No pulsed radio emission during a bursting phase of a Galactic magnetar.

Fast radio bursts (FRBs) are millisecond-duration radio transients of unknown physical origin observed at extragalactic distances1-3. It has long been speculated that magnetars are the engine powering repeating bursts from FRB sources4-13, but no convincing evidence has been collected so far14. Recently, the Galactic magnetar SRG 1935+2154 entered an active phase by emitting intense soft γ-ray bursts15. One FRB-like event with two peaks (FRB 200428) and a luminosity slightly lower than the faintest extragalactic FRBs was detected from the source, in association with a soft γ-ray/hard-X-ray flare18-21. Here we report an eight-hour targeted radio observational campaign comprising four sessions and assisted by multi-wavelength (optical and hard-X-ray) data. During the third session, 29 soft-γ-ray repeater (SGR) bursts were detected in γ-ray energies. Throughout the observing period, we detected no single dispersed pulsed emission coincident with the arrivals of SGR bursts, but unfortunately we were not observing when the FRB was detected. The non-detection places a fluence upper limit that is eight orders of magnitude lower than the fluence of FRB 200428. Our results suggest that FRB-SGR burst associations are rare. FRBs may be highly relativistic and geometrically beamed, or FRB-like events associated with SGR bursts may have narrow spectra and characteristic frequencies outside the observed band. It is also possible that the physical conditions required to achieve coherent radiation in SGR bursts are difficult to satisfy, and that only under extreme conditions could an FRB be associated with an SGR burst.

Role of oedema and shrinkage patterns for prediction of response to neoadjuvant chemotherapy and survival outcomes in luminal breast cancer.

AIMS: To explore the independent and additional value of oedema and shrinkage patterns for predicting the disease-free survival (DFS) and neoadjuvant chemotherapy (NAC) response in luminal breast cancer (BC). MATERIALS AND METHODS: Patients with luminal BC who underwent NAC were enrolled in this study from 2017 to 2022. Traditional MRI features include BI-RADS-based MRI descriptors, tumor size, and ADC values, while emerging MRI features include oedema and shrinkage patterns, all of which were evaluated before, early, and after NAC. The changes in features during NAC were also evaluated. The value of features was evaluated through univariate, multivariate analyses. RESULTS: A total of 258 patients were enrolled in this study, of which 77 responded to NAC. Diffuse oedema, stable or increased oedema during early NAC were adverse predictors for treatment response, while a greater reduction in tumor size and increase in ADC value were favorable predictors (all P<0.05). Furthermore, 20 of 60 patients who were followed up experienced recurrence. Diffuse oedema, pre-pectoral or subcutaneous oedema, and non-concentric shrinkage patterns after NAC were risk factors for DFS, whereas a greater increase in ADC value was a protective factor. Incorporating oedema and shrinkage patterns into traditional MRI features improved the predictive performance for treatment response (AUC from 0.76-0.78 to 0.80-0.83) and DFS (C-index from 0.67-69 to 0.75-0.80). CONCLUSIONS: Oedema is an unfavorable predictor for treatment response and survival outcomes, while shrinkage patterns contribute more to the prognostic value, both of which could offer supplementary benefits for clinical outcomes in luminal BC.

Association of adverse and positive childhood experiences with health-related quality of life in adolescents.

OBJECTIVES: To investigate the independent impacts of adverse childhood experiences (ACEs) and positive childhood experiences (PCEs) on the health-related quality of life (HRQOL) of Chinese adolescents, and to explore the potential moderating role of PCEs in the association between ACEs and HRQOL. STUDY DESIGN: This was a cross-sectional study. METHODS: We surveyed 6982 students aged 11-20 in Guangzhou, China, from November to December 2021. Adolescents self-reported their ACEs, PCEs, and HRQOL by the Childhood Trauma Questionnaire Short Form, the Adverse Childhood Experiences-International Questionnaire, the Benevolent Childhood Experiences Scale, and the Paediatric Quality of Life Inventory Version 4.0, respectively. Multivariable linear regressions were performed to examine the associations between ACEs, PCEs, and HRQOL controlled for adolescents' age, gender, single-child status, boarding school attendance, primary caregivers, as well as parental age and occupational status. Likelihood-ratio tests were further applied to explore the moderating role of PCEs. RESULTS: In the models that considered both ACEs and PCEs, ACEs were significantly associated with lower HRQOL scores in all dimensions, summary scales, and total scale (ß = -13.88, 95% confidence interval [CI]: -14.82, -12.94 for total scale). Conversely, exposure to an above-average number of PCEs was associated with higher HRQOL scores in all measured aspects (ß = 7.20, 95%CI: 6.57, 7.84 for total scale). PCEs significantly moderated the association between ACEs and all HRQOL dimensions, summary scales, and total scale, except school functioning. CONCLUSION: ACEs and PCEs exert independent and opposite impacts on adolescents' HRQOL. PCEs could mitigate the negative impacts of ACEs. Enhancing resilience, like PCEs, may contribute to improving the HRQOL among adolescents who have exposed to ACEs.

