Objective To investigate the inhibitory effect of Tongsai Granules(TSG)on macrophage-mediated inflammatory response to alleviate acute exacerbation of chronic obstructive pulmonary disease(AECOPD)in rats and explore the underlying mechanism.Methods Twenty-four rats were divided into control group,AECOPD model group,TSG treatment group,and moxifloxacin+salbutamol(MXF+STL)treatment group.In the rat models of COPD,AECOPD was induced by nasal instillation of Klebsiella pneumoniae on day 3 of week 9 after modeling,and saline,TSG or MXF+STL were administered via gavage on days 1 and 2 and days 4 to 7 of week 9.After the treatments,lung tissues were collected for examining for pathologies and expressions of inflammatory markers,MMP2,and MMP9.In cultured macrophage MH-S cells with LPS stimulation,the effect of TSG-medicated serum on IL-1β,IL-6,TNF-α,COX-2,and iNOS expressions and phosphorylation levels of p38,p-p62,LC3,FoxO3a,and mTOR were evaluated.Results TSG significantly improved lung pathologies and lung function in AECOPD rats by reducing bronchial wall thickness and mean alveolar linear intercept,increasing alveolar numbers,and reducing pulmonary expression of IL-1β,IL-6,TNF-α,MMP2 and MMP9.In MH-S cells,TSG significantly suppressed LPS-induced expressions of inflammatory cytokines,COX-2 and iNOS.Serum pharmacology coupled with network pharmacology identified 10 chemical components in TSG-medicated serum,and functional analysis of their 466 targets suggested that the therapeutic effect of TSG on AECOPD was mediated primarily by luteolin and quercetin,which regulate the MAPK,mTOR,FoxO,and autophagy pathways.In MH-S cells,luteolin significantly inhibited LPS-induced inflammatory responses and expressions of p-p38,FoxO3a,mTOR,p-p62 and LC3.Conclusion TSG reduces macrophage-mediated inflammatory responses to alleviate AECOPD in rats possibly by modulating p38,mTOR,and FoxO3a pathways and inhibiting autophagy.

Objective:To investigate the effects of Five-Element music intervention on anxiety, depression, and weaning successful rate in intensive care unit (ICU) patients with difficult weaning.Methods:A prospective randomized controlled trial was conducted. Eighty patients with difficulty in weaning accompanied by anxiety and depression disorders admitted to the respiratory intensive care unit (RICU) of Henan Provincial People's Hospital from January 2019 to January 2021 were enrolled as research subjects. They were divided into an observation group and a control group using a random number table method, 40 cases in each group. The patients in the control group received routine respiratory rehabilitation treatment, with daily assessments of weaning and gradual reduction of mechanical ventilation support until weaning was achieved. The patients in the observation group received additional Five-Element music therapy, in addition to routine respiratory rehabilitation treatment. Based on the clinical manifestations of the patients and applying traditional Chinese medicine theory for syndrome differentiation, music therapy was applied accordingly. The intervention used traditional Chinese Five-Element music (composed by Shi Feng, published by China Medical Electronic Audio and Visual Publishing House). Baseline data including the gender, age, etiology of acute respiratory distress syndrome (ARDS), and acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score of patients were recorded. A twelve-lead synchronous Holter monitor continuously recorded the R-wave dominant electrocardiogram signal for 24 hours or more. Heart rate variability (HRV) indices [standard deviation of all normal sinus R-R intervals (SDNN), standard deviation of 5-minute average R-R intervals (SDANN), percentage of continuous normal R-R intervals with differences greater than 50 ms (PNN50), and the root mean square of successive differences in adjacent R-R intervals (RMSSD)] were calculated, as well as HRV frequency domain parameters [low-frequency band (LF, 0.05-0.15 Hz), high-frequency band (HF, 0.16-0.50 Hz), and LF/HF ratio]. Additionally, the incidence of delirium, weaning successful rate, reintubation rate within 7 days, length of ICU stay, and hospital mortality were documented.Results:There were 8 cases in the control group dropping out, and resulting in 32 were participated, and the 40 cases in the observation group were all enrolled the analysis. There were no statistically significant differences in terms of gender, age, ARDS etiology, and APACHEⅡ score between the two groups, indicating balanced baseline data for comparison. There were also no significant differences in HRV indices and frequency domain parameters before the intervention between the two groups. After the intervention, the observation group showed significant increases in HRV indices and frequency domain parameters as compared with the control group [SDNN (ms): 77.21±11.75 vs. 63.81±13.50, SDANN (ms): 83.51±19.45 vs. 50.40±14.55, PNN50: (10.75±3.42)% vs. (7.79±3.13)%, RMSSD (ms): 47.15±6.57 vs. 31.74±6.37, HF (ms 2/Hz): 568.50±144.48 vs. 496.94±151.56, LF (ms 2/Hz): 840.13±110.76 vs. 587.81±144.51, LF/HF ratio: 1.60±0.60 vs. 1.22±0.21, all P < 0.05]. Seventeen patients in the control group developed delirium, including 12 cases of hyperactive delirium, 3 cases of hypoactive delirium, and 2 cases of mixed-type delirium; whereas in the observation group, 9 patients developed delirium, including 7 cases of hyperactive delirium, 1 case of hypoactive delirium, and 1 case of mixed-type delirium. There was no significant difference in the types of delirium between the two groups ( P > 0.05); however, the incidence of delirium in the observation group was significantly lower than that in the control group (22.50% vs. 53.12%, P < 0.01). The weaning successful rate in the observation group was significantly higher than that in the control group [95.00% (38/40) vs. 78.12% (25/32), P < 0.05], the reintubation rate within 7 days and hospital mortality were slightly lower than those in the control group [reintubation rate within 7 days: 5.00% (2/40) vs. 15.62% (5/32), hospital mortality: 0% (0/40) vs. 3.12% (1/32), both P > 0.05], and the length of ICU stay was also slightly shorter than that in the control group [days: 18.00 (17.00, 25.75) vs. 22.50 (15.00, 34.50), P > 0.05]. Conclusion:Five-Element music therapy is beneficial in improving anxiety and depression disorders in ICU patients with difficult weaning, reducing the incidence of delirium, and increasing the weaning successful rate.

