Assessment of post-COVID-19 fatigue among female survivors 2 years after hospital discharge: a nested case-control study.

BACKGROUND: Fatigue is a common symptom of long COVID syndrome. Compared to male survivors, females have a higher incidence of post-COVID fatigue. Therefore, long-term follow-up is necessary to understand which groups of females are more vulnerable to post-COVID fatigue. METHODS: This is a nested case-control study of female COVID-19 survivors who were discharged from two designated hospitals in Wuhan, China in 2020, and received 2-year follow-up from March 1 to April 6, 2022. All patients completed the Checklist Individual Strength-subscale subjective fatigue (CIS-fatigue), a chronic obstructive pulmonary disease (COPD) assessment test (CAT), and the Hospital Anxiety and Depression Scale (HADS; including the HADS-Anxiety [HADS-A] and the HADS-Depression [HADS-D]). Individuals with CIS-fatigue scores of 27 or higher were classified as cases. The risk factors for fatigue was analysed with multivariable logistic regression analysis. RESULTS: A total of 899 female COVID-19 survivors were enrolled for analysis, including 47 cases and 852 controls. Compared with controls, cases had higher CAT, HADS-A and HADS-D scores, and showed a higher prevalence of symptoms, including anxiety (cases vs. controls, 44.7% vs. 4.0%, p < 0.001), chest tightness (21.2% vs. 2.3%, p < 0.001), dyspnoea (19.1% vs. 0.8%, p < 0.001) and so on. In multivariable logistic regression analysis, age (OR, 1.03; 95% CI, 1.01-1.06; p = 0.02) and cerebrovascular disease (OR, 11.32; 95% CI, 2.87-43.00; p < 0.001) were risk factors for fatigue. Fatigue had a statistically significant moderate correlation with depression (r = 0.44, p < 0.001), but not with CAT ≥ 10. CONCLUSION: Female COVID-19 patients who had cerebrovascular disease and older age have higher risk of fatigue. Patients with fatigue have higher CAT scores, and are more likely to have concurrent depression.

Symptom Burden among Older COVID-19 Survivors Two Years after Hospital Discharge.

To study the long-term symptom burden among older COVID-19 survivors 2 years after hospital discharge and identify associated risk factors. The current cohort study included COVID-19 survivors aged 60 years and above, who were discharged between February 12 and April 10, 2020, from two designated hospitals in Wuhan, China. All patients were contacted via telephone and completed a standardized questionnaire assessing self-reported symptoms, the Checklist Individual Strength (CIS)-fatigue subscale, and two subscales of the Hospital Anxiety and Depression Scale (HADS). Of the 1,212 patients surveyed, the median (IQR) age was 68.0 (64.0-72.0), and 586 (48.3%) were male. At the two-year follow-up, 259 patients (21.4%) still reported at least one symptom. The most frequently self-reported symptoms were fatigue, anxiety, and dyspnea. Fatigue or myalgia, which was the most common symptom cluster (11.8%; 143/1212), often co-occurred with anxiety and chest symptoms. A total of 89 patients (7.7%) had CIS-fatigue scores ≥ 27, with older age (odds ratio [OR], 1.08; 95% CI: 1.05-1.11, P < 0.001) and oxygen therapy (OR, 2.19; 95% CI: 1.06-4.50, P= 0.03) being risk factors. A total of 43 patients (3.8%) had HADS-Anxiety scores ≥ 8, and 130 patients (11.5%) had HADS-Depression scores ≥ 8. For the 59 patients (5.2%) who had HADS total scores ≥ 16, older age, serious illness during hospitalization and coexisting cerebrovascular diseases were risk factors. Cooccurring fatigue, anxiety, and chest symptoms, as well as depression, were mainly responsible for long-term symptom burden among older COVID-19 survivors 2 years after discharge.

Single-center experience in the diagnosis and treatment of lymphoepithelioma-like hepatic carcinoma.

