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Abstract Background Pulmonary alveolar proteinosis (PAP) is a special clinical presentation mostly associated with autoimmune disorders. Here we report a rare case of PAP secondary to infection of Bacillus megaterium. Case presentation A 58-year-old woman presented with intermittent cough and dyspnea for half a year. Chest CT scan showed “crazy paving” pattern. B. megaterium was identified by percutaneous CT-guided needle biopsy. She continuously received antimicrobial treatment since the diagnosis and follow-up examination suggested great improvement. Conclusions To our knowledge, this is the first case of B. megaterium infection presented with PAP pattern in healthy individuals. Attention should be paid on the secondary causes including rare pathogen infection when patients presented with PAP syndrome.

Abstract Background The prevalence of muscle atrophy in patients suffering from chronic kidney disease (CKD) presents a significant challenge to healthcare providers, necessitating innovative approaches to management and care. Against this backdrop, this study embarks on a comprehensive review of literature concerning the application of exercise interventions in the nursing care of these patients. Such interventions are critical in addressing the debilitating effects of the condition, which include progressive loss of muscle mass and strength, adversely affecting patient mobility, quality of life, and overall survival. This review aims to identify the specific exercise modalities, contents, outcome indicators, and application effects associated with this intervention, in the context of the complex interplay of metabolic, inflammatory, and hormonal factors contributing to muscle wasting in CKD patients. By examining the efficacy of various exercise interventions, this study seeks to elucidate optimal strategies for mitigating the impact of CKD-induced muscle atrophy, thereby informing clinical practices and improving patient outcomes. Methods According to the method of a scoping review, nine databases (Cochrane, PubMed, EMBASE, Web of Science, ProQuest, Ovid, CNKI, Wanfang Data, and VIP) were searched until September 28, 2023. The included literature was screened, summarized, and analyzed. Results A total of 20 pieces of literature were included. Some types include aerobic exercise, resistance exercise, and aerobic combined resistance exercise. The exercise intensity primarily falls within the mild to moderate range, with a recommended frequency of 2 − 3 times a week, lasting 30 − 60 min each time. The types of outcomes encompassed in this study include body composition, functional testing, strength measurements, laboratory examinations, cardiopulmonary function assessments, and patient-reported outcomes. To varying degrees, exercise intervention positively impacts the subjects' physical activity ability, body composition, and skeletal muscle status. Currently, resistance training is the primary type of intervention used for preventing and treating CKD patients induced by muscle atrophy. Conclusion Exercise intervention can improve muscle strength, physical function, and quality of life in patients with CKD muscle atrophy. Therefore, patients should be fully informed of the effect of exercise intervention in the treatment of chronic kidney disease-induced muscle atrophy in future, so as to promote the standardized implementation of exercise intervention.

Objective Non-malignant pleural effusions (NMPE) are common in hospitalised patients. Data on NMPE inpatients are scarce and the factors influencing the prognosis are unknown.Design This was a retrospective cohort study.Setting and participants We conducted a retrospective cohort of inpatients (n=86 645) admitted to the Chinese PLA General Hospital from 2018 to 2021, based on electronic medical records. The observations of 4934 subjects with effusions confirmed by chest radiological tests (CT or X-ray) without a diagnosis of malignancy were followed during admission. Logistic regression was used to analyse organ damage and other factors associated with in-hospital death. Patients were clustered according to their laboratory indicators, and the association between the clustering results and outcomes was studied.Outcome The outcome of this study was in-hospital mortality.Results Among 4934 patients, heart failure + pneumonia + renal dysfunction was the most common (15.12%) among 100 different diagnostic groups. 318 (6.4%) patients died during hospitalisation. Lung (OR 3.70, 95% CI 2.42 to 5.89), kidney (OR 2.88, 95% CI 2.14 to 3.90) and heart (1.80, 95% CI 1.29 to 2.55) damage were associated with in-hospital mortality. Hierarchical clustering of laboratory indicators (estimated glomerular filtration rate, white blood cell count, platelet count, haemoglobin, N-terminal pro-B-type natriuretic peptide, serum albumin) demonstrated the ability to discriminate patients at high risk of in-hospital death.Conclusion Comorbidities and multiorgan failure are the prominent characteristics of NMPE patients, which increase the risk of in-hospital mortality, and comprehensive intervention for specific comorbidity patterns is suggested.

Abstract Background CCRT is presently the standard treatment for LA-NSCLC. RP is one of the main obstacles to the completion of thoracic radiation therapy, resulting in limited survival benefits in NSCLC patients. This research aims to explore the role of Endostar in the occurrence of grade≥2 RP and clinical curative effect in LA-NSCLC patients. Methods This study retrospectively analyzed 122 patients with stage III NSCLC who received CCRT from December 2008 to December 2017, or Endostar intravenous drip concurrently with chemoradiotherapy (Endostar + CCRT group). Standard toxicity of the pneumonitis endpoint was also collected by CTCAE V5.0. We further summarized other available studies on the role of Endostar in the prognosis of NSCLC patients and the incidence of RP. Results There were 76 cases in the CCRT group and 46 cases in the CCRT+ Endostar group. In the CCRT+ Endostar group, the occurrence of grade ≥2 RP in patients with V20Gy ≥25% was significantly higher than that in patients with V20Gy < 25% (p = 0.001). In the cohorts with V20Gy < 25%, 0 cases of 29 patients treated with Endostar developed grade ≥2 RP was lower than in the CCRT group (p = 0.026). The re-analysis of data from other available studies indicated that Endostar plus CCRT could be more efficient and safely in the occurrence of grade≥2 RP with LA-NSCLC. Conclusions When receiving CCRT for LA-NSCLC patients, simultaneous combination of Endostar is recommended to enhance clinical benefit and reduce pulmonary toxicity.

We aimed to test whether red blood cell distribution width (RDW) to monocyte percentage ratio (RMR) was associated with the acute-phase prognosis of coronavirus disease 2019 (COVID-19) in chronic kidney disease (CKD) patients. Prospective enrollment and 90-day follow-up of CKD patients with COVID-19 were conducted from December 1, 2022 to January 31, 2023. Demographics, clinical data, and laboratory and radiographic findings were collected, and multiple logistic regression, subgroup analysis, and receiver operating characteristic (ROC) curve analysis were performed. A total of 218 patients were enrolled, with a mean age of 59 years and 69.7% being male. The 90-day mortality rate was 24.8%. The lnRMR level was 5.18 (4.91-5.43) and emerged as an independent risk factor (OR: 3.01, 95% CI: 1.72-5.85). The lnRMR-mortality association was consistent across sex, age, CKD stage, COVID-19 vaccination, and comorbidity subgroups. The area under the ROC curve of lnRMR was 0.737 (95% CI: 0.655-0.819). Our findings indicate that lnRMR is a simple and practical predictor for identifying high-risk CKD patients during the acute phase of COVID-19.

Summary: Aging is closely associated with inflammation, which affects renal function reserve (RFR) in the kidneys. This study aims to investigate the impact of reduced RFR reduction on kidney aging and the influence of renal inflammation and RFR reduction on this process. Natural aging rats and those subjected to unilateral nephrectomy (UNX), 1/6 nephrectomy (1/6NX), and unilateral ureteral obstruction (UUO) were observed at 6, 12, 18, and 21 months. Our findings suggest that RFR reduction and renal inflammation can accelerate kidney aging, and inflammation contributes more. Metabolomics analysis revealed alterations in amino acid metabolism contribute to RFR decline. Furthermore, experiments in vitro confirmed the involvement of pentose phosphate pathway (PPP) in promoting aging though inflammation. Our research provides novel insights into for the mechanism of kidney aging and provides indirect support for clinical treatment decisions, such as addressing kidney inflammation, stones, or tumors that may necessitate partial or complete nephrectomy.

