Role of Autophagy Mediated by AMPK/DDiT4/mTOR Axis in HT22 Cells Under Oxygen and Glucose Deprivation/Reoxygenation.

Background: cerebral ischemia/reperfusion (I/R) injury is an important complication of ischemic stroke, and autophagy is one of the mechanisms of it. In this study, we aimed to determine the role and mechanism of autophagy in cerebral I/R injury. Methods: the oxygen and glucose deprivation/reoxygenation (OGD/R) method was used to model cerebral I/R injury in HT22 cells. CCK-8 and LDH were conducted to detect viability and damage of the cells, respectively. Apoptosis was measured by flow cytometry and Tunel staining. Autophagic vesicles of HT22 cells were assessed by transmission electron microscopy. Western blotting analysis was used to examine the protein expression involving AMPK/DDiT4/mTOR axis and autophagy-related proteins. 3-Methyladenine and rapamycin were, respectively, used to inhibit and activate autophagy, compound C and AICAR acted as AMPK inhibitor and activator, respectively, and were used to control the starting link of AMPK/DDiT4/mTOR axis. Results: autophagy was activated in HT22 cells after OGD/R was characterized by an increased number of autophagic vesicles, the expression of Beclin1 and LC3II/LC3I, and a decrease in the expression of P62. Rapamycin could increase the viability, reduce LDH leakage rate, and alleviate cell apoptosis in OGD/R cells by activating autophagy. 3-Methyladenine played an opposite role to rapamycin in OGD/R cells. The expression of DDiT4 and the ratio of p-AMPK/AMPK were increased after OGD/R in HT22 cells. While the ratio of p-mTOR/mTOR was reduced by OGD/R, AICAR effectively increased the number of autophagic vesicles, improved viability, reduced LDH leakage rate, and alleviated apoptosis in HT22 cells which suffered OGD/R. However, the effects of compound C in OGD/R HT22 cells were opposite to that of AICAR. Conclusions: autophagy is activated after OGD/R; autophagy activator rapamycin significantly enhanced the protective effect of autophagy on cells of OGD/R. AMPK/DDiT4/mTOR axis is an important pathway to activate autophagy, and AMPK/DDiT4/mTOR-mediated autophagy significantly alleviates cell damage caused by OGD/R.

Mitoxantrone hydrochloride injection for tracing helps to decrease parathyroid gland resection and increase lymph node yield in thyroid cancer surgery: a randomized clinical trial.

The identification and preservation of parathyroid glands (PGs) during thyroid surgery can be challenging. Many techniques have been developed to help surgeons find PGs. We have developed a novel mitoxantrone hydrochloride injection that can be used for lymphatic targeting. After local application during surgery, mitoxantrone hydrochloride injection for tracing (MHI) helps surgeons better identify and preserve PGs and helps pathologists find more lymph nodes. We conducted an open-label, multicenter, randomized clinical trial (CTR20171137) in six centers in China from 08/2017 to 12/2018. Patients with thyroid carcinoma were randomized to the MHI group or the control group. All patients received total thyroidectomy and bilateral central compartment lymph node dissection. The primary outcomes were the PG resection rate and lymph node staining rate. The full analysis set (FAS) included 461 patients, of which 228 were assigned to the MHI group, and 233 were assigned to the control group. The PG resection rates of the MHI group and the control group were 6.6% (15/228) and 26.6% (62/233), respectively, with a significant difference (P < 0.001). No PGs were stained blue with MHI. The central lymph nodes were stained blue with MHI, and the staining rate was 90.5%±12.0%. More lymph nodes were detected in the MHI group than in the control group (13.0±7.3 vs. 10.1±6.4 nodes/patient, P < 0.001). No adverse events related to MHI were observed. MHI is a safe and effective tracer that may help to preserve PGs and identify more central lymph nodes in patients with thyroid cancer.

High expression of HOXB7 is an unfavorable prognostic factor for solid malignancies: A meta-analysis.