PURPOSE: Lymphoepithelioma-like hepatic carcinoma (LELC) is a rare malignant liver tumor and its preoperative diagnosis is challenging. The aim of this study was to optimize the diagnosis and treatment of LELC in a single large center. METHODS: We conducted this retrospective analysis of 16 patients diagnosed with LELC in the First Affiliated Hospital of Zhejiang University between 2010 and 2022. Thirty-two cases of cholangiocarcinoma (ICC) and 48 cases of hepatocellular carcinoma (HCC) served as controls. RESULTS: Most of the 16 patients with LELC included in this study had no specific symptoms. Histologically, 9 patients had lymphoepithelioma-like hepatocellular carcinoma (LEL-HCC), 5 had lymphoepithelioma-like cholangiocarcinoma (LEL-ICC) and 2 had LEL-HCC-ICC. LEL-HCC was usually accompanied by hepatitis B virus infection, while LEL-ICC was often accompanied by Epstein Barr virus (EBV) infection. During the follow-up period, no complication and deaths were observed and only one patient experienced recurrence. These results were obviously better than those in patients with HCC and ICC. CONCLUSION: LELC is a rare malignant hepatic tumor. There are no specific symptoms or imaging modalities for accurate preoperative diagnosis of LELC. The diagnosis can be confirmed by pathology; however, the prognosis of LELC after resection is promising.

Facilitated Photocatalytic Degradation of Rhodamine B over One-Step Synthesized Honeycomb-Like BiFeO3/g-C3N4 Catalyst.

In the present work, a facile one-step methodology was used to synthesize honeycomb-like BiFeO3/g-C3N4 composites, where the well-dispersed BiFeO3 strongly interacted with the hg-C3N4. The 10BiFeO3/hg-C3N4 could completely degrade RhB under visible light illumination within 60 min. The degradation rate constant was remarkably improved and approximately three times and seven times that of pristine hg-C3N4 and BiFeO3, respectively. This is ascribed to the following factors: (1) the unique honeycomb-like morphology facilitates the diffusion of the reactants and effectively improves the utilization of light energy by multiple reflections of light; (2) the charged dye molecules can be tightly bound to the spontaneous polarized BiFeO3 surface to form the Stern layer; (3) the Z-scheme heterojunction and the ferroelectric synergistically promoted the efficient separation and migration of the photogenerated charges. This method can synchronously tune the micro-nano structure, surface property, and internal field construction for g-C3N4-based photocatalysts, exhibiting outstanding potential in environmental purification.

Two-Year Health Outcomes in Hospitalized COVID-19 Survivors in China.

Importance: Relatively little is known about the persistence of symptoms in patients with COVID-19 for more than 1 year after their acute illness. Objective: To assess the health outcomes among hospitalized COVID-19 survivors over 2 years and to identify factors associated with increased risk of persistent symptoms. Design, Setting, and Participants: This was a longitudinal cohort study of patients who survived COVID-19 at 2 COVID-19-designated hospitals in Wuhan, China, from February 12 to April 10, 2020. All patients were interviewed via telephone at 1 year and 2 years after discharge. The 2-year follow-up study was conducted from March 1 to April 6, 2022. Statistical analysis was conducted from April 20 to May 5, 2022. The severity of disease was defined by World Health Organization guideline for COVID-19. Exposures: COVID-19. Main Outcomes and Measures: The main outcome was symptom changes over 2 years after hospital discharge. All patients completed a symptom questionnaire for evaluation of symptoms, along with a chronic obstructive pulmonary disease assessment test (CAT) at 1-year and 2-year follow-up visits. Results: Of 3988 COVID-19 survivors, a total of 1864 patients (median [IQR] age, 58.5 [49.0-68.0] years; 926 male patients [49.7%]) were available for both 1-year and 2-year follow-up visits. The median (IQR) time from discharge to follow-up at 2 years was 730 (719-743) days. At 2 years after hospital discharge, 370 patients (19.8%) still had symptoms, including 224 (12.0%) with persisting symptoms and 146 (7.8%) with new-onset or worsening of symptoms. The most common symptoms were fatigue, chest tightness, anxiety, dyspnea, and myalgia. Most symptoms resolved over time, but the incidence of dyspnea showed no significant change (1-year vs 2-year, 2.6% [49 patients] vs 2.0% [37 patients]). A total of 116 patients (6.2%) had CAT total scores of at least 10 at 2 years after discharge. Patients who had been admitted to the intensive care unit had higher risks of persistent symptoms (odds ratio, 2.69; 95% CI, 1.02-7.06; P = .04) and CAT scores of 10 or higher (odds ratio, 2.83; 95% CI, 1.21-6.66; P = .02). Conclusions and Relevance: In this cohort study, 2 years after hospital discharge, COVID-19 survivors had a progressive decrease in their symptom burden, but those with severe disease during hospitalization, especially those who required intensive care unit admission, had higher risks of persistent symptoms. These results are related to the original strain of the virus, and their relevance to infections with the Omicron variant is not known.

