[Advance the construction of "health promotion, prevention, diagnosis, control, treatment, rehabilitation" six-in-one working system of chronic obstructive pulmonary disease in China].

Chronic obstructive pulmonary disease (COPD) is a common chronic respiratory disease that seriously threatens people's health. It significantly affects the quality of life of patients and presents an overwhelming economic burden on the governmental perspectives, which makes COPD a major public health issue in China. In this paper, we propose some methods that can help to accelerate the implementation of the Healthy China Strategy and promote the change of people's attitudes towards COPD from disease-centered to health-centered. Those methods are composed of many important aspects including the concepts of"population medicine", the improvement of the national health policy for COPD, the consolidation of the original troika strategy of respiratory disciplines and the high-quality implementation of the three major national projects, aiming to inspire people to participate in the six-in-one work system of dealing with COPD encompassing the health promotion, the prevention, the diagnosis, the control, the treatment, and the rehabilitation.

[Sinusitis, otitis media and diffuse bronchiectasis in both lungs].

Primary ciliary dyskinesia (PCD) is a rare autosomal recessive or X-linked biallelic mutations inherited disease, characterized by motile cilia dysfunction. Typical manifestations include bronchiectasis, secretory otitis media, sinusitis, situs inversus, and infertility. PCD often needs to be differentiated from cystic fibrosis (CF) because of similar clinical manifestations. In this paper, a juvenile female who presented with recurrent cough and expectoration with fever since early childhood, had a history of secretory otitis media and sinusitis, and had been considered for the diagnosis of CF. After the discovery of compound heterozygous mutations in PCD related pathogenic genes by gene sequencing, combined with the clinical manifestations and imaging characteristics, PCD was finally diagnosed.

[The fundus autofluorescence of retinal astrocytic hamartomas in tuberous sclerosis complex].

Objective: To investigate the autofluorescence findings of retinal astrocytic hamartoma (RAH) in patients with tuberous sclerosis complex (TSC). Methods: It was a retrospective case series study. Twenty-three patients (35 eyes) who were referred to Department of Internal Medicine and Department of Ophthalmology, Peking Union Medical College Hospital between November 2012 and June 2018 with established TSC-associated RAH diagnosis were included. The findings of fundus autofluorescence, fundus photos and spectral-domain optical coherence tomography (SD-OCT) were retrospectively reviewed. RAH lesions were classified into three types based on the morphology shown in fundus photos. The fundus autofluorescence features of TSC-associated RAH were described. The Welch's test and Fisher's exact test were used for statistical analysis. Results: The patients were 8 males and 15 females aged (28±9) years old (range, 15-55 years). Seventy-two RAH lesions were examined, including 59 type 1 RAHs, 7 type 2 RAHs and 6 type 3 RAHs. According to fundus autofluorescence, type 1 RAHs could be further divided into reduced, speckled and background autofluorescence patterns, among which the hypoautofluorescence pattern accounted for the majority (69.5%, 41/59), while the speckled pattern was usually accompanied by outer retinal disorganization and discontinuation of photoreceptor outer segment as revealed by SD-OCT. No significant difference was revealed in tumor thickness for reduced, speckled and background autofluorescence patterns of type 1 RAHs [(490.2±97.9) vs. (589.2±221.6) vs. (463.0±76.2) µm respectively, F=1.426, P=0.283]. Among type 1 RAHs, the number of reduced autofluorescence pattern lesions found in perifoveal, peripapillary, inferonasal, inferotemporal, superonasal, superotemporal quadrants were 9, 4, 4, 7, 4, 13 respectively, while that of speckled autofluorescence pattern lesions were 3, 0, 3, 2, 3, 2 and background autoflurorescence pattern lesions 3, 0, 1, 1, 0, 0. No significant difference was revealed in location distribution (P=0.452) either. Type 2 RAHs featured numerous hyperautofluorescent spots or plaques, and calcification in type 2 RAHs varied in autofluorescence intensity. Type 3 RAHs, combining the features of type 1 and 2 RAHs, were characterized by central hyperautofluorescent spots and hypoautoflurescent rim, but the area of hyperautofluorescence was smaller than that of calcification as shown in fundus photos. Conclusions: In TSC, the fundus autofluorescence of RAHs varies from hypoautofluorescence to hyperautofluorescence patterns according to RAH types. The retinal involvement and calcification degree of TSC-associated RAHs could be reflected on the autofluorescence, which was beneficial to the full assessment. (Chin J Ophthalmol, 2020, 56: 211-216).