Background: Persistent cough is one of the most common complications following pulmonary resection, that impairs patients’ quality of life and prolongs recovery time. However, a comprehensive review of persistent cough after pulmonary resection (CAP) has not been performed. Methods: A literature search of PubMed/MEDLINE, Web of Science, and Embase database was conducted for persistent-CAP up to June 2023. Subsequent qualitative systematic review focused on definition, risk factors, prevention, and treatment of persistent-CAP. Results: Persistent-CAP stands as a prevalent postoperative complication subsequent to pulmonary resection procedures. with an incidence of 24.4–55.0 %. Although persistent-CAP has a minor impact on survival, this condition is of critical importance because it presents a major hurdle in recovery after surgery. In this review, we proposed a systemic definition for persistent-CAP based on available evidence and our own data. Several assessment tools used to assess severity of persistent-CAP are also introduced. Risk factors associated with persistent-CAP are explored, including surgical approaches, resection extent, surgical site, lymph node dissection, postoperative gastroesophageal acid reflux, tracheal intubation anesthesia, preoperative comorbidity, and sex among others. Surgical and anesthesia preventions targeting risk factors to prevent persistent-CAP are elaborated. A number of studies have shown that a multidisciplinary approach can effectively relieve persistent-CAP. Conclusions: Although the mechanisms underlying persistent-CAP are still unclear, existing studies demonstrated that persistent-CAP is related to surgical and anesthesia factors. Therefore, in the future, prevention and treatment should be developed based on risk factors to overcome the hurdle of persistent-CAP.

Abstract Background Persistent cough is one of the most frequent complications following lung cancer surgery. To promote optimal recovery, we conducted a study to investigate the trajectories of coughing symptoms and their impact on quality of life (QOL), as well as to identify potential risk factors of persistent cough after pulmonary resection (CAP). Methods This prospective observational study assessed patients who underwent pulmonary resection for lung tumor at two medical centers in China. Persistent CAP was evaluated before surgery, at discharge, and 1, 3, and 6 months following surgery using visual analog scale (VAS), cough symptom score (CSS), and Leicester Cough Questionnaire in Mandarin Chinese (LCQ‐MC). Univariate and multivariate logistic regression analyses were conducted to explore independent risk factors for persistent CAP. Results Of the 506 enrolled patients, 130 patients were diagnosed with persistent CAP with an incidence of 25.69%. Compared to the noncough group, patients with persistent CAP reported significantly higher VAS (p

Objectives: To explore the efficacy and safety of five traditional Chinese exercises (TCEs) in patients with fibromyalgia syndrome (FMS). Methods: The PubMed, Embase, Scopus, ProQuest, Web of Science, Cochrane, CNKI, WanFang, and VIP databases were comprehensively searched for randomized controlled trials (RCTs) related to TCEs published from inception until February 2023. Standardized mean differences (SMD) and 95% confidence intervals (CI) were used to determine the combined effects of the intervention, and the Cochrane risk-of-bias assessment tool and Review 5.2 software were used to assess methodological quality. The data were extracted and analyzed by the Stata15.0 random effects model. Results: Nineteen RCTs including 1315 participants were included in the analysis. The studies were found to be heterogeneous (I2 =86.2, P = 0.000), and thus a random effects model was used to combine the data. The results showed that traditional Chinese exercises had potentially beneficial effects on reducing pain (SMD =−0.66,95% CI [−1.08, −0.25], P = 0.002), improving sleep (SMD = −0.35,95% CI [−0.68,0. 01], P = 0.041) and relieving depression (SMD= −0.24,95% CI [−0.47, −0.02], P = 0.034) in FMS patients. However, no significant effects were found on improved quality of life (SMD =−0.20,95% CI [−0.48,0.09], P = 0.176). Conclusions: TCEs can improve pain, sleep quality and depression in patients with FMS and are safe. However, they do not improve the quality of life significantly. Further large-scale, high-quality, and multi-center RCTs are required to verify the efficacy of TCEs.

BackgroundIncreased arterial stiffness and low handgrip strength (HGS) are associated with poor health outcomes and are a severe health risk for older adults. However, there is limited evidence and mixed results on whether there is an association between them. Therefore, this study focused on the association between arterial stiffness and HGS in relatively healthy older adults in Beijing, China.MethodsIn 2016, 2,217 adult volunteers were recruited in Beijing. Brachial-ankle pulse wave velocity (baPWV) and the ankle-brachial index were measured using an automatic vascular profiling system. Carotid artery intima-media thickness and common carotid artery-internal diameter (CCAID) were evaluated using Doppler ultrasound, and HGS was measured with a dynamometer. Low HGS was determined using the Asian Sarcopenia Working Group 2019 criteria. Multivariate linear and logistic regressions evaluated the relationship between arterial stiffness and HGS.ResultsUltimately, 776 relatively healthy older adults (mean age 69.05 ± 6.46 years) were included. Based on the AWGS2019 criteria, 137 participants were defined as having low HGS. Compared to the normal HGS group, the low HGS group was older and had higher baPWV (p

Purpose: To look into the relationship between cardiac substructures (CS) dosimetric parameters and cardiac events (CE) or overall survival (OS) in patients undergoing radiation therapy (RT) for esophageal squamous cell carcinoma (ESCC). Methods and materials: A retrospective study included 350 patients with ESCC receiving definitive chemoradiotherapy or radiotherapy (d-CRT/d-RT) or neoadjuvant chemoradiotherapy (NCRT) from March 2013 to May 2022. Our study examined the adverse cardiac events of any grade or G3+, as defined by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Competing risk analysis and Cox regression analysis were used to assess the relationship between CS doses and CEs or OS. Results: 201 (57.4 %) patients received any grade CEs over a median follow-up time of 22.50 months (IQR, 12.40–45.60), and 24 (6.86 %) patients suffered G3+ CEs. On landmark analysis, patients with any grade CEs had significantly lower OS (P = 0.003). Multivariable analysis revealed that any grade CEs were predicted by the dose of CSs in all populations. In addition, for G3+ cardiac events, arrhythmic and small probability of cardiac events, LAD V20 ((HR: 1.02, 95 % CI: 1.00–1.03, P = 0.012; HR: 1.01, 95 % CI: 1.00–1.02, P = 0.005; HR; 1.01, 95 % CI: 1.00–1.02, P = 0.012) was also an independent predictive factor. LAD V50 (HR: 1.07, 95 % CI: 1.03–1.10, P

The use of human aging markers, which are physiological, biochemical and molecular indicators of structural or functional degeneration associated with aging, is the fundamental basis of individualized aging assessments. Identifying methods for selecting markers has become a primary and vital aspect of aging research. However, there is no clear consensus or uniform principle on the criteria for screening aging markers. Therefore, we combine previous research from our center and summarize the criteria for screening aging markers in previous population studies, which are discussed in three aspects: functional perspective, operational implementation perspective and methodological perspective. Finally, an evaluation framework has been established, and the criteria are categorized into three levels based on their importance, which can help assess the extent to which a candidate biomarker may be feasible, valid, and useful for a specific use context.

Abstract Background Patients with pulmonary nodules (PNs) often suffer from the psychological burden of their disease and trap in sleep problems. This is insufficiently identified and addressed in clinical practice. The aim of this study was to investigate the psychological distress and sleep quality among PN patients and identify potential risk or protective factors for sleep quality. Methods We conducted a cross-sectional study, which included 731 PN patients who visited the thoracic clinic of Guangdong Provincial People’s Hospital. Each participant completed a structured questionnaire consisting of demographic characteristics, clinical characteristics, the Hospital Anxiety and Depression Scale (HADS) and the Pittsburgh Sleep Quality Index (PSQI). The reliability of the HADS (Cronbach’s α = 0.944) and PSQI (Cronbach’s α = 0. 0.757) in this study was satisfactory. Results A total of 328 patients (44.9%) had PSQI global scores > 5, indicating poor quality of sleep. Age ≥ 50 years (OR 1.88, 95% CI 1.35–2.58; P

