[Relationship between coagulation status, autoantibodies, and conception method with subchorionic hematoma].

Objective: To investigate the relationship between subchorionic hematoma (SCH) and coagulation status, autoantibodies, and conception method. Methods: A total of 100 pregnant women diagnosed with SCH from June 2020 to December 2021 in the Third Affiliated Hospital of Zhengzhou University were included in the SCH group, while 100 healthy pregnant women during the same period were selected as the control group. The coagulation status (including platelet, prothrombin time, thrombin time, activated partial thromboplastin time, fibrinogen, antithrombin Ⅲ, fibrin degradation products, D-dimer, homocysteine, protein S activity, protein C activity), the positive rate of autoantibodies [including antiphospholipid antibodies (anticardiolipin antibody and anti-ß2 glycoprotein Ⅰ antibody), antinuclear antibody] and the mode of conception of the two groups were analyzed. Results: Compared to the control group, the SCH group had higher levels of platelet [(240±45)×109/L vs (227±37)×109/L], fibrinogen [(4.0±0.8) vs (3.6±0.7) g/L], D-dimer [(0.42±0.18) vs (0.31±0.15) mg/L], blood homocysteine [(8.9±4.2) vs (6.9±2.3) µmol/L], and lower level of protein S activity [(55±14)% vs (68±20)%], and there were significant differences between the two groups (all P<0.05). The SCH group had higher positive rates of autoantibodies [24.0% (24/100) vs 8.0% (8/100)], antiphospholipid antibodies [15.0% (15/100) vs 6.0% (6/100)], anti-ß2 glycoprotein Ⅰ antibody [10.0% (10/100) vs 3.0% (3/100)], antinuclear antibody [11.0% (11/100) vs 2.0% (2/100)] and assisted reproduction rate [10.0% (10/100) vs 2.0% (2/100)] than those of the control group (all P<0.05). Conclusion: The occurrence of SCH is related to blood hypercoagulability, positive autoantibodies, and assisted reproduction.

[Analysis of characteristics of drug resistance gene mutation in HBV RT region of hepatitis B infected patients].

Objective: This article investigated the clinical characteristics and distribution of drug resistance mutation sites in HBV RT region of hepatitis B infected patients. Methods: Retrospective analysis was made on 1 948 patients with HBV infection, who had been tested for NAs resistance mutation and had a medical history of NAs in the Laboratory Department of the Fifth Medical Center of the PLA General Hospital from January 2020 to December 2021. Basic clinical information and drug resistance related mutation information were recorded. Meanwhile, the serological index data of hepatitis B were collected. Drug resistance gene mutant group and non-mutated group were grouped according to whether the drug resistance genes had a mutation in HBV RT region, and the clinical characteristics and genotype distribution of the two groups were statistically analyzed. The pattern of drug resistance gene mutation, number of mutation sites, drug resistance type and mutation of NAs resistance-related sites were analyzed in 917 patients with drug resistance gene mutation in HBV RT region. χ2 Inspection was used for counting data. Meanwhile, two independent samples t-test and Wilcoxon rank sum test were used for measurement data. Results: Among the 1 948 patients with chronic HBV infection, 917 patients had drug resistance gene mutation in RT region (47.07%). The proportion of patients with acute hepatitis B and CHB in HBV RT resistance gene mutant group was lower than that in the non-mutated group, while the proportion of patients with HBV-related cirrhosis was higher than that in the non-mutated group, these differences were statistically significant. Compared with the non-mutated group in HBV RT region, the age, the positive rates of HBeAg and HBV DNA, and HBV DNA load of these patients were increased in drug resistance gene mutant group, these differences were statistically significant. Genotypes of patients in both groups were dominated by C, followed by B and D. The proportion of patients with genotype C in HBV RT drug resistance gene mutant group was higher than that of non-mutated group, the difference was statistically significant. There were 53 gene mutation patterns in 917 patients with drug resistance gene mutation in HBV RT region, and the main pattern was rtL180M+rtM204V+rtS202G (9.70%). The mutation sites were dominated by 3 (20.74%). There were 5 types of drug resistance, LAM+Ldt (21.25%) was the most. Among the 18 sites that were clearly associated with LAM, ADV, ETV and Ldt resistance in the HBV RT region, 14 sites were mutated, and the most common mutation sites were rtL180M, rtM204V, rtM204 and rtS202G. what's more, the proportion of patients with NAs drug resistance was LAM>Ldt>ETV>ADV. Conclusion: In order to prevent adverse consequences of this study such as disease recurrence or disease progression caused by HBV drug resistance, HBV infected patients, who have long-term use of NAs antiviral therapy, should monitor the level of HBV DNA and drug resistance genes in HBV RT region in order to optimize the treatment plan in time or guide individualized treatment.