[Clinical analysis of ankle arthroscopy technique for treatment of tarsal tunnel syndrome].

Objective: To explore the effects of ankle arthroscopy technique in treating the tarsal tunnel syndrome. Methods: From May 2014 to May 2016, the ankle arthroscopy technique was used for surgical treatment of tarsal tunnel syndrome in the Department of Hand and Foot Microsurgery in Xuzhou Central Hospital. Twenty-two patients with 24 feet with tarsal tunnel syndrome were hospitalized for treatment, with 10 left feet and 14 right feet, aged 26-57 years. The disease duration ranged from 4 to 15 months (mean 8.3 months). The dual-portals ankle arthroscopic neurolysis and fiber membrane resection were performed. The Pfeiffer scoring system was used to evaluate the post-operative outcomes. Results: Primarily healing of the wound was achieved in all the patients. No postoperative infection was found during the follow-up. The postoperative hospitalization time was 2 to 5 days (mean 3.7 days). All patients were followed up for 12 to 24 months. At the final follow-up, all the patients had significant improvement in numbness and pain. According to the Pfeiffer scoring system, the results were excellent in 16 feet, good in 8 feet, with an excellent and good rate of 100%. Conclusion: The ankle arthroscopic neurolysis is a safe and easy treatment option for the tarsal tunnel syndrome and provides satisfactory results.

[The clinical characteristics of 17 cases of primary ciliary dyskinesia].

Objective: To review the clinical data of cases of primary ciliary dyskinesia (PCD), and to explore the clinical characteristics for the understanding of PCD. Methods: We retrospectively summarized 17 patients with PCD diagnosed in Peking Union Medical College Hospital from Jan 2009 to Dec 2014. There were 7 male and 10 female patients, with the age from 6 to 57 years at the time of diagnosis. The mean onset age of the disease was 11.7±2.1 years, and the mean age at diagnosis was 29.5±3.5 years. We analyzed their clinical symtoms, radiologic images, pulmonary function test and the electron microscopic findings for the clinical characteristics of PCD. Results: The most common onset symptoms were cough (15/17) or sputum (13/17) among our 17 patients with PCD. Only 5 patients had situs inversus in our group. Sixteen patients had bronchiectasis on chest CT scan. Nasal sinusitis was confirmed by nasal CT scan in 15 patients. The most common pathogens from sputum cultures included Pseudomonas aeruginosa, Haemophilus influenzea, Aspergillus fumigates and Candida (3/14 respectively). None of the patients had evidence of mycobacterial infection. Twelve patients underwent spirometry and obstructive pattern was the most common disorder (8/12). Diffusion impairment (5/10) and restrictive pattern dysfunction (3/10) were also present in our patients. Two patients had normal pulmonary function test results. Thirteen patients underwent bronchial mucosal ciliary electron microscopy and the most abnormalities were outer or inner dynein arms deficiency (8/13), and other abnormalities included microtubule arrangement disorder (3/13), reduction of the number of microtubules (3/13) and reduction of the number of dynein arms (2/13). Four of our patients had multiple dysfunctions on their ciliaries. Conclusions: PCD should be considered in bronchiectasis patients with disease onset at childhood even without situs inverse, especially those accompanied with nasal sinusitis or otitis media. Chest or paranasal sinus CT scan, and male sperm examination were helpful for the diagnosis. Mucosal ciliary electron microscopy was an efficient diagnostic method for PCD.

