2019年 · 第132卷第11期

Background: In China, the prevalence of allergic rhinitis (AR) and asthma has increased in the past decade. As these two diseases frequently coexist, the Asia-Pacific Survey of Physicians on Asthma and Allergic Rhinitis (ASPAIR) study aimed to assess physicians’ beliefs and treatment patterns of coexistent asthma-AR across six Asian countries. This analysis presents the results from China. Methods: The 200 hospital-based general physicians and pediatricians were interviewed from five cities in China. Physicians were questioned in-person about their knowledge, beliefs and management practices for patients with coexistent asthma-AR. Results: Approximately 70% of the physicians interviewed routinely evaluated their patients with asthma or AR for signs of coexistent disease. While the majority of physicians (>90% of physicians) recognized the increased burden of coexistent asthma-AR vs. one condition alone and that coexistent disease requires additional treatment, most physicians (96%) also believed that patients with coexistent asthma-AR were well managed if either condition alone improved. Similarly, although 71% of physicians selected a combination of intranasal and inhaled corticosteroids as their preferred treatment for coexistent asthma-AR, in line with treatment guidelines, two fifths of physicians indicated that treatment for coexistent disease requires too much medication and that their patients prefer oral medications and a third of physicians believed that corticosteroids should be delayed in children. Conclusions: This survey demonstrates that physicians interviewed in China have a broad understanding of coexistent asthma-AR and its impact on patients. A holistic approach to patient management with informed decisions regarding patients’ overall treatment will benefit patients who suffer from coexistent disease.

Background: Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) syndrome are highly prevalent respiratory conditions. Their coexistence is referred to as the overlap syndrome. They are both related to pulmonary hypertension (PH) development. This study investigated the effects of OSA on PH in patients with COPD and the associated factors. Methods: Consecutive patients with stable COPD were recruited for an observational cross-sectional study from September 2016 to May 2018 at Peking University Third Hospital. In total, 106 patients with COPD were enrolled and performed home portable monitoring and echocardiography. OSA was defined by an apnea hypopnea index (AHI) ≥10 events/h. Based on OSA absence or presence, patients were divided into the COPD with OSA and COPD without OSA groups. Factors affecting pulmonary artery pressure (PAP) and PH were identified using univariate analysis and logistic regression models. Results: In the 106 patients with COPD, the mean age was 69.52 years, 91.5% were men, and the mean forced expiratory volume in 1 s (FEV1) percentage of predicted was 56.15%. Fifty-six (52.8%) patients with COPD were diagnosed with OSA, and 24 (22.6%) patients with COPD were diagnosed as PH. Compared with COPD without OSA group, the median PAP in COPD with severe OSA group increased by 5 mmHg (36.00 [26.00–50.00] mmHg vs. 31.00 [24.00–34.00] mmHg, P = 0.036). COPD with percent of night-time spent with oxygen saturation below 90% (T90) > 10% group had higher PAP than COPD with T90 ≤ 1% group (36.00 [29.00–50.00)] mmHg vs. 29.00 [25.50–34.00] mmHg, F = 7.889, P = 0.007). Univariate analysis revealed age, FEV1% predicted, T90, and Charlson index had statistically significant effects on PH. Multiple regression analysis showed a significant and independent effect of both FEV1% predicted (odds ratio [OR] = 3.46; 95% confidence interval [CI]: 1.15–10.46; P = 0.028) and AHI (OR = 3.20; 95% CI: 1.09–19.35; P = 0.034) on PH. Conclusions: Patients with COPD with OSA are more susceptible to PH, which is associated with declining lung function and increased severity of OSA. Thus, nocturnal hypoxemia and OSA in elderly patients with COPD should be identified and treated.