Abstract Background Frailty and sarcopenia are prevalent in chronic kidney disease (CKD) populations and could increase the risk for adverse health outcomes. Few studies assess the correlation between frailty, sarcopenia and CKD in non‐dialysis patients. Therefore, this study aimed to determine frailty‐associated factors in elderly CKD stage I–IV patients, expected to early identify and intervene in the frailty of elderly CKD patients. Methods A total of 774 elderly CKD I–IV patients (>60 years of age) recruited from 29 clinical centers in China between March 2017 and September 2019 were included in this study. We established a Frailty Index (FI) model to evaluate frailty risk and verified the distributional property of FI in the study population. Sarcopenia was defined according to the criteria of the Asian Working Group for Sarcopenia 2019. Multinomial logistic regression analysis was used to assess the associated factors for frailty. Results Seven hundred seventy‐four patients (median age 67 years, 66.0% males) were included in this analysis, with a median estimated glomerular filtration rate of 52.8 mL/min/1.73 m2. The prevalence of sarcopenia was 30.6%. The FI exhibited a right‐skewed distribution. The age‐related slope of FI was 1.4% per year on a logarithmic scale (r2 = 0.706, 95% CI 0.9, 1.8, P

Abstract Background Pericyte-myofibroblast transition (PMT) has been confirmed to contribute to renal fibrosis in several kidney diseases, and transforming growth factor-β1 (TGF-β1) is a well-known cytokine that drives PMT. However, the underlying mechanism has not been fully established, and little is known about the associated metabolic changes. Methods Bioinformatics analysis was used to identify transcriptomic changes during PMT. PDGFRβ + pericytes were isolated using MACS, and an in vitro model of PMT was induced by 5 ng/ml TGF-β1. Metabolites were analyzed by ultraperformance liquid chromatography (UPLC) and tandem mass spectrometry (MS). 2-Deoxyglucose (2-DG) was used to inhibit glycolysis via its actions on hexokinase (HK). The hexokinase II (HKII) plasmid was transfected into pericytes for HKII overexpression. LY294002 or rapamycin was used to inhibit the PI3K-Akt-mTOR pathway for mechanistic exploration. Results An increase in carbon metabolism during PMT was detected through bioinformatics and metabolomics analysis. We first detected increased levels of glycolysis and HKII expression in pericytes after stimulation with TGF-β1 for 48 h, accompanied by increased expression of α-SMA, vimentin and desmin. Transdifferentiation was blunted when pericytes were pretreated with 2-DG, an inhibitor of glycolysis. The phosphorylation levels of PI3K, Akt and mTOR were elevated during PMT, and after inhibition of the PI3K-Akt-mTOR pathway with LY294002 or rapamycin, glycolysis in the TGF-β1-treated pericytes was decreased. Moreover, PMT and HKII transcription and activity were blunted, but the plasmid-mediated overexpression of HKII rescued PMT inhibition. Conclusions The expression and activity of HKII as well as the level of glycolysis were increased during PMT. Moreover, the PI3K-Akt-mTOR pathway regulates PMT by increasing glycolysis through HKII regulation.

Abstract Objectives To identify and synthesize existing research on the effectiveness and feasibility of multiform humor therapy on people suffering from depression or anxiety, with the hope of benefiting future research. Methods An integrative literature review of quantitative, qualitative, and mixed studies was performed. The PubMed, Cochrane Library, Web of Science, Embase, and CINAHL databases were searched up to March 2022. Two independent reviewers conducted each stage of the review process, by assessing eligibility using preferred reporting items for systematic review and meta‐analyses (PRISMA) and quality appraisal using the Mixed Methods Appraisal Tool, and data extraction. Results In this integrative review, 29 papers were included, containing 2964 participants across a diverse range of studies, including quantitative, qualitative, and mixed methods. The articles were from the United States, Australia, Italy, Turkey, South Korea, Iran, Israel, China, and Germany. The findings indicated that most of the subjects thought humor therapy was effective in improving depression and anxiety while a few participants considered the effect insignificant. However, more high‐quality studies will be needed to confirm these conclusions. Discussion This review collated and summarized findings from studies examining the impact of humor therapy (medical clowns, laughter therapy/yoga) on people with depression or anxiety, including children undergoing surgery or anesthesia, older people in nursing homes, patients with Parkinson's disease, cancer, mental illness, and undergoing dialysis, retired women, and college students. The results from this review may help inform future research, policy, and practice in humor therapy to improve people's symptoms of depression and anxiety. Impact This systematic review objectively evaluated the effect of humor therapy on depression and anxiety. As a simple and feasible complementary alternative therapy, humor therapy may provide a favorable alternative for clinicians, nurses, and patients in the future.

Anemia is a common and important complication in patients with chronic kidney disease (CKD). Accordingly, the current treatment is based on erythropoiesis stimulating agents (ESAs) and iron. Hypoxia-inducible factor (HIF) prolyl hydroxylase domain (PHD) inhibitors (HIF-PHIs) have been developed to treat renal anemia through a novel mechanism. HIF-PHIs increase EPO at physiologic blood concentrations and also improve the supply of hematopoietic iron. Iron is the main component of hemoglobin, and ensuring efficient iron metabolism is essential in the treatment of anemia. HIF-PHIs may have advantages in improving iron utilization and mobilization compared to ESAs. Most HIF-PHIs trials revealed a significant decline of hepcidin, increase transferrin level and total iron binding capacity in patients. From a clinical point of view, improvements in iron metabolism should translate into a reduction in the need for iron supplementation, although timely and comparative assessment of iron supplementation across studies are complicated due to the large variability in the iron regimen employed. This review summarizes the mechanism of HIF-PHIs on improved iron metabolism and the route of iron usage in the trials for dialysis-dependent CKD and non-dialysis CKD. And this review also makes an interpretation of the clinical practice guidelines in China and recommendation by Asia Pacific Society of Nephrology.

For the razor clam Solen grandis, siphonal autotomy and regeneration is a necessary means of facing external stress, which is accompanied by a large amount of energy consumption. To explore the function of the ENO4 gene in the siphonal autotomy and regeneration of S. grandis, the full-length cDNA of the ENO4 in S. grandis was cloned and characterized. The full-length cDNA of SgENO4 was 2,773 base pairs (bp), with an 1,851 bp coding sequence (CDS) encoding 616 amino acids. ​Bioinformatic analysis revealed a slightly lower codon usage bias and a relatively stable nucleotide composition in the SgENO4 sequence. Three conserved motifs were found from the SgENO4 sequence. These conserved motifs vary in length from 14 to 27 amino acids. Moreover, in the siphonal pre-autotomy of razor clams, expression level of the SgENO4 gene was significantly higher in the hepatopancreas and siphonal base than other tissues (P < 0.05). However, the expression of the SgENO4 gene in the siphonal base decreased significantly in the siphonal post-autotomy 7 hours and gradually recovered as the regeneration process continued. ​Linear correlation analysis showed that there was a significant linear correlation between specific weight of siphon and relative expression levels of SgENO4 (R2 = 0.826). RNA interference (RNAi) result showed that the specific weight (the proportion of siphonal weight to body weight) is significantly lower than other groups on the seventh day (P < 0.05), suggesting that interfering with the expression of the SgENO4 gene could inhibit the siphonal regeneration of S. grandis. These results further demonstrate that SgENO4 is a conserved sequence and that it plays a crucial role in the siphonal autotomy and regeneration of S. grandis, advancing further understanding in exploring molecular mechanisms in the siphonal autotomy and regeneration.

Background A significant proportion of incident and prevalent hemodialysis patients have central venous catheters for vascular access. No consensus is available on the prevention of catheter dysfunction or catheter-related bloodstream infections in patients undergoing hemodialysis by means of catheter lock solutions.Method We reviewed the effects of single and combined anticoagulants with antibacterial catheter lock solutions or other antimicrobials for the prevention of thrombosis or infections in hemodialysis patients. Relative risks with 95% confidence intervals for trials of the same type of catheter locking solution were pooled.Sources of information We included original research articles in English from PubMed, EMBASE, SpringerLink, Elsevier and Ovid using the search terms ‘hemodialysis,’ ‘central venous catheter,’ ‘locking solution,’ ‘UFH,’ ‘low molecular weight heparin,’ ‘EDTA,’ ‘citrate,’ ‘rt-PA,’ ‘urokinase,’ ‘gentamicin,’ ‘vancomycin’, ‘taurolidine,’ ‘sodium bicarbonate,’ ‘hypertonic saline’ and ‘ethanol’ and ‘catheter’.Findings Low-dose heparin lock solution (< 5000 U/ml) can efficiently achieve anticoagulation and will not increase the risk of bleeding. Low-concentration citrate (< 5%) combined with rt-PA can effectively prevent catheter infection and dysfunction. Catheter-related infections may be minimized by choosing the appropriate antibiotic and dose.Limitations There is a lack of follow-up validation data for LMWH, EDTA, taurolidine, sodium bicarbonate, ethanol, and other lock solutions.Implications Since catheterization is common in hemodialysis units, studies on long-term treatment and preventative strategies for catheter dysfunction and catheter-related infection are warranted.

