Diagnostic accuracy and cellular origin of pleural fluid CXCR3 ligands for tuberculous pleural effusion.

BACKGROUND: Pleural biomarkers represent potential diagnostic tools for tuberculous pleural effusion (TPE) due to their advantages of low cost, short turnaround time, and less invasiveness. This study evaluated the diagnostic accuracy of two CXCR3 ligands, C-X-C motif chemokine ligand 9 (CXCL9) and CXCL11, for TPE. In addition, we investigated the cellular origins and biological roles of CXCL9 and CXCL11 in the development of TPE. METHODS: This double-blind study prospectively enrolled patients with undiagnosed pleural effusion from two centers (Hohhot and Changshu) in China. Pleural fluid on admission was obtained and levels of CXCL9 and CXCL11 were measured by an enzyme-linked immunosorbent assay (ELISA). The receiver operating characteristic (ROC) curve and the decision curve analysis (DCA) were used to evaluate their diagnostic accuracy and net benefit, respectively. THP-1 cell-derived macrophages were treated with Bacillus Calmette-Guérin (BCG), and quantitative real-time PCR (qRT-PCR) and ELISA were used to determine the mRNA and protein levels of CXCL9 and CXCL11. The chemoattractant activities of CXCL9 and CXCL11 for T helper (Th) cells were analyzed by a transwell assay. RESULTS: One hundred and fifty-three (20 TPEs and 133 non-TPEs) patients were enrolled in the Hohhot Center, and 58 (13 TPEs and 45 non-TPEs) were enrolled in the Changshu Center. In both centers, we observed increased CXCL9 and CXCL11 in TPE patients. The areas under the ROC curves (AUCs) of pleural CXCL9 and CXCL11 in the Hohhot Center were 0.70 (95 % CI: 0.55-0.85) and 0.68 (95 % CI: 0.52-0.84), respectively. In the Changshu Center, the AUCs of CXCL9 and CXCL11 were 0.96 (95 % CI: 0.92-1.00) and 0.97 (95 % CI: 0.94-1.00), respectively. The AUCs of CXCL9 and CXCL11 decreased with the advancement of age. The decision curves of CXCL9 and CXCL11 showed net benefits in both centers. CXCL9 and CXCL11 were upregulated in BCG-treated macrophages. Pleural fluid from TPE and conditioned medium from BCG-treated macrophages were chemotactic for Th cells. Anti-CXCL9 or CXCL11 neutralizing antibodies could partly block the chemotactic activity. CONCLUSIONS: Pleural CXCL9 and CXCL11 are potential diagnostic markers for TPE, but their diagnostic accuracy is compromised in elderly patients. CXCL9 and CXCL11 can promote the migration of peripheral Th cells, thus representing a therapeutic target for the treatment of TPE.

Inhibition of Bcl-6 Expression Ameliorates Asthmatic Characteristics in Mice.

OBJECTIVE: The function of Bcl-6 in T follicular helper (Tfh) cell maturation is indispensable, and Tfh cells play a pivotal role in asthma. This study investigated the impact of Bcl-6 on asthmatic traits. METHODS: The microscopic pathological alterations, airway resistance (AR), and lung compliance (LC) were determined in asthmatic mice and Bcl-6 interference mice. The surface molecular markers of Tfh cells and the Bcl-6 mRNA and protein expression were determined by flow cytometry, RT-qPCR, and Western blotting, respectively. The relationships between the Tfh cell ratio and the IgE and IgG1 concentrations in peripheral blood mononuclear cells (PBMCs) and bronchoalveolar lavage fluid (BALF) were determined. RESULTS: Asthmatic inflammatory changes were observed in the lung tissue and were attenuated by Bcl-6 siRNA and dexamethasone (DXM). Asthmatic mice exhibited an increased AR and a decreased LC, while Bcl-6 siRNA or DXM mitigated these changes. The percentages of Tfh cells and eosinophils were significantly increased in the asthmatic mice, and they significantly decreased after Bcl-6 inhibition or DXM treatment. RT-qPCR and Western blotting analyses revealed that the Bcl-6 expression level in PBMCs was significantly higher in asthmatic mice, and it decreased following Bcl-6 inhibition or DXM treatment. The IgE expression in the serum and BALF and the B cell expression in PBMCs exhibited a similar trend. In asthmatic mice, the ratio of Tfh cells in the peripheral blood showed a strong positive correlation with the IgE levels in the serum and BALF, but not with the IgG1 levels. CONCLUSION: The amelioration of airway inflammation and airway hyper-responsiveness is achieved through Bcl-6 suppression, which effectively hinders Tfh cell differentiation, ultimately resulting in a concurrent reduction in IgE production.

The effects of health education and exercise style changes on the maturation of autologous arteriovenous fistula in hemodialysis patients: A randomized controlled trial.