[Study on the relationship between hemoglobin glycosylation index and arteriosclerosis- related blood lipids].

Objective: To study the relationship between hemoglobin glycation index (HGI) and blood lipid indices such as low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and plasma atherogenic index (AIP). Methods: This cross-sectional study included 16 049 participants from the Beijing Apple Garden community between December 2011 and August 2012. The subjects were divided into three groups based on the HGI quartile: low (n=5 388), medium (n=5 249), and high (n=5 412). The differences in blood lipid indicators between different HGI groups were compared and multivariate logistic regression model was established to analyze the association between HGI and dyslipidemia. And multivariate logistic regression model was established to analyze the relationship between HGI and blood lipid indicators in different glucose metabolism populations. Results: There were 16 049 participants in all (mean age: 56 years), including 10 452 women (65.1%). They were classified into normal glucose tolerance (9 093 cases), prediabetes (4 524 cases), and diabetes (2 432 cases) based on glucose tolerance status. In the general population, with the increase of HGI, LDL-C, non-HDL-C, and AIP gradually increased (all P values for trends were <0.05), and the proportion of abnormalities increased significantly (χ2=101.40, 42.91, 39.80; all P<0.001). A multivariate logistic regression model was established, which suggested a significant correlation between HGI and LDL-C, non-HDL-C, and AIP (all P<0.05), after adjusting for factors such as age, sex, fasting blood glucose, hypertension, body mass index, smoking, and alcohol consumption. In the overall population, normal glucose tolerance group, and diabetes group, HGI had the highest correlation with non-HDL-C (OR values of 1.325, 1.678, and 1.274, respectively); in the prediabetes group, HGI had a higher correlation with LDL-C (OR value: 1.510); and in different glucose metabolism groups, AIP and HGI were both correlated (OR: 1.208-1.250), but not superior to non-HDL-C and LDL-C. Conclusion: HGI was closely related to LDL-C, non HDL-C, and AIP in the entire population and people with different glucose metabolism, suggesting that HGI may be a predictor of atherosclerotic cardiovascular disease.

[Bronchoscopic intervention therapy for pulmonary mucormycosis with main bronchial occlusion: a case report].

Pulmonary mucormycosis is one of the most common types of mucormycosis. Tracheobronchial pulmonary mucormycosis primarily affects the tracheobronchial tree, causing lesions that can invade the airway mucosa and muscular layer, damaging the cartilage. It is characterised by acute onset, rapid progression, and high mortality rate, making clinical treatment challenging. This article reports the diagnosis and treatment of a patient with pulmonary mucormycosis complicated by left main bronchus occlusion. In addition to systemic treatment, which consisted mainly of an intravenous injection of amphotericin B combined with an oral suspension of posaconazole, the patient underwent multiple bronchoscopic interventions, including local infusion of amphotericin B under endoscopy, balloon dilation and silicone stent placement. After four months of comprehensive treatment, the therapeutic effect was satisfactory. This report demonstrates that bronchoscopic intervention therapy plays an important role in the comprehensive treatment of pulmonary mucormycosis, especially in preventing death from the progression to obstructive pneumonia.

[Analysis of pre-operative factors affecting vault after posterior chamber phakic intraocular lens implantation].

