Objective To investigate characteristics and alternation of cerebral evoked potentials (CEP) response to esophageal mucosal acid exposure and distention in patients with non-erosive gastro-oesoph- ageal reflux disease (NERD) and in healthy subjects,and to study the mechanism of visceral hypersensitivity in NERD.Methods Twenty-one NERD patients and 10 volunteers were recruited.Mechanical distention stimulation and acid perfusion of the esophagus were performed using the balloon-affixed and polyvinyl multi- lumen catheter.First,maximally tolerated pain thresholds of all subjects were recorded,then esophageal mechanical stimulation with a 75% of maximal tolerated intensity and a frequency of 0.2 Hz was performed altogether 64 times by means of a computer-controlled barostat.The alternation of esophageal CEP was recorded before and after acid perfusion with a multichannel international 10-20 system of electroencephalography. Experimental data was analyzed by student's t-test and one way analysis of variance.Results Esophageal mu- cosal distention may evoke recognizable and reproducible and multi-peak CEP.The latencies for N1,P1 and N2 in volunteers were (246?77),(388?84)and (502?78) ms,CEP morphology of NERD patients was charac- terized by randomly distributed patterns,and the latencies for N1 ,P1 and N2 were (192?46),(293?76) and (440?79)ms,significantly shorter for mechanical stimulation compared with those of control group respectively (all P value

Objective To investigate the effect of esophageal mucosal acid exposure on visceral sensation of patients with non-erosive gastroesophageal reflux disease (NERD) and to evaluate the role of visceral hypersensitivity in NERD pathogenesis. Methods We recruited 21 NERD patients and 10 normal healthy volunteers. Mechanical distentions stimulation and acid perfusion through esophagus were performed using the balloon-affixed and polyvinyl multilumen catheter. Esophageal visceral perception thresholds were examined before and after acid perfusion with esophageal balloon distention by means of a computer-controlled barostat. Results As compared with healthy subjects, NERD patients demonstrated significantly lower initial perception threshold and maximally tolerated pain threshold (P

Objective To observe the effect of total intravenous anesthesia (TIVA) on intrapulmonary shunt fraction and arterial oxygenation during one-lung ventilation (OLV) for thoracoscope surgery.Methods Forty patients scheduled for thoracoscope surgery were randomly assigned to two groups ( n =20),group of TIVA (A) and group of intravenous anesthesia combined with inhalational anesthesia(B).After inducing and intubating,patients were assigned to maintenance of anesthesia with propofol ( group A)or with sevoflurane ( group B) in order to maintain a BIS between 40 and 60.Mean arterial pressure (MAP),heart rate (HR),SpO2 and Paw were measured in four phases,always in the lateral position,10min after beginning two-lung ventilation (TLV),15 min after beginning OLV (OLV + 15 ),30 rain after beginning OLV ( OLV + 30) and 60 min after beginning OLV ( OLV + 60).Blood samples were drawn simultaneously and analyzed within 5 min.The Qs/Qt at each phase was calculated.Adverse events including hypotension,bradycardia,hypoxemia,delayed emergence and restlessness in recovery period were recorded.Results In all patients,a decrease in PaO2 and an increase in the Qs/Qt occurred during OLV were observed.But PaO2 values in group A were significantly higher than those in group B ( 177 ±88 vs 125 ±63;150 ±65 vs 110 ±67;188 ±69 vs 128 ±52) ( P ＜0.05).The Qs/Qt in group B was significantly higher than those in group A (34.2 ±5 vs 28.8 ±2;38.4 ±8 vs 32.1 ±6;37.1 ±2 vs 29.5 ±2,P ＜0.05).MAP values in group A were significantly lower than those in group B at the phase:OLV + 15 and OLV +30(72 ± 10 vs 88 ± 14;74 ± 12 vs 89 ± 10) ( P ＜ 0.05 ).The incidence of hypotension and delayed emergence in group A was higher than those in group B ( 10 case vs 4 case;9 case vs 2 case).The incidence of restlessness in recovery period in group B was more than those in group A (9 case vs 3 case).The differences between two groups were significant ( P ＜ 0.05).Conclusions Compared with sevoflurane-sufentanyl combined anesthesia,TIVA with propofol can efficiently decrease intrapulmonary shunt fraction and improve arterial oxygenation during OLV for thoracoscope surgery,which is good for the prevention of hypoxemia.