[Advances in clinical studies of chronic cough].

Chronic cough is a common complaint in respiratory specialist clinics, with a significant impact on cough-specific quality of life and psychophysiological health. The diagnosis, treatment and management of chronic cough remains a major challenge. We summarized a series of recent advances from clinical studies in the epidemiology, diagnosis and management of chronic cough over the past year.

[Prognostic significance of immunoparesis in newly diagnosed multiple myeloma patients who achieved deep response].

Objective: To evaluate the effect of immune status on disease progression in patients with newly diagnosed multiple myeloma (NDMM) achieving deep response. Methods: Clinical data of 125 NDMM patients at Beijing Chaoyang Hospital from August 2015 to February 2020 were retrospectively analyzed who achieved very good partial response (VGPR) or better after front-line treatment. The immune status and its influence on progression-free survival (PFS) were analyzed. Results: (1) All patients received novel drug regimens, and 50.4% (63/125) patients followed by autologous stem cell transplantation (ASCT). The rate of complete response (CR) as best efficacy was 89.6%, in which 66.4% achieved CR and MRD negativity tested by second generation flow cytometry. (2) Cox multivariate analysis suggested that persistent severe immunoparesis 3 months and 6 months since the best response was an independent poor prognostic factor for PFS. (3) The 3-year PFS rate in the severe immunoparesis group was significantly lower than that in the control group (41.3% vs. 64.4%, P=0.021). (4) The 3-year PFS rates in patients with persistent severe immunoparesis at 3 months or 6 months were significantly lower (30.0% vs. 63.5%, P<0.001; 16.4% vs. 63.8%, P<0.001 respectively). (5) Even in those achieving CR and negative MRD, the 3-year PFS rate when severe immunoparesis lasted 6 months was significantly lower (22.2% vs. 83.2%, P=0.005). Conclusion: The immune status in NDMM patients achieving deep response is closely related to survival. Persistent severe immunoparesis indicates early progression of the disease.

[Atezolizumab therapy in Chinese patients with locally advanced or metastatic solid tumors: An open-label, phase â study].

OBJECTIVE: To evaluate pharmacokinetics (PK), efficacy, and safety of atezolizumab (anti-PD-L1) in high interest cancers in China, including esophageal cancer (EC), gastric cancer (GC), hepatocellular carcinoma (HCC), nasopharyngeal cancer (NPC), and non-small cell lung can-cer (NSCLC). METHODS: This phase I, open-label study was conducted at 6 Chinese sites from August 4, 2016 to April 15, 2019. The patients were ≥18 years old with a histologically documented incurable or metastatic solid tumor that was advanced or recurrent and had progressed since the last anti-tumor the-rapy. The PK phase characterized PK and safety of atezolizumab following multiple-dose administration when atezolizumab was administered as a single agent. The extension phase studied safety and efficacy of atezolizumab, as monotherapy (EC, GC, HCC, NPC) and with chemotherapy (NSCLC). RESULTS: This study enrolled 120 patients (PK phase: n=20; extension phase: n=20/cohort). Fourty-two patients (42.0%) were PD-L1 positive in atezolizumab monotherapy group (100 patients), of the 9 patients (9.0%) with microsatellite instability-high (MSI-H) tumors. Atezolizumab clearance was 0.219 L/d, and steady state was reached after 6 to 9 weeks (2-3 cycles) of repeated dosing. Objective response rates (ORRs) in EC, GC, HCC, NPC, and NSCLC were 10.0%, 15.0%, 10.0%, 5.0%, and 40.0%, respectively. In the patients with PD-L1 positive tumors, ORR was 11.9% with atezolizumab and 46.2% with atezolizumab plus gemcitabine and cisplatin. Two GC patients achieved durable response after pseudo-progression. The most common treatment-related adverse events in the atezolizumab monotherapy group were fatigue, anemia, fever, and decreased white blood cell count. The most common treatment-related adverse events in the combination group were anemia, decreased white blood cell count, and decreased appetite. No new safety signals were identified. CONCLUSION: Atezolizumab's PK, efficacy, and safety were similar in Chinese patients vs. global patients in previous studies.

