from several clinical samples within 20 min. In conclusion, the developed LAMP assay together with isothermal amplifier could rapidly detection MTB.

[Application of augmented reality navigation combined with indocyanine green fluorescence imaging technology in the accurate guidance of laparoscopic anatomical segment 8 liver resection].

Objective: To investigate the application value of augmented reality navigation combined with indocyanine green(ICG) fluorescence imaging technology in laparoscopic anatomical segment 8 liver resection. Methods: Clinical and pathological data from 8 patients with hepatocellular carcinoma located in segment 8 of the liver admitted to the First Department of Hepatobiliary Surgery,Zhujiang Hospital,Southern Medical University from October 2021 to October 2022 were collected restrospectively. Among them,there were 5 males and 3 females,aged between 40 and 72 years. During the operation,the self-developed laparoscopic augmented reality surgical navigation system was used to integrate the three-dimensional liver model with the laparoscopic scene,and ICG fluorescence imaging technology was used to guide the anatomical liver resection of segment 8. The predicted liver resection volume and actual liver resection volume,related surgical indicators and postoperative complications were analyzed. Results: Among the 8 patients, 4 underwent laparoscopic anatomical segment 8 liver resection,1 underwent laparoscopic anatomical ventral subsegment of segment 8 liver resection,2 underwent laparoscopic anatomical ventral subsegment combined with medial subsegment of segment 8 liver resection, and 1 underwent laparoscopic anatomical dorsal subsegment of segment 8 liver resection. All operations were completed under the guidance of augmented reality navigation combined with ICG fluorescence imaging,without conversion to open surgery. The operation time was (276.3±54.8)minutes(range:200 to 360 minutes). Intraoperative blood loss was (75.0±35.4)ml(range:50 to 150 ml). No blood transfusion was performed during the operation. The length of postoperative hospital stay was (7.6±0.8)days(range:7 to 9 days). There were no deaths or postoperative complications such as bleeding or biliary fistula during the perioperative period. Conclusion: Augmented reality navigation combined with ICG fluorescence imaging technology can guide the implementation of laparoscopic anatomical segment 8 liver resection.

[Predictive value of plasma exosomal miR-124-3p for the risk of chronic cerebral hypoperfusion].

Objective: To investigate the predictive value of plasma exosomal microRNA (miR)-124-3p in the risk of chronic cerebral hypoperfusion (CCH). Methods: A case-control study. Thirty patients who were diagnosed with CCH (CCH group) based on cranial artery spin labeling (ASL) in the neurology outpatient clinic of Sichuan Provincial People's Hospital from March 2022 to June 2022 and 30 healthy volunteers (control group) were included. Age, gender, smoking history, alcohol consumption history, diabetes history, hypertension, hyperlipidemia history, uric acid, fasting blood glucose, homocysteine and plasma exosomal miR-124-3p expression level were compared between the two groups. Comparisons of categorical variables were analyzed by either χ2 test or Fisher's exact test. If the data of continuous variables followed a normal distribution, they were expressed as mean±standard deviation (SD) and compared by t-test for two independent samples; otherwise, the data were expressed as M(Q1, Q3), and analyzed by Mann-Whitney U test for comparison between two groups. The correlation between cerebral blood flow and exosomal miR-124-3p levels was analyzed by Pearson's correlation. Binary multifactorial logistic regression analysis was used to determine the risk factors associated with CCH, and corresponding odds ratios (OR) and 95% confidence intervals (CI) were calculated. P<0.05 was considered significant. Results: There was no significant difference in age (64±8 vs. 60±8 years old), gender (33.3% vs. 30.0%), history of smoking (20.0% vs. 3.3%), alcohol consumption (20.0% vs. 6.7%), diabetes mellitus (13.3% vs. 13.3%), hypertension (53.3% vs. 30.0%), history of hyperlipidemia (46.7% vs. 36.7%), uric acid (288±60 vs.319±67 µmol/L), and fasting glucose [4.99(4.63, 5.91) vs. 5.28(5.09, 6.05) mmol/L] and homocysteine [11.35(10.18, 13.08) vs.11.00(9.78, 13.03) µmol/L] between the CCH and control groups (P>0.05). Plasma exosomal miR-124-3p expression was significantly higher in the CCH group than in the control group [13.08 (8.59, 21.55) vs. 2.85 (1.44, 5.10), respectively; U=169.50, P<0.001]. Pearson's correlation test showed that the level of exosomal miR-124-3p was negatively correlated with cerebral blood flow in the hypoperfused region in patients with CCH (r=-0.932, P<0.001). Multi-factor logistic regression analysis showed that plasma exosomal miR-124-3p was independently associated with the risk of CCH (OR=1.169,95%CI 1.063-1.286,P=0.001). Conclusions: The expression of plasma exosomal miR-124-3p is negatively correlated with cerebral blood flow in areas of low perfusion and is an independent risk factor for CCH. Plasma exosomal miR-124-3p may thus serve as a valid biomarker for CCH risk prediction.