BACKGROUND: HOXB7 is abnormally expressed in a variety of tumors, but its prognostic value remains unclear due to sample size limitation and outcome inconsistency in previous studies. This meta-analysis was performed to explore the effect of HOXB7 expression on prognoses and clinicopathological factors in range of the whole solid tumors. METHODS: PubMed, EMBASE, and Web of Science databases were searched to identify included studies. Hazard ratios (HR) with its 95% confidence interval (CI) and clinicopathological factors were extracted. Subgroup analyses were performed according to histopathological type, tumor occurrence systems, and HOXB7 detection methods. RESULTS: A total of 3430 solid tumors patients from 20 studies (21 cohorts) were included in the meta-analysis. The results showed that high HOXB7 expression was significantly associated with worse survival (overall survival: HR = 1.98, 95%CI: 1.74-2.26, P < .001 and disease-free survival: HR = 1.59, 95%CI: 1.21-2.09, P = .001), more advanced tumor-node-metastasis (TNM) stage (odds ratio [OR] = 2.14, 95%CI: 1.68-2.73, P < .001), positive lymph node metastasis (OR = 2.16, 95%CI: 1.74-2.70, P < .001), more distant metastasis (OR = 1.63, 95%CI: 1.01-2.63, P = .048), poorer differentiation (OR = 1.48, 95%CI: 1.14-1.91, P = .003), and higher Ki-67 expression (OR = 2.53, 95%CI: 1.68-3.84, P < .001). Subgroup analysis showed that survival of patients with HOXB7 high expression was worse in either squamous cell carcinomas or non-squamous cell carcinomas, digestive tumors or non-digestive tumors, and protein level or mRNA level. CONCLUSION: High HOXB7 expression might be a valuable biomarker of poor prognosis for solid tumors. HOXB7 promotes tumor proliferation and metastasis, and is associated with poorer differentiation, more advanced stage, even the chemotherapy resistance, suggesting that HOXB7 is a potential therapeutic target for solid tumors.

Research progress on CD169-positive macrophages in tumors.

CD169/Siglec1/sialoadhesin, a sialic acid-binding immunoglobulin-like lectin, is mainly expressed in metallophilic macrophages in the marginal zone of the spleen and in macrophages in the subcapsular sinus and medulla of lymph nodes. In addition to participating in anti-infectious immunity, recent studies have demonstrated that CD169+ macrophages are involved in tumor immunity and are associated with a favorable prognosis. The roles of CD169+ macrophages in tumors and the mechanisms of CD169+ macrophages and CD169 molecules involved in the tumor microenvironment and tumor immunity are described in this review.

Pembrolizumab-induced autoimmune Stevens-Johnson syndrome/toxic epidermal necrolysis with myositis and myocarditis in a patient with esophagogastric junction carcinoma: a case report.

Immune checkpoint inhibitors (ICIs) have significantly improved outcomes for cancer patients. With the widespread clinical application of ICIs, their adverse reactions have gradually been recognized. The side effects of ICIs are generally less severe than those of chemotherapy. However, some adverse events with ICIs can be life-threatening. Fatal adverse events require a deep understanding and vigilance. Here, we report the case of a 69-year-old patient with esophagogastric junction carcinoma who experienced multiple immune-related adverse events, including Stevens-Johnson syndrome/toxic epidermal necrolysis, myositis, myocarditis, and liver toxicity, after receiving pembrolizumab. The patient experienced skin rash, bilateral ptosis, limb weakness, and shortness of breath. The symptoms progressed rapidly. Following treatment with methylprednisolone, intravenous immunoglobulin, and plasmapheresis, the patient recovered well. No tracheal intubation or tracheotomy was required owing to the timely and effective treatment. From this case, it can be seen that severe skin rash is an important indication of abnormal immune status and an early warning sign of subsequent multiple-organ involvement. As the most dangerous adverse event, myocarditis is closely related to the patient's prognosis. Severe irAEs appear early, progress rapidly, and involve multiple systems and organs, resulting in a high fatality rate. Early recognition and high-dose corticosteroids are key to successful treatment of such patients.

Monitoring and Control of Medical Air Disinfection Parameters of Nosocomial Infection System Based on Internet of Things.

To include the two key parameters of circulating air volume and instantaneous ultraviolet illuminance, as well as the minor influencing factors such as temperature, humidity, comings and goings of personnel and other parameters into the scope of conventional monitoring, and monitor and alarm each parameter, the key problem is to design the data transmission of sensors of existing products and debug the network management system, and solve every problem in the research process through the cycle of experiment-trial-experiment. The specific functions of a single instrument and system software can be achieved by solving the key links such as type selection of various sensors, circuit interface, guarantee measures for measurement accuracy of various parameters, research and development of networked air disinfection management system software, design of WiFi interface, cost control of single machine and system and so on. And ultraviolet luminance sensors can be used to monitor the ultraviolet intensity in the machine in real time, and monitor 7 parameters, including circulating air volume, ozone concentration, comings and goings of personnel, temperature, humidity and leaked ultraviolet intensity.