BACKGROUND: Upper limb exercise has long been considered to be the main means to promote autogenous arteriovenous fistula (AVF) maturation, but in practice exercise intensity and compliance are both typically lacking. Several randomized controlled trials (RCTs) have demonstrated the good effects of functional resistance or pressure exercise in patients with AVF. However, many patients' have difficulty complying with upper limb exercise programs without systematic health education. Therefore, we argue that resistance and pressure exercise supported by health education is actually the most beneficial for AVF patients. METHODS: We randomly divided 114 patients into a control group and an experimental group of 57 patients each. In the control group, conventional care was used, and in the experimental group, online health education based on the IMB (Information-Motivation-Behavior skills) model and functional resistance and pressure upper limb exercises was implemented with the AVF side arm. The failure rate of AVF maturation, clinical maturation time, cephalic venous blood flow, vessel diameter, and vessel skin thickness were compared between the two groups. RESULTS: Fifty-five cases were included for each in the final study. The primary outcome of this study was the failure rate of AVF maturation. Secondary outcomes included clinical maturation time, cephalic vein flow, vessel diameter, and vessel thickness. The failure rate of AVF maturation in the experimental group was significantly lower than that in the control group, and the clinical maturation time in the experimental group was significantly shorter than that in the control group. For the remaining three indicators, there were between-group effects, time effects, and interaction effects in both groups. Comparison between groups showed that there was no statistical difference in the observed indicators of cephalic vein flow, vessel diameter, or vessel thickness between the two groups before the intervention but that there was a statistical difference at the end of the 4th, 8th, and 12th weeks of the intervention. A 2 × 2 comparison also showed that there was a statistical difference between the three indicators at each time point within the two groups. CONCLUSION: IMB model-based online health education combined with functional resistance and pressure exercises can improve AVF maturation status and accelerate AVF maturation within 12 weeks of surgery.

Long-term stability of pleural fluid carcinoembryonic antigen and its effect on the diagnostic accuracy for malignant pleural effusion.

BACKGROUND: The in vitro stability assessment is essential for investigating the diagnostic accuracy of pleural biomarkers. This study aimed to investigate the long-term stability of pleural fluid carcinoembryonic antigen (CEA) at -80°C to -70°C. In addition, we analyzed the effects of frozen storage on the diagnostic accuracy of CEA for malignant pleural effusion (MPE). METHODS: Pleural fluid CEA of participants in two prospective cohorts were stored at -80°C to -70°C for 1-3 years. The CEA level in the stored specimen was measured with an immunoassay, and its level in the fresh specimen was extracted from medical records. The Bland-Altman method, Passing-Bablok regression, and Deming regression were used to analyze the agreement of CEA between the fresh and frozen pleural fluid. In addition, we used receiver operating characteristic (ROC) curves to evaluate the diagnostic accuracy of CEA in the fresh and frozen specimens for MPE. RESULTS: A total of 210 participants were enrolled. The median CEA levels in frozen and fresh pleural fluid specimens were similar (frozen, 2.32 ng/mL; fresh, 2.59 ng/mL; p < 0.01). The slopes and intercepts in the Passing-Bablok regression (intercept 0.01, slope 1.04) and Deming regression (intercept 0.65; slope 1.00) were not statistically significant (p > 0.05 for all). No significant difference was observed between the area under the ROC curves of CEA in the fresh and frozen specimens (p > 0.05 for all). CONCLUSION: Pleural fluid CEA is seemingly stable when stored at -80°C to -70°C for 1-3 years. Frozen storage does not significantly affect the diagnostic accuracy of CEA for MPE.

Diagnostic accuracy of pleural fluid to serum carcinoembryonic antigen ratio and delta value for malignant pleural effusion: findings from two cohorts.

BACKGROUND: Pleural fluid (PF) carcinoembryonic antigen (CEA) is a widely used diagnostic marker for malignant pleural effusion (MPE). Recent studies revealed that PF to serum CEA was also a promising diagnostic parameter for MPE. OBJECTIVE: We aimed to investigate whether PF to serum CEA ratio and delta CEA (PF minus serum CEA) provided added value to PF CEA in diagnosing MPE. METHODS: Patients with pleural effusion in a retrospective cohort (BUFF) and a prospective cohort (SIMPLE) were included. The clinical characteristics of the patients were extracted from their medical records. The diagnostic value of CEA ratio and delta CEA was estimated by a receiver operating characteristics (ROC) curve, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). RESULTS: A total of 148 patients in the BUFF cohort and 164 patients in the SIMPLE cohort were enrolled. The BUFF cohort had 46 MPE patients and 102 benign pleural effusion (BPE) patients, and the SIMPLE cohort had 85 MPE patients and 79 BPE patients. In both cohorts, MPE patients had significantly higher PF CEA, serum CEA, CEA ratio, and delta CEA. The area under ROC curves (AUCs) of PF CEA, CEA ratio, and delta CEA were 0.78 (95% CI: 0.67-0.88), 0.80 (95% CI: 0.72-0.89) and 0.83 (95% CI: 0.75-0.91) in the BUFF cohort, and 0.89 (95% CI: 0.83-0.94), 0.86 (95% CI: 0.80-0.92), and 0.84 (95% CI: 0.78-0.91) in the SIMPLE cohort. The differences between the AUCs of PF CEA, CEA ratio, and delta CEA did not reach statistical significance. The continuous NRI and IDI of CEA ratio and delta CEA were <0. CONCLUSION: CEA ratio and delta value cannot provide added diagnostic value to PF CEA. The simultaneous determination of serum and PF CEA should not be adopted in clinical practice.