Therapeutic effect of micropump intravenous infusion of ambroxol hydrochloride on respiratory distress syndrome in premature infants.

OBJECTIVE: This work aimed to explore the therapeutic effect of micropump intravenous infusion of ambroxol hydrochloride (AH) on respiratory distress syndrome (RDS) in premature infants. PATIENTS AND METHODS: 56 premature infants from 28 to 34 weeks were recruited for analysis in this work. According to the treatment methods, they were randomly divided into two groups, with 28 patients in each group. Patients in the experimental group were given intravenous AH by micropump, while those in the control group inhaled atomized AH. The therapeutic effects were evaluated by comparing the data after treatment. RESULTS: The results showed that the serum 8-iso-PGP2α level in the experimental group was 166.32 ± 49.52, which was substantially inferior to that in the control group (183.32 ± 52.54), p < 0.05. In the experimental group, PaO2, SaO2, and PaO2/FiO2 were 95.88 ± 12.82 mmHg, 95.86 ± 2.27%, and 346.81 ± 51.93 mmHg, respectively, after 7 days of treatment. Compared with the control group (88.21 ± 12.82 mmHg, 93.18 ± 3.13%, and 266.83 ± 48.09 mmHg), the difference was statistically significant, p < 0.05. The oxygen duration, respiratory distress relief time, and length of stay were 95.12 ± 12.53 h, 4.4 ± 0.6 d, and 19.84 ± 2.8 d, respectively, in the experimental group, while they were 145.92 ± 13.85 h, 6.9 ± 0.9 d, and 28.42 ± 3.7 d, respectively, in the control group, showing great differences (p < 0.05). CONCLUSIONS: Micropump infusion of AH in the treatment of premature RDS patients was more conducive to efficacy. It can alleviate the clinical symptoms of children with RDS, improve their blood gas indicators, relieve and repair the damage to alveolar epithelial cell lipids in children with RDS, and ultimately improve the therapeutic effect, which can be used for the clinical treatment of premature RDS.

[Preoperative serum creatinine as an independent prognostic biomarker in patients with early-stage cervical adenocarcinoma].

Objective: To investigate the effect of preoperative serum creatinine (Scr) level on the prognosis of patients with early cervical adenocarcinoma (ADC) and its predictive value. Methods: A retrospective review was performed on 199 patients with the International Federation of Gynecology and Obstetrics (FIGO) stage ⅠA1-ⅡA1 and pathology-proven invasive ADC from January 2005 to December 2015. Patients were followed up by phone and outpatient, with a median follow-up time 77.5 (57.0, 114.0) months, 11 cases (5.5%) were missing, 19 cases (10.1%) recurred, and 17 cases (9.0%) died. Multivariate analysis was performed by Cox regression model to analyze the related factors of the prognosis of ADC patients. The optimal cut-off point was determined by the analysis of receiver operating characteristics (ROC), and the predictive value of related factors for prognosis was evaluated by the area under the curve (AUC). Results: The median age of 199 patients was 44.0 (39.0-50.0) years. Overall, 16 patients (8.0%) were stage ⅠA1; 4 patients (2.0%) were stage ⅠA2; 147 patients (74.0%) were stage ⅠB1; 13 patients (6.5%) were stage ⅠB2; 19 patients (9.5%) were stage ⅡA1. The multivariate analysis showed that FIGO stage [4.570 (1.625-12.854)] and elevated Scr [1.065 (1.006-1.128)] were correlated with DFS in patients with early ADC, as well as correlated with OS [4.412 (1.458-13.350) and 1.076 (1.012-1.144), respectively (all P<0.05)]. The optimal cut-off point of Scr level was 75.2 µmoI/L. The AUC showed that the Scr level was a predictor of DFS (AUC=0.677, 95%CI: 0.608-0.742, P=0.006) and OS (AUC=0.677, 95%CI: 0.607-0.741, P=0.012). Conclusions: The preoperative Scr level independently predicts the prognosis of early-stage ADC; patients with Scr levels>75.2 µmoL/L might require more follow-up and adjuvant treatment, as they might have a poorer prognosis.