Predictive Factors of Lateral Lymph Node Metastasis in Papillary Thyroid Microcarcinoma.

This study was designed to determine the incidence and predictive factors for lateral lymph node metastasis (LNM) in patients with papillary thyroid microcarcinoma (PTMC). From January 2014 to July 2015, a retrospective review was conducted of 215 patients with PTMC who underwent total thyroidectomy and central lymph node dissection (LND) with lateral LND. Correlations of lateral LNM with clinicopathological features were examined using univariate analyses. Risk factors for lateral LNM were identified by multivariate analysis. Lateral LNM was observed in 163(75.8%) cases of 215 patients and often involved in level III (82.2%) and level IV (65.6%), with most found in two-levels (41.1%) and single-level (33.7%) models. Multivariate analyses showed that central LNM (odds ratio [OR]: 8.28, 95% confidence interval [CI]: 3.43-19.98, p < 0.001) and upper portion location (OR: 2.87 [CI: 1.34-6.09]; p = 0.007) were independent predictive factors for lateral LNM. The incidence of skip metastasis-Lateral LNM with central Lymph nodes negative-was 8.6% (14/163). Age ≥ 45 years old (OR: 4.37 [CI: 1.14-16.66]; p = 0.031) and upper portion location (OR: 4.34 [CI: 1.27-14.78]; p = 0.019) were independent risk factors for skip metastasis by multivariate analyses. Taken together, patients with PTMC with central LNM and tumor in the upper pole were more likely to present with lateral LNM. Even if there was no central LNM, patients with an age ≥ 45 years old and tumors in the upper portion of the thyroid should be evaluated carefully for possible lateral LNM.

CHK2 Promotes Anoikis and is Associated with the Progression of Papillary Thyroid Cancer.

BACKGROUND/AIMS: Cell cycle checkpoint kinase 2 (CHK2) performs essential cellular functions and might be associated with tumorigenesis and tumor progression. Here, we explored the function and molecular mechanisms of CHK2 in the progression of papillary thyroid cancer (PTC). METHODS: The expression levels of both total CHK2 and activated CHK2 (p-CHK2) in tissues from 100 PTC patients were detected and evaluated using immunohistochemistry. The roles of CHK2 on cell proliferation, invasion, migration, apoptosis and cancer stem cell (CSC) markers were investigated by CCK-8, Transwell, flow cytometry, western blot and ALDEFLOUR assay. PTC cells cultured in suspension conditions were assayed for anoikis. The anchorage-independent condition was further detected by soft agar colony formation assay. Furthermore, anoikis associated regulatory proteins were explored by western blot and verified by forced downregulation experiment, respectively. RESULTS: We found that the levels of both CHK2 and p-CHK2 were significantly upregulated in PTC cancer tissues compared with those in tumor-adjacent tissues. The overexpression of p-CHK2 in primary tumor tissues was associated with tumor aggressiveness and metastatic potential. However, the levels of both CHK2 and p-CHK2 were decreased in metastatic lymph nodes. Our results showed that CHK2 upregulated the levels of CSC markers with no effect on cell proliferation, invasion and migration. Interestingly, we revealed a previously undescribed anoikis-promoting role for CHK2 in PTC. Specifically, the detachment of PTC cells from the extracellular matrix (ECM) triggers CHK2 degradation. Then, the forced downregulation of CHK2 rescued PTC cells from anoikis, but no effect was observed on the apoptosis of adherent PTC cells. Additionally, as a novel regulator of anoikis, CHK2 can induce cell death in a p53-independent manner via the regulation of PRAS40 activation. CONCLUSION: High expression levels of CHK2 and p-CHK2 were associated with the progression of PTC. Our results defined an unexpected role for CHK2 as a mediator of anoikis that functions through the regulation of PRAS40 activation, which may be associated with the survival of circulating tumor cells and metastatic behavior.

Gastrointestinal Mucormycosis of the Jejunum in an Immunocompetent Patient: A Case Report.