Objective: To analyze the early changes in vault height and its influencing factors after implantation of posterior chamber phakic intraocular lenses (pIOL). Methods: A retrospective case series study was conducted, including patients who underwent pIOL implantation at Zhongshan Ophthalmic Center, Sun Yat-sen University, from September 2020 to August 2021, and completed a 3-month follow-up. Data were collected from myopic or myopic astigmatism patients. Preoperative ocular examinations, including Pentacam anterior segment analysis system, Sirius anterior segment analysis system, ultrasound biomicroscopy (UBM), and IOLMaster optical biometry, were performed to measure parameters such as refractive power, corneal curvature, corneal horizontal diameter, anterior chamber volume, anterior chamber depth, pupil diameter, sulcus-to-sulcus diameter (STS), and lens thickness. The degree and position of implanted pIOL, as well as vault height measured by anterior segment optical coherence tomography (AS-OCT) at 1 day, 1 week, 1 month, and 3 months postoperatively, were recorded. Statistical analyses were conducted using repeated measures analysis of variance, Pearson correlation analysis, and multiple linear regression analysis. Results: A total of 314 patients (314 eyes) were included, with 52 male (16.56%) and 262 female (83.44%) patients, and an average age of (26.44±4.60) years. The preoperative equivalent spherical power was (-8.09±2.41) D. Postoperative vault heights at 1 day, 1 week, 1 month, and 3 months were (671.88±273.02) µm, (652.26±272.21) µm, (615.08±259.69) µm, and (591.14±250.71) µm, respectively, with statistically significant differences among groups (P<0.001). Eyes with vault height>750 µm showed a greater decrease in early postoperative vault height (P<0.001). The eyes implanted with 12.1 mm pIOL had the lowest postoperative vault height, while those with 13.2 mm had the highest (P>0.05). Factors correlated with vault height at 1 day postoperatively included corneal horizontal diameter, anterior chamber depth, preoperative cylinder power, angle degree, lens thickness, and pIOL cylinder power. Factors correlated with vault height at 3 months postoperatively included corneal horizontal diameter, anterior chamber depth, preoperative cylinder power, anterior chamber volume, angle degree, lens thickness, axial length, pIOL spherical and cylinder power. Factors associated with changes in early postoperative vault height included corneal curvature K2, anterior chamber depth, anterior chamber volume, pupil diameter, horizontal STS, vertical STS, axial length, and preoperative spherical power (all P<0.05). Multiple linear regression analysis revealed that lens thickness significantly influenced vault height at 1 day postoperatively, anterior chamber volume significantly influenced vault height at 3 months postoperatively, and pupil diameter significantly influenced changes in early postoperative vault height (all P<0.05). Conclusions: Vault height after pIOL implantation is unstable in the early postoperative period and gradually decreases within 3 months. A higher baseline vault height is associated with a greater decrease. Anterior chamber volume, pupil diameter, and lens thickness are influencing factors on vault height during the first 3 months postoperatively.

Identification of ovarian endometriotic cysts in cystic lesions of the ovary by amide proton transfer-weighted imaging and R2∗ mapping.

AIM: To investigate the value of amide proton transfer weighted (APTw) imaging and R2∗ mapping of cystic fluid in differentiating ovarian endometriotic cysts (OE) from other ovarian cystic (OOC) lesions. MATERIALS AND METHODS: A total of 42 patients who underwent 3 T pelvic magnetic resonance imaging (MRI) were enrolled. Nineteen lesions were OE and 27 lesions were OOC. The APTw imaging and R2∗ values of the cystic fluid were measured and compared between the two groups using the independent sample t-test or Mann-Whitney U-test. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic efficacy of different parameters. The area under ROC curves (AUCs) was compared using the Delong test. Spearman's correlation analysis was used to assess the correlation between APTw imaging and R2∗ values. RESULTS: APTw imaging values of OE were lower, while R2∗ values were higher in OE than those in OOC (p=0.001 and < 0.001). The AUCs of APTw imaging and R2∗ values to identify OE from OOC were 0.910 and 0.975. The AUC increased to 0.990 when combining APTw imaging and R2∗ values, yet without a significant difference to the APTw imaging or R2∗ value alone (p=0.229 and 0.082, respectively). APTw imaging values were negatively correlated with R2∗ values (r=-0.522, p<0.001). CONCLUSION: Both APTw imaging and R2∗ values of OE are significantly different from other ovarian cystic lesions. APTw imaging combined with R2∗ values show excellent diagnostic efficacy to differentiate between OE and OOC.

Impact of rhG-CSF on Clinical Efficacy and Immune Cell Subsets after Initial Induction Chemotherapy in AML.