Evaluating the efficacy of recombinant human bone morphogenic protein-2 in the treatment of alveolar clefts with autologous bone grafting using computer-aided engineering techniques.

Recent studies have indicated the use of recombinant human bone morphogenetic protein-2 (rhBMP-2) to be a viable adjunctive to alveolar cleft reconstruction owing to its osteoinductive capacity. This study aimed to evaluate the efficacy of rhBMP-2 in the treatment of alveolar cleft with autologous bone grafts by precise volumetric analysis. Twenty-six patients (aged 8-14) with unilateral alveolar clefts were enrolled in this comparative study. Patients were divided into two groups: the iliac crest bone graft (ICBG) was placed at the side of the cleft in the control group (ICBG group), and rhBMP-2 was mixed with the ICBG in the rhBMP-2 group (BMP group). Helical computed tomographic images were obtained preoperatively and 12 months postoperatively. The datasets were reconstructed as three-dimensional (3D) images using Mimics software and processed using Geomagic Wrap. The newly formed bone of the alveolar cleft was segmented by identifying the differences between preoperative and postoperative 3D images. In the ICBG group, the volume of newly formed bone ranged from 0.25 to 0.88 cm3, and the mean (SD) bone formation percentage was 42.01% (15.57%). In the BMP group, the volume of newly formed bone ranged from 0.34 to 1.09 cm3, and the bone formation mean (SD) percentage was 55.79% (11.84%). There was a statistically significant difference between the two groups in terms of the postoperative percentage of bone formation (p = 0.022). Thus, rhBMP-2 combined with an autologous bone graft is a promising technique to improve the results of secondary alveolar bone grafting.

[Application of septal extension graft with autogenous septal cartilage and auricular cartilage in rhinoplasty].

Objective: To explore the feasibility of reconstruction of nasal tip with septal cartilage and auricular cartilage. Methods: From September 2018 to October 2019, 17 patients (two males and fifteen females) with low noses underwent rhinoplasty under general anesthesia. The age of the patients ranged from 19 to 39, with an average of 27 years old. Among them, all the 17 cases were primary rhinoplasty. During the operation, autologous nasal septum cartilage was used as septal extension graft to extend the caudal septum, and the auricular cartilage was used to enhance the stability of the strut and to elevate the tip for adjusting the shape of nose by making into spreader graft, columellar strut graft, derotation graft and onlay graft. The nasal dorsum was filled with polytetrafluoroethylene. Digital scanning technology was used to evaluate the nasal structure before and after operation. SPSS 22 software was used to analyze the data with paired t-test. Results: The follow-up was from 6 to 12 months, with an avaerge of 7.6 months. Seventeen patients were satisfied with postoperative nasal morphology and height. There was no infection, prosthesis displacement, skin flap necrosis, no auricle deformation and other complications. Statistical software SPSS 22 performed paired t-test on the preoperative and postoperative data obtained by digital technology: postoperative nasal length and nasal tip protrusion increased compared with that before surgery, and it was statistically significant(length:(3.60±0.77)mm, tip protrusion:(3.61±0.64)mm, t value was -19.203 and -23.132 respectively, both P<0.001). The nasolabial Angle was smaller than that before surgery, and the data were statistically significant(3.40°±2.11°,t=6.635, P<0.001). Conclusion: The nasal tip and nasal septum extension complex constructed by autogenous nasal septal cartilage combined with auricular cartilage can increase the length of nasal tip, increase the height of nasal tip and reduce the angle of nasolabial angle.

[Expression and significance of chemokine CXCL12 and receptor CXCR4 in adenomyosis].

