Journal Article Accepted manuscript Human umbilical cord mesenchymal stem cells treated anti-MDA5 antibody-positive dermatomyositis with interstitial lung disease: a case report Get access Runlu Zhou, Runlu Zhou The Second Clinical Medical School of Nanjing Medical University, Nanjing, Jiangsu, ChinaDepartment of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China Search for other works by this author on: Oxford Academic PubMed Google Scholar Xiao Jin, Xiao Jin The Second Clinical Medical School of Nanjing Medical University, Nanjing, Jiangsu, ChinaDepartment of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China Search for other works by this author on: Oxford Academic PubMed Google Scholar Juan Li, Juan Li Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China Search for other works by this author on: Oxford Academic PubMed Google Scholar Yucong He, Yucong He The Second Clinical Medical School of Nanjing Medical University, Nanjing, Jiangsu, ChinaDepartment of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China Search for other works by this author on: Oxford Academic PubMed Google Scholar Tianming Gao, Tianming Gao Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China Search for other works by this author on: Oxford Academic PubMed Google Scholar Chenghua Zhu, Chenghua Zhu Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China Search for other works by this author on: Oxford Academic PubMed Google Scholar Yan Wang, Yan Wang Jiangsu Cell Tech Medical Research Institute, Nanjing, Jiangsu, 211166, China Search for other works by this author on: Oxford Academic PubMed Google Scholar Ganzhu Feng Ganzhu Feng Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China Correspondence to Ganzhu Feng, Address: No. 121 Jiangjiayuan Rd, Gulou District, Nanjing 210011, Jiangsu, China, Email: fgz62691@163.com Search for other works by this author on: Oxford Academic PubMed Google Scholar Rheumatology, keae285, https://doi.org/10.1093/rheumatology/keae285 Published: 22 May 2024 Article history Received: 09 October 2023 Revision received: 27 March 2024 Accepted: 25 April 2024 Published: 22 May 2024

Inflammasome-mediated pyroptosis and cytokine release are crucial host defenses against intracellular pathogens. Mycobacterium tuberculosis (M. tb) is a successful intracellular pathogen, and it is largely unclear how it evades immune clearance and persists in macrophages. This study investigated whether the Rv2647 protein acts as a key virulence factor of M. tb and explored the potential mechanism of inhibiting macrophage pyroptosis and promoting M. tb survival. The results showed Rv2647 promoted NLRP3 degradation via enhancing its ubiquitination, which led to the inactivation of NLRP3/caspase-1/GSDMD and reduction of IL-1β secretion, thereby inhibiting macrophage pyroptosis and facilitating M. tb survival. Furthermore, Rv2647-mediated enhancement of NLRP3 ubiquitination and degradation depended on its binding to ISG15, competitively inhibiting ISGylation of NLRP3. The study identified Rv2647 as the key virulence factor that promoted M. tb survival by inhibiting macrophage pyroptosis, whose mechanism was to competitively inhibit the ISGylation of NLRP3 and enhance its ubiquitination, thus suppressing NLRP3/caspase-1/GSDMD-mediated pyroptosis. This finding highlighted Rv2647 as a promising drug target or vaccine antigen for tuberculosis prevention and control.

Objective To demonstrate the feasibility of oblique lumbar interbody fusion (OLIF) combined with 4-screw fixation for treating two-level lumbar degenerative diseases.Methods An intact finite element model of L3-S1 (M0) was constructed and validated.Then,we constructed the M1 model by simulating OLIF surgery at L3/4 and L4/5 segments on the M0 model.By attachment of posterior 4-screw or 6-screw fixation to the M1 model,three 4-screw fixation models (M2-M4) and one 6-screw fixation model (M5) were established.The segmental and overall range of motion (ROM) and the peak von Mises stresses of superior endplate,cage,and posterior screw-rod were investigated under each implanted condition.Results Under the motion modes of forward flexion,backward extension,bilateral (left and right) flexion,and left and right rotation,the L3/4 ROM of M2 model and L4/5 ROM of M3 model increased,while the L3/4 and L4/5 ROM of M4 and M5 models significantly decreased compared with those of M1 model.Under all motion modes,the L4 superior endplate in M2 model and the L5 superior endplate in M3 model showed the maximum peak von Mises stress,and the peak von Mises stresses of L4 and L5 superior endplates in M4 and M5 models were close.The L3/4 cage in M2 model and the L4/5 cage in M3 model showcased the largest peak von Mises stress,and the peak von Mises stresses of cages in M4 and M5 models were close.The peak stresses of internal fixation in M2-M5 models were close.Conclusion Four-screw fixation can replace 6-screw fixation in the OLIF surgery for treating two-level degenerative lumbar diseases.