Relationships of prenatal organophosphate ester exposure with pregnancy and birth outcomes: A systematic scoping review of epidemiological studies.

Exposure to organophosphate esters (OPEs) during pregnancy has been suggested to be associated with adverse pregnancy and birth outcomes. However, relevant investigations are scarce, and the findings are inconsistent. We aimed to conduct a scoping review to provide an overview of these associations. Electronic databases, including MEDLINE (through PubMed), Web of Science, and CNKI (China National Knowledge Infrastructure), were searched from inception to March 2022 and updated in July 2022. A total of 8 studies (1860 participants) were included. Limited evidence indicates that OPE exposure during pregnancy may be negatively associated with both maternal and neonatal triiodothyronine and tetraiodothyronine concentrations but positively associated with thyroid-stimulating hormone concentrations. OPE exposure during pregnancy may be associated with lower insulin concentrations. OPE exposure during pregnancy was associated with gestational age in a sex-specific manner. Intrauterine OPE exposure might increase the risk of preterm birth in female infants but decrease the risk of preterm birth in male infants. Prenatal OPE exposure might be associated with an increased risk of low birth weight. The current scoping review suggests that OPE exposure during pregnancy may disturb pregnancy and birth health, including adverse thyroid function and birth size. Because of the limited evidence obtained for most associations, additional studies followed by a traditional systematic review are needed to confirm these findings.

CircMAT2B facilitates the progression of head and neck squamous cell carcinoma via sponging miR-491-5p to trigger ASCT2-mediated glutaminolysis.

Circular RNAs (circRNAs) are well-known to exert significant roles in regulating the pathological processes, including human carcinogenesis. Currently, less is known about their exact roles in head and neck squamous cell carcinoma (HNSCC). Herein, we aimed to investigate and validate the role of a novel circRNA, circMAT2B, as well as its potential molecular mechanism in HNSCC progression. A cohort of 41 paired of HNSCC tumor tissues and adjacent normal tissues from HNSCC patients were collected. Further, we characterized circMAT2B expression patterns in HNSCC tissues and cell lines, as well as exploring its association with the prognosis of HNSCC patients. Biological functions on cell proliferation, apoptosis, migration, and invasion were assessed using Cell Counting Kit-8, EdU incorporation, TUNEL, wound healing, and transwell assays. Glutaminolysis was evaluated by measuring glutamine, glutamate, and α-ketoglutarate (α-KG) levels. The regulatory network of circMAT2B/miR-491-5p/ASCT2 axis was verified by RNA immunoprecipitation and luciferase reporter assays. Western blot was conducted to detect the level of ASCT2 and GLS1. Remarkably overexpressed circMAT2B was observed in HNSCC tissues and cell lines, of which high abundance was positively correlated with patients' poor prognosis. Silencing of circMAT2B inhibited cell proliferation, migration, and invasion, as well as glutaminolysis. miR-491-5p, interacted with ASCT2, was identified to be a downstream target of circMAT2B, thereby involving in circMAT2B-mediated biological effects. In summary, we draw a conclusion that circMAT2B could modulate the processes of cell proliferation, migration, invasion, and glutaminolysis of HNSCC cells partly via the miR-491-5p/ASCT2 axis by a molecular mechanism of competing endogenous RNA (ceRNA), implying an underlying circRNA-targeted therapy for HNSCC treatment.

A Circular RNA, hsa_circ_0018180 (circPARD3), Triggers Glycolysis and Promotes Malignancy of Head and Neck Squamous Cell Carcinoma Through the miR-5194/ENO1 Axis.

Emerging evidence has demonstrated the pivotal roles of circular RNAs (circRNAs) in the modulation of malignancy and pathological progression among multiple human cancers. Glucose metabolism reprogramming is a widely identified characteristic for contributing to facilitate tumorigenesis. Nonetheless, their contributions to head and neck squamous cell carcinoma (HNSCC) cell glycolysis remain to be further elucidated. Herein, we aim to investigate the role of circRNA, hsa_circ_0018180 (also named as circPARD3) in HNSCC. Expression patterns of circPARD3 in HNSCC tissues and different cell lines were determined by qRT-PCR assay, as well as its correlation with the prognosis of survival. CCK-8, EdU incorporation, and transwell assays were carried out to assess the cell viability, proliferation, migration, and invasion, respectively. Glucose uptake and lactate production were evaluated by preforming glycolysis. Mechanistically, the circPARD3/miR-5194/ENO1 axis was verified by RNA immunoprecipitation (RIP) and luciferase reporter assays. Western blot analysis was employed to measure the epithelial-mesenchymal transition (EMT)-associated biomarkers. Upregulated circPARD3 observed in HNSCC tissues and cell lines indicated the poor prognosis of patients. Stable knockdown of circPARD3 dramatically exerted the suppressive effects on cell viability, proliferation, migration, and invasion, as well as glucose uptake and lactate production. Mechanistically, circPARD3 harbored miR-5194, serving as a miRNA sponge, thereby increasing ENO1 expression. Moreover, ENO1 evidently reversed miR-5194-mediated attenuated malignant behaviors. Collectively, our study identified an oncogenic role of circPARD3 in HNSCC through a novel machinery of circPARD3/miR-5194/ENO1 and provided a promising therapeutic target for HNSCC.