An association analysis between psychophysical characteristics and genome-wide gene expression changes in human adaptation to the extreme climate at the Antarctic Dome Argus.

Genome-wide gene expression measurements have enabled comprehensive studies that integrate the changes of gene expression and phenotypic information to uncover their novel associations. Here we reported the association analysis between psychophysical phenotypes and genome-wide gene expression changes in human adaptation to one of the most extreme climates on Earth, the Antarctic Dome Argus. Dome A is the highest ice feature in Antarctica, and may be the coldest, driest and windiest location on earth. It is considered unapproachable due to its hostile environment. In 2007, a Chinese team of 17 male explorers made the expedition to Dome A for scientific investigation. Overall, 133 psychophysical phenotypes were recorded, and genome-wide gene expression profiles from the blood samples of the explorers were measured before their departure and upon their arrival at Dome A. We found that mood disturbances, including tension (anxiety), depression, anger and fatigue, had a strong, positive, linear relationship with the level of a male sex hormone, testosterone, using the Pearson correlation coefficient (PCC) analysis. We also demonstrated that significantly lowest-level Gene Ontology groups in changes of gene expression in blood cells with erythrocyte removal were consistent with the adaptation of the psychophysical characteristics. Interestingly, we discovered a list of genes that were strongly related to significant phenotypes using phenotype and gene expression PCC analysis. Importantly, among the 70 genes that were identified, most were significantly related to mood disturbances, where 42 genes have been reported in the literature mining, suggesting that the other 28 genes were likely novel genes involved in the mood disturbance mechanism. Taken together, our association analysis provides a reliable method to uncover novel genes and mechanisms related to phenotypes, although further studies are needed.

Effects of islet neogenesis-associated protein pentadecapeptide on cell mass and insulin secretion of pancreatic ß-cells.

OBJECTIVE: To explore the effects of islet neogenesis- associated protein pentadecapeptide (INGAP-PP) on proliferation and secretion function of ß-cells. METHODS: Islets of adult Sprague Dawley rats were isolated by collagenase digestion and treated with 10 µg/ml INGAP-PP, after 12, 24, 48 h, glucose-stimulated insulin secretion (GSIS) and acridine orange/pro pidium iodide (AO/PI) staining were used to detect the secretion function and cell viability. The INS-1 cells were treated with 0, 1, 10, 25, 50, 100, 250, and 500 µg/ml INGAP-PP for 24 or 48 h, MTT cell proliferation assay was adopted to survey the dose-response relationship between INGAP-PP and cell proliferation. The mRNA expression of roliferating cell nuclear antigen (PCNA), Cyclin D1, Cdk4, P27, p38MAPK, and JNK in INS-1 cells were examined by RT-PCR, and the protein expression of PCNA was examined by Western blot. The statistical significance was determined by Student's t-test or one-way analysis of variance. RESULTS: The insulin secreted by islets and the cell viability were increased by INGAP-PP. MTT indicated a dose-response relationship between INGAP-PP and quantity of INS-1 cells, and treatment for 48 h had a stronger effect on cell proliferation than the 24 h. INGAP-PP up-regulated the mRNA expression of PCNA, Cyclin D1, Cdk4 and downregulated P27, p38MAPK, and JNK. Moreover, the protein expression of PCNA was up-regulated by 45% after INGAPPP exposure for 48 h. CONCLUSIONS: INGAP-PP increased the insulin secretion, enhanced the proliferation and might reduce apop tosis of ß-cells. The mechanism may contribute to the changed expression of some genes related to cell cycle.

Intrauterine growth retardation leads to the functional change of insulin secretion in the newborn rats.