Pseudomonas aeruginosa (P. aeruginosa), a common opportunistic pathogen, is highly prone to chronic infection and is almost impossible to eradicate, especially attributed to virulence factors and adaptive mutations. In the present study, pseudomonas effector candidate 1 (Pec 1), a novel virulence factor of P. aeruginosa, was investigated, which inhibited bacterial clearance by the host and aggravated lung injury. Further, it demonstrated that Pec 1 inhibited miR-155 via suppressing integrin β3 expression, thereby activating PI3K-AKT-mTOR and inhibiting autophagy in macrophages. Additionally, the identification of Pec 1 in sputum was related to the bacterial load and assisted in rapid diagnosis of P. aeruginosa infection. This finding underlined the importance of Pec 1 in the pathogenesis of P. aeruginosa infection and indicated that Pec 1 could be a vital independent virulence factor during chronic infection with P. aeruginosa, providing new insights in rapid diagnosis, therapeutic targets, and vaccine antigens of P. aeruginosa infection.

Lung cancer is one of the most malignant tumors with fastest morbidity and mortality. Small cell lung cancer (SCLC) is the most malignant pathological type of lung cancer with early metastasis and poor prognosis. At present, there is a lack of effective indicators to predict prognosis of SCLC patients. Delta-like 3 protein (DLL3) is selectively expressed on the surface of SCLC and is involved in proliferation and invasion. Neuron-specific enolase (NSE) is an enolase isoenzyme that is generally regarded as a biomarker for SCLC and may correlate with stage of SCLC, prognosis and chemotherapy response. NSE can be influenced by different types of factors. To explore the associations between expression levels of DLL3 in tumor tissues with platinum/etoposide chemotherapy response, and assess the prognostic values of DLL3, NSE and other potential prognostic factors in advanced SCLC patients were herein studied. Ninety-seven patients diagnosed with SCLC in Zhongda Hospital from 2014 to 2020 were enrolled in the study. Serum NSE levels were tested using ELISA methods before any treatment. The expression of DLL3 in tumor tissue was detected by Immunohistochemistry (IHC). We investigated the relationship of DLL3 expression with chemotherapy and survival. Progression free survival (PFS) and overall survival (OS) were estimated by the Kaplan–Meier method. Multivariate Cox-proportional hazard regression was used to identify predictors of PFS and OS. DLL3 was detected in 84.5% (82/97) of all patients’ tumor samples by IHC, mainly located on the surface of SCLC cells. Lower DLL3 expression was associated with longer PFS and better chemotherapy response. OS had no significant differences. Multivariate analysis by Cox Hazard model showed that, high DLL3 expression and maximum tumor size >5 cm were independent risk factors for PFS, where NSE < 35 ng/mL and age < 70 were independent prognostic factors for OS. Early stage was independent prognostic factors for PFS and OS (P < .05 log-rank). DLL3 was expressed in the most of SCLCs. DLL3 expression level in the tumor and NSE level in the serum may be useful biomarkers to predict the prognosis of SCLC. DLL3 may be a potential therapeutic target for SCLC in the future.

Novel antimicrobial strategies are urgently needed to treat extensively drug-resistant (XDR) bacterial infections due to the high mortality rate and lack of effective therapeutic agents. Herein, nanoengineered human umbilical cord mesenchymal stem cells (hUC-MSCs), named PMZMU, are designed as a sonosensitizer for synergistic sonodynamic-nano-antimicrobial therapy against gram-negative XDR bacteria. PMZMU is composed of a bacterial targeting peptide (UBI29-41) modified hUC-MSCs membrane (MSCm), a sonosensitizer meso-tetra(4-car-boxyphenyl) porphine doped mesoporous organo-silica nanoparticle and an acidity-responsive metal-organic framework ZIF-8. This innovative formulation enables efficient loading of polymyxin B, reduces off-target drug release, increases circulation and targeting efficacy, and generates reactive oxygen species upon ultrasound irradiation. PMZMU exhibits remarkable in vitro inhibitory activity against four XDR bacteria: Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa (PA), and Escherichia coli. Taking advantage of the bacterial targeting ability of UBI29-41 and the inflammatory chemotaxis of hUC-MSC, PMZMU can be precisely delivered to lung infection sites thereby augmenting polymyxin B concentration. PMZMU-mediated sonodynamic therapy significantly reduces bacterial burden, relieves inflammatory damage by promoting the polarization of macrophages toward M2 phenotype, and improves survival rates without introducing adverse events. Overall, this study offers promising strategies for treating deep-tissue XDR bacterial infections, and guides the design and optimization of biomimetic nanomedicine.