BACKGROUND: The impact of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in acute myeloid leukemia (AML) is still controversial. The purpose of this study is to explore the impact of rhG-CSF administration on clinical efficacy and immune cell subsets after initial induction chemotherapy in AML. METHODS: The clinical efficacy and immune cell subsets were compared in the newly diagnosed patients with AML according to whether rhG-CSF was used after initial induction chemotherapy. Next, rhG-CSF stimulation experi-ments on leukemia cell lines and primary leukemia blasts were performed in vitro. RESULTS: There was no statistical difference between control group and rhG-CSF therapy group in complete remission rate and relapse free survival. The duration of agranulocytosis was significantly shortened in rhG-CSF therapy group compared with control group. The percentage of circulating monocytic myeloid-derived suppressor cells (M-MDSCs) and regulatory T cells (Tregs) were significantly increased after the administration of rhG-CSF. Furthermore, it was found that rhG-CSF did not promote the proliferation of leukemia cell lines and primary leukemia blasts, but increased the proportion of M-MDSCs and Tregs in vitro. CONCLUSIONS: Administration of rhG-CSF after initial induction therapy of AML does not affect the clinical remission and relapse rate, but reduces the duration of agranulocytosis and increases the proportion of M-MDSCs and Tregs.

Genetically elevated bioavailable testosterone level was associated with the occurrence of benign prostatic hyperplasia.

BACKGROUND: Recent studies identified several risk factors of benign prostatic hyperplasia (BPH), including dyslipidemia, type 2 diabetes mellitus, hypertension, and obesity. But they were not so reliable and some studies contradicted with one another. Hence, a reliable method is urgently needed to explore exact factors that facilitated BPH development. METHODS: The study was based on Mendelian randomization (MR) design. All participants were from the most recent genome-wide association studies (GWAS) with large sample size. The causal associations between nine phenotypes (total testosterone level, bioavailable testosterone level, sex hormone-binding globulin, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, type 2 diabetes mellitus, hyper-tension, and body mass index) and BPH outcome were estimated. Two sample MR, bidirectional MR, and multivariate MR (MVMR) were performed. RESULTS: Increase in bioavailable testosterone level was able to induce BPH based on nearly all combination methods [beta (95% confidence interval (CI)): 0.20 (0.06-0.34) for inverse variance weighted (IVW)]. The other traits seemed to interact with testosterone level and did not cause BPH generally. Higher triglycerides level was likely to raise bioavailable testosterone level [beta (95% CI): 0.04 (0.01-0.06) for IVW]. In MVMR model, bioavailable testosterone level was still associated with BPH occurrence [beta (95% CI) 0.27 (0.03-0.50) for IVW]. CONCLUSIONS: We for the first time validated the central role of bioavailable testosterone level in the pathogenesis of BPH. The complex associations between other traits and BPH should be further investigated.

Postoperative pulmonary complications in older patients undergoing elective surgery with a supraglottic airway device or tracheal intubation.

The two most commonly used airway management techniques during general anaesthesia are supraglottic airway devices and tracheal tubes. In older patients undergoing elective non-cardiothoracic surgery under general anaesthesia with positive pressure ventilation, we hypothesised that a composite measure of in-hospital postoperative pulmonary complications would be less frequent when a supraglottic airway device was used compared with a tracheal tube. We studied patients aged ≥ 70 years in 17 clinical centres. Patients were allocated randomly to airway management with a supraglottic airway device or a tracheal tube. Between August 2016 and April 2020, 2900 patients were studied, of whom 2751 were included in the primary analysis (1387 with supraglottic airway device and 1364 with a tracheal tube). Pre-operatively, 2431 (88.4%) patients were estimated to have a postoperative pulmonary complication risk index of 1-2. Postoperative pulmonary complications, mostly coughing, occurred in 270 of 1387 patients (19.5%) allocated to a supraglottic airway device and 342 of 1364 patients (25.1%) assigned to a tracheal tube (absolute difference -5.6% (95%CI -8.7 to -2.5), risk ratio 0.78 (95%CI 0.67-0.89); p < 0.001). Among otherwise healthy older patients undergoing elective surgery under general anaesthesia with intra-operative positive pressure ventilation of their lungs, there were fewer postoperative pulmonary complications when the airway was managed with a supraglottic airway device compared with a tracheal tube.

Recombinant Treponema pallidum protein Tp47 promoted the phagocytosis of macrophages by activating NLRP3 inflammasome induced by PKM2-dependent glycolysis.