Optimal modes of mind-body exercise for treating chronic non-specific low back pain: Systematic review and network meta-analysis.

Background: There were limited studies that directly compare the outcomes of various mind-body exercise (MBE) therapies on chronic non-specific low back pain (CNLBP). Objectives: To compare the efficacy of the four most popular MBE modes [Pilates, Yoga, Tai Chi (TC), and Qigong] in clinically CNLBP patients, we conducted a systematic review and network meta-analysis (NMA). Methods: We searched databases for eligible randomized controlled trials (RCTs) (from origin to July 2022). RCTs were eligible if they included adults with CNLBP, and implemented one or more MBE intervention arms using Pilates, yoga, TC, and qigong. In addition, pain intensity and physical function were evaluated using validated questionnaires. Results: NMA was carried out on 36 eligible RCTs involving 3,050 participants. The effect of exercise therapy on pain was in the following rankings: Pilates [Surface under cumulative ranking (SUCRA) = 86.6%], TC (SUCRA = 77.2%), yoga (SUCRA = 67.6%), and qigong (SUCRA = 64.6%). The effect of exercise therapy on function: Pilates (SUCRA = 98.4%), qigong (SUCRA = 61.6%,), TC (SUCRA = 59.5%) and yoga (SUCRA = 59.0%). Conclusion: Our NMA shows that Pilates might be the best MBE therapy for CNLBP in pain intensity and physical function. TC is second only to Pilates in improving pain in patients with CNLBP and has the value of promotion. In the future, we need more high-quality, long-term follow-up RCTs to confirm our findings. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=306905, identifier: CRD42022306905.

Efficacy and safety of pomalidomide and low-dose dexamethasone in Chinese patients with relapsed or refractory multiple myeloma: a multicenter, prospective, single-arm, phase 2 trial.

BACKGROUND: Pomalidomide in combination with dexamethasone has demonstrated positive results in patients with relapsed or refractory multiple myeloma (RRMM), but no data are available in China. We conducted a multicenter, single-arm trial to examine the efficacy and safety of bioequivalent generic pomalidomide plus low-dose dexamethasone in Chinese RRMM patients. METHODS: Adult (≥ 18 years of age) RRMM patients who progressed after at least two previous treatments, including bortezomib and lenalidomide, were eligible. Pomalidomide was given orally at 4 mg/day on days 1 to 21 of a 28-day cycle. Dexamethasone was given at 40 mg/day (either orally or intravenously; 20 mg/day at 75 years or older) on days 1, 8, 15, and 22 of each cycle. Treatment continued until disease progression or intolerable adverse events (AEs). The primary end point was objective response rate (ORR). RESULTS: Seventy-four patients were enrolled between February 2017 and February 2019. All patients had progressed within 60 days of their last therapy. 74.3% of the patients were resistant to lenalidomide, 31.1% had renal insufficiency and 33.8% had high-risk cytogenetic RRMM. The median follow-up duration was 33.0 months (range 31.1-34.8 months). The ORR was 37.8% in the overall analysis, 32.7% in lenalidomide-refractory patients, 36.0% in patients with high-risk cytogenetics and 34.8% in RRMM patients with renal impairment. The median progression-free survival was 5.7 months (95% CI 3.7-8.8 months). The median overall survival was 24.3 months (95% CI 14.4-41.1 months). The most common grade 3 and 4 treatment-emergent adverse events (TEAEs) were neutropenia (63.5%), leukopenia (37.8%), thrombocytopenia (28.4%), and anemia (31.1%). Pulmonary infection (27.0%) was the most frequent grade 3 and 4 nonhematologic TEAE. No previously unreported AEs were observed. No venous thromboembolism was reported. CONCLUSIONS: Pomalidomide in combination with low-dose dexamethasone is effective and safe in Chinese RRMM patients. TRIAL REGISTRATION: The study is registered at Chinese Clinical Trial Registry (ChiCTR) ( ChiCTR-OIC-17013234 , first registered on 03/11/2017).

Are Mind-Body Exercise Beneficial for Treating Pain, Function, and Quality of Life in Middle-Aged and Old People With Chronic Pain? A Systematic Review and Meta-Analysis.