Objective To explore the effects of removing-stasis and resuscitating methods on patients with severe cerebral injury. Methods Retrospective analysis was performed with clinical data of 47 patients. All 47 patients were recruited into a control group(n=21) and a treatment group(n=26). The control group was treated with conventional western medicines; while the treatment group was additional treated with traditional Chinese medicine on the basis of the control group. Results The rate for resuscitation after one week's treatment was 73.08% and 57.14% in the treatment group and the control group respectively, showing significant differences (P<0.01). The total effective rate was 76.92% and 61.90% in the treatment group and the control group respectively, also showing significant difference (P<0.05) . Conclusion The method of removing-stasis and resuscitating can promote severe cerebral injury patients regain their consciousness, and improve their prognosis.

Objective:To explore the effect of α7 nicotinic acetylcholine receptor (α7nAchR) and changes of inflammatory factors during vagus nerve electrical stimulation in ischemic stroke model mice.Methods:Ninety SPF grade mice were randomly divided into sham operation+ vagus nerve electrical stimulation group (sham+ VNS group), model group (permanent middle cerebral artery occlusion group, pMCAO group), model+ vagus nerve electrical stimulation (pMCAO+ VNS group) and model group+ α7nAchR agonist group (pMCAO+ P group), model + vagus nerve electrical stimulation+ α7nAchR antagonist (pMCAO+ VNS+ A group), model+ vagus nerve electrical stimulation+ α7nAchR antagonist placebo group (pMCAO+ VNS+ AC group), with 15 mice in each group. The changes of vital signs of mice in each group were monitored during modeling.At 7, 14 and 21 days after successful modeling, neurological severity score (NSS) and adhesive removal test were used to evaluate the neurological deficit of mice.Immunofluorescence and Western blot were used to detect the expression of α7nAchR and its neural cell localization. ELISA was used to detect the level of TNF-α and IL-6. Prism 8.0 software was used for statistical analysis, and one-way ANOVA was used to analyze the physiological parameters during modeling.Repeated measurement ANOVA was used to compare the neurobehavioral score results, and t-test was used to compare the protein level and fluorescence intensity. Results:(1)The results of repeated measurement ANOVA showed that the interaction between group and time in NSS score was not significant ( F=0.91, P>0.05), and the group main effect ( F=46.68, P<0.05) and time main effect ( F=25.56, P<0.05) were significant. The results of Tukey's test showed that the NSS scores of pMCAO+ VNS group and pMCAO+ P group were significantly lower than those of pMCAO group (both P<0.05). There was no significant difference between pMCAO+ P group and pMCAO+ VNS group ( P>0.05). The NSS scores in pMCAO+ VNS+ A group were higher than that in pMCAO+ VNS group ( P<0.05), and significantly lower than that in pMCAO+ VNS+ AC group ( P<0.05). In the adhesive removal test, the interaction between group and time in the adhesive tape contact time and tear off time of mice was not significant ( F=0.67, 0.71, all P>0.05), and the group main effect ( F=30.12, 42.46, all P<0.05) and time main effect ( F=52.18, 47.34, all P<0.05) of mice in each group were significant.Tukey's test showed that the adhesive removal test on the 21st day, the adhesive tape contact time and tear off time of pMCAO+ VNS group were significantly shorter than those of pMCAO group (both P<0.05), and there was no significant difference between pMCAO+ P group and pMCAO+ VNS group (both P>0.05). (2)Western blot showed that compared with pMCAO group (0.36±0.01), the expression of α7nAchR in pMCAO+ VNS group (0.83±0.03) and pMCAO+ P group (0.67±0.02) increased ( t=13.53, 16.08, both P<0.01). The expression of α7nAchR in PCAO+ VNS+ A group (0.37±0.01) was significantly lower than that in PCAO+ VNS group ( t=12.88, P<0.01). Immunofluorescence results also showed that compared with pMCAO group (3.75±0.19), the expression of α7nAchR in pMCAO+ VNS group (8.96±0.48) and pMCAO+ P group increased (8.17±0.64) ( t=10.04, 6.67, both P<0.05). Immunofluorescence results also showed that compared with the pMCAO group (3.75±0.19), the expression of α7nAchR protein in the brain tissue of mice in the pMCAO+ VNS group and pMCAO+ P group increased ((8.96±0.48), (8.17±0.64), t=10.04, 6.67, all P<0.05). (3)The results of ELISA showed that compared with pMCAO group, the levels of TNF-a and IL-6 in serum and tissue supernatant of pMCAO+ VNS group and pMCAO+ P group were significantly lower than those of pMCAO group ( t=23.28, 15.30, 12.26, 11.08; all P<0.05). TNF in serum and tissue supernatant of mice in pMCAO+ VNS+ A group The levels of IL-6 in serum and tissue supernatant were significantly higher than those in pMCAO+ VNS group ( t=12.70, 11.01, 11.69, 17.37; all P<0.05) and pMCAO+ VNS+ AC group ( t=12.29, 11.07, 14.61, 29.27; all P<0.05). Conclusion:VNS may reduce inflammation by increasing the expression of α7nAchR protein in brain tissue, thereby playing a certain neuroprotective effect on ischemic stroke.