[Expression of RAGE in asthmatic rats and the intervention of Roxithromycin].

Objective: To observe the expression of the Receptor of Advanced glycation end products (RAGE) in asthmatic rats, and explore the intervention of Roxithromycin. Methods: A total of 18 Specific Pathogen Free-class Brown Norway male rats were randomly divided into control group, asthma model group and Roxithromycin group, with 6 rats in each group. The asthmatic model was sensitized by intraperitoneal injection of Ovalbumin (OVA)+Al(OH)(3), and challenged with OVA. Rats in Roxithromycin group were given Roxithromycin 30 mg/kg 30 minutes before each challenge. Rats in control group and asthma model group were treated with equal volume of saline. The concentrations of RAGE and interleukin (IL)-4 in serum and bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent (ELISA); the pathological changes of lung tissues were observed by HE-staining; the thickness of airway wall and airway smooth muscle were measured by Image-Pro Plus; the relative expression of RAGE in lung tissues were detected by Western blot. Results: In asthma model group, the concentrations of RAGE and IL-4 in the serum and BALF were obviously higher than those in control group [(494±32) vs (327±45) ng/L; (32.4±5.8) vs (13.1±2.9) ng/L; (553±38) vs (399±56) ng/L; (37.8±3.4) vs (19.4±2.5) ng/L] (all P<0.01); in Roxithromycin group, the concentrations of RAGE and IL-4 in the serum and BALF were obviously lower than those in asthma model group [(438±18) vs (494±32) ng/L; (22.8±6.0) vs (32.4±5.8) ng/L; (444±42) vs (553±38) ng/L; (25.6±4.5) vs (37.8±3.4) ng/L] (all P<0.05). In asthma model group, the bronchial wall was thickened, the lumen was narrow, the mucosal wrinkles were significantly increased, edema appeared under the mucosa, and a large number of inflammatory cells infiltrated and aggregated in the bronchi, perivascular and alveolar spaces; the thickness of airway wall and airway smooth muscle were significantly increased than those in control group (P<0.01); in Roxithromycin group, airway inflammation and remodeling were alleviated compared with those in asthma model group (P<0.05). In asthma model group, the expression of RAGE in lung tissues were significantly increased than those in control group (P<0.01); in Roxithromycin group, the expression of RAGE were significantly decreased than those in asthma model group (P<0.01). There were positive correlations between the expression of RAGE and IL-4 in BALF and serum (r=0.782, 0.804, all P<0.01); there were positive correlations between RAGE and total white cell counts, eosinophil counts, smooth muscle thickness (r=0.897, 0.927, 0.860, all P<0.01). Conclusions: The increasing of RAGE in asthmatic rats are positively correlated with airway inflammation and airway remodeling. Roxithromycin may inhibit the development of asthma by reducing the expression of RAGE.

[The relationship between dietary pattern and serum C-reactive protein concentration].

In order to explore the relationship between dietary pattern and C-reactive protein (CRP) in Xiamen residents, 2 904 subjects from 3 districts of Xiamen City were selected by a multi-stage stratified random sampling method. The food frequency questionnaire was used for dietary survey and serum CRP concentration was determined simultaneously. The dietary model was established by factor analysis and the relationship between different dietary patterns and serum CRP concentration was analyzed. Five dietary patterns were obtained by the factor analysis. After the adjustment of gender, age, occupation, education, marriage status, income, smoking, drinking and body mass index, the healthy dietary pattern was negative associated with the serum CRP concentration [OR(95%CI):0.62(0.42-0.90)]. The Serum CRP concentration of residents with a healthy dietary pattern is lower.

[The role of S100A8/RAGE and Caveolin-1 and the effect of roxithromycin on their expression in a rat model of neutrophilic asthma].

