Objective To investigate the effect of co-expression of neuropilin-1(Nrp-1)and transforming growth factor-β(TGF-β)on regulatory T cell(Treg)-mediated immunosuppression. Methods CD4+CD25+Tregs were isolated from the spleens of male Balb/c mice. CD4+CD25+Tregs were blocked with various doses of Nrp-1 antibody(Ab-Nrp-1,0.5,5,10 μg/ml)for 24 hours with anti-CD3/CD28 and lipopolysaccharide(LPS)stimulation, and expression of Nrp-1 and TGF-βwas determined by flow cytometry. Meanwhile,CD4+CD25+Tregs were cultured with different doses of Ab-Nrp-1 for 1 hour,and co-cultured with CD4+CD25-T cell for 12,24 and 48 hours respectively,the proliferative activity of CD4+CD25-T cells was analyzed by microplate reader. Results Compared to control group,the expressions of Nrp-1 and TGF-β were significantly increased under anti-CD3/CD28 and LPS stimulation(both P<0.05),and treatment with Ab-Nrp-1 markedly inhibited the expression of TGF-β in a dose-dependent manner(P<0.05). The normal Treg had the potential to inhibit the proliferation of CD4+CD25-T cells(P<0.05),while various doses of Ab-Nrp-1 had the ability to reverse the immunosuppressive function of CD4+CD25+Treg in a dose-and time-dependent response manner,5μg/ml has the strongest ability,expecially after 24 hours. Conclusion Treg cell plays an important role in mediating immunosuppressive response via membrane associated TGF-β,and co-expression of Nrp-1 can markedly promote the immunosuppressive function.

Objective To evaluate the efficacy and safety of continuous infiltration of Lidocaine in joint replacement surgery.Methods From May 2013 to October 2013,patients scheduled to undergo total hip or total knee arthroplasty were randomized into two groups:the local infiltration analgesia group received continuous infiltration of Lidocaine while the other group received PCIA filled with fentanyl after surgery.The equipments were removed 48 hours after the surgery.The visual analogue scale score at five points (immediate postoperative,24 hours after the surgery while resting,24 hours after the surgery while exercising,48 hours after the surgery while resting,48 hours after the surgery while exercising) were recorded and if the score was higher than 4,analgesics wound be given to the patients.The vital sign,blood test,ECG,the circumference of lower limbs,the range of motion of the joint,the rehabilitation and complications were also recorded.Results 42 patients were included,11 male and 31 female.There were 25 patients and 36 total knee arthroplasties.17 patients underwent a total of 19 hip arthroplasties.The demographic data,the diagnosis and the surgery type were comparable between two groups.The VAS scores at immediate postoperative,24 hours and 48 hours after the surgery while resting,the average dose of analgesics and the complication rate were statistically different be tween two groups.However,the VAS scores at 24 hours after the surgery and 48 hours after the surgery while exercising,the change of the circumferences of the lower limb,the range of motion of the joint,the rehabilitation satisfactory rate and length of stay were comparable between two groups,while no significant difference was observed.One patient in the PCIA group suffered from incision fat liquefaction and healed after three weeks.There were no infection and subcutaneous hydrocele in both groups.Conclusion Continuous infiltration of Lidocaine is more effective than the PCIA while resting after joint replacement surgery and no inferior to it while exercising.It can decrease the amount of Opioid.