Objective To investigate the inhibitory effect of Tongsai Granules(TSG)on macrophage-mediated inflammatory response to alleviate acute exacerbation of chronic obstructive pulmonary disease(AECOPD)in rats and explore the underlying mechanism.Methods Twenty-four rats were divided into control group,AECOPD model group,TSG treatment group,and moxifloxacin+salbutamol(MXF+STL)treatment group.In the rat models of COPD,AECOPD was induced by nasal instillation of Klebsiella pneumoniae on day 3 of week 9 after modeling,and saline,TSG or MXF+STL were administered via gavage on days 1 and 2 and days 4 to 7 of week 9.After the treatments,lung tissues were collected for examining for pathologies and expressions of inflammatory markers,MMP2,and MMP9.In cultured macrophage MH-S cells with LPS stimulation,the effect of TSG-medicated serum on IL-1β,IL-6,TNF-α,COX-2,and iNOS expressions and phosphorylation levels of p38,p-p62,LC3,FoxO3a,and mTOR were evaluated.Results TSG significantly improved lung pathologies and lung function in AECOPD rats by reducing bronchial wall thickness and mean alveolar linear intercept,increasing alveolar numbers,and reducing pulmonary expression of IL-1β,IL-6,TNF-α,MMP2 and MMP9.In MH-S cells,TSG significantly suppressed LPS-induced expressions of inflammatory cytokines,COX-2 and iNOS.Serum pharmacology coupled with network pharmacology identified 10 chemical components in TSG-medicated serum,and functional analysis of their 466 targets suggested that the therapeutic effect of TSG on AECOPD was mediated primarily by luteolin and quercetin,which regulate the MAPK,mTOR,FoxO,and autophagy pathways.In MH-S cells,luteolin significantly inhibited LPS-induced inflammatory responses and expressions of p-p38,FoxO3a,mTOR,p-p62 and LC3.Conclusion TSG reduces macrophage-mediated inflammatory responses to alleviate AECOPD in rats possibly by modulating p38,mTOR,and FoxO3a pathways and inhibiting autophagy.