Background: Aging is a significant risk factor in chronic pain development with extensive disability and greater health care costs. Mind-body exercise (MBE) has been scientifically proven to affect the pain intensity and physical health. Objectives: To assess the effects of MBE modes (Tai Chi, yoga, and qigong) for treating chronic pain among middle-aged and old people, compared with nonactive and active treatment, as well as function, quality of life, and adverse events. Methods: We searched PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Database, and Chinese Scientific Journals Full-Text Database (VIP) till March 2022. No restrictions were chartered within the year and language of publication. We included randomized controlled trials of MBE treatment in middle-aged and elderly people with chronic pain. The overall certainty of evidence was evaluated by using the GRADE approach. Results: A total of 17 studies (n = 1,332) were included in this review. There was low-certainty evidence indicating that MBE had a moderate effect on reducing pain compared with the nonactive and active control group (standard mean difference (SMD): -0.64, 95% confidence interval (CI): -0.86 to -0.42, P < 0.001). Very-low-certainty evidence showed that the pooled SMD for the functional improvement was -0.75 (95% CI: -1.13 to -0.37, P < 0.001). Low-certainty evidence presented that no influence was observed in physical component summary (SMD: 0.23, 95% CI: -0.16 to 0.62, P = 0.24) and mental component summary (SMD: -0.01, 95% CI -0.39 to 0.36, P = 0.95). Conclusion: Our results indicated that MBE was an effective treatment for reducing symptoms of middle-aged and elderly people with chronic pain compared with nonactive and active control groups. TC and qigong had obvious benefits for knee osteoarthritis in self-reported function, but the efficacy of chronic low back pain was uncertain. No significant benefit of MBE on quality of life in older adults with chronic pain was found. More high-quality RCTs should be conducted to explore the efficacy and mechanism of MBE on chronic pain in middle-aged and elderly people from various dimensions, such as affective and cognitive dimensions. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=316591, identifier CRD42022316591.

Anlotinib combined with TQB2450 in patients with platinum-resistant or -refractory ovarian cancer: A multi-center, single-arm, phase 1b trial.

This is a phase Ib study of anlotinib plus a programmed death-ligand 1 (PD-L1) inhibitor TQB2450 for platinum-resistant or -refractory ovarian cancer. Thirty-four patients are enrolled and receive treatment. The objective response rate (ORR) is 47.1%, and the disease control rate is 97.1%. The median duration of response (DOR) has not been reached, and 61.3% of patients have a DOR of at least 8 months. The median progression-free survival (PFS) is 7.8 months, and the median overall survival (OS) has not been reached. The PD-L1-positive group has an ORR of 25.0%, whereas the PD-L1-negative group has an ORR of 92.9%. Treatment-related grade 3 or 4 adverse events (AEs) occur in 70.6% of patients, with the most common being hypertension (29.4%) and palmar-plantar erythrodysesthesia syndrome (29.4%). Anlotinib plus TQB2450 show promising antitumor activity and manageable toxicities in patients with platinum-resistant or -refractory ovarian cancer. A phase 3 randomized controlled trial to further validate our findings is ongoing.

Characteristics of Patients with Primary Sjögren's Syndrome and Non-specific Chronic Sialadenitis: A Subtype in Elderly Patients.

INTRODUCTION: Non-specific chronic sialadenitis (NSCS) is a common pathology of labial salivary glands (LSGs), and NSCS with positive anti-SSA/SSB antibodies is common in clinical practice. Previous studies have evaluated the associations of high focus score (FS) with clinical manifestations in primary Sjögren's syndrome (pSS) patients extensively, but the characteristics of pSS with NSCS have seldom been investigated. We here analyzed the characteristics of pSS patients with NSCS. METHODS: Among 425 patients who underwent LSG biopsies, 217 had pSS and 37 non-SS sicca patients had NSCS without other diseases (i.e., sicca controls). We categorized these 217 pSS patients into three groups based on the pathology of LSGs: FS ≥ 1 (n = 104), 0 ≤ FS < 1 (n = 76), and NSCS (n = 37). We then compared the three groups while focusing on the NSCS group. Multivariate logistic regression analysis was performed to identify variables that influenced NSCS. RESULTS: The mean age of pSS patients with NSCS (58.3 ± 11.0 years) was significantly higher than those with FS ≥ 1 (48.5 ± 14.9 years) and 0 ≤ FS < 1 (45.3 ± 13.7 years), but other clinical characteristics were similar. NSCS had a significant positive correlation with age (OR = 7.282, 95% CI 2.085-25.44 and OR = 13.130, 95% CI 3.368-51.189 for patients aged 45-64 years and > 65 years, respectively). Significantly higher levels of lymphocytic infiltration were found in the pSS NSCS group than in the sicca NSCS controls (48.6 vs. 10.8%, respectively). CONCLUSIONS: The pSS patients with NSCS were older than corresponding non-NSCS pSS individuals, but they had similar clinical features. NSCS is associated with age and seldom occurred below the age of 45 years, regardless of the presence or absence of pSS. NSCS may be a subtype of pSS in elderly patients.

