[The impact of diabetes on bronchiectasis].

Objective: To study the impact of diabetes on bronchiectasis. Methods: From January 1 2017 to December 31 2021, data of 1 310 inpatients with bronchiectasis were retrospectively collected from Shanghai Pulmonary Hospital, Tongji University. This cohort inclueded 78 patients with bronchiectasis and diabetes (bronchiectasis-diabetes group) and 1 232 patients of bronchiectasis without diabetes (simple bronchiectasis group). To mitigate confounding variables, 269 patients with bronchiectasis but without diabetes (bronchiectasis non-diabetes group) were matched with 78 patients of bronchiectasis with diabetes (bronchiectasis-diabetes group) using the propensity score method in a 1∶4 ratio. A comparative analysis of clinical characteristics, laboratory test results, pathogenic infections, and disease severity was performed between the two groups. Analysis of continuous variables was performed using either a t-test or non-parametric test, while categorical data was assessed using the chi-square test. Results: The mean age of individuals in the bronchiectasis-diabetes group (62.99±8.09 years) was significantly higher than that of subjects in the simple bronchiectasis group (57.05±13.07 years) (t=-6.012, P<0.001). After propensity score matching, the pre-albumin level in the bronchiectasis-diabetes group (188.44±71.65 g/L) was found to be lower than in the bronchiectasis non-diabetes group (208.17±62.50 g/L) (t=2.023, P=0.044). In addition, the hospitalization cost for the bronchiectasis-diabetes group [1.59 (1.34, 2.15) Ten thousand yuan] was higher than that in the bronchiectasis non-diabetes group [1.39 (1.23, 1.62) Ten thousand yuan] (U=-3.744, P<0.001).The severity of mMRC in the bronchiectasis-diabetes group was significantly higher than that in the bronchiectasis non-diabetes group (χ2=25.392, P<0.001), and the frequency of previous hospitalization due to aggravation and acute exacerbation within the previous year were higher than in bronchiectasis non-diabetes group (χ2=34.031, 40.841, respectively, P<0.001). In additional, the BSI score was significantly increased in patients with bronchiectasis-diabetes compared to those with bronchiectasis non-diabetes (8.07±4.07 vs. 10.44±3.82) (P<0.001). Furthermore, fasting blood glucose concentration, urine glucose level, and BSI score exhibited positive correlations, whereas pre-albumin concentration showed a negative correlation with the BSI score (all P<0.05). Conclusion: Compared to those without diabetes, patients of bronchiectasis with diabetes have poorer nutritional status, more severe symptoms, increased risk of acute exacerbation, higher BSI score severity, and greater financial burden.

[Screening status of warning signs for mental and behavioral development and influencing factors of infants and young children in poverty eliminated regions of Henan province].

Objectives: To investigate the screening status of warning signs for mental and behavioral development (WS) and influencing factors of infants and young children (IYC) in poverty eliminated regions of Henan Province. Methods: This study was a cross-sectional study. A total of 15 680 IYC aged 6-23 months from 51 poverty eliminated counties in Henan province from June to September of 2023 were selected through a multi-stage random sampling method. IYC's early warning signs were screened using the WS checklist (WSC). Children's socio-demographic characteristics, maternal information, birth status, and illness conditions such as fever and diarrhea within 2 weeks were measured through a uniformly designed questionnaire. All participants also received the measurement of height, weight, and hemoglobin concentration level. Logistic regression model was used to explore the influencing factors of positive WSC and conducted sensitivity analyses. Results: Among the sample of 15 680 IYC, there were 8 462 boys (53.97%) and 7 218 girls (49.03%), with their age of (15±5) months. A total of 291 (1.86%) IYC were positive in WSC. Parenting risk (OR=5.07, 95%CI 3.93-6.52, P<0.001) and preterm birth (OR=1.63, 95%CI 1.06-2.52, P=0.027) were both positively associated with the odds of WSC's positivity. Being girls (OR=0.66, 95%CI 0.52-0.85, P=0.001), age (12-17 months, OR=0.47, 95%CI 0.35-0.62, P<0.001; 18-23 months, OR=0.40, 95%CI 0.30-0.54, P<0.001), and maternal educational level (junior high school, OR=0.46, 95%CI 0.32-0.66, P<0.001; senior high school or vocational high school, OR=0.35, 95%CI 0.23-0.56, P<0.001; college and above, OR=0.36, 95%CI 0.23-0.57, P<0.001) were all negatively associated with the risk of WSC's positivity. Sensitivity analyses demonstrated that, after excluding anemic children, the association between preterm birth and WSC's positivity was not significant (OR=1.54, 95%CI 0.95-2.49, P=0.081). Despite this situation, being girls, age and maternal educational level were still negatively associated with the odds of WSC's positivity (all P<0.05); preterm birth, parenting risk were remained positive associated with the risk of WSC's positivity (all P<0.05) either by excluding children with protein-energy malnutrition or 2-week morbidity, or using prevalence ratio instead of OR. Conclusions: Among the IYC in poverty eliminated regions of Henan Province, the risk of positivity of WSC was higher for those IYC with parenting risk, preterm birth, boys, younger age, and lower maternal education level. These influencing factors, such as gender, age, preterm birth, parenting risk and maternal educational level, were in certain stability across different IYC characteristics and estimation models.