AIM:To investigate the effect of Tongsai granules(TSG)on epithelial barrier dysfunction in acute exacerbation of chronic obstructive pulmonary disease(AECOPD)and the underlying mechanism.METHODS:Twenty-four Sprague-Dawley rats were randomly divided into control group,model group,TSG group,and moxifloxacin(MXF)+salbutamol(STL)group.Rat COPD model was established over 8 weeks.On day 3 of week 9,the rats with COPD were intratracheally administered Klebsiella pneumoniae to establish the AECOPD model.On days 1 to 2 and 4 to 7 in week 9,saline was administered via oral gavage to the rats in control and model groups,and the rats in TSG and MXF+ STL groups were treated daily with TSG and MXF+STL by gavage,respectively.Peak expiratory flow(PEF),histopatho-logical changes,and the expression levels of interleukin-1β(IL-1β),IL-6,tumor necrosis factor-α(TNF-α),matrix me-talloproteinase 2(MMP2),MMP9,zonula occludens-1(ZO-1),E-cadherin(E-Cad)and occludin(OCC)were deter-mined.Moreover,human bronchial epithelial BEAS-2B cells were exposed to cigarette smoke extract(CSE)and treated with different TSG fractions,and the protein levels of ZO-1,E-Cad,OCC,epidermal growth factor receptor(EGFR),phosphorylated EGFR(p-EGFR),extracellular signal-regulated kinase(ERK)and phosphorylated ERK(p-ERK)were determined.RESULTS:Treatment with TSG significantly reduced bronchial wall thickness,mean linear intercept,and the levels of IL-1β,IL-6,TNF-α,MMP2 and MMP9(P＜0.05 or P＜0.01),significantly increased mean alveolar number and PEF(P＜0.01),and up-regulated the ZO-1,E-Cad and OCC protein levels(P＜0.01)in the lungs of AECOPD rats.Treatment with TSG2,the second TSG fraction,increased the protein levels of ZO-1,E-Cad and OCC in a dose-dependent manner in CSE-exposed BEAS-2B cells(P＜0.05 or P＜0.01).Network pharmacology analysis of 328 targets of the com-pounds in TSG2 and 3 864 genes related to AECOPD suggested that TSG2 relieved AECOPD likely through the regulation of ERBB2,ERK,EGFR,IL and WNT signaling pathways.Treatment with TSG2 also inhibited CSE-induced increases in p-EGFR and p-ERK levels in BEAS-2B cells(P＜0.05 or P＜0.01).CONCLUSION:Treatment with TSG could maintain airway epithelial barrier function in AECOPD rats,likely through the inhibition of EGFR/ERK signaling pathway.

Objective:To investigate the clinical effect of Ilizarov bone transport technique with assisted guiding pin in medullary cavity for treatment of posttraumatic bone defect of tibia.Methods:A retrospective case series study was conducted to analyze the clinical data of 17 patients with post-traumatic bone defect of tibia admitted to Third Hospital of Hebei Medical University form November 2014 to March 2018.There were 13 males and 4 females, aged 19-60 years [(37.2±13.4)years]. The bone defect length was 4.6-14.0 cm [(8.6±2.8)cm] after debridement. All patients underwent treatment with Ilizarov bone transport technique. The alignment of transport bone segment was controlled by a guiding pin in medullary cavity of tibia. Bone grafts were performed to accelerate fracture healing of docking point. The wound healing, bone healing, external fixation time, external fixation index (EFI), alignment recovery were recorded. Bone healing and functional results were evaluated according to the criteria given by Association for the Study and Application of the Method of Ilizarov (ASAMI). The complication was recorded according to Paley's criteria. The physical component summary score (PCS) and mental component summary score (MCS) ware recorded according to the MOS 36-item Short-form Health Survey (SF-36) questionnaire and compared with the national norm to evaluate the quality of life.Results:After removal of the apparatus, follow-up period was 12-37 months [(29.9±4.4)months]. Wound healing was achieved without flap transfer. At the latest follow-up, all patients achieved bone healing without recurrent infection. External fixation time was 242-801 days [(436.5±154.6)days] and external fixation index was 35.7-60.5 d/cm [(50.6±6.2)d/cm]. The affected extremity alignment was restored in all patients except for residual angular deformity in one patient. According to ASAMI, the excellent and good rate of bony results and functional results were 88% and 94%. According to Paley's criteria, complications included 12 problems, 7 obstacles and 1 sequelae. The PCS and MCS in SF-36 questionnaire were (85.8±11.6)points and (69.6±11.1)points. Compared with the national norm [PCS: (87.6±16.8)points, MCS: (78.8±15.4)points], PCS showed no statistical difference ( P>0.05), but MCS showed statistical difference ( P<0.05). Conclusions:Ilizarov bone transport combined with intramedullary guiding pin can accelerate wound and fracture healing, control infection and restore lower limb alignment. The physical function of the affected extremity can be restored in spite of some complications and psychological effects. The technique is an effective treatment for posttraumatic bone defect of tibia.