The evidence from clinical studies suggests that lung carcinoma (LC) patients exhibit dysregulation in lipid metabolism. However, the causal relationship between plasma lipidome and LC, and whether inflammatory proteins mediate, remains to be determined. Genetic data for 179 plasma lipids and 91 inflammatory proteins were obtained from the latest published genome-wide association studies. Genetic data on LC and subtypes were from the largest available meta-analysis. The causal relationship between plasma lipidome and LC was determined by the two-sample Mendelian randomization (MR) method. Mediation MR analysis was employed to ascertain whether inflammatory proteins mediate the impact of plasma lipidome on LC. We identified 39 causal relationships between genetically predicted plasma lipidome and LC and subtypes. These relationships involve the influence of phosphatidylcholines, phosphatidylethanolamines, diacylglycerols, triacylglycerols, sphingomyelins, and Sterol esters. Additionally, the mediating role of 5 inflammatory proteins in the causal relationship between plasma lipidome and LC and subtypes was determined. Our results highlight the complex network of plasma lipidome and inflammatory proteins regulating LC. Integrating plasma lipidome and inflammatory proteins into clinical practice may open new avenues for the prevention and treatment of LC.

BackgroundObservational studies have revealed associations between diet and lung cancer. However, it is unclear whether the association is disturbed by confounding factors. We used a two-sample Mendelian randomization (MR) method to characterize the associations between diet and the lung cancer risk (including 3 subtypes: lung adenocarcinoma (LA), squamous cell lung carcinoma (SqCLC), and small cell lung cancer (SCLC)).Materials and methodsData on 20 diets were screened from the UK Biobank. Lung cancer data came from a large meta-analysis of 85,716 individuals. The inverse-variance weighted method was used as the main analysis. Sensitivity analysis was also used to explain the different multiplicity patterns of the final model.ResultsOur results showed significant evidence that 3 diets were associated with lung cancer [odds ratio (OR): 0.271, 95% confidence interval (CI): 0.150–0.488, p = 1.46 × 10−4, dried fruit; OR: 3.010, 95% CI: 1.608–5.632, p = 5.70 × 10−4, beer] and SqCLC (OR: 0.135, 95% CI: 0.062–0.293, p = 2.33 × 10−5, dried fruit; OR: 0.485, 95% CI: 0.328–0.717, p = 2.9 × 10−4, cheese). There were also suggestive correlations between 5 dietary intakes and lung cancer (OR: 0.441, 95% CI: 0.250–0.778, p = 0.008, cereal; OR: 2.267, 95% CI: 1.126–4.564, p = 0.022, beef), LA (OR: 0.494, 95% CI: 0.285–0.858, p = 0.012, dried fruit; OR: 3.536, 95% CI: 1.546–8.085, p = 0.003, beer) and SCLC (OR: 0.006, 95% CI: 0.000–0.222, p = 0.039, non-oily fish; OR: 0.239, 95% CI: 0.086–0.664, p = 0.006, dried fruit). No other association between diet and lung cancer was observed.ConclusionOur study preliminary found that cheese, dried fruit, and beer intake were significantly associated with the risk of lung cancer or its subtypes, while cereal, beef, and non-oily fish intake were suggestively associated with the risk of lung cancer or its subtypes. Well-designed prospective studies are still needed to confirm our findings in the future.

