Objective To investigate the changes of serum homocysteine (Hcy) level before and after treatment in patients with colorectal cancer,and provide the reference for clinical therapeutic efficacy and prognosis.Methods Enzymatic circling assay was used to measure the serum Hcy levels in 50 controls and 58 patients with colorectal cancer before and after treatment with a.follow-up of 12 months.The changes of Hcy aud the relationship between Hcy and therapeutic efficacy or prognosis were analyzed.Results Scrum Hcy level in patients with colorectal cancer was significantly higher than that in controls [(16.90±5.35) μmol/L vs (10.23±3.06) μmol/L] (P ＜ 0.01),and it was closely associated with TNM stage.Serum Hcy level in patients of stage Ⅲ-Ⅳ was significantly higher than that of stage Ⅰ-Ⅱ [(18.49±5.13) μmol/L vs (15.20±4.86) μmol/L] (P ＜ 0.05).The Hcy level in patients at the end of treatment was significantly lower than that before treatment [(13.39±4.98) μmol/L vs (16.90±5.35) μmol/L] (P ＜ 0.01),and the Hcy level after the treatment for 3 month was significantly lower than that at the end of treatment [(10.23±3.17) μmol/L] (P ＜ 0.05).The Hcy level in patients with recurrence during 12 months after operation was significantly higher than that without recurrence [(17.18±4.82) μmol/L vs (12.36±3.19) μmol/L] (P ＜ 0.01).Conclusion Serum level of Hcy might be a useful marker for predicting therapeutic efficacy and prognosis in patients with colorectal cancer.

Objective:To investigate the expression of fibroblast growth factor 7 (FGF7) and related inflammatory factors in the serum of patients with acute exacerbation of chronic obstructive pulmonary disease (COPD).Methods:A case control study was conducted. The patients with AECOPD admitted to the First Affiliated Hospital of Xinjiang Medical University from November 2016 to January 2020 were enrolled. The patients were divided into mild group [forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) ratio (FEV1/FVC) < 0.70, FEV1 percentage in predicted value (FEV1%) ≥ 80%], moderate group (FEV1/FVC < 0.70, 50% ≤ FEV1% < 80%), and severe group (FEV1/FVC < 0.70, 30% ≤ FEV1% < 50%) based on their lung function test results, with 20 patients in each group, and 20 patients with normal pulmonary function who underwent elective non-thoracic surgery such as gastrointestinal surgery and orthopedics surgery in the same period were selected as controls. The demographic data, FEV1/FVC, FEV1%, FVC, maximum mid-expiratory flow percentage in predicted value (MMEF%), 6-minute walking test (6MWT), and St George Respiratory Questionnaire (SGRQ) score were recorded respectively. Serum levels of FGF7, interleukins (IL-6, IL-1β) and tumor necrosis factor-α (TNF-α) were determined by enzyme linked immunosorbent assay (ELISA). Pearson correlation was used to analyze the correlation between TNF-α and lung function.Results:Compared with the normal pulmonary function group, the levels of FEV1/FVC, FEV1%, MMEF% and 6MWT in the mild, moderate and severe groups were significantly decreased, and the SGRQ scores were increased, the indicators continued to deteriorate with the aggravation of the disease, the statistical differences were found between severe group and normal pulmonary function group [FEV1/FVC: 0.39±0.09 vs. 0.81±0.04, FEV1%: (38.80±6.28)% vs. (109.58±13.80)%, MMEF%: (0.34±0.14)% vs. (2.69±0.99)%, 6MWT (m): 279.00±41.61 vs. 402.85±53.97, SGRQ scores: 34.95±6.71 vs. 2.60±2.06, all P < 0.05]. Compared with the normal pulmonary function group, the levels of FGF7 in the mild, moderate and severe groups were significantly lowered (ng/L: 6.31±2.65, 6.10±1.39, 6.64±1.77 vs. 8.29±3.51, all P < 0.05), but no significant difference was found among the mild, moderate and severe groups (all P > 0.05). Compared with the normal pulmonary function group, IL-6 and TNF-α levels were significantly increased in the mild, moderate and severe groups, and TNF-α increased with the aggravation of the disease, the statistical difference was found between severe group and normal pulmonary function group (ng/L: 7.42±2.28 vs. 3.83±0.92, P < 0.05). There was no significant difference in IL-1β level between the normal pulmonary function group and the mild, moderate, severe groups. Correlation analysis showed that TNF-α was negatively correlated with FEV1/FVC and FEV1% ( r values were -0.350 and -0.527, respectively, both P < 0.01). Conclusion:In AECOPD patients, serum FGF7 was decreased, while IL-6 and TNF-α were increased; however, with the aggravation of the disease, there was no significant change in the level of FGF7 in the peripheral blood, but the TNF-α level might be increased, accompanied by severe damage of small airway function.