Objective To observe neuropsychological development status in children after surgical treatment of congenital heart diseases(CHDs)and analyze the risk factors. Methods 89 children who received outpatient review in Fuwai Hospital from September 2015 to March 2016 after surgical treatment of CHDs were recruited in this study and 90 normal children were recruited as the control group. The children with CHDs were divided into simple CHDs group(RACHS- 1 score≤2)and com-plex CHDs group(RACHS- 1 score≥3)according to RACHS- 1 classification. Neuropsychological development status was meas-ured according to pediatric-psychological mental test scale developed by Capital institute of pediatrics,Beijing and statistical a-nalysis was compared. Results The measurements of neuropsychological development showed the normal children behaved better than the children with CHDs(P < 0. 05). The simple CHDs group achieved better distribution of development quotient than complex CHDs group(P = 0. 032)and there was no difference between the normal control group and simple CHDs group (P = 0. 420). Multivariate regression analysis indicated that younger age at cardiac surgery,lower preoperative blood urea ni-trogen(BUN),higher preoperative creatinine(Cr)and prolonged duration of cardiopulmonary bypass(CPB)accounted for low-er scores in the test scale(P < 0. 05). Conclusion Distinct neuropsychological difficulties could be present especially in chil-dren with complex CHDs. Younger age at cardiac surgery,preoperative BUN,Cr and CPB duration were perioperative factors that were associated with long-time neuropsychological development.

Objective: To explore the expression of long noncoding RNA (lncRNA) HOXA11-AS in esophageal squamous cell carcinoma tissues and the relationship of HOXA11-AS level with clinical outcomes. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to detect the expression level of HOXA11-AS in cell lines HET-1A, EC9706, EC109, and in tumor tissue and paired adjacent tissue samples from 73 ESCC patients who received surgical resection.The correlations of the expression level of HOXA11-AS with clinicopathological features and prognosis were also analyzed. Results: The relative expression levels of HOXA11-AS in tumor tissue and paired adjacent tissue were 0.832±0.387 and 2.486±1.087, respectively, with significant difference (P<0.001). The expression of HOXA11-AS was upregulated in 63.0%(46/73)ESCC tissues. The relative expression levels of HOXA11-AS in HET-1A, EC-9706 and EC-109 cells were 1.000, 23.553±3.221 and 17.217±1.968, respectively. The expression level of HOXA11-AS was upregulated in ESCC cell lines (P<0.001). High expression level of HOXA11-AS was correlated with histological grade and lymph node metastasis of ESCC patients (P<0.05). However, it was not associated with the age, gender, depth of infiltration and TNM staging (P>0.05). The median overall survival (OS) and median disease-free survival (DFS) of patients with low HOXA11-AS expression were 43 months and 42 months, respectively, significantly longer than 37 months and 28 months of patients with HOXA11-AS high expression (P<0.05). Cox model multivariate analysis showed that the expression of HOXA11-AS and lymph node metastasis were independent factors of poor prognosis of ESCC patients. Conclusions The expression of HOXA11-AS is upregulated in esophageal cancer cell lines and tissues. High expression of HOXA11-AS is associated with poor prognosis of ESCC patients.Therefore, LncRNA HOXA11-AS may serve as a predictive marker of postoperative ESCC patients.

Objective: To analyze the expression and prognostic significance of esophageal squamous cell carcinoma associated long non-coding RNA-1 (ESCCAL-1) in esophageal squamous cell carcinoma (ESCC) tissues. Methods: From August 2011 to May 2013, 73 patients with ESCC, who received radical resection in The First Affiliated Hospital of Zhengzhou University and Henan Cancer Hospital, were enrolled. The expressions of ESCCAL-1 in esophageal tumor tissues and corresponding adjacent non-tumor tissues were detected by quantitative real-time polymerase chain reaction (qRT-PCR). T test, chi square test and multivariate analysis were performed for statistical analysis. Results: The expression of ESCCAL-1 was 28.03±9.37 in esophageal tumor tissues of patients with ESCC, which was higher than that in corresponding adjacent normal tissues (11.39±4.15), and the difference was statistically significant (t=2.964, P<0.01). However there were no statistically significant differences in the expressions of ESCCAL-1 among the patients with different age, gender, histological grade, classification of Union for International Cancer Control (UICC), T stage or lymph nodes metastasis (all P>0.05). The median disease-free survival (DFS) time and overall survival (OS) time of patients with low ESCCAL-1 expression were 39 months and 42 months, respectively, which were longer than those of patients with high ESCCAL-1 expression (30 months and 37 months), and the differences were statistically significant (χ²=9.049, P=0.003; χ²=10.165, P=0.001). The results of multivariate analysis showed that ESCCAL-1 expression was the independent risk factor of DFS and OS (high risk (HR)=2.45, 95% confidence interval (CI) 1.22 to 4.93, P=0.012; HR=2.29, 95%CI 1.14 to 4.59, P=0.019). Conclusions ESCCAL-1 may be involved the genesis and development of ESCC. The expression of ESCCAL-1 in esophageal tumor tissues may be a prognostic parameter for patients with ESCC receiving radical resection.