Objective: To explore the role of S100A8, the receptor for advanced glycation endproducts (RAGE) and Caveolin-1 in neutrophilic asthmatic rats, and to further study the intervention of roxithromycin and the possible mechanisms. Methods: Male Brown Norway rats were randomly assigned to a control group, an asthma group and a Roxithromycin group. The asthmatic rat model was established by intraperitoneal injection of ovalbumin (OVA) and Freund's complete adjuvant (FCA) mixture, and aerosol inhalation of OVA. Rats in the Roxithromycin group were given roxithromycin injection 30 mg/kg 30 minutes before each challenge. Rats in the control and the asthma groups were replaced with equal volumes of saline, respectively. Bronchoalveolar lavage fluid (BALF) neutrophil percentage (Neu%) and pathological changes of pulmonary tissue (hematoxylin-eosin, HE staining) were measured to confirm the establishment of asthmatic models. The concentration of inflammatory cytokines and S100A8 were quantified by enzyme-linked immunosorbent assay (ELISA), and the expression of Caveolin-1 and RAGE at protein levels were detected by immunohistochemistry and Western blot. Results: Neu% in BALF of the asthma group was significantly higher than those of the control group, and Neu% in the Roxithromycin group was lower than the asthma group (all P<0.01). Pulmonary histology revealed that there were a large number of inflammatory cells infiltrated in the bronchial and perivascular, pulmonary interstitial and alveolar spaces, and the bronchial wall and smooth muscles were thickened obviously in the asthma group. Rats in the Roxithromycin group showed milder inflammation and airway remodeling change than the asthma group. There was no obvious pathological damage in the control group. The concentration of IL-6 and IL-17 in BALF and serum of rats in the asthma group were significantly higher than those in the control group (P<0.01), and Roxithromycin inhibited the high expression of these cytokines (P<0.05). The expression of S100A8 and RAGE in the asthma group were significantly higher than those in the control group [(20.6±4.4) vs (7.1±2.0) ng/L; (885±118) vs (462±102) ng/L; (14.2±1.7) vs (7.6±1.8) ng/L; (774±166) vs (406±69) ng/L, all P<0.05], and Roxithromycin inhibited the high expression of these proteins [(14.3±3.7) vs (20.6±4.4) ng/L; (650±53) vs (885±118) ng/L; (10.4±1.2) vs (14.2±1.7) ng/L; (560±64) vs (728±72) ng/L] (all P<0.05). Meanwhile, the expression of Caveolin-1 in the asthma group was significantly lower than that in the control group (P<0.01), and Roxithromycin up-regulated its expression (P<0.01). Correlation analysis showed that there was a significantly positive correlation between the expression of S100A8 and RAGE (r=0.706, P<0.01), while there was a significantly negative correlation between the expression of S100A8 and Caveolin-1 (r=-0.775, P<0.01), and between the expression of Caveolin-1 and RAGE (r=-0.919, P<0.01). Conclusion: S100A8 and Caveolin-1 may play an important role in neutrophilic asthma via RAGE, and Roxithromycin may exerts anti-inflammatory effects and inhibition of airway remodeling partly through this signaling pathway.

[Study on the efficiency of tertiary public hospitals and its influencing factors in Beijing].

OBJECTIVE: To evaluate the comprehensive technical efficiency of the tertiary public hospitals in Beijing between 2006 and 2015 and explore its influencing factors, so as to propose corresponding policy suggestions. METHODS: The data envelopment analysis was employed to evaluate the comprehensive technical efficiency, pure technical efficiency and scale efficiency of the tertiary public hospitals in Beijing. Malmquist index model was used to analyze the changes of the above three dynamic efficiencies. Finally, randomeffect panel tobit model was utilized to analyze the influencing factors of the comprehensive technical efficiency. RESULTS: The average comprehensive technical efficiency and pure technical efficiency of the tertiary public hospitals in Beijing were relatively high, and they had respectively increased from 0.44 and 0.51 in 2006 to 0.62 and 0.68 in 2015, and the highest proportion of two kinds of efficiency values was between 0.5 and 0.8. Most of the scale efficiency values distributed between 0.8 and 1.0, and the majority of hospitals were in a state of decreasing returns to scale. The total factor productivity of hospitals had been increasing at an average rate of 5.78% per year due to the double progress of technical efficiency and technology at annual rates of 3.77% and 1.94% respectively, further decomposing technological efficiency change, and the pure technical efficiency change increased at the speed of 3.21% per year, and the annual average rate of progress in scale efficiency was only 0.53%. The comprehensive technical efficiency was positively correlated with the turnover rate of beds, annual visits per doctor, the ratio of doctors to nurses, and negatively correlated with the number of beds, the ratio of outpatients to inpatients, the proportion of medical technical personnel, and the proportion of drugs. CONCLUSION: Future health policies should strictly control the scale of tertiary public hospitals, pay attention to the innovation and application of hospital technology, change the hospital internal management level and management model, promote refined management, and achieve sustainable development.