Objective To report 9 HIV-negative patients with talaromycosis marueffei (TSM)complicated by Sweet syndrome,and to analyze the relationship of the anti-interferon-γ (anti-IFN-γ)autoantibody with TSM complicated by Sweet syndrome.Methods HIV-negative patients with TSM complicated by Sweet syndrome were collected from the First Affiliated Hospital of Guangxi Medical University between 2013 and 2018.Their clinical and laboratory data were analyzed retrospectively.Meanwhile,19 HIV-positive patients with TSM and 107 health checkup examinees served as controls.Anti-IFN-γ autoantibody was detected in peripheral blood samples of the patients and controls.Results A total of 9 HIV-negative patients with TSM (5 males and 4 females) were included in this study,and the age of onset ranged from 38 to 60 years.The 9 patients all presented with disseminated infections,manifesting as long-term irregular fever,multiple lymph node enlargement,cough,emaciation and anemia.All of the 9 patients met the diagnostic criteria for classical Sweet syndrome,and microbiological examination of Sweet syndrome lesions was negative.Besides Talaromyces marneffei,6 patients also were infected with nontuberculous mycobacteria,4 with varicella-zoster virus,and 2 with Salmonella.All the 9 HIV-negative patients with TSM were positive for anti-IFN-γ autoantibody,while the 107 healthy controls and 19 HIV-positive patients with TSM were negative for anti-IFN-γ autoantibody.Conclusion Anti-IFN-γ autoantibody may be associated with HIV-negative TSM complicated by Sweet syndrome.

Objective:To explore the timing of sequential noninvasive positive pressure ventilation (NIPPV) following endotracheal intubation mechanical ventilation (ETI-MV) in aged patients with severe community-acquired pneumonia (SCAP).Methods:A prospective cohort study was conducted. The SCAP patients aged ≥ 75 years old admitted to respiratory intensive care unit (RICU) of the First Affiliated Hospital of Xinjiang Medical University from July 2017 to August 2019 were enrolled. SCAP was diagnosed according to the criteria of Guidelines for the diagnosis and treatment of community-acquired pneumonia in adults in China (2016) published by Chinese Thoracic Society. ETI-MV was initially performed as respiratory support after RICU admission. Sequential NIPPV was performed immediately following extubation when the patients exhibited pulmonary infection abated (PIA) window. The gender, age, underlying diseases, and body temperature, heart rate (HR), respiratory rate (RR), oxygenation index (PaO 2/FiO 2) after RICU admission, as well as acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score, improved pneumonia score of British Thoracic Society (confusion, uremia, respiratory, blood pressure, age 65 years, CURB-65), and pneumonia severity index (PSI) score within 24 hours after RICU admission were recorded. The duration and times of ETI, the incidences of ventilator associated pneumonia (VAP) and aspiration, the duration of mechanical ventilation (MV), the length of RICU and hospital stay and RICU prognosis were also recorded. The patients were divided into the ETI ≤ 7 days group and the ETI > 7 days group according to the duration of ETI, and the clinical data were compared between the two groups. Multivariate Logistic regression analysis was used to screen the risk factors of aged patients with SCAP whose ETI was more than 7 days, and receiver operator characteristic (ROC) curve was drawn to evaluate the predictive value of risk factors. Results:Fifty aged patients with SCAP were enrolled, with 24 patients in the ETI ≤ 7 days group and 26 in the ETI > 7 days group. Univariate analysis showed that compared with the patients with ETI ≤ 7 days, the incidences of concurrent cerebrovascular diseases [46.2% (12/26) vs. 16.7% (4/24)], VAP [61.5% (16/26) vs. 16.7% (4/24)] and aspiration [69.2% (18/26) vs. 25.0% (6/24)] were significantly increased in patients with ETI > 7 days (all P < 0.05). Multivariate Logistic regression analysis indicated that VAP and aspiration were independent risk factors of ETI > 7 days in the aged SCAP patients [VAP: odds ratio ( OR) = 4.852, 95% confidence interval (95% CI) was 1.076-21.877, P = 0.040; aspiration: OR = 5.903, 95% CI was 1.474-23.635, P = 0.012]. ROC curve analysis showed that the area under ROC curve (AUC) of VAP for predicting ETI > 7 days in aged patients with SCAP was 0.724, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), negative likelihood ratio (NLR) and Youden index were 61.54%, 83.33%, 80.00%, 66.67%, 3.69, 0.46 and 0.45, respectively. Similarly, the AUC of aspiration was 0.721, the sensitivity, specificity, PPV, NPV, PLR, NLR and Youden index were 69.23%, 75.00%, 75.00%, 69.23%, 2.77, 0.41 and 0.44, respectively. Analysis of prognostic indicators showed that compared with patients with ETI ≤ 7 days, the reintubation rate and RICU mortality were significantly increased in patients with ETI > 7 days [53.8% (14/26) vs. 4.2% (1/24), 38.5% (10/26) vs. 12.5% (3/24), both P < 0.05]. Moreover, the patients with ETI > 7 days had significantly prolonged total duration of MV, the length of RICU stay and total hospital stay as compared with the patients with ETI ≤ 7 days [total duration of MV (days): 23.8±11.8 vs. 11.3±3.1, length of RICU stay (days): 30.6±14.1 vs. 16.0±5.1, total length of hospital stay (days): 33.0±14.9 vs. 20.2±6.1, all P < 0.01]. Conclusions:Sequential NIPPV performed immediately following extubation within 7 days in the aged SCAP patients might reduce the mortality and shorten the duration of MV. The prolonged ETI duration because of the VAP or aspiration would lead to a reduced function of sequential NIPPV and an increased mortality of the aged patients with SCAP.