Post-sequelae one year after hospital discharge among older COVID-19 patients: A multi-center prospective cohort study.

BACKGROUND: To systematically evaluate the prevalence of post-sequelae and chronic obstructive pulmonary disease assessment test (CAT) scoring one year after hospital discharge among older COVID-19 patients, as well as potential risk factors. METHODS: A multi-center prospective cohort study involving 1,233 eligible older COVID-19 patients was conducted. All patients were followed-up between Mar 1, 2021 and Mar 20, 2021. CAT scoring was adopted to measure symptom burden in COVID-19 patients. RESULTS: Of the 1233 eligible cases, 630 (51.1%) reported at least one sequelae. The top six post-sequelae included fatigue (32.4%), sweating (20.0%), chest tightness (15.8%), anxiety (11.4%), myalgia (9.0%), and cough (5.8%). Severe patients had significantly higher percentage of fatigue, sweating, chest tightness, myalgia, and cough (P<0.05), while anxiety was universal in all subjects. Sweating, anxiety, palpitation, edema of lower limbs, smell reduction, and taste change were emerging sequelae. Disease severity during hospitalization (OR: 1.46, 95% CI: 1.15-1.84, P = 0.002), and follow-up time (OR: 0.71, 95% CI: 0.50-0.99, P = 0.043) were independently associated with risk of post-sequelae, while disease severity during hospitalization was significantly associated with increased risk of emerging sequelae (OR: 1.33, 95% CI: 1.03-1.71, P = 0.029). The median of CAT score was 2 (0-5) in all patients, and a total of 120 patients (9.7%) had CAT scores ≥10. Disease severity during hospitalization (OR: 1.81, 95% CI: 1.23-2.67, P = 0.003) and age (OR: 1.07, 95% CI: 1.04-1.09, P<0.001) were significantly associated with increased risk of CAT scores ≥10. CONCLUSIONS: While the dramatic decline in the prevalence rate of persistent symptoms is reassuring, new sequelae among older COVID-19 patients cannot be ignored. Disease severity during hospitalization, age, and follow-up time contributed to the risk of post-sequelae and CAT scoring one year after hospital discharge among older COVID-19 patients. Our study provides valuable clues for long-term post-sequelae of the older COVID-19 patients, as well as their risk factors.

Symptoms and Health Outcomes Among Survivors of COVID-19 Infection 1 Year After Discharge From Hospitals in Wuhan, China.

Importance: The long-term health outcomes and symptom burden of COVID-19 remain largely unclear. Objective: To evaluate health outcomes of COVID-19 survivors 1 year after hospital discharge and to identify associated risk factors. Design, Setting, and Participants: This retrospective, multicenter cohort study was conducted at 2 designated hospitals, Huoshenshan Hospital and Taikang Tongji Hospital, both in Wuhan, China. All adult patients with COVID-19 discharged between February 12 and April 10, 2020, were screened for eligibility. Of a consecutive sample of 3988 discharged patients, 1555 were excluded (796 declined to participate and 759 were unable to be contacted) and the remaining 2433 patients were enrolled. All patients were interviewed via telephone from March 1 to March 20, 2021. Statistical analysis was performed from March 28 to April 18, 2021. Exposures: COVID-19. Main Outcomes and Measures: All patients participated in telephone interviews using a series of questionnaires for evaluation of symptoms, along with a chronic obstructive pulmonary disease (COPD) assessment test (CAT). Logistic regression models were used to evaluate risk factors for fatigue, dyspnea, symptom burden, or higher CAT scores. Results: Of 2433 patients at 1-year follow-up, 1205 (49.5%) were men and 680 (27.9%) were categorized into the severe disease group as defined by the World Health Organization guideline; the median (IQR) age was 60.0 (49.0-68.0) years. In total, 1095 patients (45.0%) reported at least 1 symptom. The most common symptoms included fatigue, sweating, chest tightness, anxiety, and myalgia. Older age (odds ratio [OR], 1.02; 95% CI, 1.01-1.02; P < .001), female sex (OR, 1.27; 95% CI, 1.06-1.52; P = .008), and severe disease during hospital stay (OR, 1.43; 95% CI, 1.18-1.74; P < .001) were associated with higher risks of fatigue. Older age (OR, 1.02; 95% CI, 1.01-1.03; P < .001) and severe disease (OR, 1.51; 95% CI, 1.14-1.99; P = .004) were associated with higher risks of having at least 3 symptoms. The median (IQR) CAT score was 2 (0-4), and a total of 161 patients (6.6%) had a CAT score of at least 10. Severe disease (OR, 1.84; 95% CI, 1.31-2.58; P < .001) and coexisting cerebrovascular diseases (OR, 1.95; 95% CI, 1.07-3.54; P = .03) were independent risk factors for CAT scores of at least 10. Conclusions and Relevance: This study found that patients with COVID-19 with severe disease during hospitalization had more postinfection symptoms and higher CAT scores.