Objective To investigate the effect of HCV RNA on virological and immunological response to highly active antiretroviral therapy (HAART),liver function and blood lipid levels in HIV/HCV co-infected patients.Methods In a cohort study,275 HIV/HCV co-infected former blood donors receiving HAART were followed up every six month in Henan province in China.HCV RNA,HIV RNA,CD+4 T cell counts,indexes of liver function and lipid levels were periodically tested.The differences of HIV viral load suppression,immunological response,liver injury and blood lipid levels between HCV RNA positive group and negative group were compared by x2 test and two independent-samples tests.Result There was no significant difference of HIV viral load suppression between HCV RNA positive group and HCV RNA negative group six-month treatment (45.6% vs.38.5% ,X2=1.150,P>0.05) and CD+4 T cell counts before (286 cells/μ1 vs.209 cells/μ1,Z=0.734,P=0.463)and after 6-month (310 cells/μ1 vs.362 cells/μl,Z=0.562,P=0.574) ,12-month(378 cells/μ1 vs.289 cells/μ1,Z=1.091,P=0.275),18-month(363 cells/μ1 vs.288 cells/μl,Z=1.435,P=0.151) ,24-month(413 cells/μ1 vs.348 cells/μ1,Z=0.939,P=0.348) HAART.The mean levels of serum ALT (55.0 U/L vs.29.5 U/L,Z=6.789,P<0.01),AST(46.0 U/L vs.33.0 U/L,Z=4.890,P<0.01)、TBIL(9.3 mmol/L vs.7.2 mmol/L,Z=3.748,P<0.01)were significantly higher in HCV RNA positive group than that in HCV RNA negative group.HCV RNA was the independent variables associated with liver injury after HAART (aOR=3.8,P<0.01).The serum triglyceride level was higher in HCV RNA positive group than that in HCV RNA negative group(1.2 mmoL/L vs.1.4 mmol/L,Z=1.936,P=0.043) .The serum HDL level was higher in HCV RNA positive group than that in HCV RNA negative group (1.5 mmol/L vs.1.3 mmol/L,Z=2.251,P=0.024).Conclusions HCV RNA does not affect HIV virological responses to HAART and CD+4 T recovery.HCV RNA is an independent risk factor associated with liver injury in HIV/HCV co-infected patients receiving HAART,but appears to provide significant protection against HAART-ieduced hyperlipidemia.

OBJECTIVETo revalidate the conversion factor（CF）for the conversion of BCR-ABL （P210）transcript levels to the international scale（BCR- ABLIS）in chronic myeloid leukemia（CML） which validated before.

METHODSPeking University People's Hospital（PKUPH）prepared the exchange samples for revalidation of CFs of 15 laboratories which validated nine or eighteen months ago. The fresh BCR-ABL（P210）（+）bone morrow or peripheral blood nucleated cells were diluted with BCR-ABL （P210）（-）cells to achieve different BCR- ABL levels, totally 16 sets and 24 samples per set were prepared. TRIzol reagent was added in each tube. Each laboratory tested BCR-ABL transcript levels of one set of samples. Agreement between BCR-ABLIS of each laboratory and PKUPH was assessed by the Bland- Altman method. For laboratories which did not meet the criteria of revalidation, linear regression equation was derived after the samples with maximum BCR-ABL deviation were removed until R²>0.98, then new CF was calculated.

RESULTS10 laboratories met the revalidation criteria with both bias within ±1.4 fold and 95% limits of agreement within ±6 folds, and their CFs still could be used for accurately conversion of BCR-ABLIS. New CFs were recalculated as of 1.8-6.3 folds of their previous CFs in 5 laboratories not met the criteria.

CONCLUSIONRevalidation of CF by sample exchange among laboratories was necessary for accurate and continuous application of BCR-ABLIS, which not only tested the validity of CF acquired before but also calculated new available CFs for those with invalid CFs.