BACKGROUND: Glycolysis is a critical pathway in cellular glucose metabolism that provides energy and participates in immune responses. However, whether glycolysis is involved in NOD-like receptor family protein 3 (NLRP3) inflammasome activation and phagocytosis of macrophages in response to Treponema pallidum infection remains unclear. OBJECTIVES: To investigate the role of glycolysis in activating the NLRP3 inflammasome for regulating phagocytosis in macrophages in response to T. pallidum protein Tp47 and its associated mechanisms. METHODS: Interactions between activation of the NLRP3 inflammasome and phagocytosis and the role of glycolysis in Tp47-treated macrophages were investigated through experiments on peritoneal macrophages and human monocytic cell line-derived macrophages. RESULTS: Activation of phagocytosis and NLRP3 inflammasome were observed in Tp47-treated macrophages. Treatment with NLRP3 inhibitor MCC950 or si-NLRP3 attenuated Tp47-induced phagocytosis. Glycolysis and glycolytic capacity were enhanced by Tp47 stimulation in macrophages, and a change in the levels of glycolytic metabolites (phosphoenolpyruvate, citrate and lactate) was induced by Tp47 in macrophages. Inhibition of glycolysis with 2-deoxy-D-glucose, a glycolysis inhibitor, decreased the activation of NLRP3. Expression of M2 isoform of pyruvate kinase (PKM2), an enzyme catalysing a rate-limiting reaction in the glycolytic pathway, was upregulated in Tp47-stimulated macrophages. Inhibition of PKM2 with shikonin or si-PKM2 decreased glycolysis and NLRP3 activation. CONCLUSION: Tp47 promotes phagocytosis in macrophages by activating the NLRP3 inflammasome, which is induced by the enhancement of PKM2-dependent glycolysis.

Cross-sectional quantitative validation of the paediatric Localized Scleroderma Quality of Life Instrument (LoSQI): A disease-specific patient-reported outcome measure.

BACKGROUND: The Localized Scleroderma Quality of Life Instrument (LoSQI) is a disease-specific patient-reported outcome (PRO) measure designed for children and adolescents with localized scleroderma (LS; morphea). This tool was developed using rigorous PRO methods and previously cognitively tested in a sample of paediatric patients with LS. OBJECTIVE: The purpose of this study was to evaluate the psychometric properties of the LoSQI in a clinical setting. METHODS: Cross-sectional data from four specialized clinics in the US and Canada were included in the analysis. Evaluation included reliability of scores, internal structure of the survey, evidence of convergent and divergent validity, and test-retest reliability. RESULTS: One hundred and ten patients with LS (age: 8-20 years) completed the LoSQI. Both exploratory and confirmatory factor analysis supported the use of two sub-scores: Pain and Physical Functioning, and Body Image and Social Support. Correlations with other PRO measures were consistent with pre-specified hypotheses. LIMITATIONS: This study did not evaluate longitudinal validity or responsiveness of scores. CONCLUSION: Results from a representative sample of children and adolescents with LS continue to support the validity of the LoSQI when used in a clinical setting. Future work to evaluate the responsiveness is ongoing.

Incidence and characteristics of aspiration pneumonia in adults in Beijing, China, 2011-2017.

OBJECTIVES: This study aimed to estimate aspiration pneumonia (AP) incidence and describe comorbid characteristics and mortality in Beijing, China. STUDY DESIGN: A historical cohort study was conducted based on medical claim records. METHODS: Patients admitted with a primary diagnosis of AP were identified from approximately 12 million adults who enrolled in the Urban Employee Basic Medical Insurance program in Beijing, China, from January 2011 to December 2017. The incidences of AP and pneumonia with risk factors for aspiration (PRFA) were estimated by a Poisson distribution. The estimated annual percentage change was reported to represent the average percentage change in incidence per year. Characteristics and 6-month and 1-year all-cause mortality rates for AP and suspected AP patients were described and compared with community-acquired pneumonia (CAP). RESULTS: The incidence rates of hospitalized AP and PRFA were 9.4 (95% confidence interval [CI]: 7.6, 11.3) and 102.9 (95% CI: 95.8, 110.3) per 100,000 person-years, respectively. The incidences increased rapidly with age and were stable across the observed years. Patients with AP and PRFA possessed a greater burden of comorbidities than CAP (mean age-adjusted Charlson comorbidity indices for AP: 7.72, PRFA: 7.83, and CAP: 2.84). The 6-month and 1-year all-cause mortality rates for those with AP and PRFA were higher than those for patients with CAP (6-month mortality, AP: 35.2%, PRFA: 21.8%, CAP: 11.1%; 1-year mortality, AP: 42.7%, PRFA: 26.6%, CAP: 13.2%). CONCLUSIONS: The incidence of AP and PRFA in Beijing was reported, presenting a full picture of the disease burden. The results provide baseline information for AP prevention.