Multifocal pleural capillary hemangioma: a rare cause of hemorrhagic pleural effusion-case report.

BACKGROUND: Capillary hemangioma can be found in many organs, but rarely in pleura. Previously, only localized pleural capillary hemangioma cases have been reported. Corticosteroids are the most commonly recommended drugs in capillary hemangioma. CASE PRESENTATION: Here, we present a case of a young woman with recurrent hemorrhagic pleural effusion. Despite repeatedly thoracentesis, the routine examinations, including chest computed tomography (CT) scan, pleural effusion biochemical test, and cytology all failed to make a definite diagnosis. Thus, single port video-assisted thoracoscopy (VATS) was then performed. Numerous nodules arising from the parietal pleura were found, and biopsies showed multifocal pleural capillary. However, recurrent pleural effusion was successfully managed by oral azathioprine, after failure of dexamethasone treatment. CONCLUSIONS: To our knowledge, this is the first case of a patient with recurrent hemorrhagic pleural effusion masquerading as malignant pleurisy, but in fact caused by multifocal pleural capillary hemangioma.

Personalized Variable vs Fixed-Dose Systemic Corticosteroid Therapy in Hospitalized Patients With Acute Exacerbations of COPD: A Prospective, Multicenter, Randomized, Open-Label Clinical Trial.

BACKGROUND: Systemic corticosteroids for the treatment of COPD exacerbations decrease treatment failure and shorten the length of hospitalization. However, the optimal dose is unclear. RESEARCH QUESTION: Is personalized-dose corticosteroid administered according to a dosing scale more effective than fixed-dose corticosteroid administration in hospitalized patients with COPD with exacerbations? STUDY DESIGN AND METHODS: This was a prospective, randomized, open-label trial. In-hospital patients with COPD with exacerbations were randomly assigned at a 1:1 ratio to either the fixed-dose group (receiving the equivalent of 40 mg of prednisolone) or the personalized-dose group for 5 days. The primary end point was a composite measure of treatment failure that included in-hospital treatment failure and medium-term (postdischarge) failure. Secondary end points were length of stay and cost. RESULTS: A total of 248 patients were randomly assigned to the fixed-dose group (n = 124) or personalized-dose group (n = 124). One patient in each group was not included in the intention-to-treat population because of incorrect initial COPD diagnosis. Failure of therapy occurred in 27.6% in the personalized-dose group, compared with 48.8% in the fixed-dose group (relative risk, 0.40; 95% CI, 0.24-0.68; P = .001). The in-hospital failure of therapy was significantly lower in the personalized-dose group (10.6% vs 24.4%; P = .005), whereas the medium-term failure rate, adverse event rate, hospital length of stay, and costs were similar between the two groups. After treatment failure, a lower additional dose of corticosteroids and a shorter duration of treatment were needed in the personalized-dose group to achieve control of the exacerbation. In the personalized-dose cohort, those receiving 40 mg or less had an average failure rate of 44.4%, compared with 22.9% among those receiving more than 40 mg (P = .027). INTERPRETATION: Personalized dosing of corticosteroids reduces the risk of failure because more patients were provided with a higher initial dose, especially > 60 mg, whereas 40 mg or less was too low in either group. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT02147015; URL: www.clinicaltrials.gov.