[Role of roxithromycin on glucocorticoid resistance of human bronchial epithelial cells and its mechanism].

Objective: To explore the effects of roxithromycin (RXM) on glucocorticoid resistance of human bronchial epithelial cells exposed to smoke and its mechanism. Methods: Beas-2B cells as the research object were grouped into: control group, 10%cigarette smoke extract (CSE) group, roxithromycin (RXM)+ 10%CSE group. With 10%CSE intervention in the 10%CSE group, 10%CSE and RXM intervention in the RXM+ 10%CSE group, complete culture solution intervention in the control group. Interleukin-8 (IL-8) levels were measured by enzyme linked immunosorbent assay (ELISA) and IL-8 inhibition rate and dexamethasone half inhibitory concentration (IC50-Dex) were calculated; the expression of histone deacetylase 2 (HDAC2) protein was detected by immunofluorescence (IF) and Western blotting (WB). Results: In response to dexamethasone at the concentration of 10(-9,) 10(-8,) 10(-7) and 10(-6) mol/L successively, the IL-8 inhibition rates of RXM+ 10%CSE group [(27.55±3.81)%, (49.60±1.45)%, (55.36±3.36)%, (60.32±3.13)%, respectively] were lower than those of control group [(32.85±2.56)%, (57.12±2.81)%, (60.81±2.08)%, (67.24±3.50)%, respectively], but higher than those of 10%CSE group [(19.15±1.69)%, (37.02±2.30)%, (47.15±2.01)%, (52.09±1.57)%, respectively] (all P<0.05). In contrast, the IC50-Dex of RXM+ 10%CSE group [(4.94±1.62)×10(-8)] was significantly higher than that of control group [(1.75±0.77)×10(-8)], but lower than that of 10%CSE group [(2.92±0.78)×10(-7)] (both P<0.01). The expression of HDAC2 protein of 10%CSE group (0.011±0.004 from IF and 0.46±0.10 from WB) was lower than that of control group (0.037±0.005 and 0.91±0.06, correspondingly), while RXM+ 10%CSE group (0.025±0.005 and 0.77±0.09, correspondingly) was lower than that of control group but higher than that of 10%CSE group (all P<0.05). Conclusion: Roxithromycin may restrain tobacco smoke exposure-induced glucocorticoid resistance in human bronchial epithelial cells through upregulating HDAC2 expression.

[Comparison of the outcomes between anterior cervical discectomy and fusion versus posterior laminectomy and fusion for the treatment of multi-level cervical spondylotic myelopathy combined with cervical kyphosis].

Objective: To compare the outcomes between anterior cervical discectomy and fusion (ACDF) and posterior laminectomy and fusion(LF) for multilevel cervical spondylotic myelopathy combined with cervical kyphosis. Methods: From January 2010 to June 2014, 54 patients with cervical spondylotic myelopathy combined with cervical kyphosis underwent surgical treatment.Among them, 29 patients were underwent ACDF, and 25 patients were underwent LF in Department of spine surgery, Tianjin Union Medical Centre. The operation time, intraoperative blood loss, fusion segments, Japanese Orthopaedic Association (JOA)score, Neck Disability Index (NDI), Visual Analog Scale (VAS), change of cervical curvature, range of motion(ROM)and complications were recorded and compared between the two groups. Results: Mean operative time was (162.7±21.3)min in the anterior approach group versus (176.3±29.8)min in the posterior group(P>0.05). Mean intraoperative blood loss was (135.6±27.8)ml in the anterior approach group and (255.2±32.3)ml in the posterior approach group(P<0.05). Mean fusion levels are (4.1±0.3)in the anterior approach group and (5.3±0.5) in the posterior approach group(P<0.05). The mean preoperative JOA score were(8.3±2.7)in the anterior approach group and( 8.9±2.1) in the posterior approach group (P>0.05). Mean postoperative JOA score were(13.6±2.5) in the anterior approach group and (14.0±1.7)in the posterior approach group at final follow-up(P>0.05). Mean improvement rate was (55.7%±16.3%)in the anterior approach group and (58.3%±15.7%) in the posterior approach group (P>0.05). Mean preoperative NDI score were(33.8±11.0)in the anterior approach group and (34.4±8.7)in the posterior approach group (P>0.05). Mean postoperative NDI score were (16.9±7.5) in the anterior approach group and (15.5±8.1) in the posterior approach group at final follow-up (P>0.05). Mean VAS score were (2.9±1.5) in the anterior approach group and (2.5±1.0) in the posterior approach group before operation(P>0.05), they are improved to (1.2±1.2) and (1.2±1.3), respectively(P>0.05). Mean Cobb angle of the operative site were (-24.3±4.4)°in the anterior approach group and (-22.7±3.7)° in the posterior approach group before operation(P>0.05). At final follow-up, the Cobb angle of the operative site were (13.7±3.2)°in the anterior approach group and (6.2±4.2)° in the posterior approach group(P<0.01). Mean preoperative ROM were (29.0±6.7)°and (30.4±5.4)° in the anterior approach group and posterior approach group, respectively(P>0.05). Mean postoperative ROM were (11.7±6.5)° and (8.2±5.9)°in the anterior approach group and the posterior approach group, respectively(P<0.05). There were 16 patients with complications in the anterior approach group and 7 patients with complications in the posterior approach group(P<0.05). Conclusion: For multilevel cervical spondylotic myelopathy combined with cervical kyphosis, ACDF can restore the lordosis better, fuse less levels but have more complications compared with LF. Patients treated with LF can get as good life quality as with ACDF and have less complications although fuse more levels compared with ACDF.