Prenatal phthalate exposure associated with age-specific alterations in markers of adiposity in offspring: A systematic review.

Childhood obesity and metabolic disorders are of concern and are public health problems globally. Environmental endocrine disruptors, including phthalates, are well known as "obesogens" and "metabolic disruptors". Several studies have investigated the relationships between prenatal phthalate exposure and childhood obesity with inconsistent conclusions. Given the child growth trajectory/pattern as a possible early marker of metabolic disorders, we aimed to assess the effect of prenatal phthalate exposure on offspring growth trajectory. A systematic literature search was conducted using MEDLINE (accessed through PubMed), Web of Science, and CNKI (Chinese National Knowledge Infrastructure) until July 2021. We evaluated the risk of bias for adherence to the prespecified criteria. Fourteen eligible articles were finally included in this systematic review according to the defined PECOS statement. The risk of bias of the included studies was "low" or "probably low", and few were "probably high" and "high". These studies were mostly carried out in the United States (N = 6); others were conducted in China (N = 2), Mexico (N = 2), France (N = 1), Spain (N = 1), Greece (N = 1), and Australia (N = 1) and published from 2015 to 2021. The combined subjects of the 14 studies were 10,396 mother-child pairs. Except for 3 studies not reporting the sex ratio, at least 4001 boys and 3366 girls were included. For the association of prenatal phthalate exposure with an absolute adiposity marker (at a specific visit timepoint), only a few studies were using the same obesity marker as the outcome endpoint and using the same statistical method to explore their associations. However, MEP appeared to be positively associated with several obesity markers, such as the absolute BMI z score, weight-for-age z score, waist circumference, and overweight status. For the association of prenatal phthalate exposure with a repeated measurement of the adiposity marker over the age range, neither associations of adiposity markers with a specific phthalate metabolite nor relationships of a specific adiposity marker with prenatal phthalate exposure were of a consistent result. All four articles reported that phthalate metabolite exposure during pregnancy was associated with children's growth trajectory. Three suggested a sex-specific association between prenatal phthalate exposure and obesity trajectory. In conclusion, the current articles did not show any relationship between prenatal phthalate exposure and children's age-specific outcomes, except for positive associations of prenatal MEP exposure with absolute adiposity markers. However, epidemiological data supported a weak relationship between prenatal phthalate exposure and children's obesity trajectory in a sex-specific manner.

Preventive and therapeutic effects of green tea on lung cancer: a narrative review of evidence from clinical and basic research.

Background and Objective: Green tea is a popular beverage worldwide and has numerous health-promoting properties. Accumulating evidence indicates that green tea has preventive and therapeutic effects on lung cancer. This study aimed to investigate the association between green tea consumption and lung cancer. Methods: We performed a narrative review to summarized the association between green tea consumption and lung cancer. Key Content and Findings: Green tea consumption is known to decrease lung cancer risk in the general population, as indicated by meta-analyses of observational studies. Two active components of green tea, theabrownin and (-)-epigallocatechin gallate (EGCG), mediate the antitumor activity of green tea. Theabrownin promotes apoptosis, induces cell cycle arrest, and inhibits the migration, clone formation, and proliferation of lung cancer cell lines in vitro and in vivo. EGCG inhibits lung cancer cell proliferation and promotes apoptosis, agenesis, and epithelial-mesenchymal transition (EMT). In addition, EGCG sensitizes lung cancer cells to cisplatin and tyrosine kinase inhibitors (TKIs). The possible molecular mechanisms underlying the antitumor activity of EGCG and theabrownin were reviewed. Conclusions: Observational studies have indicated that green tea has preventive effects on lung cancer. In vitro and animal studies have indicated that green tea has therapeutic effects on lung cancer. Further clinical trials are needed to illustrate the therapeutic effects of green tea or its active components (i.e., theabrownin, EGCG) on lung cancer.

Tumor cell-derived exosomal microRNA-146a promotes non-small cell lung cancer cell invasion and proliferation by inhibiting M1 macrophage polarization.

Background: Tumor-associated macrophages (TAMs) affects the outcomes of non-small cell lung cancer (NSCLC). NSCLC cells released exosomes to suppress the antitumor activity of TAMs. MiR-146a is a critical regulator in TAM polarization. We hypothesized that NSCLC cells released exosomal miR-146a to regulate TAM polarization and thus affected its antitumor activity. Methods: We used H1299 cells-derived exosomes to stimulate THP-1 cells that was pretreated with phorbol 12-myristate 13-acetate (M0 macrophage). Flow cytometry and reverse transcription-quantitative polymerase chain reaction (PCR) were used to determine the polarization of macrophages. The conditioned medium of exosome-treated M0 cells was used to culture H1299 cells, and the Cell Counting Kit-8, Ki67, transwell and scratch wound assays were used to determine the biological behavior of H1299 cells. To investigate whether exosomal miR-146a regulates TAM macrophages through targeting tumor necrosis factor receptor-associated factor 6 (TRAF-6) and interleukin-1 receptor-associated kinase 1 (IRAK-1), we used small interfering RNA to knockdown the expressions of them. Results: Upregulation of miR-146a inhibited M1 polarization and thus impaired the antitumor activity of TAMs. Exosomes released by H1299 cells can be taken by M0 macrophage, and they upregulated the expression of miR-146a in M0 macrophage. The exosome suppresses M1 polarization by exosomal miR-146a. TRAF-6 and IRAK-1 mediated the inhibitive effects of exosomal miR-146a on M1 polarization. Conclusions: NSCLC cells released exosomal miR-146a to inhibit the expressions of TRAF-6 and IRAK-1 in TAMs, resulting in the impaired antitumor activity of TAMs. NSCLC cell-derived exosomal miR-146a represents a novel therapeutic target for NSCLC treatment.