Recently, development of drug delivery systems for accurate delivery of antitumor drugs to tumor sites to improve their antitumor efficacy has attracted great interest in the area of cancer immunotherapy. In this report, an intelligent biodegradable hollow manganese dioxide (HMnO2) nanoparticle (NP) with a human umbilical cord mesenchymal stem cell (hUC-MSC) membrane coating was designed to exert efficient chemo-immunotherapy for cancer treatment. A TAT peptide-modified membrane structure was constructed for nuclear targeting. Our findings showed that this new nanoreactor inherited the active targeting capability of MSCs and exhibited tumoritropic accumulation significantly at the cancerous parts. Compared with other formulations, intravenous injection of the NPs markedly inhibited tumor growth, relapse, and metastasis. Moreover, we found that the NPs effectively boosted dendritic cell maturation and recruited effector T cells into tumors. Overall, this work demonstrates the great potential of applying MSC membrane-coated manganese dioxide NPs as nucleus-targeting nanocarriers in cancer chemo-immunotherapy.

Acinetobacter baumannii is a gram-negative bacterium and a crucial opportunistic pathogen in hospitals. A. baumannii infection has become a challenging problem in clinical practice due to the increasing number of multidrug-resistant strains and their prevalence worldwide. Vaccines are effective tools to prevent and control A. baumannii infection. Many researchers are studying subunit vaccines against A. baumannii . Subunit vaccines have the advantages of high purity, safety, and stability, ease of production, and highly targeted induced immune responses. To date, no A. baumannii subunit vaccine candidate has entered clinical trials. This may be related to the easy degradation of subunit vaccines in vivo and weak immunogenicity. Using adjuvants or delivery vehicles to prepare subunit vaccines can slow down degradation and improve immunogenicity. The common immunization routes include intramuscular injection, subcutaneous injection, intraperitoneal injection and mucosal vaccination. The appropriate immunization method can also enhance the immune effect of subunit vaccines. Therefore, selecting an appropriate adjuvant and immunization method is essential for subunit vaccine research. This review summarizes the past exploration of A. baumannii subunit vaccines, hoping to guide current and future research on these vaccines.

Objective:To improve the clinical understanding of the characteristics, diagnosis and treatment methods and prognosis of empyema caused by Candida krusei infection.Methods:The clinical data of a patient with empyema caused by Candida krusei infection admitted to the Second Affiliated Hospital of Nanjing Medical University in July 2022 was analyzed, retrospectively. Relevant literatures at home and abroad were searched to explore the pathogenesis, clinical characteristics, diagnosis and treatment of the disease.Results:This patient had a history of long-term drug abuse and bronchial asthma, and had severe hypoproteinemia at the initial stage of admission. After the diagnosis of Candida krusei empyema was confirmed, micafungin and voriconazole were given successively during chest drainage, and he was discharged after the empyema was completely absorbed. Total of 6 case reports (including 8 cases) of empyema caused by Candida krusei infection were retrieved, there were 4 patients with esophageal perforation, 2 patients with esophageal-tracheal fistula formation, and 1 patient after heart transplantation, 1 patient after occlusion of the ductus arteriosus; this patient had a bronchial-pleural fistula during the course of the disease; the initial clinical manifestations of this case and the 8 patients reported in the literature were cough, expectoration, and dyspnea, while the etiological diagnosis of empyema was all routine culture; according to the literatures, 4 cases among the 8 patients died, 1 patient was treated with amphotericin B, 2 patients with voriconazole, and 1 patient with echinocandin combined with voriconazole, and 1 case among the 4 survived patients was treated with echinocandin alone, 3 patients were treated with echinocandin combined with voriconazole.Conclusions:This case of empyema caused by Candida krusei infection is the first reported case in China. Patients with this disease are more common inesophageal-tracheal fistula formation and surgical trauma, the clinical manifestations are not characteristic, treatment with echinocandoxin or combined with triazole voriconazole may improve the survival.

Plant-derived extracellular vesicles (PDEVs) have shown remarkable potential as sustainable, green, and efficient drug delivery nanocarriers. As natural nanoparticles containing lipids, protein, nucleic acids and secondary metabolites, they have received widespread attention as a replacement for mammalian exosomes in recent years. In this review, the advances in isolation, identification, composition, therapeutic effect, and clinical application prospect were comprehensively reviewed, respectively. In addition, the specific modification strategies have been listed focusing on the inherent drawbacks of the raw PDEVs like low targeting efficiency and poor homogeneity. With emphasis on their biology mechanism in terms of immune regulation, regulating oxidative stress and promoting regeneration in the anti-inflammatory field and application value demonstrated by citing some typical examples, this review about PDEVs would provide a broad and fundamental vision for the in-depth exploration and development of plant-derived extracellular vesicles in the in-vivo anti-inflammation and even other biomedical applications.