The impact of a complex school nutrition intervention on double burden of malnutrition among Thai primary school children: a 2-year quasi-experiment.

OBJECTIVE: This study assessed the impacts of the Dekthai Kamsai programme on overweight/obesity, underweight and stunting among male and female primary school students. STUDY DESIGN: A quasi-experiment was conducted in 16 intervention and 19 control schools across Thailand in 2018 and 2019. In total, 896 treated and 1779 control students from grades 1 to 3 were recruited. In intervention schools, a set of multifaceted intervention components were added into school routine practices. Anthropometric outcomes were measured at baseline and at the beginning and end of every school term. METHODS: Propensity score matching with linear and Poisson difference-in-difference analyses were used to adjust for the non-randomisation and to analyse the intervention's effects over time. RESULTS: Compared with controls, the increases in mean BMI-for-age Z-score (BAZ) and the incidence rate of overweight/obesity were lower in the intervention schools at the 3rd, 4th and 8th measurements and the 3rd measurement, respectively. The decrease in mean height-for-age Z-score (HAZ) was lower at the 4th measurement. The decrease in the incidence rate of wasting was lower at the 5th, 7th and 8th measurements. The favourable impacts on BAZ and HAZ were found in both sexes, while the favourable impact on overweight/obesity and unfavourable impact on wasting were found in girls. CONCLUSIONS: This intervention might be effective in reducing BAZ, overweight/obesity, poor height gain, but not wasting. These findings highlight the benefits of a multifaceted school nutrition intervention and a need to incorporate tailor-made interventions for wasting to comprehensively address the double burden of malnutrition.

A Standardized Botanical Composition Mitigated Acute Inflammatory Lung Injury and Reduced Mortality through Extracellular HMGB1 Reduction.

HMGB1 is a key late inflammatory mediator upregulated during air-pollution-induced oxidative stress. Extracellular HMGB1 accumulation in the airways and lungs plays a significant role in the pathogenesis of inflammatory lung injury. Decreasing extracellular HMBG1 levels may restore innate immune cell functions to protect the lungs from harmful injuries. Current therapies for air-pollution-induced respiratory problems are inadequate. Dietary antioxidants from natural sources could serve as a frontline defense against air-pollution-induced oxidative stress and lung damage. Here, a standardized botanical antioxidant composition from Scutellaria baicalensis and Acacia catechu was evaluated for its efficacy in attenuating acute inflammatory lung injury and sepsis. Murine models of disorders, including hyperoxia-exposed, bacterial-challenged acute lung injury, LPS-induced sepsis, and LPS-induced acute inflammatory lung injury models were utilized. The effect of the botanical composition on phagocytic activity and HMGB1 release was assessed using hyperoxia-stressed cultured macrophages. Analyses, such as hematoxylin-eosin (HE) staining for lung tissue damage evaluation, ELISA for inflammatory cytokines and chemokines, Western blot analysis for proteins, including extracellular HMGB1, and bacterial counts in the lungs and airways, were performed. Statistically significant decreases in mortality (50%), proinflammatory cytokines (TNF-α, IL-1ß, IL-6) and chemokines (CINC-3) in serum and bronchoalveolar lavage fluid (BALF), and increased bacterial clearance from airways and lungs; reduced airway total protein, and decreased extracellular HMGB1 were observed in in vivo studies. A statistically significant 75.9% reduction in the level of extracellular HMGB1 and an increase in phagocytosis were observed in cultured macrophages. The compilations of data in this report strongly suggest that the botanical composition could be indicated for oxidative-stress-induced lung damage protection, possibly through attenuation of increased extracellular HMGB1 accumulation.

[Chinese multidisciplinary expert consensus on the management of adverse drug reactions associated with savolitinib].