Backgrounds: Hypersensitivity pneumonitis (HP) is an immune-mediated interstitial lung disease (ILD) that develops in response to the inhalation of various antigens. The clinical pathologies are very complex and undetermined. The clinical features and outcomes of HP have not been fully elucidated. The aim of this study was to analyze the incidence, clinical features, and outcomes of HP patients and construct a simple clinical model for diagnosing chronic HP (CHP). Methods: The cohort study included 101 patients with HP admitted to the Nanjing Drum Tower Hospital from January 2009 to December 2017. The patients were categorized into acute HP (AHP, n = 72) and CHP (n = 29) groups according to the updated international criteria. The clinical, imaging, treatment, and follow-up data were retrospectively reviewed. All patients were followed up until December 31, 2017. Statistical analysis was performed, and a clinical scoring system for CHP was constructed by SPSS 20.0 software. Results: The incidence of HP was 2.4% in ILD inpatients in our center. Patients in the CHP group were older (t = -2.212, P = 0.029), had more smokers (χ2 = 8.428, P = 0.004), and longer duration of symptoms (t = -4.852, P < 0.001) than those in the AHP group. Weight loss, crackles, digital clubbing, and cyanosis were more common in the CHP group than those in the AHP group (χ2 = 5.862, P < 0.001; χ2 = 8.997, P = 0.003; χ2 = 11.939, P = 0.001; and χ2 = 4.025, P = 0.045, respectively). On chest high-resolution computed tomography (HRCT), reticular patterns, traction bronchiectasis, and accompanying honeycombing were more common in CHP cases than those in AHP cases (χ2 = 101.000, P < 0.001; χ2 = 32.048, P < 0.001; and χ2 = 36.568, P < 0.001, respectively). The clinical scoring system for CHP was established based on the clinical variables (age [A], duration of symptoms [D], smoking history [S], unidentified exposure [U], and chest HRCT [C]; ADSUC) (area under the curve 0.935, 95% confidence interval: 0.883–0.987, P < 0.001). Eleven patients (15.3%) in the AHP group developed CHP, and unidentified exposure was an independent risk factor for the progression of disease (P = 0.038). The survival of patients with CHP, smoking history, unidentified antigens and fibrosis on Chest HRCT were significantly worse (P = 0.011, P = 0.001, P = 0.005, and P = 0.011, respectively) by Kaplan-Meier analysis. Cox multivariate regression analysis revealed that unidentified exposure and total lung volume (TLC pred%) were independent prognostic predictors for HP patients (P = 0.017 and P = 0.017, respectively). Conclusions: The clinical features and outcomes of the CHP patients differ from those of the AHP patients. ADSUC is a simple and feasible clinical model for CHP. Unidentified exposure is an independent risk factor for the progression of AHP to CHP. Unidentified exposure and a low baseline TLC pred% are independent predictors for survival in HP patients.

Background: Human-immunodeficiency virus (HIV) infection is increasing worldwide and nontuberculous mycobacteria (NTM) is an established microbiologic cause of pulmonary disease, lymphadenitis, and disseminated disease in cases of advanced immune suppression. Data on patients coinfected with HIV and NTM are limited. Thus, this study aimed to analyze the clinical characteristics, drug resistance, and pathogen spectrum of patients coinfected with both HIV and NTM in the Chengdu area of China. Methods: Data of 59 patients coinfected with both HIV and NTM collected from the Public Health Clinical Center of Chengdu, between January 2014 and December 2018, were analyzed. NTM drug sensitivity testing was performed using the microporous plate ratio method. Data were analyzed using SPSS 19.0, and the change in drug resistance rate was analyzed using the chi-square (χ2) test. Results: Seven species/complex of NTM were identified from patients coinfected with HIV and NTM in this study, with Mycobacterium avium–intracellulare complex (52.5%) and M. kansasii (27.1%) as the predominant species. Male patients were more affected 50/59 (84.7%); the mean age of the 59 cases was 45 years. The clinical characteristics mainly included anemia (86.4%), cough and expectoration (79.7%). The baseline CD4 count was <50 cells/μL (84.7%). Patients were mainly in advanced acquired immunodeficiency syndrome (AIDS) stage. Chest imaging mainly showed patchy shadows (42.4%) and nodules (32.2%), with various degrees of AIDS-defining diseases. The drug resistance of NTM was severe, and the rate of isoniazid resistance (100.0%) was the highest, followed by rifampicin (94.9%), streptomycin (94.9%), ofloxacin (93.2%), and others. Ethambutol (52.5%) and clarithromycin (33.9%) were relatively low. No significant difference was found in the drug resistance rate of NTM strain against nine antituberculosis drugs in 5 years (P > 0.05). Conclusions: The immune level of patients coinfected with HIV and NTM is low in advanced AIDS stage; more male are affected in patients who are mainly infected with MAC and M. kansasii and with serious drug resistance. The drug resistance rate of ethambutol and clarithromycin is relatively low.