Objective: By constructing the three-dimensional finite element model of two-level OLIF lumbar spine, the aim of this study was to demonstrate the feasibility and effectiveness of posterior four-screw fixation for treatment of two-level lumbar degenerative diseases from the perspective of biomechanics.Methods: An intact L3-S1 segment nonlinear lumbar finite element model (M0) was constructed from the CT scanning data of a healthy adult. After verification, two-level OLIF procedure were simulated, and three patterns of finite element analysis models were constructed: two-level stand-alone OLIF group (M1), two-level OLIF + four-screw fixation group (M2) and two-level OLIF + six-screw fixation group (M3). Range of motion, stress of the cage, and stress of fixation were evaluated in the different models.Results: Under various motion modes,the ROM of M2 and M3 were significantly lower than those of M1. The ROM reduction of M2 relative to M1 was much greater than that of M3 relative to M2. Moreover, the peak von Mises stresses of endplates in M2 were almost the same as those in M3. In terms of the maximum stresses of cages, M2 and M3 were essentially identical. Besides, the maximum stresses of posterior instrumentation in M2 and M3 were similar, which were mainly concentrated at the root of pedicle screws.Conclusion: There were no significant differences between M2 and M3 from the biomechanical analysis. In two-level OLIF, posterior four-screw fixation can replace six-screw fixation, which reduces surgical trauma and decreases economic burden of patients, and will be a cost-effective alternative.

Background Previous studies have found that the persistence of herpesvirus significantly increases the risk of idiopathic pulmonary fibrosis (IPF), but it is unclear whether this effect is causal. We conducted a two-sample Mendelian randomization (MR) study to evaluate the causal relationship between three herpesvirus infections and IPF. Methods We used genome-wide association studies (GWAS) data from three independent datasets, including FinnGen cohort, Milieu Intérieur cohort, and 23andMe cohort, to screen for instrumental variables (IVs) of herpesvirus infection or herpesvirus-related immunoglobulin G (IgG) levels. Outcome dataset came from the largest meta-analysis of IPF susceptibility currently available. Results In the FinnGen cohort, genetically predicted Epstein-Barr virus (EBV) (OR = 1.105, 95%CI: 0.897–1.149, p = 0.815), cytomegalovirus (CMV) (OR = 1.073, 95%CI: 0.926–1.244, p = 0.302) and herpes simplex (HSV) infection (OR = 0.906, 95%CI: 0.753–1.097, p = 0.298) were not associated with the risk of IPF. In the Milieu Intérieur cohort, we found no correlations between herpesvirus-related IgG EBV nuclear antigen-1 (EBNA1) (OR = 0.968, 95%CI: 0.782–1.198, p = 0.764), EBV viral capsid antigen (VCA) (OR = 1.061, 95CI%: 0.811–1.387, p = 0.665), CMV (OR = 1.108, 95CI%: 0.944–1.314, p = 0.240), HSV-1 (OR = 1.154, 95%CI: 0.684–1.945, p = 0.592) and HSV-2 (OR = 0.915, 95%CI: 0.793–1.056, p = 0.225) and IPF risk. Moreover, in the 23andMe cohort, no evidence of associations between mononucleosis (OR = 1.042, 95%CI: 0.709–1.532, p = 0.832) and cold scores (OR = 0.906, 95%CI: 0.603–1.362, p = 0.635) and IPF were found. Sensitivity analysis confirmed the robustness of our results. Conclusions This study provides preliminary evidence that EBV, CMV, and HSV herpesviruses, and herpesviruses-related IgG levels, are not causally linked to IPF. Further MR analysis will be necessary when stronger instrument variables and GWAS with larger sample sizes become available.