MET gene is a proto-oncogene, which encodes MET protein with tyrosine kinase activity. After binding to its ligand, hepatocyte growth factor, MET protein can induce MET dimerization and activate downstream signaling pathways, which plays a crucial role in tumor formation and metastasis. Savolitinib, as a specific tyrosine kinase inhibitor (TKI) targeting MET, selectively inhibits the phosphorylation of MET kinase with a significant inhibitory effect on tumors with MET abnormalities. Based on its significant efficacy shown in the registration studies, savolitinib was approved for marketing in China on June 22, 2021 for the treatment of advanced non-small cell lung cancer with MET 14 exon skipping mutations. In addition, many studies have shown that MET TKIs are equally effective in patients with advanced solid tumors with MET gene amplification or MET protein overexpression, and relevant registration clinical studies are ongoing. The most common adverse reactions during treatment with savolitinib include nausea, vomiting, peripheral edema, pyrexia, and hepatotoxicity. Based on two rounds of extensive nationwide investigations to guide clinicians, the consensus is compiled to use savolitinib rationally, prevent and treat various adverse reactions scientifically, and improve the clinical benefits and quality of life of patients. This consensus was prepared under the guidance of multidisciplinary experts, especially including the whole-process participation and valuable suggestions of experts in Traditional Chinese Medicine, thus reflecting the clinical treatment concept of integrated Chinese and western medicines.

[A phase I study of subcutaneous envafolimab (KN035) monotherapy in Chinese patients with advanced solid tumors].

Objective: To evaluate the safety and antitumor activity of envafolimab monotherapy in Chinese patients with advanced solid tumors. Methods: This open-label, multicenter phase I trial included dose escalation and dose expansion phases. In the dose escalation phase, patients received subcutaneous 0.1, 0.3, 1.0, 2.5, 5.0 or 10.0 mg/kg envafolimab once weekly (QW) following a modified "3+ 3" design. The dose expansion phase was performed in the 2.5 mg/kg and 5.0 mg/kg (QW) dose cohorts. Results: At November 25, 2019, a total of 287 patients received envafolimab treatment. During the dose escalation phase, no dose-limiting toxicities (DLT) was observed. In all dose cohorts, drug-related treatment-emergent adverse events (TEAEs) for all grades occurred in 75.3% of patients, and grade 3 or 4 occurred in 20.6% of patients. The incidence of immune-related adverse reactions (irAE) was 24.0% for all grades, the most common irAEs (≥2%) included hypothyroidism, hyperthyroidism, immune-associated hepatitis and rash. The incidence of injection site reactions was low (3.8%), all of which were grades 1-2. Among the 216 efficacy evaluable patients, the objective response rate (ORR) and disease control rate (DCR) were 11.6% and 43.1%, respectively. Median duration of response was 49.1 weeks (95% CI: 24.0, 49.3). Pharmacokinetic (PK) exposure to envafolimab is proportional to dose and median time to maximum plasma concentration is 72-120 hours based on the PK results from the dose escalation phase of the study. Conclusion: Subcutaneous envafolimab has a favorable safety and promising preliminary anti-tumor activity in Chinese patients with advanced solid tumors.

[IL-8 Links NF-κB and Wnt/ß-Catenin Pathways in Persistent Inflammatory Response Induced by Chronic Helicobacter pylori Infection].

Helicobacter pylori (H. pylori) infection can cause persistent inflammatory response in human gastric mucosal epithelial cells, which may result in the occurrence of cancer. However, the underlying mechanism of carcinogenesis has not been elucidated yet. Herein, we established the models of chronic H. pylori infection in GES-1 cells and C57BL/6J mice. Interleukin 8 (IL-8) level was detected by ELISA. The expression of NF-κB p65, IL-8, Wnt2 and ß-catenin mRNA and proteins was evaluated by real-time PCR, Western blotting, immunofluorescence staining, and immunohistochemistry. The infection of H. pylori in mice was evaluated by rapid urease test, H&E staining and Warthin-Starry silver staining. The morphological changes of gastric mucosa were observed by electron microscopy. Our results showed that in H. pylori infected gastric mucosal cells along with activation of NF-κB signaling pathway and increase of IL-8 level, the expression of Wnt2 was also increased significantly, which preliminarily indicates that IL-8 can positively regulate the expression of Wnt2. Studies in chronic H. pylori infected C57BL/6J mice models showed that there was an increased incidence of premalignant lesions in the gastric mucosa tissue. Through comparing changes of gastric mucosal cell ultrastructure and analyzing the relationship between NF-κB signaling pathway and Wnt2 expression, we found that H. pylori infection activated NF-κB signal pathways, and the massive release of IL-8 was positively correlated with the high expression of Wnt2 protein. Subsequently, the activated Wnt/ß-catenin signal pathways may be involved in the malignant transformation of gastric mucosal cells. Collectively, H. pylori chronic infection may continuously lead to persistent inflammatory response: activate NF-κB pathway, promote IL-8 release and thereby activate Wnt/ß-catenin pathway. IL-8 probably plays an important role of a linker in coupling these two signal pathways.