Objective:To explore the efficacy and case selection of non-invasive positive pressure ventilation (NIPPV) in the treatment of acute respiratory distress syndrome (ARDS) caused by viral pneumonia.Methods:These patients who were continuously admitted in the Respiratory Intensive Care Unit (RICU) of the First Affiliated Hospital of Xinjiang Medical University from December 2017 to June 2019 and met the inclusion and exclusion criteria were enrolled in this prospective cohort study. All subjects accepted NIPPV as the initial intervention and they were divided into the NIPPV failure group and NIPPV success group according to the requirement of endotracheal intubation (ETI). Univariate analysis and multivariate logistic regression analysis were used to identify the risk factors for NIPPV failure. Receiver operating characteristic (ROC) was plotted to evaluate the predictive value of risk factors for NIPPV failure in these patients.Results:Forty-three patients were studied in this experiment. The success rate of NIPPV was 62.8% (27/43), and the failure rate was 37.2% (16/43). Compared with the NIPPV success group, the incidence of nosocomial infection [44% (7/16) vs 0 (0/27), χ 2 =11.082, P<0.05] and mortality rate [50% (8/16) vs 7% (2/27), χ 2 =7.965, P<0.05] were significantly increased in the NIPPV failure group. The univariate analysis indicated that the acute physiology and chronic health evaluation II (APACHEⅡ) score, the ratio of early concurrent bacterial or fungal infections, and the proportion of patients with insufficient NIPPV at the early 72 h were significantly higher in the NIPPV failure group (all P<0.05). Meanwhile, multivariate logistic regression analysis identified that the baseline APACHEⅡ score ( OR=1.941, 95% CI:1.159-3.249, P=0.012), the rate of early concurrent bacterial or fungal infections ( OR=8.602, 95% CI:1.267-58.416, P=0.028), and insufficient use of NIPPV at the early 72 h ( OR=10.06, 95% CI:1.592-63.527, P=0.014) were independent risk factors associated with NIPPV failure. The ROC curve showed the area under curve (AUC), the sensitivity, and the specificity was 0.748, 62.5%, and 74.1% respectively, which demonstrates that that APACHE Ⅱ score at admission was the most predictive factor of NIPPV failure. For the observed indicator without enough NIPPV treatment within 72 h, the AUC, the sensitivity, and the specificity was 0.714, 68.8%, and 74.1%, respectively. And for the observed indicator with concurrent bacterial or fungal infections, the AUC, the sensitivity and the specificity is 0.707, 56.3% and 85.2%, respectively. Conclusions:Early use of enough NIPPV in patients with ARDS caused by viral pneumonia can significantly decrease ETI and mortality rates. However, NIPPV should not be conducted in patients suffered from severe ARDS or early concurrent bacterial or fungal infections.