Background: Acute lung injury (ALI) is characterized by an acute inflammatory process, and oxidative stress in the lung tissue leads to a lack of effective therapeutics. This study aimed to identify whether the overexpression of transcription factor EB (TFEB) regulates mitophagy to protect against lipopolysaccharide (LPS)-induced ALI. Methods: We detected the expression of inflammatory factors, cytochrome c (Cyt.c) and nicotinamide adenine dinucleotide phosphate (NADPH), and autophagy-related proteins and observed the changes in lung histopathology induced by ALI in rats and the changes in the cell ultrastructure of primary alveolar type II epithelial cells induced by changing the expression of TFEB in the context of ALI. Results: The overexpression of TFEB could reduce the expression of proinflammatory factors, such as IL-1 and IL-6, and increase the expression of anti-inflammatory factors, such as IL-10, both in vitro and in vivo. In addition, the overexpression of TFEB could reduce the Cyt.c and NADPH levels both in vivo and in vitro. The overexpression of TFEB could upregulate the expression of autophagy-related proteins, such as lysosomal-associated membrane protein 1 (LAMP1), microtubule-associated protein light chain 3B (LC3B), and Beclin both in vivo and in vitro, and promote mitochondrial autophagy. The overexpression of TFEB significantly improved the histopathologic changes induced by LPS-induced ALI in rats. However, low TFEB expression produced the opposite results. Conclusion: TFEB overexpression can decrease inflammation and mitochondrial damage in the lung tissue and alveolar epithelial cells through regulating mitochondrial autophagy to protect against LPS-induced ALI. Therefore, TFEB is likely a potential therapeutic target in LPS-induced ALI.

Background: Extranodal natural killer/T-cell lymphoma (ENKTL), nasal type, is an aggressive entity within the World Health Organization classification of lymphoid tumors. The International Prognostic Index is reported to be prognostically meaningful for ENKTL, but lacks discriminatory power for stage I/II ENKTL with extensive local invasion. This study aimed to evaluate the prognostic effects of local invasion by site and tissue type in patients with ENKTL. Methods: We retrospectively analyzed data of 86 patients who were diagnosed with ENKTL by the Department of Pathology of Beijing Tongren Hospital from June 2002 to April 2016, and ascertained tumor infiltration of adjacent structures (AS), bone, and soft tissue for each patient, using physical findings and imaging scans. We used univariate and multivariate analysis to assess the association of each involved tissue or site with patients’ overall survival (OS). Results: Of the 86 patients, 71(82.6%) experienced invasion of AS, 22(25.6%) of soft tissue, and 26(30.2%) had bone involvement. Overall, patients with AS involvement did not show significantly shorter survival than those without AS involvement (Log rank χ2 = 1.177, P = 0.278); however, patients who had involved eyeballs or brains showed significantly lower 2-year OS rates than those without eyeball involvement (Log rank χ2 = 4.105, P = 0.043) or brain involvement (Log rank χ2 = 7.126, P = 0.008). Patients with involved local soft tissue or bones, respectively, showed lower 2-year OS rates than those without involved local soft tissue (Log rank χ2 = 10.390, P = 0.001) or bones (Log rank χ2 = 8.993, P = 0.003). Multivariate analysis showed that involvement of the cheek or facial muscles (hazard ratio, HR = 5.471, 95% confidence interval [CI]: 1.466–20.416, P = 0.011) and the maxilla bone (HR = 6.120, 95% CI: 1.517–24.694, P = 0.011) were significantly independent predictors of lower 2-year OS rates. Conclusions: Imaging can accurately detect ENKTL invasion of AS, soft tissue, and bone. Involvement of local soft tissue or bone was significantly associated with lower 2-year OS rates. Involvements of the cheek or facial muscle, as well as maxilla bone, are independent predictors of lower 2-year OS rates in ENKTL patients.