Objective To compare the clinical efficacy of postoperative analgesia between intercostal nerve freezing and con‐trolled intravenous analgesia in patients of thoracic surgery .Methods 80 patients of thoracic surgery from January 2012 to June 2013 were randomly divided into two groups :Intercostal nerve cryotherapy group (frozen group n=40) and intravenous analgesia group(control group n=40) .Frozen group :the intercostal incision and down each one intercostal and chest tube placement of inter‐costal nerve roots were frozen before sternal closure ;control group :intravenous analgesia pump were used postoperative .According to VAS method to evaluate pain level and observe adverse reactions ,complications and analgesic drug usage of postoperative pa‐tients .Results The analgesic effect of frozen group was better than that of control group within five days after thoracotomy .Com‐pared with the control group ,the incidence of adverse reactions ,postoperative complications ,and analgesic drug usage was signifi‐cantly reduced in frozen group ,there was a significant difference between the two groups (P<0 .05) .Postoperative follow‐up dis‐play :intercostal nerve area in some patients may appear numbness ,dysesthesia ,etc .,but the above situation can return to normal gradually .Conclusion The analgesic effect of intercostal nerve cryotherapy for thoracotomy patients is excellent ,and with few side effects and good safety ,and it is worthy of promotion .

Objective To compare the clinical efficacy of high-flow nasal cannula oxygen therapy (HFNC) with non-invasive positive pressure ventilation (NPPV) in patients with traumatic cervical spinal cord injury complicated with acute respiratory failure (ARF).Methods A prospective randomized controlled trial was performed in EICU of the First Affiliated Hospital of Zhengzhou University from May 2016 to January 2018.One hundred sixty-eight consecutive patients with traumatic cervical spinal cord injury complicated with ARF,who did not respond to conventional oxygen therapy,were assigned to the HFNC or NPPV treatment group sequenced by the random number table.The baseline clinical characteristics of randomized participants and respiratory frequency (RR),PaCO2,mean arterial pressure (MAP) at 1,12,24,48 h after treatment were evaluated.Comfortable scale,tracheal intubation rate within 28 d,duration of mechanical ventilation,length of stay in ICU and mortality rate were compared as well.Results There was no significant differences in baseline clinical characteristics,such as sex,age.between the two groups (P＞0.05).RR and PaCO2 were lower in the HFNC group at all time point.In addition,the HFNC group had significantly lower PaCO2 than the NPPV group at 24 and 48 h after treatment (P＜0.01);Oxygenation index (PaO2/FiO2) was improved in both groups,and the HFNC group had superior oxygenation index than the NPPV group at 12,24,48 h after treatment (P＜0.01).Furthermore,the HFNC group had better comfort scale (6.93±0.71 vs 4.29±0.93,P＜0.01),shorter length of stay in ICU and duration of mechanical ventilation compared to the NPPV group (P＜0.01).There was no significant differences in tracheal intubation rate and mortality rate between the two groups (P＞0.05).Conclusions In addition to the superior efficacy in improving respiratory function and shortening length of stay in ICU,HFNC was well tolerated by patients with traumatic cervical spinal cord injury complicated with ARF,and could be recommended in clinical practice.

Clinical data of 93 patients with severe craniocerebral injury admitted in the Emergency Intensive Care Unit (EICU) of the First Affiliated Hospital of Zhengzhou University from September 2016 to September 2018 were retrospectively analyzed. Forty six patients received 10% hypertonic salt solution 60 ml (hypertonic salt group) and 47 patients received 20% mannitol 125 ml (mannitol group) for relieving early postoperation cerebral edema. The changes of intracranial pressure, central venous pressure, heart rate, mean arterial pressure (MAP), urine volume and serum sodium level at 2, 4 and 6 h after dehydrating agents were compared between two groups. There were no significant differences in the intracranial pressure, central venous pressure, heart rate and urine volume between two groups at 2, 4 and 6 h after the first dehydration treatment (all P>0.05). The MAP values of the two groups were (88±11) and (80±10), (85±10) and (78±9), (79±12) and (73±13) mmHg (1 mmHg=0.133 kPa) at 2, 4 and 6 h after the first dehydration treatment; and the serum sodium levels were (145±5) and (136±4), (144±6) and (133±5), (140±5) and (135±4) mmol/L, respectively. There were significant differences between two groups (all P<0.05). It is suggested that hypertonic salt can reduce intracranial pressure and increase cerebral perfusion better than mannitol in severe craniocerebral injury.