To investigate the observed variation in glucose tolerance and insulin secretion in intrauterine growth retarded newborn rats and to explore the mechanism of the variations, Sprague-Dawley pregnant rats were allocated into two groups: a control group and an intrauterine energy restricted group. The intrauterine growth retardation (IUGR) in the rats was induced by 50% calorie restriction in pregnant rats from gestational day 15 until term as compared to the control group. The pancreata of control and IUGR newborn rats were dissected respectively. RT-PCR was used to study the mRNA level related to insulin synthesis and exocytosis. Intraperitoneal glucose tolerance tests were done to study the function of the pancreatic islet. We found that birth weight and pancreas mass of IUGR newborn rats were significantly lower than those of controls. Although no significant differences were observed in mRNA level of insulin and PDX-1, the expression of genes related to insulin exocytosis such as munc13-1, vamp-2, syntaxin1a, rab3a were reduced significantly in IUGR newborn rats. IUGR animals were glucose-intolerant. The observed blood insulin level and insulin secretion response to glucose challenge were both found to be at reduced level in IUGR newborn rats as compared with the normal control group rats. With these findings, we hypothesize that IUGR can induce changes in glucose homeostasis due to, at least in part, a reduced function of insulin exocytosis in newborn rats.

Hydrogen gas (XEN) inhalation ameliorates airway inflammation in asthma and COPD patients.

BACKGROUND: Hydrogen was proven to have anti-oxidative and anti-inflammation effects to various diseases. AIM: We wish to investigate the acute effects of inhaled hydrogen on airway inflammation in patients with asthma and chronic obstructive pulmonary disease (COPD). DESIGN: Prospective study. METHODS: In total, 2.4% hydrogen containing steam mixed gas (XEN) was inhaled once for 45 min in 10 patients with asthma and 10 patients with COPD. The levels of granulocyte-macrophage colony stimulating factor, interferon-γ, interleukin-1ß (IL-1ß), IL-2, IL-4, IL-6 and so on in peripheral blood and exhaled breath condensate (EBC) before and after 'XEN' inhalation were measured. RESULTS: 45 minutes 'XEN' inhalation once decreased monocyte chemotactic protein 1 level in both COPD (564.70-451.51 pg/mL, P = 0.019) and asthma (386.39-332.76 pg/mL, P = 0.033) group, while decreased IL-8 level only in asthma group (5.25-4.49 pg/mL, P = 0.023). The level of EBC soluble cluster of differentiation-40 ligand in COPD group increased after inhalation (1.07-1.16 pg/mL, P = 0.031), while IL-4 and IL-6 levels in EBC were significantly lower after inhalation in the COPD (0.80-0.64 pg/mL, P = 0.025) and asthma (0.06-0.05 pg/mL, P = 0.007) group, respectively. CONCLUSIONS: A single inhalation of hydrogen for 45 min attenuated inflammatory status in airways in patients with asthma and COPD.

Polychlorinated biphenyls affect thyroid function and induce autoimmunity in Sprague-Dawley rats.

Polychlorinated biphenyls (PCBs) have been reported to cause a variety of toxic effects. In order to assess the thyroid function after exposure to PCBs and investigate whether PCBs induce autoimmune process in the thyroid gland, we determined the levels of serum thyroid hormones (FT3, FT4, and T4), thyroid-stimulating hormone (TSH), and thyroid peroxidase antibody (TPOAb) in Sprague-Dawley rats treated with a commercial mixture of PCBs, Aroclor 1,254 (PCBs group), or the antithyroid drug, propylthiouracil (PTU group). The histopathology of the thyroid was also examined. Serum FT3, FT4, and T4 concentrations were significantly reduced, while TSH values were dramatically increased in PCBs group and PTU group compared with control rats (p < 0.05). TPOAb levels were significantly elevated in PCBs-treated rats (p < 0.05) but not in PTU group (p > 0.05). In contrast to the controls, treatment with PCBs lead to distinct histopathological changes in the thyroid gland, such as hyperplasia of the epithelia in follicles, colloid content reduction, vascularization, and lymphocytic infiltration in the perifollicular areas, whereas the major changes in the thyroid in PTU-treated rats were follicles shrinkage or collapse and colloid content reduction compatible with induced hypothyroidism. The results indicate that PCBs affect thyroid function via the induction of autoimmunity, which is a mechanism different from the effect of antithyroid drug on the thyroid gland.