Background: Fusion genes may play an important role in tumorigenesis, prognosis, and drug resistance; however, studies on fusion genes in endometrial cancer (EC) are rare. This study aimed to identify new fusion genes and to explore their clinical significance in EC. Methods: A total of 28 patients diagnosed with EC were enrolled in this study. RNA sequencing was used to obtain entire genomes and transcriptomes. STAR-comparison and STAR-fusion prediction were applied to predict the fusion genes. Chi-square tests and Student t tests were used to verify the clinical significance with SPSS 13.0 software. Results: New fusion genes were found, and the number of fusion genes varied from 3 to 110 among all patients with EC. The type of fusion genes varied and included messenger RNA (mRNA)-mRNA, long non-coding RNA (lncRNA)-lncRNA, and lncRNA-mRNA. There were six fusion genes with high fusion rates, namely, RP11–123O10.4–GRIP1, RP11–444D3.1–SOX5, RP11– 680G10.1–GSE1, NRIP1–AF127936.7, RP11–96H19.1–RP11–446N19.1, and DPH7–PTP4A3. Further studies showed that these fusion genes are related to stage, grade, and recurrence, in which NRIP1–AF127936.7 and DPH7–PTP4A3 were found only in stage III patients with EC. DPH7–PTP4A3 was found in grades 2 and 3, and recurrent patients with EC. Conclusion: Fusion genes play an essential role in EC. Six genes that are overexpressed with high fusion rates are identified. NRIP1– AF127936.7 and DPH7–PTP4A3 might be related to stage, and DPH7–PTP4A3 be related to grade and recurrence.

Background: The transcription factor paired box 8 (PAX8) was associated with type 2 congenital non-goitrous hypothyroidism (CHNG2), a clinical phenotype of congenital hypothyroidism (CH). Though studied in a few regions with different ethnicities, the incidence of PAX8 mutations varied, even among Chinese cohorts in different regions. This study aimed to identify and characterize PAX8 mutations and explore the prevalence of its mutations in another cohort of CH. Methods: The 105 unrelated Chinese patients with CH were collected from four major hospitals. Exomes of the 105 samples were sequenced by Hiseq 2000 platform to identify mutations of PAX8 on genomic DNAs extracted from peripheral blood samples. Luciferase reporter assays were used to assess the effects of mutations on the transcription of thyroid peroxidase (TPO). Results: Three PAX8 mutations in four subjects were identified in 105 samples. One variant, rs189229644, was detected in two subjects, and categorized as uncertain significance. The other two missense mutations (275T>C/Ile92Thr and 398G>A/Arg133Gln) were not detected in three large-scale genotyping projects, namely 1000 Genome Project, Exome Aggregation Consortium and GO Exome Sequencing Project. Functional studies for the two mutations revealed that they could impair the transcription ability of PAX8 on one of its target genes, TPO. Therefore, the two mutations were causative for the pathogenesis of CHNG2. After combining the studies of PAX8 mutations, an average frequency of 1.74% (21/1209) could be obtained in Chinese patients with CH. Conclusion: The study specifically demonstrates the role of two mutations in impairing the transcription ability of PAX8, which should be considered as pathogenic variants for CH.

Background: Acute kidney injury (AKI) is a serious complication in critically ill patients with septic shock treated in the intensive care unit. Renal replacement therapy (RRT) is a treatment for severe AKI; however, the time of initiation of RRT and factors that affect the recovery of kidney function remains unclear. This study was to explore whether early initiation of RRT treatment for fluid management to reduce central venous pressure (CVP) can help to improve patients’ kidney function recovery. Methods: A retrospective analysis of septic patients who had received RRT treatment was conducted. Patients received RRT either within 12 h after they met the diagnostic criteria of renal failure (early initiation) or after a delay of 48 h if renal recovery had not occurred (delayed initiation). Parameters such as patients’ renal function recovery at discharge, fluid balance, and levels of CVP were assessed. Results: A total of 141 patients were eligible for enrolment: 40.4% of the patients were in the early initiation group (57 of 141 patients), and 59.6% were in the delayed initiation group (84 of 141 patients). There were no significant differences in the characteristics at baseline between the two groups, and there were no differences in 28-day mortality between the two groups (χ2 = 2.142, P = 0.143); however, there was a significant difference in the recovery rate of renal function between the two groups at discharge (χ2 = 4.730, P < 0.001). More importantly, early initiation of RRT treatment and dehydration to reduce CVP are more conducive to the recovery of renal function in patients with AKI. Conclusion: Compared with those who received delayed initiation RRT, patients who received early-initiation RRT for dehydration to reduce CVP have enhanced kidney function recovery.