RATIONALE: Gastrointestinal Mucormycosis (GIM) is a kind of opportunistic fungal infection with poor prognosis. It usually occurs in patients with immune deficiency. We reported a case of immunocompetent male patient. PATIENT CONCERNS: This patient was presented as abdominal distension and gastrointestinal bleeding. DIAGNOSES: A variety of hemostatic methods was ineffective to stop the bleeding. The patient finally received laparotomy, and the jejunum lesions were found. INTERVENTIONS: Pathological examination confirmed it to be gastrointestinal mucormycosis in jejunum. OUTCOMES: However, after systemic anti-fungi therapy, the patient died of septic shock. LESSONS: The diagnosis mainly relies on pathological examination. Early diagnosis and early application of systemic amphotericin B liposome were fundamental for improving the prognosis.

The Effect of Prophylactic Central Neck Dissection on Locoregional Recurrence in Papillary Thyroid Cancer After Total Thyroidectomy: A Systematic Review and Meta-Analysis : pCND for the Locoregional Recurrence of Papillary Thyroid Cancer.

BACKGROUND: The use of prophylactic central neck dissection (pCND) for papillary thyroid cancer (PTC) without clinical evidence of nodal metastasis (cN0) remains controversial. This study was designed to examine whether pCND for PTC affected locoregional recurrence (LRR). METHODS: A systematic review was performed to compare the LRR between patients with PTC who underwent total thyroidectomy (TT) and pCND and those who underwent TT alone. The primary outcome was LRR. Other outcomes, including postoperative radioiodine (RAI) ablation and surgically related complications, were evaluated. A meta-analysis was performed using the random-effects model. RESULTS: We included 17 studies, which comprised 4437 patients. Patients in the TT+pCND group had a significantly reduced risk of LRR (risk ratio [RR] = 0.66; 95% confidence interval [CI]: 0.49-0.90; P = 0.008). The LRR in the central neck compartment (RR = 0.35; 95% CI 0.18-0.68; P = 0.002) was significantly lower in the TT+pCND group, whereas the LRR in the lateral neck compartment was similar between the two groups. Compared with the TT alone group, patients in the TT+pCND group tended to receive higher RAI (74.6% vs. 59.9%) and experience temporary hypocalcemia (odds ratio [OR] = 2.37; 95% CI 1.89-2.96; P < 0.00001), permanent hypocalcemia (OR = 1.93; 95% CI 1.05-3.57; P = 0.03), and increased overall morbidity (OR = 2.56; 95% CI 1.75-3.74; P < 0.00001). CONCLUSIONS: This meta-analysis suggested that although pCND reduced the LRR in PTC-specifically in the central neck compartment-it was accompanied by an increased rate of postoperative hypocalcemia. However, the evidence is limited and randomized, controlled trials are needed to clarify this role further.

One case of rare gastric cancer combined with lack of factor XI.

The patient, a 50-year-old woman, was admitted to hospital diagnosed with gastric cancer. While performing preoperative examination, we found that this patient had a lack of factor XI. This is the first case diagnosed with gastric cancer combined with lack of emitted factor XI, at least in China. We used only fresh frozen plasma to correct the blood coagulation disorder to perform an operation. Firstly, we think this is a rare case that should be reported. Secondly, what we have done to help this patient may help other doctors to make decisions when they meet any similar cases.

[Effect of corticosteroids upon the prognosis of idiopathic pulmonary fibrosis].

OBJECTIVE: To investigate the therapeutic effect of corticosteroids upon idiopathic pulmonary fibrosis (IPF) and the impact of corticosteroids upon survival time. METHODS: Clinical data of 94 corticosteroid treatment and 32 non-corticosteroid treatment IPF patients during 2000 - 2004 were retrospectively analyzed and their survival rates compared between two groups. The corticosteroid treatment patients were divided into 3 groups: improved, steady and worsened group according to the pulmonary function data. Therapeutic effects and survival rates were compared between these 3 groups. RESULTS: In the treatment group, 6 (6.4%) patients could not be located, 22 (23.4%) patients survived, and 66 (70.2%) patients died. In the non-corticosteroid treatment group, 1 (3.1%) patients could not be located, 2 (6.3%) patients survived and 29 (90.6%) patients died. No statistically significant difference existed between the two groups (P > 0.05). Sixty-two corticosteroid treatment patients were followed up for 3-6 months. Among them, 19 (30.7%) patients improved, 11 (17.7%) patients remained steady and 32 (51.6%) patients worsened in pulmonary function. In 19 improved patients, 7 (36.8%) survived and 12 (63.2%) died. In 11 steady patients, 3 (27.2%) survived and 8 (72.7%) died. In 32 worsened patients, 3 (9.4%) could not be located, 1(3.1%) survived and 28 (87.5%) died. The survival rate of the improved and steady groups was higher than that of the worsened group (P < 0.01). CONCLUSIONS: There is some therapeutic effect of corticosteroids in the early alveolitis stage of IPF. The prognosis of the patients with improved and steady pulmonary function parameters during the first 3 - 6 months is better than that of worsened patients.