[Clinical Analysis of B-Cell Non-Hodgkin Lymphoma Treated with Modified Conditioning Regimen].

OBJECTIVE: To investigate the efficacy, safety and prognosis of auto-HSCT between classical and modified conditioning regimen in patients with B-cell non-Hodgkin lymphoma. METHODS: 36 patients diagnosed as B-cell non-Hodgkin lymphoma treated with autologous hematopoietic stem cell transplantation from January 2015 to June 2018 in Tianjin Cancer Hospital were retrospectively analyzed. The patients were divided into two groups: Idarubicin group and non-Idarubicin group. The overall survival (OS), progression-free survival (PFS), adverse reactions and hematopoietic reconstitution time between the two groups were compared. Survival analysis was performed by using the Kaplan-Meier method. Log-rank test was used for comparison between groups, and Cox regression was used for multivariate analysis. RESULTS: The median follow-up time was 29 months. Among these 36 patients with B-cell non-Hodgkin lymphoma before transplantation, 21 patients achieved CR and 15 patients achieved PR. The reconstitution time of neutrophil (P>0.05) and platelet (P>0.05) was not significantly different between Idarubicin and non-Idarubicin group. Also, the adverse reactions were not significantly different between two groups. The addition of idarubicin showed not aggravate the adverse reactions of patients. The OS and PFS of patients with idarubicin was longer than that of patients without idarubicin. The multivariate analysis showed that, the modified conditioning regimen and the remission state before transplantation were closely associated with prognosis. CONCLUSION: The above-mentioned results indicated that the combination of modified conditioning regimen with idarubicin can lengthen the OS and PFS of the patients significantly, and show not aggravate of bone marrow inhibition, moreover, the hematopoietic reconsititution time show not lengthen, which means that it can be a safe and effective choice for autologous HSCT in the patients with B cell non-Hodgkin lymphoma.

[Clinical Characteristics of 219 Patients with Primary Gastrointestinal Non-Hodgkin's Lymphoma].

OBJECTIVE: To analyze the clinical and pathological characteristics of primary gastrointestinal non-Hodgkin's lymphoma (PGI-NHL) patients, and to explore the factors affecting the patients' survival and prognosis. METHODS: The clinical data of 219 patients with PGI-NHL diagnosed in our hospital from March 2009 to April 2016 was collected and retrospectively analyzed. Survival analysis was performed by using the Kaplan-Meier method. Log-rank test was used for comparison among the groups, and Cox regression was used for multivariate analysis. RESULTS: Among the 219 patients with PGI-NHL, 126 patients were males and 93 patients were females. 182 patients were IPI 0 to 2 and 37 patients were IPI 3 to 5. There were 205 cases (93.6%) of B cell phenotype and 14 cases (6.4%) of T cell phenotype. 140 patients (63.9%) were patients with primary gastric NHL, including 85 DLBCL and 19 MALT. 79 cases (36.1%) were patients with primary intestinal NHL, including 46 DLBCL, 4 MALT, 7 FL, 3 MCL and 4 Burkitt lymphoma. 23 cases were HP positive and received anti-HP therapy. 57 cases and 32 cases received surgery and chemotherapy respectively. 84 cases received combination treatment of surgery and chemotherapy and 11 cases received combination treatment of radiotherapy and chemotherapy. Overall survival (OS) of indolent B-cell non-Hodgkin's lymphoma was longer than that of invasive B-cell non-Hodgkin's lymphoma, which shows better prognose. Kaplan-Meier analysis showed that there was no difference between progression-free survival (PFS) and OS in the patients with different origin sites, age and sex. There was no significant difference in PFS between B-cell and T-cell-derived patients, whereas OS of B-cell-derived PGI-NHL patients was longer than that of T-cell-derived PGI-NHL patients. The OS and PFS of patients with IPI 0-2 were longer than those of patients with IPI 3-5. According to Lugano and Ann Arbor staging systems, there was no difference in prognosis of patients between phase I/II and III/IV. The prognosis of patients treated with surgery alone was worse than that of patients treated with combination therapy, and the prognosis of patients with surgery combined with chemotherapy was not significantly different from that of patients with chemotherapy alone. CONCLUSION: B-cell phenotype, indolent and low IPI score lymphoma indicate better prognosis, while that of different origin site, sex and age shows no different in prognosis. Surgery is used only for emergency case or pathological materials, and these patients should be treated with chemotherapy-based combined treatment.