Abstract Background Nontuberculous mycobacteria (NTM) usually invades vulnerable hosts. Disseminated NTM (dNTM) infection can affect nearly all organs and be easily misdiagnosed as metastatic carcinoma or other systemic diseases, especially in seemingly immunocompetent hosts. Identification of underlying immunodeficiency is critical for the diagnosis and treatment of dNTM. Adult-onset immunodeficiency (AOID) with anti-IFN-γ autoantibodies has recently been recognized as a crucial but frequently neglected risk factor for dNTM infection. Frequent relapses of infection are common in AOID patients despite appropriate anti-infective treatment and B-cell-depleting therapy has shown some promising results. Herein, we report a case of dNTM infection mimicking malignancy in an AOID patient who was successfully treated with rituximab. Case presentation A middle-aged male presented with fever, productive cough, multifocal skin abscesses and multiple osteolytic lesions with pathological fractures. Chest CT revealed consolidation of the lingula while bronchoscopy showed a mass completely blocking the airway opening of the inferior lingual segment. Metagenomic next-generation sequencing and mycobacterial culture of skin pus and bronchoalveolar lavage fluid reported Mycobacterium Colombiense, confirming the diagnosis of dNTM infection. However, anti-NTM antibiotics alone failed to prevent disease relapse and progression. Further evaluation indicated undetectable serum IFN-γ concentration and high-titer autoantibodies against IFN-γ, suggesting that AOID was the underlying reason for dNTM. Rituximab was added to treatment and successfully controlled the infection without relapse at one-year follow-up. Conclusion We reported a rare case of disseminated Mycobacterium Colombiense infection manifested with pulmonary mass, pathological fracture and dermapostasis in a host with AOID. Our case demonstrated that AOID should be screened when patients get the episode of disseminated NTM infection particularly when other risk factors are excluded. Besides prolonged anti-NTM therapy, AOID-associated NTM infection should be treated with B-cell-depleting therapy to prevent recurrence.

BackgroundNephrotic syndrome that is resistant to steroid therapy is termed refractory nephrotic syndrome (RNS), a condition that is associated with an increased risk of end-stage renal disease. Immunosuppressants are used to treat RNS; however, prolonged use may lead to significant adverse effects. Mizoribine (MZR) is a novel agent used in long-term immunosuppressive therapy, which has few adverse effects, but data on its long-term use in patients with RNS are unavailable. ObjectiveWe propose a trial to examine the efficacy and safety of MZR compared with cyclophosphamide (CYC) in Chinese adult patients with RNS. MethodsThis is a multicenter, randomized, controlled interventional study with a screening phase (1 week) and a treatment phase (52 weeks). This study has been reviewed and approved by the Medical Ethics Committees of all 34 medical centers that are participating. Patients with RNS consent to participation, and are enrolled and randomized to an MZR group or a CYC group (1:1 ratio), with each group receiving tapering doses of oral corticosteroids. Participants are assessed for adverse effects, and laboratory results are collected at 8 visits during the treatment phase (weeks 4, 8, 12, 16, 20, 32, 44, and 52 [exit visit]). Participants are able to withdraw voluntarily, and investigators are required to remove patients when there are safety concerns or deviations from the protocol. ResultsThe study started in November 2014 and was completed in March 2019. A total of 239 participants from 34 hospitals in China have been enrolled. Data analysis has been completed. The results are being finalized by the Center for Drug Evaluation. ConclusionsThis study examines the safety and efficacy of MZR as a long-term treatment approach for Chinese adults with RNS. It is the longest lasting and largest randomized controlled trial to examine MZR in Chinese patients. The results can help determine whether RNS should be considered as an additional indication for MZR treatment in China. Trial RegistrationClinicalTrials.gov NCT02257697; https://clinicaltrials.gov/ct2/show/NCT02257697 International Registered Report Identifier (IRRID)RR1-10.2196/46101

Background: Aspirations without a tissue core are common in endobronchial ultrasound-guided transbronchial needle aspiration procedures. However, the diagnostic value of all-shot aspirations and no-tissue-core aspirations is unclear. Patients and Methods: A retrospective analysis of patients who underwent endobronchial ultrasound-guided transbronchial needle aspiration with the description of all-shot or no-tissue-core aspirations was conducted at a tertiary hospital between January 2017 and March 2021. Patients’ pathologic and clinical diagnoses were retrieved and compared between all-shot patients (all aspirations had a tissue core) and no-tissue-core patients (at least one aspiration had no tissue core). Results: Among all 505 patients with 1402 aspirations, 356 (70.5%) patients, and 1184 (84.5%) aspirations were all-shot. Pathologic diagnosis after endobronchial ultrasound-guided transbronchial needle aspiration revealed neoplasms in 46.1% of all-shot patients, but 33.6% of no-tissue-core patients (odds ratio, 1.69; 95% confidence interval, 1.14-2.52; P = .009). Final clinical diagnosis revealed malignancy in 53.1% of all-shot patients, but 37.6% of no-tissue-core patients (odds ratio, 1.88; 95% confidence interval, 1.27-2.78; P = .001). In 133 patients with pathologic nonspecific findings, a clinical diagnosis of malignancy was proven in 25 of 79 (31.6%) of all-shot patients, but only 6 of 54 (11.1%) of no-tissue-core patients (odds ratio, 3.70; 95% confidence interval, 1.40-9.79; P = .006). Conclusions: Patients with all-shot aspirations in endobronchial ultrasound-guided transbronchial needle aspiration are more likely to have the pathologic and clinical diagnosis of malignancy. More measures should be taken to exclude malignancy in all-shot patients when the endobronchial ultrasound-guided transbronchial needle aspiration was nondiagnostic.

Biological age (BA) is a common model to evaluate the function of aging individuals as it may provide a more accurate measure of the extent of human aging than chronological age (CA). Biological age is influenced by the used biomarkers and standards in selected aging biomarkers and the statistical method to construct BA. Traditional used BA estimation approaches include multiple linear regression (MLR), principal component analysis (PCA), Klemera and Doubal’s method (KDM), and, in recent years, deep learning methods. This review summarizes the markers for each organ/system used to construct biological age and published literature using methods in BA research. Future research needs to explore the new aging markers and the standard in select markers and new methods in building BA models.

The Qinling Mountain Range (QMR), where more than 500 hominin fossils and Paleolithic sites have been preserved, was a major center of hominin evolution and settlement and an important link for the hominin migration and dispersal between the north and the south during the Pleistocene in China. The rich culture remains and the related data make it possible and meaningful to study the characteristics and mechanisms of hominin occupation and dispersal in the region. This paper has summarized and analyzed the geographical distributions and chronologies of 55 dated hominin fossils and Paleolithic sites in the QMR to date. By combining them with the evidence from the loess–paleosol sequence, a relatively continuous and chronological sequence of hominin occupation and dispersal has been established, in which we have identified five stages, viz. ~before 1.2 Ma, the sporadic occurrence stage of early hominin occupation; ~1.2–0.7 Ma, the initial expansion stage; ~0.7–0.3 Ma, the stability and maintenance stage; ~0.3–0.05 Ma, the large-scale expansion stage; ~0.05–0.01 Ma, the sharp decline stage of the record of hominin occupation. We conclude that the environmental and ecosystem changes associated with the MPT drove early hominins to disperse southwards across the QMR. In addition, the evidence suggests that the hominin occupation and dispersal here was broadly continuous during both glacial and interglacial scales from early to late Pleistocene, and that the southern QMR provided a glacial refuge.