Antigen-induced airway inflammation in the Brown Norway rat results in airway smooth muscle hyperplasia.

Asthma is characterized by chronic airways inflammation, airway wall remodeling, and airway hyperresponsiveness (AHR). An increase in airway smooth muscle has been proposed to explain a major part of AHR in asthma. We have used unbiased stereological methods to determine whether airway smooth muscle hyperplasia and AHR occurred in sensitized, antigen-challenged Brown Norway (BN) rats. Ovalbumin (OA)-sensitized BN rats chronically exposed to OA aerosol displayed airway inflammation and a modest level of AHR to intravenously administered ACh 24 h after the last antigen challenge. However, these animals did not show an increase in smooth muscle cell (SMC) number in the left main bronchus, suggesting that short-lived inflammatory mechanisms caused the acute AHR. In contrast, 7 days after the last aerosol challenge, there was a modest increase in SMC number, but no AHR to ACh. Addition of FCS to the chronic OA challenge protocol had no effect on the degree of inflammation but resulted in a marked increase in both SMC number and a persistent (7-day) AHR. These results raise the possibility that increases in airway SMC number rather than, or in addition to, chronic inflammation contribute to the persistent AHR detected in this model.

[Pulmonary nocardia infection].

Four cases of pulmonary Nocardia infection were reported and the 22 cases reported in our country between 1980 and 1993 were analyzed together for the purpose of revealing the clinical picture of this disease in China. There was approximately a ratio of two male patients to one female (18:8) with a mean age of 40 years in this series of patients. Various underlying diseases were found as predisposing factors in 69% (18/26) of the cases. 34.5% (9/26) of the cases had a history of corticosteroid therapy. Pleural effusion was identified in 50% (13/26) of the patients. 38% (10/26) of the patients died. Patients with primary pulmonary Nocardia infection had a better prognosis than those with secondary infection. Appropriate culture media, sufficient culture time and repeated cultures were recommended to improve the positive identification rate of this special causative agent. The sulfonamides were the drugs of first choice along with prompt drainage of thoracic empyema and abscess.

mTORC1 enhancement of STIM1-mediated store-operated Ca2+ entry constrains tuberous sclerosis complex-related tumor development.

The protein complex of tuberous sclerosis complex (TSC)1 and TSC2 tumor suppressors is a key negative regulator of mammalian target of rapamycin (mTOR). Hyperactive mTOR signaling due to the loss-of-function of mutations in either TSC1 or TSC2 gene causes TSC, an autosomal dominant disorder featured with benign tumors in multiple organs. As the ubiquitous second messenger calcium (Ca(2+)) regulates various cellular processes involved in tumorigenesis, we explored the potential role of mTOR in modulation of cellular Ca(2+) homeostasis, and in turn the effect of Ca(2+) signaling in TSC-related tumor development. We found that loss of Tsc2 potentiated store-operated Ca(2+) entry (SOCE) in an mTOR complex 1 (mTORC1)-dependent way. The endoplasmic reticulum Ca(2+) sensor, stromal interaction molecule 1 (STIM1), was upregulated in Tsc2-deficient cells, and was suppressed by mTORC1 inhibitor rapamycin. In addition, SOCE repressed AKT1 phosphorylation. Blocking SOCE either by depleting STIM1 or ectopically expressing dominant-negative Orai1 accelerated TSC-related tumor development, likely because of restored AKT1 activity and enhanced tumor angiogenesis. Our data, therefore, suggest that mTORC1 enhancement of store-operated Ca(2+) signaling hinders TSC-related tumor growth through suppression of AKT1 signaling. The augmented SOCE by hyperactive mTORC1-STIM1 cascade may contribute to the benign nature of TSC-related tumors. Application of SOCE agonists could thus be a contraindication for TSC patients. In contrast, SOCE agonists should attenuate mTOR inhibitors-mediated AKT reactivation and consequently potentiate their efficacy in the treatment of the patients with TSC.