Hyperglycemia and Correlated High Levels of Inflammation Have a Positive Relationship with the Severity of Coronavirus Disease 2019.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is a considerable global public health threat. This study sought to investigate whether blood glucose (BG) levels or comorbid diabetes are associated with inflammatory status and disease severity in patients with COVID-19. METHODS: In this retrospective cohort study, the clinical and biochemical characteristics of COVID-19 patients with or without diabetes were compared. The relationship among severity of COVID-19, inflammatory status, and diabetes or hyperglycemia was analyzed. The severity of COVID-19 in all patients was determined according to the diagnostic and treatment guidelines issued by the Chinese National Health Committee (7th edition). RESULTS: Four hundred and sixty-one patients were enrolled in our study, and 71.58% of patients with diabetes and 13.03% of patients without diabetes had hyperglycemia. Compared with patients without diabetes (n = 366), patients with diabetes (n = 95) had a higher leucocyte count, neutrophil count, neutrophil to lymphocyte ratio (NLR), and erythrocyte sedimentation rate (ESR). There was no association between severity of COVID-19 and known diabetes adjusted for age, sex, body mass index (BMI), known hypertension, and coronary heart disease. The leucocyte count, NLR, and C-reactive protein (CRP) level increased with increasing BG level. Hyperglycemia was an independent predictor of critical (OR 4.00, 95% CI 1.72-9.30) or severe (OR 3.55, 95% CI 1.47-8.58) COVID-19, and of increased inflammatory levels (high leucocyte count (OR 4.26, 95% CI 1.65-10.97), NLR (OR 2.76, 95% CI 1.24-6.10), and CRP level (OR 2.49, 95% CI 1.19-5.23)), after adjustment for age, sex, BMI, severity of illness, and known diabetes. CONCLUSION: Hyperglycemia was positively correlated with higher inflammation levels and more severe illness, and it is a risk factor for the increased severity of COVID-19. The initial measurement of plasma glucose levels after hospitalization may help identify a subset of patients who are predisposed to a worse clinical course.

Development and validation of a prognostic nomogram for predicting in-hospital mortality of COVID-19: a multicenter retrospective cohort study of 4086 cases in China.

To establish an effective nomogram for predicting in-hospital mortality of COVID-19, a retrospective cohort study was conducted in two hospitals in Wuhan, China, with a total of 4,086 hospitalized COVID-19 cases. All patients have reached therapeutic endpoint (death or discharge). First, a total of 3,022 COVID-19 cases in Wuhan Huoshenshan hospital were divided chronologically into two sets, one (1,780 cases, including 47 died) for nomogram modeling and the other (1,242 cases, including 22 died) for internal validation. We then enrolled 1,064 COVID-19 cases (29 died) in Wuhan Taikang-Tongji hospital for external validation. Independent factors included age (HR for per year increment: 1.05), severity at admission (HR for per rank increment: 2.91), dyspnea (HR: 2.18), cardiovascular disease (HR: 3.25), and levels of lactate dehydrogenase (HR: 4.53), total bilirubin (HR: 2.56), blood glucose (HR: 2.56), and urea (HR: 2.14), which were finally selected into the nomogram. The C-index for the internal resampling (0.97, 95% CI: 0.95-0.98), the internal validation (0.96, 95% CI: 0.94-0.98), and the external validation (0.92, 95% CI: 0.86-0.98) demonstrated the fair discrimination ability. The calibration plots showed optimal agreement between nomogram prediction and actual observation. We established and validated a novel prognostic nomogram that could predict in-hospital mortality of COVID-19 patients.

Behçet's disease with invasive pulmonary aspergillosis and Aspergillus auriculatus infection: A case report.