Objective:To explore the effect of Hsp22 on the activation of cardiac fibroblasts stimulated by TGFβ1 and its possible molecular mechanism.Methods:Cardiac fibroblasts of adult mice were isolated and cultured, and stimulated with TGFβ1 to induce fibroblast activation. Fibroblasts were incubated with Hsp22 of different concentrations (1, 2, 4, 8, 10 μg/mL) for 24 h, and their activation, proliferation and secretion were observed. CCK8 kit was used to detect cell proliferation. RT-PCR was used to detect the transcription of fibrogenic factor. Immunofluorescence was used to detect the expression of α-SMA protein. Immunoblotting was used to detect the possible signal protein.Results:CCK8 results showed that fibroblast increased significantly after TGFβ1 stimulation ( P<0.05). The expression of α-SMA in fibroblasts and the transcription of fibrosis-related genes increased significantly after TGFβ1 stimulation ( P<0.05). Different concentrations (1, 2, 4, 8, and 10 μg/mL) of Hsp22 all inhibited the proliferation of fibroblasts significantly (( P<0.05). Eight μg/mL and 10 μg/mL Hsp22 inhibited the expression of α-SMA ( P<0.05). and reduced the transcription of fibrosis-related genes ( P<0.05). Immunoblotting results indicated that after induced by TGFβ1, the expression of WNT and β-catenin, the phosphorylation level of GSK3β, and the nuclear translocation of β-catenin increased ( P<0.05). Ten μg/mL Hsp22 inhibited the expression of WNT and β-catenin, and reduced the phosphorylation of GSK3β the nuclear translocation of β-catenin and the phosphorylation of smad2 and smad3( P<0.05). Conclusions:Hsp22 could block TGFβ1-induced fibroblast activation, proliferation and secretion via inhibiting the WNT/β-catenin signaling pathway.

Objective:To explore the efficacy and safety of sivelestat, a neutrophil elastase (NE) inhibitor, in the treatment of acute lung injury (ALI) in the intensive care unit (ICU).Methods:A retrospective analysis was performed on 171 patients with ALI in the ICU of the First Affiliated Hospital of Zhengzhou University from June 2020 to June 2021, including 77 patients in the sivelestat group and 94 patients in the conventional treatment group. Acute physiology and chronic health evaluation (APACHE) Ⅱ score, Murray lung injury score, oxygenation index (PaO 2/FiO 2 ratio), inflammatory cytokines (IL-6, IL-10, TNF-α), ventilator-free days (VFD), the length of ICU stay, and the 28-day mortality were collected to assess the efficacy of sivelestat. At the same time, adverse reactions and laboratory test results within 30 days after the use of sivelestat were recorded to assess the safety. Results:Compared with conventional treatment, oxygenation index, Murray lung injury scores, IL-6, IL-10, and TNF-α were significantly improved after 7 days of sivelestat treatment. Compared with the conventional treatment group, the VFD was significantly longer ( P = 0.0119) and the length of ICU stay was significantly shorter ( P = 0.0269) in the sivelestat group. The mortality was 14.29% in the sivelestat group and 22.34% in the conventional treatment group and, with no statistically significant. In the meantime, sivelestat did not increase adverse reactions within 30 days after treatment. Conclusions:Sivelestat treatment is safe and more effective than conventional treatment for ALI patients in the ICU.