BackgroundPeritoneal dialysis (PD) care in mainland China has been progressing in the past 10 years. ObjectiveTo complement information from the dialysis registry, a large-scale nationwide survey was conducted to investigate the current infrastructure and management of PD care at hospitals of different tiers. MethodsA web-based multiple-choice questionnaire was distributed through the National Center for Nephrology Medical Quality Management and Control to PD centers of secondary and tertiary hospitals in October 2020. The 2-part survey collected the information of PD centers and the clinical management of patients on PD. A total of 788 effective surveys from 746 hospitals were voluntarily returned, and data were extracted and analyzed. ResultsThe effective survey data covered 101,537 patients on PD, with 95% (96,460/101,537) in the tertiary hospitals. The median number of patients per PD center was 60 (IQR 21-152); this number was 32 (IQR 8-65) and 70 (IQR 27-192) for secondary and tertiary hospitals, respectively. There was a discrepancy in the availability of designated physical areas for different functions of PD care between the secondary and tertiary hospitals. The proportion of tertiary hospitals with PD training (P=.01), storage (P=.09), and procedure area (P

Introduction Roxadustat is a first-in-class oral therapy that treats chronic kidney disease (CKD) anaemia with the benefit of a novel mechanism of action that consistently corrects and maintains haemoglobin (Hb) across the spectrum of non-dialysis-dependent (NDD) CKD anaemia with an acceptable safety profile.Methods and analysis This is a randomised, control, open-label, multicentre trial. About 250 adult Chinese participants with stage 3–5 CKD NDD in approximately 30 centres will be enrolled, randomly assigned in a 1:1 ratio, to receive a 16-week treatment and 4-week follow-up. The interventions for study arm are

To determine the relevance of morphometric properties attributed to the meat yield and fatness index of the saltwater hard clam Meretrix meretrix. A new strain of M. meretrix with red shell color was produced after five generations of selection within a family of full-sibs. 7 morphometric traits, including shell length (SL), shell height (SH), shell width (SW), ligament length (LL), projection length (PL), projection width (PW), and live body weight (LW), and 2 meat characteristics, including meat yield (MY) and fatness index (FI) were measured from 50 individuals of three-year-old M. meretrix. The correlation coefficients, path coefficients, determination coefficients among attributes were analyzed. The results indicated that correlation achieved very significant levels (P

IntroductionTo explore the CT characteristics for the prediction of long term survival in gastric cancer patients with synchronous peritoneal metastasis (PM).Materials and methodsSixty-six patients diagnosed as gastric cancer with synchronous peritoneum metastasis were enrolled in this retrospective study. Ten anatomic peritoneal regions were evaluated to check for the signs of PM on CT. One positive area equaled one score. The CT characteristic-based PM score (CT-PMS) was the sum of the total points assigned to all 10 regions, with a range of 0–10. The triple tract dilatation (TTD) sign caused by peritoneal metastasis, the presence of extensive lymph node metastasis (ELM), and the grade of ascites were recorded. The overall survival (OS) was used as the prognostic indicator. The performance of the CT characteristics was assessed by the Kaplan–Meier analysis and Cox proportional hazards model, while its reproducibility was evaluated by Kappa statistic and weighted Kappa statistic.ResultsPatients with a CT-PMS of 3–10 had significantly poorer OS (P = .02). Patients with either the presence of TTD sign, or ELM had a trend toward unfavorable OS (both P = .07), and when CT-PMS of 3–10 was detected simultaneously, the survival was further reduced (P = .00 for TTD sign; P = .01 for ELM). The grade of ascites failed to show a significant correlation with OS. The interobserver reproducibility for assessing the CT-PMS, the presence of TTD sign, the presence of ELM, and the grade of ascites had a substantial to almost perfect agreement.ConclusionThe prognosis of gastric cancer patients with PM has a correlation with the extent of metastasis dissemination on baseline CT. A CT-PMS of 3–10 is associated with a worse prognosis than that of 0–2. The presence of TTD sign and ELM may help further select patients with extraordinarily poor prognoses.

Abstract Background Established prediction models of Diabetic kidney disease (DKD) are limited to the analysis of clinical research data or general population data and do not consider hospital visits. Construct a 3-year diabetic kidney disease risk prediction model in patients with type 2 diabetes mellitus (T2DM) using machine learning, based on electronic medical records (EMR). Methods Data from 816 patients (585 males) with T2DM and 3 years of follow-up at the PLA General Hospital. 46 medical characteristics that are readily available from EMR were used to develop prediction models based on seven machine learning algorithms (light gradient boosting machine [LightGBM], eXtreme gradient boosting, adaptive boosting, artificial neural network, decision tree, support vector machine, logistic regression). Model performance was evaluated using the area under the receiver operating characteristic curve (AUC). Shapley additive explanation (SHAP) was used to interpret the results of the best performing model. Results The LightGBM model had the highest AUC (0.815, 95% CI 0.747–0.882). Recursive feature elimination with random forest and SHAP plot based on LightGBM showed that older patients with T2DM with high homocysteine (Hcy), poor glycemic control, low serum albumin (ALB), low estimated glomerular filtration rate (eGFR), and high bicarbonate had an increased risk of developing DKD over the next 3 years. Conclusions This study constructed a 3-year DKD risk prediction model in patients with T2DM and normo-albuminuria using machine learning and EMR. The LightGBM model is a tool with potential to facilitate population management strategies for T2DM care in the EMR era.

The present study investigates the diachronic development of the bipartite negative construction hǎa…mây in Thai, aiming to account for its syntactic and semantic peculiarity. Based on the historical data from the Sukhothai period to Modern Thai, I suggest that the development of hǎa…mây construction relates to the grammaticalization of the expression hǎa NP míɁ dây ‘fail to find something’. From around the mid-14th century, hǎa NP míɁ dây came to gain a new function as an irregular negative existential construction under the pressure of the recession of the anterior negative existential form bɔ̀ɔ mii ‘not have, not exist’. This function is especially prominent in the 17th century during which the old negator bɔ̀ɔ shows a continuous decrease in the frequency of use and the newer negator mây was not widely used. When the newer negative existential form mây mii emerged around the early 18th century and eventually prevailed over hǎa NP míɁ dây in the 19th and 20th centuries, hǎa NP míɁ dây gradually lost its function as a negative existential form but survived its evolution into a negative adverbial construction through a syntagmatic change (from hǎa NP to hǎa VP), accompanied by a phonetic reduction (from hǎa…míɁ dây to hǎa…mây ) and a semantic reinterpretation(from ‘fail to find something or not exist, not have’ to ‘not VP as one thought’).

China is a crucial region for investigating the relationship between climate change and hominin evolution across diverse terrestrial ecosystems. With the continuous development of palaeoclimatology, chronology, and archaeology, the environmental and hominin record of the Early and Middle Pleistocene in China is steadily accumulating, shedding light on the effects of climate change on the distribution of early human settlements and population dynamics. However, the migration and dispersal of these early humans within long-term climate fluctuations and their underlying mechanisms remain to be clarified. Based on the spatial-temporal distribution of 95 Early to Middle Pleistocene archaeological sites in China, we found that intensified hominin activities gradually shifted southward under the influence of multiple glacial–interglacial cycles. The frequent bidirectional movements of these early humans between north and south were assumed as follows. During glacial periods, hominins living in North China migrated to southern areas, while inter-glacial periods witnessed the northward expansion of hominins inhabiting South China. Among all the potential driving mechanisms, we suggest that the available resources in terrestrial ecosystems may be the most fundamental factor. Combined with paleoenvironmental and archaeological records, we provide an Asian perspective for a better understanding of how the glacial–interglacial cycles shaped early human evolution.

