Regular Observation of De-Acclimatization and Randomized Controlled Research of Diagnostic Criteria of High Altitude De-Acclimatization Syndrome among Different Plateau Migrants Crowd after Their Return to the Plain

Objective: The objective of this study was to investigate the diagnostic methods of high altitude de-acclimatization syndrome and to formulate diagnostic criteria. Methods: This study was conducted using epidemiological surveys and a multi-center randomized controlled clinical trial. A total of 3011 subjects were studied, and the following indices were collected after their return to low altitude areas from the plateau: general health status, blood, urine and stool samples, myo-cardial enzyme levels, liver and kidney function, nerve function, sex hormone levels, microalbuminuria, electrocardiogram (ECG), echocardiography, pulmonary function, and hemorheological markers. These data were compared to those of randomized healthy subjects in the same age range who lived at the same altitude to determine the characteristics of high altitude de-acclimatization syndrome. Based on these characteristics, diagnostic criteria for high altitude de-acclimatization syndrome were formulated. Results: This study demonstrated that the incidence of high altitude de-acclimatization syndrome was 84.36%. Sixty percent of the cases were mild, 30% were medium, and 10% were severe. The incidence was higher among those who returned to a place of lower altitude, resided at a high altitude for a longer period of time, or engaged in heavy labor while at high altitude. Patients with high altitude de-acclimatization syndrome manifested hematological abnormalities and abnormal ventricular function, notably a right ventricular diastolic function, which recovered to baseline function after one to five years. Exposure to long-term hypoxia often caused obvious changes in cardiac morphology, i.e., left and right ventricular hypertrophy, particularly within the right ventricle. In addition, patients with high altitude de-acclimatization syndrome often presented with low blood pressure, low pulse pressure, and microalbuminuria. A few patients presented with occult blood in their feces. The diagnosis of high altitude de-acclimatization syndrome can be made if a patient who recently returns to the plain from the plateau complains of dizziness, weakness, sleepiness, chest tightness, edema, memory loss, and other symptoms and signs that do not alleviate under short-term rehabilitation or symptomatic treatment, and if organic diseases of the heart, lung, kidney, and other organs have been excluded. Conclusion: The diagnosis of high altitude de-acclimatization syndrome should be made after a comprehensive analysis of the patient’s clinical symptoms and signs.

Effect of Dexamethasone on Expression of AGR2 Protein in Asthmatic Mice

This study examined the expression of the anterior gradient-2 （AGR2） protein and Muc5ac protein in the lung tissues of asthmatic mice and the effect of dexamethasone, with an at- tempt to explore the role of AGR2 in the over-secretion of mucus in the airway. Eighteen BALB/c mice were divided into asthma group, control group and dexamethasone group. In dexamethasone group, dexamethasone was intraperitoneally administered. Expression of AGR2 protein and Muc5ac protein in the murine lung tissues was immunohistochemically detected. IL-13 level was determined in the bronchoalveolar lavage fluid （BALF） by ELISA. The results exhibited that the expression of AGR2 protein in asthma group （0.522±0.041） was significantly higher than that in normal controls （0.361±0.047） （P〈0.01） and bore a positive linear relationship to the expression of Muc5ac protein （r=0.873, P〈0.05） and IL-13 level （r=0.828, P〈0.05）. Expression of AGR2 protein in the dexa- methasone group （0.456±0.049） was significantly lower than that in the asthma group. It was concluded that： （1） the expression of AGR2 protein was significantly higher in asthmatic mice as com- pared with their normal counterparts; （2） the expression was obviously related to the expression of Muc5ac protein and IL-13; （3） dexamethasone could down-regulate the expression of AGR2 protein. Our findings suggested that AGR2 might be involved in the over-secretion of mucus in the airway in asthma.

Primary Culture of Alveolar Epithelial Type Ⅱ Cells and Its Bionomic Study

To establish a better method of primary culture for alveolar epithelial type Ⅱ cells （AEC Ⅱ ） and to study its bionomics, alveolar epithelial type Ⅱ cells were isolated by digestion with trypsin and collagenase, which were then purified by plated into culture flask coated with rat immunoglobulin （i The purified AEC Ⅱ were identified by alkaline phosphatase staining, electron mi- croscopy, immunocytochemical staining of pulmonary surfactant protein A （SPA）. The SPA expression and transfection characteristics were compared with those of A549 cell line. The results showed that AEC Ⅱ could be isolated by digestion with trysin and collagenase and purified by adhesive purification by using IgG, with a yield of about 2-3 × 10^7, and a purity of about 75%-84 %. Cells could be quickly identified with AKP staining. AEC Ⅱ were different from A549 cell line in terms of SPA expression and transfection characteristics. It is concluded that adhesive purification with IgG can improve the purity of AEC Ⅱ, and AKP staining is simple in cell identification. AEC Ⅱ can not be completely replaced by A549 cells in some studies because the differences between them, such as SPA expression.