Objective: To observe the expression, correlation and significance of chemokine (C-X-C motif) ligand 12 (CXCL12) and chemokine (C-X-C motif) receptor 4 (CXCR4) in endometrium and myometrium of adenomyosis. Methods: Totally 38 patients were selected in this study, who underwent hysterectomy for adenomyosis at Beijing Obstetrics and Gynecology Hospital from October 2017 to December 2018 as the adenomyosis group, and, in the same period, selected 31 patients with cervical intraepithelial neoplasia Ⅲ or cervical cancer undergoing hysterectomy served as control group. The expression levels of mRNA and protein for CXCL12, CXCR4 in the endometrium and myometrium of the two groups were detected by immunohistochemistry and real-time PCR. Results: (1) The protein levels of CXCL12 and CXCR4 in endometrium in uterus with adenomyosis (0.229±0.025 and 0.226±0.016) were significantly higher than those in endometrium in uterus without adenomyosis (0.153±0.018 and 0.178±0.026); compared with each other, the differences were statistically significant (all P<0.05). And the expressions of CXCL12 and CXCR4 proteins in uterine myometrium of adenomyosis were 0.222±0.045 and 0.126±0.058, respectively, which were higher than those in the control group (0.091±0.029 and 0.099±0.020); compared with each other, the differences were statistically significant (all P<0.05). (2) The expression levels of CXCL12 and CXCR4 mRNA in endometrium of patients with adenomyosis were 6.31±0.12 and 8.49±0.21, respectively, which were higher than those in the control group (1.23±0.10 and 1.36±0.13); compared with each other, the differences were statistically significant (all P<0.05). Moreover, the expression levels of CXCL12 and CXCR4 mRNA in myometrium of patients with adenomyosis were 9.11±0.12 and 8.45±0.16, respectively, which were higher than those in the control group (1.18±0.08 and 1.46±0.13); compared with each other, the differences were statistically significant (all P<0.05). (3) In endometrium and myometrium of uterus with adenomyosis, CXCL12 and CXCR4 mRNA expression levels were positively associated (r=0.478, 0.542, all P<0.05). Conclusions: The levels of CXCL12 and CXCR4 in the endometrium and myometrium of adenomyosis are increased and positively correlated. The two chemokine may be involved in the development of adenomyosis.

Analysis of Consistency between Forensic Psychiatry Identification Diagnosis and Clinical Diagnosis of 1 369 Cases.

ABSTRACT: Objective To explore the consistency between identification diagnosis and pre-identification clinical diagnosis of patients with mental disorder undergoing forensic psychiatry identification. Methods The identification data of 1 369 appraised individuals who underwent criminal responsibility identification carried out by the Forensic Institute of Second Affiliated Hospital of Jining Medical University from 2014 to 2017 were collected retrospectively using self-designed investigation data sorting table. A comparative analysis of the mental disorder diagnosis results of expert opinion and past clinical diagnosis results was made. Results Among 1 369 appraised individuals, 964 cases （70.4%） were identified and diagnosed with mental disorder and 405 cases （29.6%） without mental disorder. Among the former, 63.3% （610 cases） were clinically diagnosed, which was higher than 43.2% （175 cases, P<0.05） in the latter. Among the various mental disorders that had been identified and diagnosed, patients with hysteria, stress, and neurosis had the highest proportion of clinical diagnoses （86.7%）, while patients with mental retardation had the lowest proportion of clinical diagnoses （9.6%）. Schizophrenia had the highest overall consistency rate of identification diagnosis and clinical diagnosis （98.4%）, while personality and behavior disorder had the lowest （33.3%）. The overall consistency rate between clinical diagnosis and identification diagnosis of the mental disorder group was 84.1%, and the Kappa value was 0.759. Compared with clinical diagnosis, the consistency rate between inpatient diagnosis and identification diagnosis was higher （85.9%, P<0.05）. Conclusion In forensic psychiatry identification that provides data of past clinical diagnosis and treatment, a high consistency between identification diagnosis and clinical diagnosis of the appraised individual who is identified and diagnosed with mental disorder exists. Clinical diagnosis （especially the inpatient diagnosis） has a relatively good reference value for forensic psychiatry identification.

[Clinical analysis of 67 cases of pure red cell aplastic anemia].