[Cross-sectional associations between reproductive lifespan duration and urinary albumin-creatinine ratio].

Objective: To investigate the association between reproductive lifespan duration (RLD) and urinary albumin-creatinine ratio (UACR) in a Chinese postmenopausal population. Methods: This cross-sectional study included 11 055 naturally postmenopausal women from seven regions of China from May to December 2011. RLD was divided into four groups. Propensity score matching was performed to reduce bias, and logistic regressions and stratifications were conducted to investigate the association between RLD and increased UACR (≥30 mg/g). Mediation effect analysis was performed to quantify the effect of RLD on cardiovascular disease (CVD) induced by elevated UACR. Results: There were 2 373 participants with a RLD of 18-31 years, 2 888 participants with a RLD of 32-34 years, 2 472 participants with a RLD of 35-36 years, and 3 322 participants with a RLD of 37-50 years. The shortest RLD (18-31 years) group was characterized with older age (P<0.001), a higher incidence of CVD (P=0.025), and the highest level of UACR (P<0.001). After adjusting for confounders, women with a longer RLD (37-50 years group) exhibited a lower risk of UACR elevation compared with those with the shortest RLD (18-31 years group) (OR=0.72, 95%CI 0.64-0.82, P<0.001). Every 1-year extension in RLD was linked to a 2% reduction in the risk of UACR elevation (OR=0.98, 95%CI 0.97-0.99, P<0.001). Stratified analysis revealed a more significant association between RLD and UACR in women who were a normal weight (P=0.003) or overweight (P=0.001), in those without CVD history (P=0.001), and in those with impaired estimated glomerular filtration rate (P=0.004). The mediation casual analysis showed that 3.0% of proteinuria inducing CVD events was mediated by RLD (P=0.048). Conclusion: A longer RLD (37-50 years) is associated with a lower UACR in Chinese postmenopausal women.

[Efficacy and safety of epidermal growth factor receptor tyrosine kinase inhibitors combined with chemotherapy as first-line treatment for epidermal growth factor receptor-mutant advanced non-small cell lung cancer].

Objective: To observe the clinical efficacy and safety of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) combined with chemotherapy as first-line treatment for EGFR mutant advanced non-small cell lung cancer (NSCLC). Methods: It was a retrospective, single-arm real-world study and a total of 39 patients with stage ⅢB to Ⅳ EGFR mutant NSCLC diagnosed in Cancer Hospital of Chinese Academy of Medical Sciences from July 2018 to December 2020 were collected. There were 16 males and 23 females, the age ranged from 25 to 73 years, with a median age of 53 years. All patients received EGFR-TKIs synchronously combined with pemetrexed and platinum-containing chemotherapy for 4-6 cycles as first-line treatment, followed by EGFR-TKI monotherapy with or without pemetrexed maintenance therapy. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and adverse reactions were evaluated. Median follow-up time was 18.6 months (95%CI: 16.2-21.0 months). The Kaplan-Meier method was used for survival analysis. Results: The ORR was 61.5% (24/39), the DCR was 94.9% (37/39) and the median PFS was 16.4 months (95%CI: 12.1-20.7 months). The main adverse reactions were liver function injury (59.0%, 23/39), myelosuppression (43.6%, 17/39), skin reaction (25.6%, 10/39), gastrointestinal reaction (17.9%, 7/39), fatigue (12.8%, 5/39) and kidney injury (5.1%, 2/39). Most of the patients had grade 1-2 adverse reactions, and the rate of grade 3 adverse events were 12.8%(5/39), which were effectively alleviated after symptomatic support treatment, no grade 4 serious adverse events occurred. Conclusion: EGFR-TKIs synchronously combined with chemotherapy followed by EGFR-TKI monotherapy with or without pemetrexed maintenance therapy has a certain therapeutic effect and fairly good safety, which can prolong PFS in patients with EGFR mutated advanced NSCLC.