The affinity of peptides is a crucial factor in studying peptide–protein interactions. Despite the development of various techniques to evaluate peptide–receptor affinity, the results may not always reflect the actual affinity of the peptides accurately. The current study provides a free tool to assess the actual peptide affinity based on virtual docking data. This study employed a dataset that combined actual peptide affinity information (active and inactive) and virtual peptide–receptor docking data, and different machine learning algorithms were utilized. Compared with the other algorithms, the random forest (RF) algorithm showed the best performance and was used in building three RF models using different numbers of significant features (four, three, and two). Further analysis revealed that the four-feature RF model achieved the highest Accuracy of 0.714 in classifying an independent unknown peptide dataset designed with the PEDV spike protein, and it also revealed overfitting problems in the other models. This four-feature RF model was used to evaluate peptide affinity by constructing the relationship between the actual affinity and the virtual docking scores of peptides to their receptors.

The quiescent muscle stem cell (QSC) pool is heterogeneous and generally characterized by the presence and levels of intrinsic myogenic transcription factors. Whether extrinsic factors maintain the diversity of states across the QSC pool remains unknown. The muscle fiber is a multinucleated syncytium that serves as a niche to QSCs, raising the possibility that the muscle fiber regulates the diversity of states across the QSC pool. Here, we show that the muscle fiber maintains a continuum of quiescent states, through a gradient of Notch ligand, Dll4, produced by the fiber and captured by QSCs. The abundance of Dll4 captured by the QSC correlates with the protein levels of the stem cell (SC) identity marker, Pax7. Niche-specific loss of Dll4 decreases QSC diversity and shifts the continuum to cell states that are biased toward more proliferative and committed fates. We reveal that fiber-derived Mindbomb1 (Mib1), an E3 ubiquitin ligase activates Dll4 and controls the heterogeneous levels of Dll4. In response to injury, with a Dll4-replenished niche, the normal continuum and diversity of the SC pool is restored, demonstrating bidirectionality within the SC continuum. Our data show that a post-translational mechanism controls heterogeneity of Notch ligands in a multinucleated niche cell to maintain a continuum of metastable states within the SC pool during tissue homeostasis.

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease, and its early pathogenesis is critical. Shear stress caused by glomerular hyperfiltration contributes to the initiation of kidney injury in diabetes. The primary cilium of renal tubular epithelial cells (RTECs) is an important mechanical force sensor of shear stress and regulates energy metabolism homeostasis in RTECs to ensure energy supply for reabsorption functions, but little is known about the alterations in the renal cilium number and length during the progression of DKD. Here, we demonstrate that aberrant ciliogenesis and dramatic increase in the cilium length, the number of ciliated cells, and the length of cilia are positively correlated with the DKD class in the kidney biopsies of DKD patients by super-resolution imaging and appropriate statical analysis methods. This finding was further confirmed in STZ-induced or db/db diabetic mice. These results suggest that the number and length of renal cilia may be clinically relevant indicators and that cilia will be attractive therapeutic targets for DKD.

Background and objectiveMetabolic syndrome (MetS) is an important risk factor for cardiovascular complications and kidney damage. Obesity- and lipid-related indices are closely related to MetS, and different indices have different predictive abilities for MetS. This study aimed to evaluate the predictive value of eight obesity- and lipid-related indicators, namely, body mass index (BMI), lipid accumulation product (LAP), body roundness index (BRI), Chinese visceral adiposity index (CVAI), body adiposity index (BAI), abdominal volume index (AVI), triglyceride glucose index (TYG), and visceral adiposity index (VAI), for MetS.MethodsA total of 1,452 relatively healthy people in Beijing were enrolled in 2016, and the correlation between the eight indicators and MetS was analyzed by multivariate logistic regression. The receiver operating characteristic (ROC) curve and the area under the curve (AUC) were used to analyze the predictive ability of the eight indicators for MetS. The Delong test was used to compare the AUC values of the eight indicators. MetS was defined according to the Chinese Guidelines for the Prevention and Treatment of Type 2 Diabetes (2020 edition), the revised National Cholesterol Education Program Adult Treatment Group (NCEP-ATPIII), and the International Diabetes Federation (IDF).ResultsUsing these three sets of criteria, LAP, TYG, CVAI, and VAI, which are based on blood lipids, had higher AUC values for MetS prediction than BMI, BRI, AVI, and BAI, which are based on anthropometry. LAP had the highest AUC values of 0.893 (0.874–0.912), 0.886 (0.869–0.903), and 0.882 (0.864–0.899), separately, based on the three sets of criteria.ConclusionThe eight obesity- and lipid-related indicators had screening value for MetS in relatively healthy people, and of the eight indicators, LAP performed the best.

Immunotherapies, such as immune checkpoint inhibitors (ICIs) and chimeric antigen receptor (CAR) T cells, have revolutionized the treatment of patients with advanced and metastatic tumors resistant to traditional therapies. However, the immunosuppressed tumor microenvironment (TME) results in a weak response to immunotherapy. Therefore, to realize the full potential of immunotherapy and obstacle barriers, it is essential to explore how to convert cold TME to hot TME. Autophagy is a crucial cellular process that preserves cellular stability in the cellular components of the TME, contributing to the characterization of the immunosuppressive TME. Targeted autophagy ignites immunosuppressive TME by influencing antigen release, antigen presentation, antigen recognition, and immune cell trafficking, thereby enhancing the effectiveness of cancer immunotherapy and overcoming resistance to immunotherapy. In this review, we summarize the characteristics and components of TME, explore the mechanisms and functions of autophagy in the characterization and regulation of TME, and discuss autophagy-based therapies as adjuvant enhancers of immunotherapy to improve the effectiveness of immunotherapy.

BackgroundLupus nephritis (LN) is one of the most common and serious complications of systemic lupus erythaematosus (SLE). Genetic factors play important roles in the pathogenesis of LN and could be used to predict who might develop LN. The purpose of this study was to screen for susceptible candidates of LN across the whole genome in the Han Chinese population.Methods592 LN patients and 453 SLE patients without renal damage were genotyped at 492,970 single nucleotide polymorphisms (SNPs) in the genome-wide association study (GWAS). Fifty-six SNPs were selected for replication in an independent cohort of 188 LN and 171 SLE without LN patients. Further quantitative real-time (qRT) PCR was carried out in 6 LN patients and 6 healthy controls. Gene-based analysis was conducted using the versatile gene-based test for GWAS. Subsequently, enrichment and pathway analyses were performed in the DAVID database.ResultsThe GWAS analysis and the following replication research identified 9 SNPs showing suggestive correlation with LN (P

The primary cilium is a hair-like, microtubule-based organelle that is covered by the cell membrane and extends from the surface of most vertebrate cells. It detects and translates extracellular signals to direct various cellular signaling pathways to maintain homeostasis. It is mainly distributed in the proximal and distal tubules and collecting ducts in the kidney. Specific signaling transduction proteins localize to primary cilia. Defects in cilia structure and function lead to a class of diseases termed ciliopathies. The proper functioning of primary cilia is essential to kidney organogenesis and the maintenance of epithelial cell differentiation and proliferation. Persistent cilia dysfunction has a role in the early stages and progression of renal diseases, such as cystogenesis and acute tubular necrosis (ATN). In this review, we focus on the central role of cilia in kidney development and illustrate how defects in cilia are associated with renal disease progression.