Objective: To investigate secondary factors, laboratory features, treatment options, and prognosis of pure red cell aplastic anemia (PRCA) . Methods: This was a multicenter retrospective clinical study. Patients aged above 18 years newly diagnosed with PRCA between June 1, 2010, and June 1, 2019, were recruited as the main study object. A comparative analysis of remission rate and overall survival rate was made according to different treatment schemes adopted by patients and different drug reduction rates. Results: A total of 67 patients with PRCA were included in this study and the secondary PRCA group accounted for 44.8% (30/67) . The most common secondary factors were thymoma (n=10) and T-cell large lymphocytic leukemia (T-LGLL) (n=6) . The overall response rate of PRCA was 85.7% and the 3-year overall survival rate of PRCA was (74.3±7.5) %. The remission rate of cyclosporine A alone was slightly higher than that of oral glucocorticoid alone or combined with glucocorticoid[90.0% (36/40) vs 75.0% (12/16) , P=0.147]. After patients applied with cyclosporine A treatment reached CR/PR and remained stable for 3-6 months, the dose of cyclosporine A was reduced by 25 mg each time. The cyclosporine A reduction interval of a 25 mg/d reduction in more than 1 month significantly prolonged the median disease-free survival compared with a 25 mg/d reduction in less than 1 month [not reached vs 15 (95% CI 7-23) months, P<0.001]. There were 62.5% (10/16) of patients who responded to the initial or incremental treatment regimen after relapse. Conclusion: PRCA has features of various secondary factors, high overall survival rate, and high remission rate. Treatment with cyclosporine A alone is preferred, and cyclosporine A should be slowly tapered to reduce the risk of later relapse after it takes effect and patients reach a steady state.

MiR-411 inhibits gastric cancer proliferation and migration through targeting SETD6.

OBJECTIVE: MicroRNAs (miRNAs) affect almost all cell behaviors of human cancers including gastric cancer (GC). However, the biological role of miR-411 in GC remains to be elucidated. MATERIALS AND METHODS: We determined the expression level of miR-411 in GC cell lines. After synthetic miRNAs or SET domain containing 6 (SETD6) expression vectors transfection, cell proliferation, colony formation, and migration were examined. Moreover, the target of miR-411 was identified by luciferase activity reporter assay and Western blot assay. RESULTS: Results revealed that the miR-411 expression was significantly down-regulated in GC cell lines compared with normal colonic epithelial cells. Overexpression of miR-411 inhibits GC cell proliferation, colony formation, and migration, whereas the overexpression of SETD6 promotes cell proliferation, colony formation, and migration. Moreover, SETD6 was identified as a putative target of miR-411. In addition, we showed miR-411 regulates GC cell behaviors by targeting SETD6. The overexpression of SETD6 promoted the activation of the nuclear factor (NF)-κB signaling pathway. CONCLUSIONS: These results suggested that miR-411 functions as a tumor suppressor in GC through targeting SETD6/NF-κB pathway. Targeting miR-411 may be a novel clue for GC treatment.

Chronic hyponatremia and association with osteoporosis among a large racially/ethnically diverse population.

Chronic hyponatremia may contribute to decreased bone density. We studied 341,003 men and women who underwent DXA testing and observed that individuals with chronic hyponatremia (sodium < 135 mEq/L) had an 11% greater likelihood of having osteoporosis. There was a dose-dependent effect with lower sodium and stronger association with osteoporosis. INTRODUCTION: Chronic hyponatremia has been associated with both neurologic deficits and increased risk of gait abnormalities leading to falls and resultant bone fractures. Whether chronic hyponatremia contributes to decreased bone density is uncertain. We evaluated whether chronic, mild hyponatremia based on serial sodium measurements was associated with increased risk of osteoporosis within a large, ethnically diverse population. METHODS: This is a retrospective cohort study between January 1, 1998 and December 31, 2014 within Kaiser Permanente Southern California, an integrated healthcare delivery system. Men and women were aged ≥ 55 years with ≥ 2 serum sodium measurements prior to dual-energy X-ray absorptiometry (DXA) testing. Time-weighted (TW) mean sodium values were calculated by using the proportion of time (weight) elapsed between sodium measurements and defined as < 135 mEq/L. Osteoporosis defined as any T-score value ≤ - 2.5 of lumbar spine, femoral neck, or hip. RESULTS: Among 341,003 individuals with 3,330,903 sodium measurements, 11,539 (3.4%) had chronic hyponatremia and 151,505 (44.4%) had osteoporosis. Chronic hyponatremic individuals had an osteoporosis RR (95% CI) of 1.11 (1.09, 1.13) compared to those with normonatremia. A TW mean sodium increase of 3 mEq/L was associated with a lower risk of osteoporosis [adjusted RR (95% CI) 0.95 (0.93, 0.96)]. A similar association was observed when the arithmetic mean sodium value was used for comparison. CONCLUSIONS: We observed a modest increase in risk for osteoporosis in people with chronic hyponatremia. There was also a graded association between higher TW mean sodium values and lower risk of osteoporosis. Our findings underscore the premise that chronic hyponatremia may lead to adverse physiological effects and responses which deserves better understanding.

[Development and Optimization of Therapeutic Analogues of Anti-TNFα Antibody Infliximab].