RATIONALE: Behçet's disease (BD) is an inflammatory disease that leads to multisystemic immune dysfunction and that involves pulmonary system alterations. PATIENT CONCERNS: A 26-year-old woman presented with dull right chest pain for 30 days and intermittent cough with expectoration for 5 days. She had a history of recurrent oral ulcer and constitutional rash 2 months prior. DIAGNOSES: The patient was diagnosed with BD complicated by IPA and Aspergillus auriculatus infection. INTERVENTIONS: The patient was administered itraconazole oral solution (200 mg b.i.d) to treat the fungal infection. After a diagnosis of BD was made, she received 40 mg of methylprednisolone sodium succinate daily for 1 week.Then, she also received 24 mg of methylprednisolone sodium succinate daily, which was decreased by 2 mg per half month, until the rash had resolved. The patient continued to receive 200 mg Q. D itraconazole orally for 3 months. Thereafter, itraconazole was stopped, while daily oral administration of 10 mg of methylprednisolone sodium succinate was continued. OUTCOMES: The rash was observed to resolve, and CT revealed that the lesions in both the right and left lung were reduced. During a telephone follow-up performed after 6 months, the patient stated that no symptoms had recurred during the follow-up period. LESSONS: This case illustrates that for patients with BD, ignoring extrapulmonary symptoms often leads to a delayed diagnosis. Physicians should perform a thorough medical history and physical examination of these patients, as the information obtained in this manner may provide important clues for disease diagnosis and treatment.

The diagnostic effect of sequential detection of ADA screening and T-SPOT assay in pleural effusion patients.

Purpose: To evaluate the diagnostic effect of sequential detection of Adenosine deaminase (ADA) screening and T-SPOT assay on tuberculosis (TB) pleurisy in pleural effusion patients. Materials and methods: 248 pleural effusion patients (172 TB and 76 non-TB) were retrospectively analyzed in the study. The concentrations of ADA and lactate dehydrogenase (LDH) were measured in pleural fluids and serum samples of the patients. T-SPOTT assays were performed in pleural fluids. The relationship between ADA, T-SPOT and the occurrence of TB pleurisy was evaluated using logistic regression analysis. Results: The level of pleural ADA and positive rate of T-SPOT were all higher in TB pleurisy group than non-TB pleurisy group (p < .001). The positive rate of T-SPOT detection reached 98.83% in the TB pleurisy group while only 40.7% in non-TB pleurisy group (p < .001). Additionally, 8 patients (4.65%) in the TB pleurisy group showed the level of pleurisy ADA exceeded 40 IU/L while only one patient (1.31%) in the non-TB pleurisy group. Conclusion: The sequential detection of ADA screening and T-SPOT assay was found to be an accurate and rapid method for identifying TB pleurisy from pleural effusion, which would promote effective treatment.

Clinical characteristics and potential indicators for definite diagnosis of tuberculous pleural effusion.

AIMS: The study aimed to investigate the clinical characteristics of patients with pleural effusion (PE), and explore the effective indicators for definite diagnosis of tuberculous pleural effusion (TBPE). METHODS: The adult patients with the presence of PE were enrolled. All the patients received pleural fluid Mycobacterium tuberculosis DNA detection, ADA activity measure and blood T-SPOT.TB test. The clinical characteristics and examination results were recorded. RESULTS: A total of 77 PE patients, including 30 (38.96%) TBPE, 19 (24.67%) malignant PE, 6 (7.79%) empyema, 10 (12.99%) parapneumonic effusion and 12 (15.58%) miscellaneous causes, were enrolled. The diagnostic sensitivity and specificity of pleural fluid M. tuberculosis DNA detection were 33.3% and 100%, respectively. The diagnostic parameters of pleural fluid ADA for TBPE were as follows: sensitivity 50% and specificity 78.7%. In PE cases with pleural fluid lactate dehydrogenase (LDH) more than 500 U/L, the diagnostic values of DNA detection and ADA activity were enhanced, and DNA detection was superior to ADA activity. In addition, the ratio of blood T-STOP.TB A + B to lymphocyte was a potential diagnostic biomarker for TBPE with the sensitivity of 83.3% and the specificity of 66.0%. CONCLUSION: The clinical significance of pleural fluid M. tuberculosis DNA detection is superior to ADA activity in the diagnosis of TBPE, especially in PE cases with LDH value more than 500 U/L. The ratio of blood T-STOP.TB A + B to lymphocyte is a potential indicator for definite diagnosis of TBPE, with high sensitivity.