Erratum - MMP-7 is upregulated by COX-2 and promotes proliferation and invasion of lung adenocarcinoma cells.

This corrects the article published in the European Journal of Histochemistry 2014;58:2262. doi: 10.4081/ejh.2014.2262.

[Changes in tumor microbiome and underlying value according to response to neoadjuvan chemotherapy for in patients with gastric cancer].

Objective: To investigate the relationship between efficacy of neoadjuvant chemotherapy (NACT) for gastric cancer and gastric microecology. Methods: This was a retrospective observational study using fresh frozen operative specimens. The specimens had been stored in the tumor sample bank of the Department of Gastrointestinal Surgery of the Affiliated Hospital of Qingdao University from January 2017 to January 2023 after having been collected from 31 patients with pathologically diagnosed gastric cancer who had no metastases and had received only neoadjuvant chemotherapy preoperatively. The study patients had all successfully undergone radical gastric cancer surgery. Patients with metastases or other primary tumor foci and/or had received other therapies within 1 month prior to surgery, including immunotherapy, targeted therapies and probiotics, were excluded. The tumors were graded and grouped in accordance with the 8th edition of the American Joint Committee on Cancer staging system and the Tumor Regression Grading System (TRG) of the College of American Pathologists. Those with TRG Grades 0-1, ypT0-1 and ypN0 were classified as responsive (Group R, 12 cases), whereas those with TRG Grades 2-3 and ypT2-4 or ypN+ were classified as non-responsive (Group NR, 19 cases). The fresh frozen samples were processed and analyzed using 16S rRNA sequencing. Alpha and beta diversity analyses were performed using the Q2-diversity plug-in for QIIME2 and STAMP was used to determine the default parameters and differentially enriched bacterial taxa in the two groups. High-dimensional class comparisons were performed by effect size linear discriminant analysis, and potential functional distributions of microbiomes were predicted using PICRUST2 (v2.3.0-b) software. Results: Groups R and NR did not differ significantly in sex, age, body mass index, smoking history, tumor location, cTNM stage before NACT, and neoadjuvant chemotherapy (all P>0.05), whereas tumor size and ypTNM stage after NACT differed significantly between the two groups (both P=0.001). Alpha and beta diversity analysis of the gastric microbiota did not reveal a statistically significant difference in alpha diversity between the two groups (P>0.05), whereas there was a statistically significant difference in beta diversity between the two groups (P=0.004). Four family-level bacterial taxa, namely Coriobacteriaceae, Ruminococcaceae, Veillonellaceae, and Lachnospiraceae, were enriched in the R group, whereas four bacterial taxa dominated by phylum Proteobacteria were enriched in the NR group. Metabolic pathways of various amino acids, including citric acid cycle and alanine, were found to be potentially predictive. Conclusions: There are significant differences in the abundance and composition of gastric microecology in gastric cancer patients with different responses to NACT.

Author Correction: Intravenous N-acetylcysteine in respiratory disease with abnormal mucus secretion.

Eur Rev Med Pharmacol Sci 2023; 27 (11): 5119-5127-DOI: 10.26355/eurrev_202306_32628-PMID: 37318485, published online on June 13, 2023. After publication, the authors have found some mistakes. This erratum corrects the following: In Figure 1, "4 withdrawal" has been corrected into "7 withdrawal" and "95 completed study" has been corrected into "97 corrected study" In the "Efficacy" paragraph at page 5123, "1.0 in the placebo group" has been corrected into "-1.0 in the placebo group". The legend of Table V has been corrected as follows: Table V. Published clinical studies of the mucolytic and expectorant efficacy of IV NAC in respiratory diseases. In Table V, the data regarding the Treatment groups (duration) by Grassi et al5 have been corrected as follows: NAC oral 200 mg TID NAC IM 300 mg BID NAC IV 500 mg OD (6 days) In Table V, the data regarding the Treatment groups (duration) by Henneghien et al8 have been corrected as follows: NAC oral 200 mg TID NAC IV 300 mg TID (3-10 days) NAC IV 500 mg BID (12 days) There are amendments to this paper. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/32628.

[Annual review of bronchiectasis research in 2023].

This review focuses on the latest advances in bronchiectasis from October 1st, 2022 to September 30th, 2023, including the etiology, diagnosis, treatment, comorbidities, and management of bronchiectasis in order to provide a reference in clinical diagnosis and treatment, and future research of bronchiectasis for domestic peers.

[Patient-reported outcomes of locally advanced gastric cancer undergoing robotic versus laparoscopic gastrectomy: a randomized controlled study].