Previously, we have reported the crystal structures of Fab fragment of Infliximab in complex with TNFα. The structurally identified epitope on TNFα revealed the mechanism of TNFα inhibition by partially overlapping with the TNFα-receptor interface and the possibility to optimize the binding affinity. In this study, we launched a screen of a phage display library to isolate novel anti-TNFα antibodies based on the infliximab epitope. To develop novel anti-TNFα antibodies, structural analysis, the phage display antibody isolation, step by step antibody optimization, CDR residues random mutagenesis, and binding affinity characterization were performed. One of the novel antibodies generated on the backbone of infliximab, Inf3D6, has the superior binding affinity to TNFα, thus, demonstrating the potential for structure guided optimization for improvement of existing antibody-based therapeutics.

[Sample size for the estimation of F-wave parameters in healthy volunteers and amyotrophic lateral sclerosis patients].

Objective: The study aimed to investigate whether sample sizes of F-wave study differed according to different nerves, different F-wave parameters, and amyotrophic lateral sclerosis(ALS) patients or healthy subjects. Methods: The F-waves in the median, ulnar, tibial, and deep peroneal nerves of 55 amyotrophic lateral sclerosis (ALS) patients and 52 healthy subjects were studied to assess the effect of sample size on the accuracy of measurements of the following F-wave parameters: F-wave minimum latency, maximum latency, mean latency, F-wave persistence, F-wave chronodispersion, mean and maximum F-wave amplitude. A hundred stimuli were used in F-wave study. The values obtained from 100 stimuli were considered "true" values and were compared with the corresponding values from smaller samples of 20, 40, 60 and 80 stimuli. F-wave parameters obtained from different sample sizes were compared between the ALS patients and the normal controls. Results: Significant differences were not detected with samples above 60 stimuli for chronodispersion in all four nerves in normal participants. Significant differences were not detected with samples above 40 stimuli for maximum F-wave amplitude in median, ulnar and tibial nerves in normal participants. When comparing ALS patients and normal controls, significant differences were detected in the maximum (median nerve, Z=-3.560, P<0.01; ulnar nerve, t=5.019, P<0.01; tibial nerve, Z=-2.475, P<0.05; peroneal nerve, Z=-2.088, P<0.05)and mean F-wave latency (median nerve, Z=-3.243, P<0.01; ulnar nerve, t=3.876, P<0.01; tibial nerve, Z=-2.206, P<0.05; peroneal nerve, Z=-2.205, P<0.05)in all four nerves, F-wave chronodispersion (Z=-3.152, P<0.01)in the ulnar nerve, F-wave persistence in the median (Z=6.139, P<0.01)and ulnar nerves(Z=5.350, P<0.01), mean F-wave amplitude in the tibial nerve(t=2.981, P<0.01), maximum F-wave amplitude in the ulnar (Z=-2.134, P<0.05)and tibial nerves (t=2.746, P<0.01)with 20 stimuli; for chronodispersion in tibial nerve (t=2.551, P<0.05)100 stimuli, for chronodispersion in peroneal nerve (Z=-2.086, P<0.05)80 stimuli, for F-wave persistence in tibial nerve (Z=2.119, P<0.05) 60 stimuli, for mean F-wave amplitude in ulnar (Z=-2.552, P<0.05)and peroneal nerve (Z=-2.228, P<0.05)40 stimuli, for maximum F-wave amplitude in peroneal nerve (t=2.693, P<0.01)60 stimuli were necessary to detect differences. Conclusions: Sample sizes of F-wave study differed according to different nerves, different F-wave parameters , and ALS patients or healthy subjects.

[Significance of bacteria detection with filter paper method on diagnosis of diabetic foot wound infection].