The Three Gorges region (TGR) located in the geographic center of China, is a transition zone between mountain and plain areas, and a probable migration corridor for hominins and other mammals between South and North China. Detailed chronological information of paleoanthropological evidence in this area could help us better understand the human evolution in East Asia. The OSL and U-series dating methods are two conventional dating methods generally adopted to date such sites; however, their applications were limited by the dating range—restricted to several hundred of millennia and ambiguous stratigraphic relationship between the archaeological remains and the dating target materials. Cosmogenic nuclide burial dating of quartzite stone artifacts and coupled electron spin resonance and uranium series dating (ESR/U-series) of fossil teeth have the potential to date Early–Middle Pleistocene hominin sites in Asia and were applied increasingly in China in recent years. However, the application of cosmogenic 26Al/10Be burial dating is limited in TGR because most sites are dominated by limestone, leading to the scarcity of the quartz component. In this case, the coupled ESR/U-series method plays a more important role in the establishment of the chronology of human settlement. In TGR, by using the coupled ESR/U-series method, we have dated seven important Early and Middle Pleistocene hominin settlement sites, including Longgupo, Jianshi, Yunxian, Meipu, Bailongdong, Changyang, and Yumidong sites. Based on our dating results, we propose that hominins were settled in TGR probably from the early stage of Early Pleistocene (∼2.5−2.2 Ma) at the Longgupo site to the late Middle Pleistocene to Late Pleistocene of the Yumidong site (∼274−14 ka) and very likely to spread to other parts of East Asia during this time period. In view of the potential of coupled ESR/U-series dating on fossil teeth from the hominin sites in the TGR, future work may consider the micro damage or non-destructive analysis of enamel fragment with the ESR method and laser ablation ICP-MS techniques that will make possible the direct dating of precious human fossils in China.

PurposeThe present study sets out to evaluate the feasibility, safety, and effectiveness of conversion surgery following induction immunochemotherapy for patients with initially unresectable locally advanced esophageal squamous cell carcinoma (ESCC) in a real-world scenario.Materials and MethodsIn this multi-center, real-world study (NCT04822103), patients who had unresectable ESCC disease were enrolled across eight medical centers in China. All patients received programmed death receptor-1 (PD-1) inhibitor plus chemotherapy every 3 weeks for at least two cycles. Patients with significant relief of cancer-related clinical symptoms and radiological responsive disease were deemed surgical candidates. Feasibility and safety profile of immunochemotherapy plus conversion surgery, radiological and pathological tumor responses, as well as short-term survival outcomes were evaluated. Moreover, data of an independent ESCC cohort receiving induction chemotherapy (iC) were compared.ResultsOne hundred and fifty-five patients were enrolled in the final analysis. Esophagectomy was offered to 116 patients, yielding a conversion rate of 74.8%. R0 resection rate was 94%. Among the 155 patients, 107 (69.0%) patients experienced at least one treatment-related adverse event (TRAE) and 45 (29.0%) patients reported grade 3 and above TRAEs. Significant differences in responsive disease rate were observed between iC cohort and induction immunochemotherapy (iIC) cohort [objective response rate: iIC: 63.2% vs. iC: 47.7%, p = 0.004; pathological complete response: iIC: 22.4% vs. iC: 6.7%, p = 0.001). Higher anastomosis fistula rate was observed in the iC group (19.2%) compared with the iIC group (4%). Furthermore, Significantly higher event-free survival was observed in those who underwent conversion surgery.ConclusionOur results supported that conversion surgery following immunochemotherapy is feasible and safe for patients with initially unresectable locally advanced ESCC. Both radiological and pathological response rates were significantly higher in the iIC cohort compared with those in the traditional iC cohort.

BackgroundThe disease pathology for diabetes mellitus patients with chronic kidney disease (CKD) may be diabetic nephropathy (DN), non-diabetic renal disease (NDRD), or DN combined with NDRD. Considering that the prognosis and treatment of DN and NDRD differ, their differential diagnosis is of significance. Renal pathological biopsy is the gold standard for diagnosing DN and NDRD. However, it is invasive and cannot be implemented in many patients due to contraindications. This article constructed a new noninvasive evaluation model for differentiating DN and NDRD.MethodsWe retrospectively screened 1,030 patients with type 2 diabetes who has undergone kidney biopsy from January 2005 to March 2017 in a single center. Variables were ranked according to importance, and the machine learning methods (random forest, RF, and support vector machine, SVM) were then used to construct the model. The final model was validated with an external group (338 patients, April 2017–April 2019).ResultsIn total, 929 patients were assigned. Ten variables were selected for model development. The areas under the receiver operating characteristic curves (AUCROCs) for the RF and SVM methods were 0.953 and 0.947, respectively. Additionally, 329 patients were analyzed for external validation. The AUCROCs for the external validation of the RF and SVM methods were 0.920 and 0.911, respectively.ConclusionWe successfully constructed a predictive model for DN and NDRD using machine learning methods, which were better than our regression methods.Clinical Trial RegistrationClinicalTrial.gov, NCT03865914.

Potassium titanyl phosphate (KTiOPO4, KTP) particle of nanometric size (nano-KTP) is an attractive material for nonlinear microscopy, and the optimized growth of large-size KTP single crystals has numerous applications for efficient frequency conversion in laser technology. Its three-dimensional orientation and nanoscale morphology are important for growth optimization. In this paper, we introduce an imaging technique based on circular dichroism second-harmonic generation (CD-SHG) to characterize the 3D distribution of KTP nanocrystal. A rigorous theoretical model of CD-SHG imaging for nano-KTP through stratified media is demonstrated. Circular dichroism analysis is used to probe the orientation of 3-axis with respect to the optical observation axis. The research results show that the azimuthal angle of the peak value (SHG) or valley value (CD-SHG) is strongly related to the excitation polarization when the KTP sample is excited by different circular polarizations. Importantly, the refractive index mismatches and the imaging depth also affect the azimuthal angle. Thus, the proposed framework enables a more precise quantitative analysis of the CD-SHG signal of KTP.

Abstract Introduction Renal interstitial fibrosis, an important pathological feature of kidney aging and chronic renal failure, is regulated by mesenchymal stem cells (MSCs). We have previously demonstrated low expression of miR-133b in MSC-derived extracellular vesicles (MSC-EVs) in aged rats. However, miR-133b can mediate the inhibition of epithelial-mesenchymal transition (EMT) of renal tubules induced by transforming growth factor-β1 (TGF-β1). We investigated the effect of miR-133b for the treatment of geriatric renal interstitial fibrosis and evaluated its target genes. Methods We performed real-time polymerase chain reaction to detect miR-133b expression induced during EMT of HK2 cells by TGF-β1 at different concentrations (0, 6, 8, and 10 ng/mL) and at different time points (0, 24, 48, and 72 h). The target genes of miR-133b were validated using the dual-luciferase reporter assay. In vitro experiments were performed to evaluate mRNA and protein expression of miR-133b targets, E-cadherin, α-smooth muscle actin (SMA), fibronectin, and collagen 3A1 (Col3A1), in HK2 cells transfected with miR-133b under TGF-β1 stimulation. A 24-month-old unilateral ureteral obstruction (UUO) mouse model was established and injected with transfection reagent and miR-133b into the caudal vein. The target gene of miR-133b and other parameters mentioned above such as mRNA and protein expression levels and renal interstitial fibrosis were detected at 7 and 14 days. Results miR-133b expression gradually decreased with an increase in TGF-β1 concentration and treatment time, and the miR-133b mimic downregulated connective tissue growth factor (CTGF) expression. The dual-luciferase reporter assay confirmed CTGF as a direct target of miR-133b. Transfection of the miR-133b mimic inhibited TGF-β1-induced EMT of HK2 cells; this effect was reversed by CTGF overexpression. miRNA-133b expression significantly increased (approximately 70–100 times) in mouse kidney tissues after injection of the miRNA-133b overexpression complex, which significantly alleviated renal interstitial fibrosis in mice with UUO. Conclusion miR-133b exerted targeted inhibitory effects on CTGF expression, which consequently reduced TGF-β1-induced EMT of HK2 cells and renal interstitial fibrosis in aged mice with UUO.