Codon optimization enhances the expression of porcine ß-defensin-2 in Escherichia coli.

Porcine ß-defensin-2 (pBD2) is a cationic antimicrobial peptide that has therapeutic potential. The amount of pBD2 in nature is limited, and the expression of pBD2 in Escherichia coli is low, probably because a different gene codon is used by prokaryotic organisms to that used by eukaryotes. Codon preference optimization is one of the ways to increase heterologous expression of pBD2. To achieve high expression of pBD2, the pBD2 gene was redesigned according to the preferred codon in E. coli without altering the amino acid sequence. The optimized gene was inserted into expression vector pET-30a and transformed into E. coli BL21 (DE3) plysS. Our results showed that pBD2 was expressed as His-Tag fusion protein at a level that was approximately 4-6 times greater than from the native gene, based on total protein expression. Expressed fusion pBD2 showed antimicrobial activity against both E. coli and Staphylococcus aureus. Moreover, pBD2 showed weak hemolytic activity and strong heat resistance. These results indicate that fusion pBD2 is functional and has similar properties to those of pBD2 from the native gene. Our current study demonstrated that codon optimization could enhance pBD2 expression in E. coli without altering its function. Therefore, the expression of pBD2 after codon optimization in heterologous host cells might be useful and is worthy of further research.

Branches of NF-κb signaling pathway regulate hepatocyte proliferation in rat liver regeneration.

Previous studies have demonstrated that the nuclear factor κB (NF-κB) pathway is involved in promoting cell proliferation. To further explore the regulatory branches and their sequence in the NF-κB pathway in the promotion of hepatocyte proliferation at the transcriptional level during rat liver regeneration, Rat Genome 230 2.0 array was used to detect the expression changes of the isolated hepatocytes. We found that many genes involved in the NF-κB pathway (including 73 known genes and 19 homologous genes) and cell proliferation (including 484 genes and 104 homologous genes) were associated with liver regeneration. Expression profile function (Ep) was used to analyze the biological processes. It was revealed that the NF-κB pathway promoted hepatocyte proliferation through three branches. Several methods of integrated statistics were applied to extract and screen key genes in liver regeneration, and it indicated that eight genes may play a vital role in rat liver regeneration. To confirm the above predicted results, Ccnd1, Jun and Myc were analyzed using qRT-PCR, and the results were generally consistent with that of microarray data. It is concluded that 3 branches and 8 key genes involved in the NF-κB pathway regulate hepatocyte proliferation during rat liver regeneration.

A platform for in-situ multi-probe electronic measurements and modification of nanodevices inside a transmission electron microscope.