Spinal cord injury (SCI) is the main cause of severe damage to the central nervous system and leads to irreversible tissue loss and neurological dysfunction. Ferroptosis is a cell death pattern, newly discovered in recent years. Ferroptosis is an oxidizing cell death induced by small molecules, and is an iron-dependent process caused by the imbalance between the generation and degradation of lipid reactive oxygen species (ROS) in cells. As an antioxidant, trehalose can effectively prevent lipid peroxidation. Studies have reported that trehalose can improve the prognosis of SCI. However, it is unclear whether these benefits are related to ferroptosis. In this study, we demonstrated for the first time that trehalose reduces the degeneration and iron accumulation of neurons by inhibiting the production of ROS and ferroptosis caused by lipid peroxides after SCI, thus promoting the survival of neurons and improving the recovery of motor function. More specifically, we found that trehalose inhibited the expansion of cavities in the nerve tissue of mice with SCI, inhibited neuron loss, and improved functional recovery. In terms of mechanism, our results indicate that the neuroprotective effect of trehalose is due to the activation of the NRF2/HO-1 pathway, which in turn inhibits ferroptosis and ferroptosis-related inflammation. Our findings provide important insights into the previously unknown role of trehalose in SCI, as well as new evidence supporting the hypothesis that suppression of ferroptosis plays a key neuroprotective role in SCI.

Metagenomic next-generation sequencing (mNGS) has been gradually applied to clinical practice due to its unbiased characteristics of pathogen detection. However, its diagnostic performance and clinical value in suspected pulmonary infection need to be evaluated. We systematically reviewed the clinical data of 246 patients with suspected pulmonary infection from 4 medical institutions between January 2019 and September 2021. The diagnostic performances of mNGS and conventional testing (CT) were systematically analyzed based on bronchoalveolar lavage fluid (BALF). The impacts of mNGS and CT on diagnosis modification and treatment adjustment were also assessed. The positive rates of mNGS and CT were 47.97% and 23.17%, respectively. The sensitivity of mNGS was significantly higher than that of CT (53.49% versus 23.26%, P < 0.01), especially for infections of Mycobacterium tuberculosis (67.86% versus 17.86%, P < 0.01), atypical pathogens (100.00% versus 7.14%, P < 0.01), viruses (92.31% versus 7.69%, P < 0.01), and fungi (78.57% versus 39.29%, P < 0.01). The specificity of mNGS was superior to that of CT, with no statistical difference (90.32% versus 77.42%, P = 0.167). The positive predictive value (PPV) and negative predictive value (NPV) of mNGS were 97.46% and 21.88%, respectively. Diagnosis modification and treatment adjustment were conducted in 32 (32/246, 13.01%) and 23 (23/246, 9.35%) cases, respectively, according to mNGS results only. mNGS significantly improved the diagnosis of suspected pulmonary infection, especially infections of M. tuberculosis, atypical pathogens, viruses, and fungi, and it demonstrated the pathogen distribution of pulmonary infections. It is expected to be a promising microbiological detection and diagnostic method in clinical practice. IMPORTANCE Pulmonary infection is a heterogeneous and complex infectious disease with high morbidity and mortality worldwide. In clinical practice, a considerable proportion of the etiology of pulmonary infection is unclear, microbiological diagnosis being challenging. Metagenomic next-generation sequencing detects all nucleic acids in a sample in an unbiased manner, revealing the microbial community environment and organisms and improving the microbiological detection and diagnosis of infectious diseases in clinical settings. This study is the first multicenter, large-scale retrospective study based entirely on BALF for pathogen detection by mNGS, and it demonstrated the superior performance of mNGS for microbiological detection and diagnosis of suspected pulmonary infection, especially in infections of Mycobacterium tuberculosis, atypical pathogens, viruses, and fungi. It also demonstrated the pathogen distribution of pulmonary infections in the real world, guiding targeted treatment and improving clinical management and prognoses.

Previous observational studies have suggested that the effect of diet-derived circulating micronutrient concentrations on lung cancer (LC) risk is controversial. We conducted a two-sample Mendelian randomization (MR) analysis to investigate the causal relationship between circulating micronutrient concentrations and the overall risk of LC and three LC subtypes (namely lung adenocarcinoma (LA), squamous cell lung cancer (SqCLC), and small cell lung cancer (SCLC)). The instrumental variables (IVs) of 11 micronutrients (beta-carotene, calcium, copper, folate, lycopene, magnesium, phosphorus, retinol, selenium, zinc, and vitamin B6) were screened from the published genome-wide association studies (GWAS). Summary statistics related to LC and its subtypes came from the largest meta-analysis, including 29,266 cases and 56,450 controls. Inverse-variance weighted (IVW) method is used as the main MR analysis, and the sensitivity analysis is carried out to ensure the MR assumptions. This MR study found suggestive evidence that genetically predicted 6 circulating micronutrient concentrations was correlated with the risk of overall LC (odds ratio (OR): 1.394, 95% confidence interval (CI): 1.041–1.868, p = 0.026, phosphorus), LA (OR: 0.794, 95% CI: 0.634–0.995, p = 0.045, beta-carotene; OR: 0.687, 95%CI: 0.494–0.957, p = 0.026, calcium), SqCLC (OR: 0.354, 95% CI: 0.145–0.865, p = 0.023, retinol), and SCLC (OR: 1.267, 95% CI: 1.040–1.543, p = 0.019, copper; OR: 0.801, 95% CI: 0.679–0.944, p = 0.008, zinc). We found no evidence that other micronutrients are associated with the risk of overall LC or its subtypes. Our study suggested that the increase in circulating beta-carotene, calcium, retinol, and zinc concentration may reduce the risk of LC; the increase in circulating copper and phosphorus concentration may be related to the increased risk of LC. In the future, larger replication samples of LC genetic data and larger micronutrient-related GWAS will be needed to verify our findings.