Objective: To investigate the effect of miR-23b/PTEN molecular axis on radio-sensitivity of lung cancerA549 cells and its mechanism. Methods: Lung cancer cell lines NCI-H1650, NCI-H175, Calu-1, LT-P-A-2, MSTO-211H, A549 and human normal lung epithelial cell line BEAS-2B were selected. The expression level of miR-23b in lung cancer cell lines was detected by qPCR. Dual-luciferase reporter gene assay was used to verify the relationship between miR-23b and PTEN. Plasmids miR-23b mimics, miR-23b inhibitor and pcDNA3.1-PTEN were transfected intoA549 cells by lipofection; PTEN expression levels in cells was detected by WB. CCK-8, Transwell andAnnexin V-FITC/PI staining flow cytometry were used to detect the effect of miR-23b/PTEN axis on proliferation, invasion and apoptosis ofA549 cells treated with 60Co γ-ray. Results: miR-23b was upregulated in lung cancer cell lines with the highest expression in A549 cells (P<0.05 or P<0.01). Knockdown of miR-23b reversed the inhibitory effect of 3 Gy 60Co γ-rays on proliferation and invasion of A549 cells, and induced apoptosis (P<0.05 or P<0.01). Dual-luciferase reporter gene assay results confirmed that miR23b could negatively regulate PTEN (P<0.05). Furthermore, knockdown of miR-23b up-regulated PTEN expression level, and furhter enhanced the inhibitory effect of 3 Gy 60Co γ-ray on the proliferation and invasion of A549 cells as well as induced apoptosis of A549 cells (P<0.05 or P<0.01). Conclusion: Knockdown of miR-23b can enhance the radio-sensitivity of A549 cells, the mechanism of which is that 60Co γ-ray down-regulates the inhibitory effect of miR-23b on PTEN, thereby inhibiting the proliferation, invasion and inducing apoptosis ofA549 cells.

Objective:Taking emergency department (ED) as a starting point, to analyze the epidemiological characteristics and mortality risk factors of sepsis, and to provide evidences for ED to carry out the strategy of "three early and two lower" for sepsis.Methods:Based on the ED and inpatient medical record management information platform of Tianjin Medical University Gernal Hospital, adult ED patients with sepsis from January 1, 2017 to December 31, 2020 were included according to the third international consensus definitions for sepsis and septic shock in 2016 and the consensus of Chinese experts on early prevention and blocking of sepsis in 2020. The epidemiological characteristics of patients were retrospectively analyzed. Chi-square test was used to compare the difference of age, sex, hospitalization times, length of stay, hospitalization cost and infection location between dead patients and survival patients, and a stepwise logistic regression model was used to analyze the influencing factors of mortality in hospitalized patients with ED sepsis.Results:A total of 7 494 patients with sepsis in ED were included in this study, and the annual and monthly component ratios varied from 3.8‰ to 6.1‰ and 2.0‰ to 9.0‰, respectively. The main characteristics of patients with sepsis in ED were as follows: 40-69 years old (46.0%), male (59.0%), mostly diagnosed with sepsis (96.8%), mainly treated with urban health insurance (59.6%), and ED diagnosis and treatment fees of 2 000-8 000 Yuan (51.1%). The mortality of hospitalized patients with ED sepsis was 24.4% and that of hospitalized patients with septic shock was 28.8%. The main characteristics of hospitalized patients with ED sepsis were as follows: most of them were male (56.2%) patients over 70 years old (56.0%), most of them were diagnosed with sepsis (94.0%) and hospitalized for the first time (76.0%), the median hospitalization time was 15 d, most of them were hospitalized under urban health insurance (65.2%), and the median hospitalization fees was 47 000 Yuan. The risk factors of death were influenced by age and length of stay. Patients aged 70 years or older had a higher risk of death than those aged from 18 to 39 years, and patients with a length of stay of more than 7 d had a lower risk of death than those with a length of stay of shorter than 7 d. The primary infection focus were mainly respiratory and urinary systems, while the death rate of patients with hematological and abdominal infections was relatively high, and the difference was statistically significant ( P<0.01). Respiratory and abdominal infections were risk factors for death in patients with ED sepsis. Conclusions:The composition ratio of sepsis in ED patients is not regular in time, so vigilance of sepsis in elderly men and patients with respiratory system, blood system, urinary system and abdominal infections should be constantly raised. Patients with sepsis who are older, hospitalized more frequently, hospitalized for a shorter time, and infected in the respiratory system or abdomen have a higher risk of death.