Objective: To evaluate the significance of bacteria detection with filter paper method on diagnosis of diabetic foot wound infection. Methods: Eighteen patients with diabetic foot ulcer conforming to the study criteria were hospitalized in Liyuan Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from July 2014 to July 2015. Diabetic foot ulcer wounds were classified according to the University of Texas diabetic foot classification (hereinafter referred to as Texas grade) system, and general condition of patients with wounds in different Texas grade was compared. Exudate and tissue of wounds were obtained, and filter paper method and biopsy method were adopted to detect the bacteria of wounds of patients respectively. Filter paper method was regarded as the evaluation method, and biopsy method was regarded as the control method. The relevance, difference, and consistency of the detection results of two methods were tested. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of filter paper method in bacteria detection were calculated. Receiver operating characteristic (ROC) curve was drawn based on the specificity and sensitivity of filter paper method in bacteria detection of 18 patients to predict the detection effect of the method. Data were processed with one-way analysis of variance and Fisher's exact test. In patients tested positive for bacteria by biopsy method, the correlation between bacteria number detected by biopsy method and that by filter paper method was analyzed with Pearson correlation analysis. Results: (1) There were no statistically significant differences among patients with wounds in Texas grade 1, 2, and 3 in age, duration of diabetes, duration of wound, wound area, ankle brachial index, glycosylated hemoglobin, fasting blood sugar, blood platelet count, erythrocyte sedimentation rate, C-reactive protein, aspartate aminotransferase, serum creatinine, and urea nitrogen (with F values from 0.029 to 2.916, P values above 0.05), while there were statistically significant differences among patients with wounds in Texas grade 1, 2, and 3 in white blood cell count and alanine aminotransferase (with F values 4.688 and 6.833 respectively, P<0.05 or P<0.01). (2) According to the results of biopsy method, 6 patients were tested negative for bacteria, and 12 patients were tested positive for bacteria, among which 10 patients were with bacterial number above 1×10(5)/g, and 2 patients with bacterial number below 1×10(5)/g. According to the results of filter paper method, 8 patients were tested negative for bacteria, and 10 patients were tested positive for bacteria, among which 7 patients were with bacterial number above 1×10(5)/g, and 3 patients with bacterial number below 1×10(5)/g. There were 7 patients tested positive for bacteria both by biopsy method and filter paper method, 8 patients tested negative for bacteria both by biopsy method and filter paper method, and 3 patients tested positive for bacteria by biopsy method but negative by filter paper method. Patients tested negative for bacteria by biopsy method did not tested positive for bacteria by filter paper method. There was directional association between the detection results of two methods (P=0.004), i. e. if result of biopsy method was positive, result of filter paper method could also be positive. There was no obvious difference in the detection results of two methods (P=0.250). The consistency between the detection results of two methods was ordinary (Kappa=0.68, P=0.002). (3) The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of filter paper method in bacteria detection were 70%, 100%, 1.00, 0.73, and 83.3%, respectively. Total area under ROC curve of bacteria detection by filter paper method in 18 patients was 0.919 (with 95% confidence interval 0-1.000, P=0.030). (4) There were 13 strains of bacteria detected by biopsy method, with 5 strains of Acinetobacter baumannii, 5 strains of Staphylococcus aureus, 1 strain of Pseudomonas aeruginosa, 1 strain of Streptococcus bovis, and 1 strain of bird Enterococcus. There were 11 strains of bacteria detected by filter paper method, with 5 strains of Acinetobacter baumannii, 3 strains of Staphylococcus aureus, 1 strain of Pseudomonas aeruginosa, 1 strain of Streptococcus bovis, and 1 strain of bird Enterococcus. Except for Staphylococcus aureus, the sensitivity and specificity of filter paper method in the detection of the other 4 bacteria were all 100%. The consistency between filter paper method and biopsy method in detecting Acinetobacter baumannii was good (Kappa=1.00, P<0.01), while that in detecting Staphylococcus aureus was ordinary (Kappa=0.68, P<0.05). (5) There was no obvious correlation between the bacteria number of wounds detected by filter paper method and that by biopsy method (r=0.257, P=0.419). There was obvious correlation between the bacteria numbers detected by two methods in wounds with Texas grade 1 and 2 (with r values as 0.999, P values as 0.001). There was no obvious correlation between the bacteria numbers detected by two methods in wounds with Texas grade 3 (r=-0.053, P=0.947). Conclusions: The detection result of filter paper method is in accordance with that of biopsy method in the determination of bacterial infection, and it is of great importance in the diagnosis of local infection of diabetic foot wound.

[Modified Prolift procedure without trachelectomy or hysterectomy for the treatment of advanced pelvic organ prolapse complicated with cervical elongation].