We developed a new platform that enables in-situ four-probe electronic measurements, in-situ three-probe field-effect measurements, nanomanipulation, and in-situ modification of nanodevices inside a transmission electron microscope (TEM). The platform includes a specially designed chip-holder and a silicon (Si) chip with suspended metal electrodes. The chip-holder can hold one Si chip with a size up to 3 mm × 3 mm and provides four electrical connections that can be connected to the micrometer-sized electrodes on the Si chip by wire-bonding. The other side of the electrical connections on the chip-holder is connected to the electronic instruments outside the TEM through a commercial Nanofactory SPM-TEM holder. The Si chip with suspended metal electrodes on one of its edges was fabricated by lithography and wet etching. Carbon nanotubes (CNTs), InAs nanowires, and tungsten disulfide nanowires were placed to stride over and connect to the suspended electrodes on the Si chip by nanomanipulations inside a scanning electron microscope (SEM). By using the platform, I-V curves of an individual single-walled CNT connecting to four electrodes were in-situ measured between any two of the four suspended electrodes, and a high-resolution TEM image of the same CNT was obtained. Furthermore, four-terminal I-V measurement on an InAs nanowire was achieved on this platform, and with a movable probe used as a gate electrode, field-effect measurement on the same InAs nanowire device was accomplished in SEM. In addition, by using the movable probe on the SPM-TEM holder, we could further in-situ modify nanomaterial and nanodevices. The present work demonstrates a method that allows a direct correlation between the atomic-level structure and the electronic property of nanomaterials or nanodevices whose structure can be further modified in-situ.

[Ultrasound-guided percutaneous cannulation for extracorporeal membrane oxygenation in children].

Objective: To evaluate the effectiveness and safety of ultrasound-guided percutaneous cannulation for extracorporeal membrane oxygenation (ECMO) in children. Methods: In this retrospective observational study, 66 cases who underwent non-cardiac surgery ECMO in pediatric intensive care unit (PICU) of Shanghai Children's Hospital from May 2016 to April 2021 were collected. The demographics, model of ECMO support, type and size of arteriovenous cannulas, way of catheterization and complications were recorded and summarized. Patients were divided into percutaneous cannulation group and surgical cannulation group according to catheterization strategies. The demographics, duration of cannulation and ECMO support, ECMO weaning rate and hospital survival rate were compared among two groups. χ2 and nonparametric rank sum test were used for comparison. Results: Among the 66 patients who received ECMO, 38 were male and 28 were female, with age 44.5 (12.0, 83.5) months and weight 15.0 (10.0, 25.0) kg; 21 patients underwent percutaneous cannulation, with a success rate of 95% (20 cases). Point-of-care ultrasound was performed for all percutaneous cannulation cases. The duration of percutaneous cannulation was significantly shorter than that of surgical cannulation (26.0 (23.3, 30.3) vs. 57.0 (53.8, 64.0) min, Z=6.31, P<0.001). Successful percutaneous cannulation cases were aged 70.5 (23.8, 109.5) months, and their weight was 23.2 (13.6, 37.0) kg. Ten cases were initially given veno-venous (VV) ECMO support, and 10 cases were given veno-arterial (VA) ECMO support. ECMO arterial cannulas were sized from 8 F to 17 F, and venous cannulas sized from 10 F to 19 F. For VV-ECMO, the right internal jugular and femoral veins were used as vascular access, while VA-ECMO used right internal jugular vein-femoral artery or right femoral vein-left femoral artery approach. Only one patient suffered severe complication (superior vena cava perforation). There was no catheter-related bloodstream infection. Conclusion: Ultrasound-guided percutaneous cannulation for ECMO can be performed with a high rate of success and safety in children.

[A case of spontaneous remission of acute myeloid leukemia with MLL-AF9 rearrangement and abnormal liver function].

Objective: To explore the clinical features and possible pathogenesis of spontaneous remission of acute myeloid leukemia (AML) . Methods: We retrospectively analyzed the clinical data of a patient with spontaneous remission of AML, MLL-AF9 rearrangement, and abnormal liver function in the First Affiliated Hospital of Zhengzhou University, and the relevant pieces of literature were summarized. Results: The patient experienced lung infection, fever, and liver dysfunction and was treated with anti-infection and blood transfusion. After complete response (CR) , the patient remained in CR with mild, indirect bilirubin elevation at 35 months of follow-up. Additionally, 56 cases of adult AML (non-acute promyelocytic leukemia) were reported in the literature from 1990 to June 2021. The cases were checked by bone marrow aspiration, and our patients were summarized and analyzed. Furthermore, 57 patients, including 37 males and 20 females, with a median age of 51 (20-83) years and a median remission time of five months; 52 patients achieved complete remission. In addition, there were five cases with long-term remission and a chromosomal record, with no recurrence so far, three with normal karyotype and two with t (9;11) (q21;q23) . Conclusion: The spontaneous remission of leukemia is rare and may be related to immunosuppression and genes.