Objective:To explore the pros and cons of sequential high-flow nasal cannula (HFNC) and non-invasive positive pressure ventilation (NIPPV) immediately following early extubated patients with severe respiratory failure (SRF) due to acute exacerbations of chronic obstructive pulmonary disease (AECOPD), so as to provide evidence for clinical selection of optimal scheme.Methods:Consecutive AECOPD patients admitted to the respiratory intensive care unit (RICU) of the First Affiliated Hospital of Xinjiang Medical University from January 2019 to September 2020 were screened for enrollment. Patients were between 40 years old and 85 years old with acute exacerbation of bronchial-pulmonary infection, who received endotracheal intubation mechanical ventilation (ETI-MV) as the initial respiratory support method. The pattern of synchronous intermittent mandatory ventilation (SIMV) was used in the study. The parameters were set as follows: tidal volume (VT) 8 mL/kg, support pressure 10-15 cmH 2O (1 cmH 2O = 0.098 kPa), positive end-expiratory pressure (PEEP) 4-6 cmH 2O and the ratio of inspiratory to expiratory time 1.5-2.5∶1. Under these conditions, the plateau pressure (Pplat) was maintained less than 30 cmH 2O. The minimum fraction of inspired oxygen was adjusted to keep the pulse oxygen saturation no less than 0.92. When the pulmonary infection control window (PIC window) occurred, the subjects were extubated immediately and randomly divided into two groups, with one group receiving HFNC (called HFNC group), the other group receiving NIPPV (called NIPPV group). Patients with failed sequential HFNC or NIPPV underwent tracheal re-intubation. The rate of tracheal re-intubation within 7 days of extubation, complications (such as nose and face crush injury and gastric distension), in-hospital mortality, duration of ETI before PIC window, length of RICU stay and length of hospital stay were compared, respectively. Results:Forty-four patients were enrolled in the study, 20 in the HFNC group and 24 in the NIPPV group. There was no significant difference in the duration of ETI before PIC window between HFNC and NIPPV groups (hours: 95.9±13.1 vs. 91.8±20.4, P > 0.05). The rate of tracheal re-intubation within 7 days in the HFNC group was significantly higher than that in the NIPPV group [35.0% (7/20) vs. 4.2 % (1/24), P < 0.05]. However, the incidence of complication in the HFNC group was significantly lower than that in the NIPPV group [0% (0/20) vs. 25.0% (6/24), P < 0.05]. Compared with the NIPPV group, the in-hospital mortality in the HFNC group was slightly higher [5.0% (1/20) vs. 4.2% (1/24)], the length of RICU stay (days: 19.5±10.8 vs. 15.5±7.2) and the length of hospital stay (days: 27.4±12.2 vs. 23.3±10.9) were slightly longer, without statistical differences (all P > 0.05). Conclusion:For early extubated patients with SRF due to AECOPD, the compliance of sequential HFNC increased and the complications decreased significantly, but the final effect may be worse than sequential NIPPV.