Nonintubated thoracoscopic lobectomy plus lymph node dissection following segmentectomy for central type pulmonary masses

Lung cancer is the most common cancer worldwide. In the United States, it causes more cancer-related deaths than the next four causes （breast cancer, prostate cancer, colon cancer, and pancreatic cancer） of cancer-related mortality combined （1）. About 30% of people have already progressed to stage III lung cancer and 40% to stage IV at the time they are diagnosed （2）. Although chest X-ray and sputum cytology, when applied in health check-ups, can identify some relatively small tumors, they are not able to lower the overall mortality （3）. More recently,

Effects of Nω-nitro-L-arginine methyl ester and aminoguanidine on lipopolysaccharide-induced airway hyperresponsiveness in guinea pigs

Background The down-regulation of constitutive nitric oxide synthase （cNOS） and up-regulation of inducible nitric oxide synthase （iNOS） are associated with the allergen-provocated airway hyperresponsiveness （AHR）. This study aimed to determine whether their alteration also plays an important role in the AHR induced by lipopolysaccharide （LPS）. Methods Hartley male guinea pigs, weighing between 250 g and 350 g, were injected with LPS at a dose of 1 mg/kg every 24 hours for three days. A non-selective NOS inhibitor, N^-nitro-L-arginine methyl ester （L-NAME）, or a selective inducible NOS inhibitor, aminoguanidine （AG）, were used thirty minutes before each injection of LPS. Airway reactions, nitric oxide （NO） production and inflammatory changes were detected 24 hours after the last dose of LPS. Results AG significantly decreased the NO production in the bronchoalveolar lavage fluid （BALF） and sharply reduced the intensity of bronchoconstdction to histamine challenge. L-NAME also significantly decreased the NO production in the BALF, but had no effect on airway reactions or, perhaps, a tendency to enhance the intensity of AHR. Conclusions The data suggest that inducible NOS contributes to the AHR induced by repetitive intraperitoneal LPS, and constitutive NOS was also involved.

Envonalkib versus crizotinib for treatment-naive ALK-positive non-small cell lung cancer: a randomized, multicenter, open-label, phase III trial

Anaplastic lymphoma kinase(ALK)rearrangements are present in about 5–6%of non-small cell lung cancer(NSCLC)cases and associated with increased risks of central nervous system(CNS)involvement.Envonalkib,a novel ALK inhibitor,demonstrated promising anti-tumor activity and safety in advanced ALK-positive NSCLC in the first-in-human phase I study.This phase III trial(ClinicalTrials.gov NCT04009317)investigated the efficacy and safety of first-line envonalkib in advanced ALK-positive NSCLC cases.Totally 264 participants were randomized 1:1 to receive envonalkib(n=131)or crizotinib(n=133).Median independent review committee(IRC)-assessed progression-free survival(PFS)times were 24.87(95%confidence interval[CI]:15.64–30.36)and 11.60(95%CI:8.28–13.73)months in the envonalkib and crizotinib groups,respectively(hazard ratio[HR]=0.47,95%CI:0.34–0.64,p<0.0001).IRC-assessed confirmed objective response rate(ORR)was higher(81.68%vs.70.68%,p=0.056)and duration of response was longer(median,25.79[95%CI,16.53–29.47]vs.11.14[95%CI,9.23–16.59]months,p=0.0003)in the envonalkib group compared with the crizotinib group.In participants with baseline brain target lesions,IRC-assessed CNS-ORR was improved with envonalkib compared with crizotinib(78.95%vs.23.81%).Overall survival(OS)data were immature,and median OS was not reached in either group(HR=0.84,95%CI:0.48–1.47,p=0.5741).The 12-month OS rates were 90.6%(95%CI,84.0%–94.5%)and 89.4%(95%CI,82.8%–93.6%)in the envonalkib and crizotinib groups,respectively.Grade≥3 treatment-related adverse events were observed in 55.73%and 42.86%of participants in the envonalkib and crizotinib groups,respectively.Envonalkib significantly improved PFS and delayed brain metastasis progression in advanced ALK-positive NSCLC.