MicroRNA-142 promotes the development of nasopharyngeal carcinoma through targeting PTEN.

OBJECTIVE: To elucidate whether microRNA-142 could regulate the development of nasopharyngeal carcinoma (NPC) by mediating gene of phosphate and tension homology deleted on chromosome ten (PTEN) expression. PATIENTS AND METHODS: The microRNA-142 expression in NPC tissues and paracancerous tissues was detected by the quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Correlation between the microRNA-142 expression and the prognosis of NPC patients was analyzed. MicroRNA-142 expression in NPC cell lines was determined as well. By transfection of microRNA-142 inhibitor or negative control, biological performances of NPC cells were accessed through cell counting kit-8 (CCK-8), colony formation, wound healing, and transwell assay. Dual-luciferase reporter gene assay was conducted to verify the binding condition between microRNA-142 and its target gene PTEN. Rescue experiments were carried out by co-transfection of microRNA-142 inhibitor and si-PTEN, followed by detecting the invasive capacity of NPC cells. Protein expressions of relative genes in the PI3K/AKT pathway after the microRNA-142 knockdown in NPC cells were determined by Western blot. RESULTS: MicroRNA-142 was highly expressed in NPC tissues than that of paracancerous tissues, which was correlated with poor prognosis of NPC patients. MicroRNA-142 was also highly expressed in NPC cells. Downregulated microRNA-142 inhibited proliferative, migratory, and invasive capacities of NPC cells. Dual-luciferase reporter gene assay verified that microRNA-142 could directly bind to PTEN. Knockdown of PTEN could reverse the inhibitory effect of microRNA-142 on invasive capacity of NPC cells. Finally, Western blot results demonstrated that the microRNA-142 knockdown inhibited the PI3K/AKT pathway in NPC cells. CONCLUSIONS: MicroRNA-142 is highly expressed in NPC. MicroRNA-142 enhances the proliferative and invasive capacities of NPC cells by inhibiting PTEN expression, thus promoting NPC development.

[Continuous renal replacement therapy combined with extracorporeal membrane oxygenation for pediatric cardiopulmonary failure].

Objective: To explore the effectiveness and safety of continuous renal replacement therapy (CRRT) combined with extracorporeal membrane oxygenation (ECMO) on rescuing pediatric patients with cardiopulmonary failure. Methods: The medical records of patients treated with ECMO admitted to pediatric intensive care unit (PICU) in Shanghai Children's Hospital from December 2015 to November 2017 were retrospectively extracted. There were 14 patients treated with ECMO combined with CRRT (ECMO+ CRRT group) due to acute kidney injury (AKI) or fluid overload, while 11 cases treated with ECMO only. The demographics and clinical characteristics of patients, the indications, details and complications of ECMO and CRRT support, and the survival rates were analyzed. Results: A total of 25 cases including 15 boys and 10 girls with cardiopulmonary failure treated with ECMO were enrolled in this study, whose median age and body weight were 9 (1-117) months and 10 (2-42) kg. The median duration of ECMO support was 199.2 h, and the median duration of CRRT was 78.6 h. Among the 14 cases in ECMO + CRRT group, 12 cases were treated with CRRT connected to ECMO pipeline, and 2 other cases were treated with independently operated CRRT. The serum level of creatinine was significantly higher in ECMO+ CRRT group than that in ECMO group (53 (22- 126) vs. 29 (12- 92) µmol/L, Z=-2.208, P=0.043). There was no significant difference in running time between ECMO+CRRT group and ECMO group ((257±203) vs. (122± 83) h, t=-2.062, P=0.051). And the incidence of thrombocytopenia was higher in ECMO+CRRT group than that in ECMO group (10/14 vs. 3/11 , χ(2)=4.812, P=0.028). There were no differences in the successful weaning rate and discharge survival rate between ECMO + CRRT and ECMO group (9 vs. 8, χ(2)= 0.203, P= 0.652 and 8 vs. 8, χ(2)= 0.659, P= 0.417, respectively). Conclusion: The combination of CRRT and ECMO is an effective and safe treatment to alleviate fluid overload and improve kidney function in pediatric patients with cardiopulmonary failure.