OBJECTIVE: To explore the diagnostic yield of bronchoscopic rapid on-site evaluation (B-ROSE) in patients with severe invasive bronchopulmonary aspergillosis (IBPA) and provide evidence for starting antifungal treatment before microbiological results were available. METHODS: A prospective cohort study was conducted to select patients with severe pneumonia suspected of IBPA admitted to the respiratory intensive care unit (RICU) in the First Affiliated Hospital of Xinjiang Medical University from June 2014 to June 2022, and those who were primarily infected with other pathogens (such as bacteria, Mycobacterium tuberculosis) at admission were excluded. Whether the antifungal treatment was initiated or not on the basis of the bedside B-ROSE, the B-ROSE was administered as soon as possible within 24 hours after admission to RICU. The current international definition of invasive aspergillosis was used as the gold diagnostic standard, the diagnostic accordance rate, the sensitivity and specificity of B-ROSE were calculated respectively, and the receiver operator characteristic curve (ROC curve) was also plotted, to evaluate the predictive value in diagnosing IBPA. RESULTS: A total of 176 patients with severe pneumonia suspected of IBPA were included in the study. According to international diagnostic standards, there were 81 cases of IBPA and 95 cases of non-IBPA. According to the early diagnosis of B-ROSE, there were 89 cases of IBPA and 87 cases of non-IBPA. The diagnostic accordance rate of B-ROSE was 84.09% (148/176), the area under the ROC curve for B-ROSE in diagnosing severe IBPA was 0.844, the 95% confidence interval (95%CI) was 0.782-0.905, the sensitivity was 87.65%, the specificity was 81.05%, the positive predictive value was 79.78%, the negative predictive value was 88.51%, the rate of underdiagnosis was 12.35% (10/81), and the rate of misdiagnosis was 18.95% (18/95). Compared with the true negative group, the proportion of long-term (≥ 14 days) use of glucocorticoid [70.0% (7/10) vs. 9.1% (7/77), P < 0.01] and the proportion of cases with diabetes [40.0% (4/10) vs. 10.4% (8/77), P < 0.05] were significantly higher in the false negative group (underdiagnosis group). However, B-ROSE of both groups showed mucosal bleeding, congestion and edema [100.0% (10/10) vs. 94.8% (73/77), P > 0.05], indicating that acute mucosal inflammation was non-characteristic. Compared with the true positive group, the proportion of long-term (≥ 14 days) use of glucocorticoid in the false positive group (misdiagnosis group) was significantly reduced [33.3% (6/18) vs. 60.6% (43/71), P < 0.05]. The B-ROSE results showed the proportion of cases with mucosal white spots, black plaques and pseudomembrane was significantly reduced [16.7% (3/18) vs. 52.1% (37/71), P < 0.01] in the misdiagnosed group, which suggest that cases of long-term use of glucocorticoid and cases with B-ROSE showing mucosal white spots, black plaques and pseudomembrane were less likely to be misdiagnosed. The main diseases that were easily misdiagnosed as IBPA included pulmonary tuberculosis (38.9%, 7/18), inflammatory lung adenocarcinoma (27.8%, 5/18) and pulmonary vasculitis (16.7%, 3/18). CONCLUSIONS Before obtaining microbiological evidence, B-ROSE can assist in decision-making of early anti-aspergillus treatment for severe IBPA. This method is prompt, simple, and has high accuracy and reliability. If B-ROSE lacks characteristic manifestations, especially for severe pneumonia in patients with long-term use of glucocorticoid or diabetes, attention should be paid to the underdiagnosis of IBPA. Diseases such as lung tuberculosis, inflammatory lung adenocarcinoma and lung vasculitis should be vigilant against misdiagnosis as IBPA.
Humans ; Prospective Studies ; Antifungal Agents ; Glucocorticoids ; Rapid On-site Evaluation ; Reproducibility of Results ; Pulmonary Aspergillosis ; Pneumonia ; Diabetes Mellitus ; Adenocarcinoma of Lung ; Vasculitis ; Retrospective Studies

OBJECTIVETo establish chronic periodontitis model in SD rats, and to investigate the effect of oral intervention on atherosclerosis.

METHODSFifty male SD rats were randomly divided into three groups, group A (normal control), group B (atherosclerosis,As) and group C (chronic periodontitis, CP). Group C was further divided into group C1 (natural process), group C2 (simple mechanical treatment), group C3 (systemic antibiotics), group C4-1 (teeth extraction) and group C4-2 (teeth extraction+systemic antibiotics), each group consisted of 7 rats. Every group received oral intervention. Serum interleukin (IL)- 6 levels were detected in five different time points (1, 3, 5, 7, 9 weeks after a successful modeling) by enzyme linked immunosorbent assay. All animals were killed after 24 weeks. Matrix metalloproteinase (MMP)- 2, 9 in the proximal aorta was detected by immuno histochemistry.