[A retrospective cohort study of prognostic factors for death in patients with idiopathic pulmonary fibrosis].

OBJECTIVE: To investigate the prognostic implications of clinical, radiographic, and physiological variables in idiopathic pulmonary fibrosis (IPF). METHODS: The clinical, pulmonary physiological, bronchoalveolar lavage fluid (BALF) cell differentials and lung high-resolution computed tomography (HRCT) at diagnosis in 126 patients with IPF were retrospectively analyzed. Univariate and multivariate Cox proportional-hazards regression analysis was used to evaluate various parameters associated with hazard ratio (HR). The survival rates of all groups were compared using the Kaplan-Meier method. RESULTS: In 29.6 months of average follow-up time, the survival rate of the IPF patients was 46.8% (59/126), and the median survival time was 30 months after diagnosis. Glucocorticoids and/or cytotoxic drugs for patients with IPF did not change the prognosis. The survival rates between groups by gender and smoking status showed no statistically significant difference (Ward: 0.11, 1.65, P>0.05). The patients were divided into 2 groups by the median (the cutoff point value) of significant variables in univariate Cox proportional-hazards regression analysis, and the survival rates showed statistically significant difference by dyspnea scale, FVC%, TLC%, DLCO%, neutrophil percentage and eosinophil percentage in BALF, and the reticular and honeycomb lung score (Logrank: 13.52-57.52, P<0.05). The results of multivariate Cox proportional-hazards regression analysis showed that TLC%, DLCO%, HRCT reticular score and honeycomb lung score were factors that affected the prognosis of patients with IPF (Wald=5.76-21.48, P<0.05). CONCLUSIONS: TLC%, DLCO%, cell differentials of BALF and the degree of pulmonary fibrosis were the main factors affecting the prognosis of patients with IPF. TLC% and DLCO% showed a negative correlation with the prognosis of patients with IPF. Glucocorticoids and/or cytotoxic drug therapy had no effect on the prognosis of patients with IPF.

[Cell profiles of bronchoalveolar lavage fluid as prognostic indicators of idiopathic pulmonary fibrosis].

OBJECTIVE: To determine whether clinical and physiologic variables and bronchoalveolar lavage fluid (BALF) cell profiles affect the survival of patients with idiopathic pulmonary fibrosis (IPF). METHODS: There were 43 patients with clinically diagnosed IPF in the study. The Kaplan-Meier method and the Log-rank test were used to estimate the survival in the two groups and Cox proportional hazard regression was used to evaluate the Hazard Ratio in the IPF patients. RESULTS: The IPF patients presented with restrictive ventilatory disorders [FVC%: (61 +/- 18)%, TLC%: (54 +/- 13)%] and gas exchange impairment [D(L)CO%: (48 +/- 14)%]. The mean follow-up time was 30.7 months, and the median survival of IPF patients was 28.5 months after diagnosis. FVC ( Wald = 6.71, P < 0.01), TLC ( Wald = 12.37, P < 0.01) , D(L)CO ( Wald = 22.78, P < 0.01), neutrophil ( Wald = 16.26, P < 0.01) and eosinophil ( Wald = 7.73, P < 0.01) percentages were prognostic variables in the univariate Cox proportional hazard regression, and only D(L)CO (HR = 0.93, Wald = 15.77, P < 0.01) and the neutrophil percentage (HR = 1.07, Wald = 6.83, P < 0.01) were prognostic variables for IPF patients in the multivariate Cox proportional hazard regression. CONCLUSIONS: The IPF patients were predominantly old males and presented with restrictive ventilatory disorders and gas exchange impairment. Glucocorticoids and/or cytotoxic drugs could not improve the prognosis for the IPF patients. DLCO and BALF neutrophil percentage were prognostic variables, and DLCO was negatively correlated with the prognosis while the neutrophil percentage was positively correlated with the prognosis in the IPF patients.