Objective: To explore the clinical useness of intraoperative functional neuronavigation and fluorescent indocyanine green(ICG) angiography as well as electrophysiological evaluation during microsurgical resection of cerebral arteriovenous malformations (AVM). Methods: A series of 42 consecutive cases with AVM underwent microsurgery by intraoperative functional neuronavigation at Department of Neurosurgery of People′s Liberation Army General Hospital from January 2009 to February 2015 were retrospectively analyzed. Of the 42 patients, 29 were males and 13 were females aging from 4 to 62 years (mean age 32.6 years). Preoperative assessment included functional magnetic resonance imaging and diffusion tensor imaging to identify the relationship between lesions and eloquent areas. The results of images were integrated into three-dimensional datasets to achieve intraoperative microscopic-based functional neuronavigation during AVM resection. Operations involved in motor areas and corticospinal tract were performed under continuous electrophysiological monitoring. ICG angiography was performed at pre-dissection, post-clipping of the feeders, and post-resection of the nidus. FLOW 800 software presented a color map and ICG intensity-time curve to demostrate the vascular architecture. Postoperative digital subtraction angiography was re-examined routinely to evaluate the extent of resection. Clinical outcomes were evaluated with the modified Rankin Scale. Results: All patients underwent surgery under intraoperative navigation. Of the 42 patients, total resection was achieved in 36 cases (85.7%, 36/42) including 14 cases of AVM in eloquent areas. A total of 40 ICG angiographies were successfully performed among 11 patients. Average number of ICG injections per operation was 3.6 (ranging from 3 to 6). Feeders were visualized in 10 patients and drainers were visualized in 9 cases. The post-surgical follow-up period varied from 3 months to 70 months (mean 22.5 months). 83.8% of the patients returned to normal work and life during the followed-up period. Conclusion Combining intraoperative neuronavigation and electrophysiological monitoring, as well as fluorescent ICG angiography contribute to microsurgical resection of cerebral AVM effectively in selecting suitable patients, further avoiding neurologic compromise as well.

Objective: To investigate the relationship of heterogeneity of esophageal squamous cell carcinoma (ESCC) and chemotherapy sensitivity. Methods: Five different region specimens isolated from primary tumor(R1~R5)and 1 specimen(R6)isolated from adjacent non-neoplastic tissue from 10 ESCC patients who underwent surgical treatment were cultured in vitro. The inhibitory effect of cisplatin on proliferation of ESCC cells from different regions was determined by methyl thiazolyl tetrazolium (MTT). The cell cycle and apoptosis induced by cisplatin was determined by flow cytometry (FCM) analysis. The mRNA levels of ATP7A and ATP7B were determined by quantitive RT-PCR (qRT-PCR). Results: The result showed that different regions of each specimen exhibited different chemotherapy sensitivity to cisplatin, and the cell survival rates of region R6 of each specimen were higher than other regions from the same specimen. The cell survival rate of region R3 from the tenth specimen was (81.42±8.84)%, which is significantly higher than (11.90±2.75)% of region R5 (P<0.01). FCM analysis showed that significant differences of early apoptosis and later apoptosis were observed in six specimens induced by cisplatin (P<0.05), and significant differences of cell cycle and G₁ period were observed in seven specimens (P<0.05). The qRT-PCR results showed that the mRNA level of ATP7A in region R1, R2, R3, R4 and R5 was (100.00±3.42)%, (118.10±2.21)%, (75.40±4.15)%, (95.40±3.32)% and (41.70±2.57)%, respectively, with significant differences (P<0.05). The mRNA level of ATP7A in region R6 was (175.20±5.32)%, significantly higher than those of regions from R1 to R5 (P<0.05). The mRNA level of ATP7B in region R1, R2, R3, R4 and R5 was (100.00±4.89)%, (73.60±2.65)%, (175.60±6.12)%, (46.10±4.62)% and (363.70±8.67)%, respectively, with significant differences (P<0.05). The mRNA level of ATP7B in region R6 was (1 165.40±7.25)%, significantly higher than those of regions from R1 to R5 (P<0.05). Conclusion The intratumor heterogeneity of ESCC results in the heterogeneity of resistance to cisplatin, which affects the chemotherapeutic effect.