Comparison of M22-based ELISA and human-TSH-receptor-based luminescence assay for the measurement of thyrotropin receptor antibodies in patients with thyroid diseases.

Previously, a new procedure for measuring serum TSH receptor autoantibodies (TRAb) was reported in which the autoantibodies inhibit binding of a human monoclonal thyroid stimulating antibody M22 to TSHR-coated ELISA plate wells (TRAb ELISA). The aim of the present study was to evaluate the clinical performance of this assay in comparison to the second generation TRAb assay (TRAb LIA) based on the recombinant human TSH-receptor and chemiluminescence technology (TRAb LIA). Among the 158 patients, 84 patients suffered from Graves' disease (GD), 34 patients had Hashimoto's thyroiditis (HT), and 40 patients had euthyroid nodular thyroid disease (NTD) without signs of autoimmunity. TRAb measurements were performed according to the manufacturer's instructions. Out of 84 GD patients, 80 (95.2%) were TRAb positive as detected by the TRAb LIA. One GD patient had TRAb values within the grey zone (1.0-1.5 IU/l). All patients with HT and NTD were negative except in 6 (8.1%) cases whose TRAb values were within the grey zone. On the basis of the recommended cutoff value (TRAb 1.0 IU/l), the TRAb ELISA found 78 of 84 (92.9%) GD patients to be TRAb positive. None of the patients with HT, but two cases (5.0%) with NTD were TRAb positive. The diagnostic sensitivity of the TRAb LIA and TRAb ELISA assays was 95.2 and 92.9%, while the specificity was 100% and 97.3%, respectively. There was a close correlation (r=0.968, p<0.0001) between both assays in 84 patients with GD. Additionally, the between-run imprecision close to the cutoff limit was assessed. The calculated between-run coefficient of variation (CV) of the TRAb ELISA was 28.2% at the recommended cutoff value of 1.0 IU/l. Due to the evaluated imprecision data we propose a higher cutoff value correlating with a between-run CV of 20% (functional assay sensitivity). Our results indicate that due to a worse imprecision the TRAb ELISA has a slightly lower sensitivity and specificity compared to the TRAb LIA assay. These findings suggest that the M22 monoclonal antibody-based TRAb ELISA is not as reliable as other second generation TRAb assays in the diagnosis of Graves' diseases.

Pulmonary complications in patients with AIDS: a report from a Beijing hospital.

OBJECTIVE: The aim of this study was to improve the awareness of pulmonary complications in patients with AIDS. METHODOLOGY: Nine patients with AIDS with pulmonary involvement from March 1992 to March 2000 were analysed. RESULTS: Of the nine cases, there were eight cases complicated with Pneumocystis carinii pneumonia (PCP). The clinical presentation of PCP was fever (8/8), dyspnoea on exertion or at rest (7/8), and hypoxaemia with a mean PaO2 of 58 mmHg. Chest X-ray films showed bilateral diffuse interstitial or alveolar infiltrates. Pulmonary tuberculosis, tuberculous lymphadenitis and bronchial fungal infection were found in three cases. CONCLUSIONS: AIDS patients are at high risk of suffering from pulmonary complications, of which PCP is most common. If young patients who were healthy in the past suddenly suffered from pneumonia and respiratory failure, PCP should be considered. When opportunistic pulmonary infection is diagnosed under special circumstances, one should be alert to the possibility of AIDS and examine serum antihuman immunodeficiency virus (HIV) antibody.