[Composition and fractal features of soil micro-aggregates in microsites of different types of treefall gaps]. / ä¸åŒæž—åž‹æ ‘å€’æž—éš™å† å¾®ç«‹åœ°ç±»åž‹çš„åœŸå£¤å¾®å›¢èšä½“ç»„æˆåŠå ¶åˆ†å½¢ç‰¹å¾.

Through field survey and laboratory analysis, we examined the composition and fractal features of soil micro-aggregates in different types of treefall gaps and microsites (pit bottom and mound top) in broad-leaved Korean pine forest and spruce-fir-Korean pine forest. Results showed that the contents of soil microaggregates under the classes of 0.25-2 mm and 0.05-0.25 mm were higher in both forest types, ranging from 25.7% to 50.7% and from 27.0% to 42.8%, respectively, and that of <0.002 mm was the lowest, ranging from 4.4% to 8.9%. In the pit bottom and mound top of gaps, soil bulk density was higher in both forest types. Soil nutrient content in mound top was higher than that in pit bottom and was higher in broad-leaved Korean pine forest than spruce-fir-Korean pine forest. Soil microaggregates of <0.002 mm had no correlation with soil physical and chemical properties, whereas that of 0.25-2 mm and 0.002-0.02 mm had significantly positive and negative correlation with soil non-capillary porosity, total porosity, aeration porosity, organic matter, total phosphorus, total nitrogen and organic carbon, respectively. On the whole, soil fractal dimension (D) and the proportion of characteristic soil micro-aggregates (PCM) in broad-leaved Korean pine forest were larger than those in spruce-fir-Korean pine forest, and the ratio of soil microaggregates diameter (RMD) in mound top and pit bottom was increased in two forest types. Soil D and PCM had no significant correlation with soil physical and chemical properties, while RMD was negatively correlated with capillary porosity, total porosity, soil bulk density and aeration porosity. In two forest types, the formation of mound and pit microsites could decrease the larger size micro-aggregates and the stability of soil micro-aggregate, increase soil D and PCM, and signifi-cantly increase RMD. RMD could be used as a quantitative index of soil physical and chemical properties in pit and mound microsites of forest.

A comparative study of clinical effect of total knee arthroplasty in the treatment of primary osteoarthritis and osteoarthritis of Kashin-Beck disease.

OBJECTIVE: To evaluate the clinical efficacy of total knee arthroplasty (TKA) in the treatment of primary osteoarthritis (OA) and osteoarthritis of Kashin-Beck disease (KBD). METHODS: This study enrolled 77 KBD patients (77 knees, KBD-TKA) and 75 OA patients (75 knees, OA-TKA) who underwent TKA from September 2008 to June 2018. Clinical assessments for each patient were performed pre-operatively and last follow-up. The efficacy measures included the visual analogue scale (VAS) pain score, range of motion (ROM), Hospital for Special Surgery (HSS) score, and short form 36 Health Survey (SF-36) as well as related influencing factors between the two groups. RESULTS: All patients were followed up; the follow-up time of KBD-TKA was 14-132 months, with an average of 72.68 ± 37.55 months; OA-TKA was 15-120 months, with an average of 49.2 ± 28.91 months. There was no difference in pre-operative VAS score (7.29 vs. 7.24) and SF-36 (PCS) score (4.87 vs. 5.49) between KBD-TKA and OA-TKA (P > 0.05), while compared with OA, KBD-TKA had significantly worse pre-operative ROM (75.48° vs. 82.87°), HSS score (36.40 vs. 41.84), and SF-36 (MCS) score (26.28 vs. 28.73) (P < 0.05). At the final follow-up, there was no significant difference in VAS score (1.13 vs. 1.16), ROM (105.79 vs. 105.79), and HSS score (92.06 vs. 92.25) between KBD-TKA and OA-TKA (P > 0.05), while compared with OA, KBD-TKA had significantly worse SF-36 (PCS) score (36.90 vs. 42.00) and SF-36 (MCS) score (55.16 vs. 59.70) (P < 0.05). In a multivariate regression, controlling for multiple potential confounders, diagnosis of KBD was associated with poor quality of life after surgery, whereas pre-operative pain was specifically associated with post-operative pain. However, preoperative gender, age, BMI, and the angles of knee prosthesis (before and after surgery) were not associated with post-operative outcome. CONCLUSION: Patients with KBD undergoing primary TKA have excellent outcomes, comparable with OA at the final follow-up, in spite of worse pre-operative ROM, HSS score, and SF-36(MCS) score. However, KBD patients are worse than OA in terms of general health. Pre-operative age, gender, BMI, and the angles of knee prosthesis were not the factors influencing the clinical efficacy of TKA. The diagnosis of KBD was an independent risk factor for poor quality of life after TKA. Pre-operative pain was a clinically important predictor of outcome.