Identification of invasion-metastasis-associated microRNAs in hepatocellular carcinoma based on bioinformatic analysis and experimental validation.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most lethal cancer, mainly attributing to its high tendency to metastasis. Vascular invasion provides a direct path for solid tumor metastasis. Mounting evidence has demonstrated that microRNAs (miRNAs) are related to human cancer onset and progression including invasion and metastasis. METHODS: In search of invasion-metastasis-associated miRNAs in HCC, microarray dataset GSE67140 was downloaded from the Gene Expression Omnibus database. Differentially expressed miRNAs (DE-miRNAs) were obtained by R software package and the potential target genes were predicted by miRTarBase. The database for annotation, visualization and integrated discovery (DAVID) was introduced to perform functional annotation and pathway enrichment analysis for these potential targets of DE-miRNAs. Protein-protein interaction (PPI) network was established by STRING database and visualized by Cytoscape software. The effects of the miR-494-3p and miR-126-3p on migration and invasion of HCC cell lines were evaluated by conducting wound healing assay and transwell assay. RESULTS: A total of 138 DE-miRNAs were screened out, including 57 upregulated miRNAs and 81 downregulated miRNAs in human HCC tumors with vascular invasion compared with human HCC tumors without vascular invasion. 762 target genes of the top three upregulated and downregulated miRNAs were predicted, and they were involved in HCC-related pathways, such as pathway in cancer, focal adhesion and MAPK signaling pathway. In the PPI network, the top 10 hub nodes with higher degrees were identified as hub genes, such as TP53 and MYC. Through constructing the miRNA-hub gene network, we found that most of hub genes could be potentially modulated by miR-494-3p and miR-126-3p. Of note, miR-494-3p and miR-126-3p was markedly upregulated and downregulated in HCC cell lines and tissues, respectively. In addition, overexpression of miR-494-3p could significantly promote HCC migration and invasion whereas overexpression of miR-126-3p exerted an opposite effect. CONCLUSIONS: Targeting miR-494-3p and miR-126-3p may provide effective and promising approaches to suppress invasion and metastasis of HCC.

Adjunctive use of prednisolone in the treatment of free-flowing tuberculous pleural effusion: A retrospective cohort study.

BACKGROUND: Adjunctive use of corticosteroids with anti-tuberculosis (TB) therapy has been reported to benefit people with tuberculous pleural effusion (TPE), while there is a paucity of data to support it as routine use. TPE can be subdivided into free-flowing type and loculated type. We evaluated the effects of adjunctive prednisolone therapy on functional sequelae, pleural thickening and pleural adhesions in patients with free-flowing TPE. METHODS: This is a retrospective cohort study, conducted from Jan 2013 to Dec 2016 (ChiCTR-ORC-16009267). All the patients were diagnosed with TPE, and treated with standard 4-drug anti-TB chemotherapy regimen and complete drainage of the effusion. We compared the incidence of a composite of roentgenographic sequelae (pleural thickening of > 2 mm, or pleural adhesions and costophrenic angle > 90°), or restrictive functional sequelae (FVC/FVC pre or TLC/TLC pre < 80%) between those who received adjunctive prednisolone therapy and those who did not. RESULTS: The final cohorts consisted of 135 subjects. Of those, 56 received adjunctive prednisolone therapy and 79 did not. The incidence of a composite of roentgenographic sequelae or restrictive functional sequelae was significantly decreased in the prednisolone group as compared with the control group (51.8% vs. 75.9%; RR 2.83, 95% confidence interval, 1.27-6.31, P = 0.011). No serious side effects due to corticosteroid were noted. CONCLUSIONS: This study detected a significant association between adjunctive prednisolone therapy and decreased incidence of a composite of radiographic sequelae, or functional sequelae in HIV-negative, free-flowing type TPE patients treated with adjunctive prednisolone.

A Novel Corynebacterium glutamicum l-Glutamate Exporter.