RESULTSThe levels of serum IL-6 in groups B and C1 increased gradually with time and became significantly higher than that in group A (P < 0.01). Levels of serum IL-6 were increased gradually in each intervention group (C2, C3, C4-1, C4-2) and reached its peak at 5 weeks after modeling [C2:(62.3 ± 14.3) ng/L, C3:(58.2 ± 8.7) ng/L, C4-1:(127.0 ± 29.9) ng/L, C4-2:(120.6 ± 23.1) ng/L]. Compared with group B, group C4- 1 and C4- 2 increased most significantly (P < 0.01). Levels of serum IL- 6 decreased gradually. Eventually, group C2 [(28.6 ± 8.1) ng/L], C3 [(40.8 ± 15.1) ng/L] and C4-2 [(32.7 ± 11.1) ng/L] were significantly lower than group B (P < 0.05), and in group C2 IL- 6 was the lowest. Although levels of serum of IL-6 significantly decreased in group C4-1 [(72.8 ± 16.4) ng/L], but remained the highest. Immunohistochemistry showed that MMP-2, 9 were expressed in group B, C1 and C4-1, and significantly higher than in group A (183.0 ± 2.0, 181.3 ± 2.0), the gray value differences were statistically significant (P < 0.01). Group C4-1 (123.1 ± 2.9, 121.0 ± 3.2) was the strongest, group B (126.4 ± 2.0, 124.8 ± 2.8) and C1 (140.0 ± 2.2, 139.7 ± 3.2) were decreased (P < 0.01). While group C2(169.3 ± 3.4, 169.7 ± 2.3), C3 (149.0 ± 1.7, 145.1 ± 2.5) and C4-2 (157.7 ± 1.2, 155.8 ± 2.7) were significantly lower than group C1 (P < 0.01), and group C2 was close to normal.

CONCLUSIONSPeriodontitis could increase the risk of atherosclerosis in rats with chronic periodontitis. Periodontal mechanical treatment and teeth extraction may increase the risk of As in the short time. However, the risk would gradually reduce in a long time.

Animals ; Anti-Bacterial Agents ; pharmacology ; Atherosclerosis ; etiology ; Carotid Arteries ; enzymology ; Chronic Periodontitis ; complications ; enzymology ; Interleukin-6 ; metabolism ; Male ; Matrix Metalloproteinase 2 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; Periodontitis ; Rats ; Rats, Sprague-Dawley ; Tooth Extraction

OBJECTIVETo investigate the effect of periodontal mechanical treatment on serum interleukin-6 (IL-6) and carotid artery matrix metalloproteinase (MMP)-2 and MMP-9 expression in chronic periodontitis (CP) SD rats with atherosclerosis (As).

METHODSForty-four six-week-old male SD rats were randomly divided into three groups: control group (group A), As group (group B), As+CP group(group C). According to different periodontal interventions, group C was randomly subdivided into four groups: natural process group (C1), the periodontal mechanical treatment group (C2), the periodontal mechanical treatment+ local drugs group (C3), and the periodontal mechanical treatment+local and system drugs group (C4). Each group received the appropriate treatment and periodontal interventions. Serum IL-6 levels were determined by enzyme linked immunosorrbent assay (ELISA). MMP-2 and MMP-9 levels in the proximal aorta were examined by immunohistochemistry.

RESULTSThe gray value of MMP-2 and MMP-9 was basically the same in all groups. Compared with group A, the gray value of MMP-2 and MMP-9 of group B and C were decreased. C1 group showed the formation of atherosclerotic plaque and fibrous cap. Compared with group B (126.4 ± 2.0, 124.8 ± 2.8) , the gray value of group C1 (101.3 ± 2.4, 101.2 ± 4.1) was significantly weaker (P < 0.05). The staining depth of MMP-2 and MMP-9 of groups C1, C2, C3 and C4 were sequentially decreased, and the differences of gray value were statistically significant(P < 0.05). The levels of serum IL-6 in groups B and C1 increased gradually with time and became significantly higher than that of group A (P < 0.01). The levels of serum IL-6 in groups C2, C3, and C4 increased gradually and reached the peak 5 weeks after the establishment of model (P < 0.001). After that, the levels of serum IL-6 decreased gradually and was lower than baseline. The levels of serum IL-6 in groups C3 and C4 were significantly lower than that in group C2 7 weeks after the establishment of model(P < 0.01).