OBJECTIVE: To evaluate the effect and safety of a modified Prolift procedure, without preceding partial trachelectomy or hysterectomy for pelvic organ prolapse (POP) with coexistent cervical elongation. METHODS: Clinical data of 72 patients that underwent a modified Prolift procedure for POP with coexistent cervical elongation, between December 2008 and June 2012 in Fuzhou General Hospital of Nanjing Military Command was retrospectively analysed. A comparison was carried out between preoperative and postoperative parameters of pelvic organ prolapse quantitation system (POP-Q), and an objective evaluation was made according to the overall cure rate and recurrence rate. Pelvic floor distress inventory-short form 20 (PFDI-20) was used to investigate the subjective cure rate and improvement of symptoms. RESULTS: Patients were followed up at median 52 months (36-78 months). One bladder perforation and one rectum perforation occurred during the procedure. Four patients (6%, 4/72) had uterine prolapse at 9-19 months after the opertaion and had transvaginal hysterectomy laterly. The overall anatomical correction rate was 94% (68/72). Six patients (8%, 6/72) had mesh exposures at 3-9 months after the opertaion. Scores of PFDI-20 decreased sifnificantly after the procedure (118.2±25.2 vs 12.1±8.0 vs 12.5±9.5 vs 13.0±9.9, P< 0.05). The patients' satisfaction rate was 92% (66/72). CONCLUSION: This modified Prolift procedure, without preceding partial trachelectomy or hysterectomy, could effectively and safely correct POP with coexistent cervical elongation.

[Curative effect analysis of different degree of hearing lossin sudden deafness patients].

Objective:Through analysis of the clinical data for different degree of hearing loss in patients with sudden deafness,to learn the relationship between degree of hearing loss and therapeutic effect.Method:By selecting for nearly three years 264 cases of patients with sudden deafness hospitalized in our department,we classified them by the level of hearing loss,to comparatively analyze the therapeutic effect on different degree of hearing loss in patients with sudden deafness.Result:The more severe the degree of low-frequency hearing loss,the worse the therapeutic effect.In all frequency sudden deafness,there were no clinically significant in mild and moderate sudden deafness(P>0.05);The cure rate and effective rate among mild,moderate and total sudden deafness are statistically significant(P<0.05),and between severe and total sudden deafness recovery rate are statistically significant(P<0.05);and mild and severe as so(P<0.05),the rest are no statistical significance(P>0.05).Conclusion:The degree of hearing loss has important influence on the curative effect of sudden deafness.

IRAK1 mediates TLR4-induced ABCA1 downregulation and lipid accumulation in VSMCs.

The activation of Toll-like receptor 4 (TLR4) signaling has an important role in promoting lipid accumulation and pro-inflammatory effects in vascular smooth muscle cells (VSMCs), which facilitate atherosclerosis development and progression. Previous studies have demonstrated that excess lipid accumulation in VSMCs is due to an inhibition of the expression of ATP-binding cassette transporter A1 (ABCA1), an important molecular mediator of lipid efflux from VSMCs. However, the underlying molecular mechanisms of this process are unclear. The purpose of this study was to disclose the underlying molecular mechanisms of TLR4 signaling in regulating ABCA1 expression. Primary cultured VSMCs were stimulated with 50 µg/ml oxidized low-density lipoprotein (oxLDL). We determined that enhancing TLR4 signaling using oxLDL significantly downregulated ABCA1 expression and induced lipid accumulation in VSMCs. However, TLR4 knockout significantly rescued oxLDL-induced ABCA1 downregulation and lipid accumulation. In addition, IL-1R-associated kinase 1 (IRAK1) was involved in the effects of TLR4 signaling on ABCA1 expression and lipid accumulation. Silencing IRAK1 expression using a specific siRNA reversed TLR4-induced ABCA1 downregulation and lipid accumulation in vitro. These results were further confirmed by our in vivo experiments. We determined that enhancing TLR4 signaling by administering a 12-week-long high-fat diet (HFD) to mice significantly increased IRAK1 expression, which downregulated ABCA1 expression and induced lipid accumulation. In addition, TLR4 knockout in vivo reversed the effects of the HFD on IRAK1 and ABCA1 expression, as well as on lipid accumulation. In conclusion, IRAK1 is involved in TLR4-mediated downregulation of ABCA1 expression and lipid accumulation in VSMCs.

Ultraviolet Lasers Realized via Electrostatic Doping Method.

P-type doping of wide-bandgap semiconductors has long been a challenging issue for the relatively large activation energy and strong compensation of acceptor states in these materials, which hinders their applications in ultraviolet (UV) optoelectronic devices drastically. Here we show that by employing electrostatic doping method, hole-dominant region can be formed in wide bandgap semiconductors, and UV lasing has been achieved through the external injection of electrons into the hole-dominant region, confirming the applicability of the p-type wide bandgap semiconductors realized via the electrostatic doping method in optoelectronic devices.