Objective:To evaluate the value of high-throughput sequencing (HTS) technology for bronchoalveolar lavage fluid (BALF) in diagnosing pulmonary infection pathogen and corresponding effects on the prognosis of patients.Methods:A computer retrieval was performed in Pubmed, Embase, Cochrane Library, Wanfang database, Web of Science, clinical trials.gov, CNKI, Wanfang database, and China biology medicine dise (CBM) from the setup date of the database to December 8, 2021.The positive rate, sensitivity and specificity of BALF metagenomic sequencing and traditional pathogen detection method on pulmonary infection detection were compared.The intensity of antibiotics used, length of hospital stay, 28/30 day mortality, and 90-day mortality were compared by adjusting the therapeutic regimen according to pathogenic test results.Review Manager 5.4.1 software was used for meta-analysis on the abovementioned indexes.Results:A total of 35 papers with 2 624 patients were included, involving 2 248 cases in the HTS group and 2 493 cases in the traditional pathogen detection group.The results of the meta-analysis showed that the positive rate of the HTS group was 79.8%(1 793/2 248), being significantly higher than that of the traditional pathogen detection group at 41.7%(1 039/2 493)( OR=6.84, 95% CI: 4.84~9.67, Z=10.88, P<0.001). The sensitivity, specificity, and the area under the curve of receiver operating characteristic curves by BALF metagenomic sequencing was higher than those by traditional pathogen detection method.The patients enrolled in nine papers were patients with severe pneumonia, and the subgroup analysis showed that the positive rate of BALF high-throughput sequencing in patients with severe pneumonia was 85.8%(495/577), being significantly higher than that in the traditional pathogen detection group at 42.9% (282/657)( OR=6.52, 95% CI: 4.04~10.52, Z=7.69, P<0.001). According to the results of pathogen detection, the intensity of antibiotic use in the high-throughput sequencing group was significantly lower than that in the traditional detection group(SMD=-40.04, 95% CI: -47.05~-33.03, Z=11.19, P<0.001); and the everage length of stay was shortened(SMD=-4.68, 95% CI: -6.12~-3.25, Z=6.40, P<0.001). The 28/30-day mortality and 90-day mortality of the HTS group was 9.09% and 12.82%, respectively, both of which were lower than those of the traditional detection group at 26.44%( OR=0.26, 95% CI: 0.13~0.51, Z=3.89, P<0.001) and 38.30%( OR=0.21, 95% CI: 0.07~0.66, Z=2.67, P=0.008). Conclusions:Compared with traditional pathogen detection methods, using BALF for HTS is found to have higher diagnostic value for pulmonary infection.The adjustment on the therapeutic regimenbased on HTS results for BALFcan reduce the intensity of antibiotic use, shorten the length of hospital stay, reduce mortality, and improve the prognosis of patients.

胃癌是一种常见的恶性肿瘤,总体生存率低,治疗手段局限.缺氧诱导因子-1(hypoxia inducible factor-1,HIF-1)是帮助细胞适应缺氧环境的关键转录因子,广泛调节缺氧基因表达,协调影响肿瘤发生的多种信号分子活动,在参与调节肿瘤细胞命运中发挥着重要作用.过去的二十年中,胃癌及HIF-1在胃癌中的影响机制进行广泛的研究,HIF-1已经成为一个有前途的抗癌治疗靶点.本文就近年来HIF-1在胃癌中的研究进展作一简要综述.