OBJECTIVE: To review the research progress of the biomechanical study of the Bristow-Latarjet procedure for anterior shoulder dislocation. METHODS: The related biomechanical literature of Bristow-Latarjet procedure for anterior shoulder dislocation was extensively reviewed and summarized. RESULTS: The current literature suggests that when performing Bristow-Latarjet procedure, care should be taken to fix the bone block edge flush with the glenoid in the sagittal plane in the direction where the rupture of the joint capsule occurs. If traditional screw fixation is used, a double-cortical screw fixation should be applied, while details such as screw material have less influence on the biomechanical characteristics. Cortical button fixation is slightly inferior to screws in terms of biomechanical performance. The most frequent site of postoperative bone resorption is the proximal-medial part of the bone block, and the cause of bone resorption at this site may be related to the stress shielding caused by the screw. CONCLUSION There is no detailed standardized guidance for bone block fixation. The optimal clinical treatment plan for different degrees of injury, the factors influencing postoperative bone healing and remodeling, and the postoperative osteoarticular surface pressure still need to be further clarified by high-quality biomechanical studies.
Humans ; Shoulder Dislocation/surgery* ; Shoulder Joint/surgery* ; Biomechanical Phenomena ; Joint Instability/surgery* ; Bone Resorption ; Arthroscopy/methods*

Aging-elevated DNMT3A R882H-driven clonal hematopoiesis (CH) is a risk factor for myeloid malignancies remission and overall survival. Although some studies were conducted to investigate this phenomenon, the exact mechanism is still under debate. In this study, we observed that DNMT3A R878H bone marrow cells (human allele: DNMT3A R882H) displayed enhanced reconstitution capacity in aged bone marrow milieu and upon inflammatory insult. DNMT3A R878H protects hematopoietic stem and progenitor cells from the damage induced by chronic inflammation, especially TNFα insults. Mechanistically, we identified that RIPK1-RIPK3-MLKL-mediated necroptosis signaling was compromised in R878H cells in response to proliferation stress and TNFα insults. Briefly, we elucidated the molecular mechanism driving DNMT3A R878H-based clonal hematopoiesis, which raises clinical value for treating DNMT3A R882H-driven clonal hematopoiesis and myeloid malignancies with aging.

Objective: To construct and identify a mouse model with conditional knockout (cKO) of p75 neurotrophin receptor (p75NTR-cKO) gene in epidermis cells by Cre-loxP system. Methods: Five p75NTR^flox/flox transgenic C57BL/6J mice (aged 6-8 weeks, male and female unlimited, the age and sex of mice used for reproduction were the same below) and five keratin 14 promotor-driven (KRT14-) Cre^{+ /-} transgenic C57BL/6J mice were bred and hybridized via Cre-loxP system. Five p75NTR^flox/+ ·KRT14-Cre^{+ /-} mice selected from the first generation of mice were mated with five p75NTR^flox/flox mice to obtain the second generation hybrids. After the second generation mice were born 20-25 days, the parts of the mice tail were cut off to identify the genotype by polymerase chain reaction method. Four p75NTR gene complete cKO mice (6 weeks old) and 4 wild-type mice (6 weeks old) were selected and sacrificed respectively. The abdominal skin tissue and brain tissue were excised to observe the expression of p75NTR in the two tissue of two types of mice by immunohistochemical staining. The abdominal skin tissue of two types of mice was obtained to observe the histomorphological changes by hematoxylin and eosin staining. Results: (1) Twenty second generation mice were bred. The genotype of 4 mice was p75NTR^flox/flox·KRT14-Cre^{+ /-}(p75NTR^-/-), i. e. p75NTR gene complete cKO mice; the genotype of 5 mice was p75NTR^flox/+ ·KRT14-Cre^{+ /-}, i. e. p75NTR gene partial cKO mice; the genotype of 5 mice was p75NTR^flox/flox·KRT14-Cre^-/-, and that of 6 mice was p75NTR^flox/+ ·KRT14-Cre^-/-, all of which were wild-type mice. (2) The expression of p75NTR was negative in skin epidermis tissue of p75NTR gene complete cKO mice, while numerous p75NTR positive expression was observed in skin epidermis tissue of wild-type mice. Abundant p75NTR positive expression was observed in brain tissue of both wild-type mice and p75NTR gene complete cKO mice. (3) There was no abnormal growth of skin epidermis tissue in both wild-type mice and p75NTR gene complete cKO mice, with intact hair follicle structure. Conclusions Applying Cre-loxP system can successfully construct a p75NTR-cKO mice model in epidermis cells without obvious changes in skin histomorphology.