Cross-sectional and longitudinal construct validity of the Saint George's Respiratory Questionnaire in patients with IPF.

BACKGROUND AND OBJECTIVE: This study was performed to confirm the cross-sectional and longitudinal construct validity of the Saint George's Respiratory Questionnaire (SGRQ) for the measurement of health-related quality of life (HRQoL) in patients with IPF. METHODS: Sixty-eight patients with IPF responded to the SGRQ and pulmonary function tests (PFT), dyspnoea testing, arterial blood gas analysis, 6-min walk tests (6MWT) and high-resolution computed tomography were performed in a baseline study. A follow-up study was performed on 45 of these patients. RESULTS: In the baseline study HRQoL as measured by the SGRQ was substantially impaired in IPF patients, especially in symptoms and activity domains. A significant decline in HRQoL was observed in the activity domain during follow up. TLC and changes in TLC showed the most significant inverse correlations with each SGRQ domain (r < -0.3, P < 0.05). In a stepwise multiple regression analysis, TLC contributed most significantly to each SGRQ component baseline score. Similar results were also observed during follow up. There was a significant correlation between total CT scores and each component of the SGRQ (r > 0.3, P < or = 0.001). Changes in ground-glass opacity on CT (CT-alv) were also correlated with changes in each SGRQ domain (r > 0.3, P < or = 0.001). Stepwise multiple regression analysis showed that interstitial opacity on CT (CT-fib) contributed to variation in the baseline activity score, and that changes in CT-alv independently contributed to overall changes in the SGRQ domains during follow up. The dyspnoea score, and changes in the dyspnoea score, correlated significantly with the SGRQ sores, with the exception of the symptoms score, in both the baseline and follow-up studies. CONCLUSIONS: HRQoL as assessed by the SGRQ showed good cross-sectional and longitudinal construct validity in patients with IPF. However, additional studies are required to analyse the reliability and responsiveness so that the SGRQ can be used in patients with IPF.

[Changes of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in the bronchoalveolar lavage fluid and the serum of patients with idiopathic pulmonary fibrosis].

OBJECTIVE: To detect the levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the bronchoalveolar lavage fluid (BALF) and the serum of patients with idiopathic pulmonary fibrosis (IPF), and to evaluate the significance of the changes in the pathogenesis of IPF. METHODS: Enzyme-linked immunoadsorbent assay (ELISA) was used to detect MMP-9 and TIMP-1 in the BALF and serum of 30 patients with IPF. RESULTS: The levels of MMP-9 in the BALF and serum of the patients showed no significant difference as compared with those of the control group. The levels of TIMP-1 in the BALF [(522 +/- 81) ng/L] and serum [(166 +/- 29) ng/L] of the patients were higher than those [(201 +/- 31), (87 +/- 16) ng/L] of the control group (P < 0.01). The ratios of MMP-9/TIMP-1 in the BALF (0.53 +/- 0.18) and serum (1.5 +/- 0.3) of patients with IPF were lower than those (1.06 +/- 0.38, 2.6 +/- 0.5) of the control group (P < 0.01, < 0.05). TIMP-1 in the BALF of the patients showed a strong positive correlation with chest CT fibrosis and pulmonary function test scores (P < 0.01), while MMP-9/TIMP-1 in the BALF had negative correlation with them (P < 0.01). CONCLUSION: Pulmonary fibrosis may be associated with increased TIMP-1 and decreased MMP-9/TIMP-1, which is able to inhibit the degradation of extracellular matrix.

[Cell apoptosis and the change of Fas/FasL gene in experimental pulmonary fibrosis].

OBJECTIVE: To investigate the changes and significance of cell apoptosis and Fas/FasL gene in pulmonary fibrosis. METHODS: Forty mice were divided into two groups randomly, each group contained twenty mice. TUNEL, immunohistochemistry and in situ hybridization were used to detect the change of cell apoptosis, Fas/FasL mRNA and protein in mice with pulmonary fibrosis caused by bleomycin. RESULTS: The apoptosis index of lung cells in the pulmonary fibrosis group (55.3 +/- 12.2) was higher than that of control group (4.7 +/- 1.0, t = 13.06, < 0.01). The expression of Fas/FasL mRNA (175.8 +/- 21.6, 5.2 +/- 1.6) and protein (956 +/- 96, 285 +/- 76) in the pulmonary fibrosis group was higher than that of control group (mRNA: 26.6 +/- 1.9, 0.5 +/- 0.4, t = 21.7, 8.79, all < 0.01; protein: 491 +/- 96, 100 +/- 18, t = 5.03, 12.81, < 0.01). CONCLUSION: The apoptosis index of lung cells, Fas/FasL genes and protein were up-regulated in lung tissue of pulmonary fibrosis, which may play an important role in the development of disease.