Background: It has recently been recognized that serum vimentin is elevated in infectious diseases, and that vimentin plays a role in regulating neutrophils and macrophages associated inflammation. However, the mechanisms are unclear. This study was designed to explore the role of vimentin in regulating monocyte survival or apoptosis as well as inflammatory cytokine secretion in response to lipopolysaccharides (LPSs). Methods: A human monocytic leukemia cell line (THP-1) was transfected with vimentin-specific small interfering RNA (siRNA) or vimentin over-expressing plasmid. Apoptosis was assessed by TdT-mediated dUTP Nick-End Labeling (TUNEL) and DNA content assay. Immunoblotting was performed to detect apoptosis-associated proteins. Cytokines (interleukin [IL]-6, IL-10, and tumor necrosis factor α [TNF-α]) were measured by enzyme-linked immuno sorbent assay. Two-way analysis of variance followed by Student’s t test was used to compare means between different groups. Results: Suppression of vimentin in THP-1 cells resulted in increased apoptotic response in the presence of LPS, while overexpression of vimentin could prevent the cells from apoptosis in response to LPS. LPS alone or suppression of vimentin resulted in significant up-regulation of caspase-3 (1.42 ± 0.20 of LPS alone and 1.68 ± 0.10 of vimentin suppression vs. control, t = 5.21 and 10.28, respectively, P < 0.05). In addition, pro-inflammatory cytokines (IL-6 and TNF-α) was significantly increased (IL-6: 577.90 ± 159.90 pg/day/105 cells vs. 283.80 ± 124.60 pg/day/105 cells of control, t = 14.76, P < 0.05; TNF-α: 54.10 ± 5.80 vs. 17.10 ± 0.10 pg/day/105 cells of control, t = 6.71, P < 0.05), while anti-inflammatory cytokine (IL-10) was significantly up-regulated in the THP-1 cells that over-expressed vimentin (140.9 ± 17.2 pg/day/105 cells vs. undetectable in control cells). Conclusions: In summary, the vimentin may regulate innate immunity through modulating monocytes viability as well as inflammatory response in sepsis through shifting the balance of pro-inflammatory and anti-inflammatory cytokines.

Background: The enteric reconstruction procedure of pancreatic stump after pancreaticoduodenectomy remains to be the critical factor influencing the mortality and morbidity. No widely accepted surgical procedure for the pancreaticojejunostomy has been erected yet. We have developed a new technique of pancreaticojejunostomy named "shark mouth pancreaticojejunostomy." The aim of this study is to assess the efficacy of "shark mouth pancreaticojejunostomy." Methods: This is a prospective single-arm observational study to evaluate the clinical efficacy of "shark mouth pancreaticojejunostomy." Patients with diseases, in whom a pancreaticoduodenectomy is indicated, would be recruited from Peking University Third Hospital. The hypothesis to be tested is that a "shark mouth pancreaticojejunostomy" will reduce fistula rate from around 20% to less than 10%. A sample size of 120 patients will be needed. The primary endpoint is the incidence rate of postoperative pancreatic fistula (POPF). The secondary endpoints of the study are anastomosis time, postoperative hospital stay, and morbidities besides the POPF such as the hemorrhage. Enrolled patients will undergo pancreaticoduodenectomy and be followed up for 3 months. The relevant data will be monitored and recorded. Conclusions: The current trial will explore the therapeutic value of the newly raised pancreaticojejunostomy procedure as the "shark mouth pancreaticojejunostomy." Its theoretical base and pragmatic feature will promise high external validity. Trial registration: Clinical Trials.gov: NCT03366038; https://www.clinicaltrials.gov.