CONCLUSIONSIn rats with periodontitis and cardiovascular diseases, chronic periodontal inflammation may significantly increase the severity of As and promote the formation of atherosclerotic plaque. Mechanical periodontal therapy may cause short-term systemic inflammation and then reduce vascular inflammation in long term.With supplement use of local and systemic antibiotics, the mechanical periodontal therapy may get the vascular disease and systemic inflammation improved.

Animals ; Atherosclerosis ; complications ; Carotid Arteries ; metabolism ; Chronic Periodontitis ; complications ; metabolism ; therapy ; Inflammation ; Interleukin-6 ; biosynthesis ; Male ; Matrix Metalloproteinase 2 ; biosynthesis ; Matrix Metalloproteinase 9 ; biosynthesis ; Periodontitis ; Rats ; Rats, Sprague-Dawley

ObjectiveTo explore the material basis and molecular mechanism of Linggui Qihua prescription （LGQH） against myocardial fibrosis in heart failure with preserved ejection fraction （HFpEF）. MethodLiquid chromatography-mass spectrometry （LC-MS） was used to qualitatively analyze the active components of LGQH. AutoDock software was employed for molecular docking between the active components of LGQH and target proteins including α-smooth muscle actin （α-SMA）， type Ⅰ collagen （ColⅠ）， type Ⅲ collagen （ColⅢ）， matrix metalloproteinase-9 （MMP-9）， and tissue inhibitor of metalloproteinase-1 （TIMP-1）. In vivo experiments were conducted on 40 spontaneously hypertensive rats （SHRs） aged 4 weeks， which were divided into an HFpEF group， an Entresto group （0.018 g·kg^-1）， and low- and high-dose LGQH groups （3.87， 7.74 g·kg^-1）. A high-fat， high-salt， and high-sugar diet was administered for 16 weeks along with intraperitoneal injection of streptozotocin solution for 8 weeks to establish an HFpEF model in rats. The blank group consisted of 10 Wistar Kyoto （WKY） rats and 10 SHRs. After successful modeling， the WKY， SHR， and HFpEF groups were given equal volumes of normal saline， while the other three groups received predetermined interventions. Daily oral gavage was performed for 6 weeks. After intervention， echocardiography was conducted to measure left ventricular （LV） anterior wall thickness （LVAWd）， LV posterior wall thickness （LVPWd）， LV internal diameter at end-diastole （LVIDd）， LV ejection fraction （LVEF）， isovolumic relaxation time （IVRT）， early diastolic peak velocity of mitral valve inflow （E）， and early diastolic mitral annular velocity （e'）. The E/e' ratio was calculated. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum atrial natriuretic peptide （ANP）， B-type natriuretic peptide （BNP）， and galectin-3 （Gal-3）. Myocardial fibrosis was observed through Masson staining of pathological sections， and collagen volume fraction （CVF） and perivascular fibrosis ratio （PFR） were calculated. Real-time polymerase chain reaction （PCR） and Western blot were employed to detect LV myocardial mRNA and protein expression of α-SMA， ColⅠ， ColⅢ， MMP-9， and TIMP-1. ResultLC-MS identified 13 active components in LGQH. Molecular docking indicated stable binding of the 13 compounds with five target proteins. In vivo experiments showed that compared with the blank group， the HFpEF group had significantly increased LVAWd， LVPWd， LVIDd， IVRT， E/e'， ANP， BNP， Gal-3， CVF， and PFR. LV myocardial α-SMA， ColⅠ， and ColⅢ mRNA and protein expression was significantly upregulated， while MMP-9/TIMP-1 mRNA and protein ratios were significantly downregulated （P<0.05， P<0.01）. Compared with the HFpEF group， LGQH might dose-dependently reduce LVAWd， LVPWd， LVIDd， IVRT， E/e'， ANP， BNP， Gal-3， CVF， and PFR， downregulated myocardial α-SMA， ColⅠ， ColⅢ mRNA expression， α-SMA， and ColⅠ protein expression， and upregulated MMP-9/TIMP-1 mRNA and protein expression （P<0.05， P<0.01）. ConclusionLGQH contains multiple active components and may inhibit myocardial fibrosis in HFpEF rats. It may further alleviate LV hypertrophy， dilation， and diastolic dysfunction， making it an effective Chinese medicinal prescription for treating HFpEF.