[Effect of Shenluotong on secretion of ECM and expression of TGF-beta1 in rats mesangial cells of rats].

OBJECTIVE: To investigate the effect of Shenluotong on the expression of transforming growth factor-beta1 (TGF-beta1) and extracellular matrix (ECM) in Ang II-induced MCs. METHOD: Fibronectin (FN) and collagen type IV (Col IV) of extracellular matrix were detected by enzyme-linked immunosorbent assay; the expression of TGF-beta1 mRNA were measured by semi-quantitative reverse transcription-polymerase chain reaction. RESULT: A positive correlation between TGF-beta1 and ECM were found in the present study. FN, Col IV and TGF-beta1 mRNA were inhibited by Shenluotong significantly. CONCLUSION: Shenluotong can decrease the accumulation of ECM and inhibit the expression of TGF-beta1, suggesting further that shenluotong can be used to prevent and treat various glomerular diseases and delay glomerular sclerosis.

[Respiratory control in obstructive sleep apnea hypopnea syndrome].

OBJECTIVE: To evaluate the role of ventilatory control in obstructive sleep apnea hypopnea syndrome (OSAHS). METHODS: Thirty-five patients with OSAHS were compared with 15 obese controls in pulmonary function, hypoxic ventilatory response (HVR), hypercapnic ventilatory response (HCVR) and polysomnography (PSG). RESULTS: (1) There were no differences in HVR and HCVR between patients with OSAHS and the control (t = 1.28, 0.57; P > 0.05). In OSAHS patients, HVR was correlated with nadir nocturnal oxygen saturation (MmS(P)O(2)) (r = -0.54, P < 0.01) and HCVR (r = 0.57, P < 0.01). (2) Patients with mild and moderate OSAHS had higher HVR than those with severe OSAHS (t = 2.74, P < 0.01). When 5 < or = apnea and hypopnea index (AHI) < 40, HVR was negatively correlated to forced expiratory volume in one second (FEV(1))/peak expiratory flow (PEF) (r = -0.42, P < 0.05) and AHI (r = -0.68, P < 0.01). For those whose AHI > or = 40, HVR was negatively correlated with MmSpO(2) (r = -0.58, P < 0.05) and positively correlated with HCVR (r = 0.59, P < 0.05). CONCLUSION: In OSAHS patients, HCVR did not show significant change, but HVR showed two phasic change-increase first and then decrease-following the elevation of AHI, which was also related to MmSpO(2) and HCVR.

[Change of prostaglandin E2 and interleukin-12, interleukin-13 in the bronchoalveolar lavage fluid and the serum of the patients with idiopathic pulmonary fibrosis].

OBJECTIVE: To detect the levels of prostaglandin E2 (PGE2) and interleukin-12 (IL-12), IL-13 in the bronchoalveolar lavage fluid (BALF) and the serum of patients with idiopathic pulmonary fibrosis (IPF) and to investigate the significance of their change in the pathogenesis of IPF. METHODS: Radioimmunoassay (RIA) and enzyme-linked immunoadsorbent assay (ELISA) were used to detect the levels of PGE2 and IL-12, IL-13 in the BALF and the serum of patients with IPF. RESULTS: In the BALF of patients with IPF, the levels of PGE2 (591 +/- 88) ng/L and IL-13 (38 +/- 5) ng/L were higher than that of the control group (P < 0.01), and the level of IL-12 (1.34 +/- 0.25) ng/L was lower than that of control group. In the patients with IPF, the change of IL-13 in the serum was consistent with the change in the BALF. But the levels of PGE2 (235 +/- 13) ng/L and IL-12 (2.35 +/- 0.14) ng/L in the serum showed no significant difference between the patients with IPF and the control group. CONCLUSIONS: In the patients with IPF the increase of PGE2 may be correlated with the increase of IL-13 and the decrease of IL-12. It suggests that disequilibrium of Th1/Th2 plays an important role in the development of IPF. The increase of PGE2 in IPF is a local event rather than a systemic effect.