Besides metabolic pathways and regulatory networks, transport systems are also pivotal for cellular metabolism and hyperproduction of biochemicals using microbial cell factories. The identification and characterization of transporters are therefore of great significance for the understanding and engineering of transport reactions. Herein, a novel l-glutamate exporter, MscCG2, which exists extensively in Corynebacterium glutamicum strains but is distinct from the only known l-glutamate exporter, MscCG, was discovered in an industrial l-glutamate-producing C. glutamicum strain. MscCG2 was predicted to possess three transmembrane helices in the N-terminal region and located in the cytoplasmic membrane, which are typical structural characteristics of the mechanosensitive channel of small conductance. MscCG2 has a low amino acid sequence identity (23%) to MscCG and evolved separately from MscCG with four transmembrane helices. Despite the considerable differences between MscCG2 and MscCG in sequence and structure, gene deletion and complementation confirmed that MscCG2 also functioned as an l-glutamate exporter and an osmotic safety valve in C. glutamicum Besides, transcriptional analysis showed that MscCG2 and MscCG genes were transcribed in similar patterns and not induced by l-glutamate-producing conditions. It was also demonstrated that MscCG2-mediated l-glutamate excretion was activated by biotin limitation or penicillin treatment and that constitutive l-glutamate excretion was triggered by a gain-of-function mutation of MscCG2 (A151V). Discovery of MscCG2 will enrich the understanding of bacterial amino acid transport and provide additional targets for exporter engineering.IMPORTANCE The exchange of matter, energy, and information with surroundings is fundamental for cellular metabolism. Therefore, studying transport systems that are essential for these processes is of great significance. Besides, transport systems of bacterial cells are usually related to product excretion as well as product reuptake, making transporter engineering a useful strategy for strain improvement. The significance of our research is in identifying and characterizing a novel l-glutamate exporter from the industrial workhorse Corynebacterium glutamicum, which will enrich the understanding of l-glutamate excretion and provide a new target for studying bacterial amino acid transport and engineering transport reactions.

Identification of a new gene yecC involved in threonine export in Escherichia coli.

Threonine (Thr), an essential amino acid for mammals, has expanded its application to industries with fast-growing market demand. One factor that limits the production of L-threonine by microbial fermentation is the lack of an effective export system. This study proposes a method based on isobaric tags for relative and absolute quantification (iTRAQ) to determine potential Thr excretion proteins. Proteomics analysis revealed that an ABC family transport protein named YecC was upregulated in response to Thr addition. When the yecC gene or yecC-yecS-fliY is overexpressed in Escherichia coli DH5α, a phenotype resistant to inhibitory concentrations of Thr was observed in the strains. In addition, Thr production was increased when the yecC gene and yecC-yecS-fliY were overexpressed in the Thr producers in which rthA or rthBC was deleted separately or in combination. Therefore, YecC protein could facilitate Thr efflux in E. coli and be suitable for application in engineering microbial cells to produce Thr.

Successful treatment of diffuse panbronchiolitis in a child from Western China: A case report.

The present report describes a case of diffuse panbronchiolitis (DPB) in a child from Western China and the favorable outcome associated with early diagnosis. DPB is an uncommon presentation in pediatric patients. A 13-year-old Chinese boy was admitted to the respiratory outpatient department due to recurrent cough and progressive exertional dyspnea that had persisted for 1 year. An initial diagnosis of bronchial asthma was made, and the patient was prescribed inhaled fluticasone combined with salmeterol (50/250 µg, twice daily), and montelukast (4 mg daily). However, 2 months later no clinical improvement was observed. The disease was re-diagnosed as DPB following the identification of features such as centrilobular small nodular opacities, a 'tree-in-bud appearance' and thickening of the bronchial walls meeting the diagnostic criteria for DPB. Complete resolution of the disease and sustained alleviation of the patient's respiratory symptoms were achieved following the early institution of erythromycin therapy, and the exacerbation of chronic bronchitis was reduced. In conclusion, it is essential to consider that successful treatment for DPB lies in early diagnosis and early treatment. DPB may be treated well by use of erythromycin.

Serum Amyloid-Beta Levels are Increased in Patients with Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is associated with cognitive decline, but the molecular link between COPD and dementia or Alzheimer's disease (AD) remains unclear. This study was aimed to investigate whether serum Aß levels are correlated with COPD. 77 cognitively normal COPD patients and 45 age- and gender-matched normal controls were admitted to the study. Serum Aß40 and Aß42 levels were measured using ELISA kits. Serum C-reactive protein (CRP), interleukin 6 (IL-6), and procalcitonin (PCT) measurements were done using standard laboratory methods. Pulmonary function tests were performed to assess the pulmonary function and determine the degree of lung damage. Significantly increased levels of serum Aß40, Aß42, and total Aß levels were found in patients with COPD in comparison with normal controls. In COPD patients, serum Aß levels were higher in subjects with serum CRP, IL-6, and PCT upper the limit of normal. Moreover, serum Aß levels were dramatically higher in COPD patients with worse pulmonary function. Our study suggests that cognitively normal COPD patients may undergo AD-related pathological changes, and COPD might facilitate AD-type pathogenesis.