Due to the rapid mutation of porcine epidemic diarrhea virus (PEDV), existing vaccines cannot provide sufficient immune protection for pigs. Therefore, it is urgent to design the affinity peptides for the prevention and control of this disease. In this study, we made use of a molecular docking technology for virtual screening of affinity peptides that specifically recognized the PEDV S1 C-terminal domain (CTD) protein for the first time. Experimentally, the affinity, cross-reactivity and sensitivity of the peptides were identified by an enzyme-linked immunosorbent assay (ELISA) and a surface plasmon resonance (SPR) test, separately. Subsequently, Cell Counting Kit-8 (CCK-8), quantitative real-time PCR (qRT-PCR), Western blot and indirect immunofluorescence were used to further study the antiviral effect of different concentrations of peptide 110766 in PEDV. Our results showed that the P/N value of peptide 110766 at 450 nm reached 167, with a KD value of 216 nM. The cytotoxic test indicated that peptide 110766 was not toxic to vero cells. Results of the absolute quantitative PCR revealed that different concentrations (3.125 μM, 6.25 μM, 12.5 μM, 25 μM, 50 μM, 100 μM, 200 μM) of peptide 110766 could significantly reduce the viral load of PEDV compared with the virus group (p < 0.0001). Similarly, results of Western blot and indirect immunofluorescence also suggested that the antiviral effect of peptide 110766 at 3.125 is still significant. Based on the above research, high-affinity peptide 110766 binding to the PEDV S1-CTD protein was attained by a molecular docking technology. Therefore, designing, screening, and identifying affinity peptides can provide a new method for the development of antiviral drugs for PEDV.

Abstract Introduction Calcium is an important coagulation factor and hypocalcemia is related to progression and poor prognosis of many cardiopulmonary diseases. However, influence of hypocalcemia on pulmonary thromboembolism (PTE) prognosis has never been reported. This study aimed to explore its prognostic value and optimize the pulmonary embolism severity index (PESI), the widely used prognosis assessment model, based on the value. Methods PTE patients’ variables in PESI and other related clinical characteristics including admission serum calcium were collected. Associations between these variables and PTE mortality were assessed by logistic regression and cox analysis. Variables significantly associated with 30-day PTE mortality were included to develop a new prognosis prediction rule and then its validity was compared with PESI and simplified PESI (sPESI). Results 496 PTE patients were included and 49.48% patients had hypocalcemia (serum calcium ≤ 2.13 mmol/L) in admission, showing higher 7-day (P = 0.021), 14-day (P = 0.002), 30-day (13.03% vs 4.98%, P = 0.002) mortalities than patients without hypocalcemia. Adjusting for variables in PESI, hypocalcemia was further revealed to be an independent predictor of 30-day mortality (P = 0.014). The optimal prediction rule contained hypocalcemia and 5 variables in PESI and sPESI, showing higher predictive validity [sensitivity (Sen): 0.930, specificity (Spec): 0.390, area under curve (AUC): 0.800] than PESI (Sen: 0.814, Spec: 0.367, AUC: 0.716) and sPESI (Sen: 0.907, Spec: 0.216, AUC: 0.703). Conclusions Hypocalcemia is an independent predictor of the mortality following acute PTE. Based on hypocalcemia, the optimal prediction rule showed higher validity than PESI and sPESI.

Immunotherapy has produced durable responses in numerous advanced and metastatic cancers, especially advanced non‐small cell lung carcinoma (NSCLC). However, opportunistic infection has become a major risk for patients who have received immune checkpoint inhibitors (ICIs). Early diagnosis of infection is difficult due to an acute disease course and heterogeneity in clinical manifestation. We retrospectively analyzed four cases with NSCLC who received ICIs and developed opportunistic infections. Two of our cases received antecedent glucocorticoids to treat immune‐related adverse events (irAEs), whereas immunosuppressive agents were not used beforehand in the other cases. We highlight that opportunistic infections complicating immunotherapy can be severe and even fatal. When patients deteriorate after initial remission from irAEs by glucocorticoids, infections should be thoroughly investigated and carefully distinguished from an irAE flare. Bronchoscopy and bronchoalveolar lavage (BAL) are essential. In patients where limited results from traditional microbiological tests have been obtained, next‐generation sequencing (NGS) of BAL fluid is beneficial in guiding a precise antimicrobial treatment. An antipneumocystis prophylaxis may also be considered in selected patients.

Abstract Background Handgrip strength (HGS) has been widely studied in clinical and epidemiological settings, but the relationship between HGS and pulmonary function is still controversial. This study analysed pulmonary function and HGS stratified by sex and age in a healthy Chinese Han population, as well as the associations between HGS and pulmonary function parameters. Methods HGS was measured by a Jamar dynamometer and pulmonary function was tested using a portable spirometer. Frequencies and variables are presented as percentages and means ± standard deviations, respectively. Chi-square tests were used for comparisons of categorical variables, and Student’s t-tests or Mann–Whitney U-tests were used for continuous variables. Pearson’s correlation coefficients were used to analyse the normally distributed variables, and Spearman correlation coefficients were used to analyse the non-normally distributed variables. Multivariate linear regression models were employed to explore the relationships between HGS and parameters of pulmonary function. The statistical significance was set at p

Abstract Introduction Extracellular vesicles (EVs), especially stem cell-derived EVs, have emerged as a potential novel therapy for acute kidney injury (AKI). However, their effects remain incompletely understood. Therefore, we performed this meta-analysis to systematically review the efficacy of EVs on AKI in preclinical rodent models. Methods We searched PubMed, EMBASE, and the Web of Science up to March 2019 to identify studies that reported the treatment effects of EVs in a rodent AKI model. The primary outcome was serum creatinine (Scr) levels. The secondary outcomes were the blood urea nitrogen (BUN) levels, renal injury score, percentage of apoptotic cells, and interleukin (IL)-10 and tumour necrosis factor (TNF)-α levels. Two authors independently screened articles based on the inclusion and exclusion criteria. The meta-analysis was conducted using RevMan 5.3 and R software. Results Thirty-one studies (n = 552) satisfied the inclusion criteria. Pooled analyses demonstrated that the levels of Scr (SMD = − 3.71; 95% CI = − 4.32, − 3.10; P

Background: Hemodialysis is the main approach for renal replacement therapy in patients with end-stage renal disease (ESRD) in China. The timing of dialysis initiation is one of the key factors influencing patient survival and prognosis. Over the past decade, the relationship between the timing of dialysis initiation and mortality has remained unclear in patients with ESRD in China. Methods: Patients who commenced maintenance hemodialysis from 2009 to 2014 from 24 hemodialysis centers in Mainland China were enrolled in the study (n = 1,674). Patients were divided into 2 groups based on the year they started hemodialysis (patients who started hemodialysis from 2009 to 2011, and patients who started hemodialysis from 2012 to 2014). Analysis of the yearly change in the estimated glomerular filtration rate (eGFR) at the initiation of dialysis was performed for the 2 groups. Meanwhile, the patients were divided into 3 groups based on their eGFR at the initiation of dialysis (8 mL/min/1.73 m2). For these 3 groups, the relationship between the eGFR at the start of dialysis and mortality were analyzed. Results: The average eGFRs were 5.68 and 5.94 mL/min/1.73 m2 for 2009–2011 and 2012–2014, respectively. Compared with the 2009–2011 group, the proportion of patients with diabetes in 2012–2014 increased from 26.7 to 37.7%. The prognosis of patients with different eGFRs at the start of dialysis was analyzed using Kaplan-Meier survival curves. After adjusting for confounding factors through a Cox regression model, no significant difference was demonstrated among the 3 groups (8 mL/min/1.73 m2 [p = 0.403]). Conclusion: In Mainland China, the eGFR at the start of dialysis did not change significantly over time from 2008 to 2014 and had no association with the mortality of patients with ESRD.

With the continuous development of China’s economy and society, people and the government have higher and higher requirements for food safety. Testing for food dopants and toxins can prevent the occurrence of various adverse health phenomena in the world’s population. By deploying new and powerful sensors that enable rapid sensing processes, the food industry can help detect trace adulteration and toxic substances. At present, as a common food safety detection method, lateral flow immunochromatography (LFI) is widely used in food safety testing, environmental testing and clinical medical treatment because of its advantages of simplicity, speed, specificity and low cost, and plays a pivotal role in ensuring food safety. This paper mainly focuses on the application of lateral flow immunochromatography and new technologies combined with test strips in food safety detection, such as aptamers, surface-enhanced Raman spectroscopy, quantum dots, electrochemical test strip detection technology, biosensor test strip detection, etc. In addition, sensing principles such as fluorescence resonance energy transfer can also more effective. Different methods have different characteristics. The following is a review of the application of these technologies in food safety detection.