Objective: To compare the patient-reported outcomes and short-term clinical outcomes between robotic-assisted and laparoscopic-assisted radical gastrectomy for locally advanced gastric cancer. Methods: This single-center prospective randomized controlled trial was conducted in the Department of Gastrointestinal Surgery,Affiliated Hospital of Qingdao University from October 2020 to August 2022. Patients with locally advanced gastric cancer who were to undergo radical gastrectomy were selected and randomly divided into two groups according to 1∶1, and received robotic surgery and laparoscopic surgery, respectively. Patient-reported outcomes and short-term clinical outcomes (including postoperative complications, surgical quality and postoperative short-term recovery) were compared between the two groups by t test, Mann-Whitney U test, repeated ANOVA, generalized estimating equation, χ2 test and Fisher's exact test. Results: A total of 237 patients were enrolled for modified intention-to-treat analysis (120 patients in the robotic group, 117 patients in the laparoscopic group). There were 180 males and 59 females, aged (63.0±10.2) years (range: 30 to 85 years). The incidence of postoperative complications was similar between the robotic group and laparoscopic group (16.7% (20/120) vs. 15.4% (18/117), χ2=0.072, P=0.788). The robotic group had higher patient-reported outcomes scores in general health status, emotional, and social domains compared to the laparoscopic group, differences in time effect, intervention effect, and interaction effect were statistically significant (general health status: χ2 value were 275.68, 3.91, 6.38, P value were <0.01, 0.048, 0.041; emotional: χ2 value were 77.79, 6.04, 6.15, P value were <0.01, 0.014, 0.046; social: χ2 value were 148.00, 7.57, 5.98, P value were <0.01, 0.006, 0.048). However, the financial burden of the robotic group was higher, the differences in time effect, intervention effect and interaction effect were statistically significant (χ2 value were 156.24, 4.08, 36.56, P value were<0.01, 0.043,<0.01). Conclusion: Compared to the laparoscopic group, the robotic group could more effectively relieve postoperative negative emotions and improve recovery of social function in patients.

Assessing hydrological connectivity for natural-artificial catchment with a new framework integrating graph theory and network analysis.

Anthropogenic activities alter the underlying surface conditions and arrangements of landscape features in a drainage basin, interfering with the pollutant (e.g., dissolved nitrogen, phosphorus) transport network configuration and altering the hydrological response. Assessing the impact of anthropogenic activities on hydrological connectivity for natural-artificial catchment is critical to understand the hydrological-driven ecosystem processes, services and biodiversity. However, quantifying this impact at catchment scale remains challenging. In this study, a new framework was proposed to quantify the impact of anthropogenic activities on hydrological connectivity combined with graph theory and network analysis. This framework was exemplified in a natural-artificial catchment of the Yangtze River basin of China. Based on remote sensing and field-investigated data, three transport networks were constructed, including natural transport network (N1), ditch-road transport network (N2), and terrace-dominated transport network (N3), which reflected the different human intervention. The results showed that human intervention improved the connectivity of the nodes and enhanced the complexity of the catchment transport network structure. Anthropogenic activities significantly decreased the hydrological structural connectivity of the catchment. In particular, compared with the N1 network, the critical nodes for hydrological connectivity which were judged by connectivity indexes were reduced by 92.94% and 95.29% in the N2 and N3 network, respectively. Furthermore, the ditch-road construction had a greater impact than terraces in decreasing hydrological structural connectivity at catchment scale. This framework has proven effective in quantifying the hydrological connectivity analysis under different human intervention at the catchment scale and facilitates the improvement of catchment management strategies.

[Safety and efficacy analysis of endovascular thrombectomy in patients with large vascular occlusion with low Alberta Stroke Program Early Computed Tomography Score].

Objective: To evaluate the safety and efficacy of endovascular thrombectomy (EVT) in acute anterior circulation large vessel occlusive stroke (ALVOS) and explore the related influencing factors for prognoses in patients with low Alberta Stroke Program Early Computed Tomography Score (ASPECT). Methods: Patients with acute ALVOS who underwent EVT in Yijishan Hospital of Wannan Medical College from January 2019 to June 2022 were sequentially enrolled. (1) Patients were divided into a low ASPECT group (0-5) and a non-low ASPECT group (6-10), and the differences between the two groups were compared with respect to incidence of perioperative complications and good prognosis rate [modified Rankin scale (mRS) score≤2] 90 days after onset. (2) According to the prognoses 90 days after onset, the low ASPECT group was divided into the good prognosis (mRS score≤2) and poor prognosis (mRS score>2) subgroup. Univariate analysis and multivariate logistic regression analysis were used to investigate the independent risk factors for prognoses of the low ASPECT patients after EVT. Results: A total of 582 patients [age 26-94(69±11) years, 345 male patients (59.3%)] were enrolled for analysis. The baseline ASPECT score was 8 (7, 10), and the baseline NIHSS score was 14 (11, 18). Among them, 102 (17.5%) patients were in the low ASPECT score group and 480 (82.5%) patients were in the non-low ASPECT score group. In the total cohort, patients in the low ASPECT score group had a higher incidence of symptomatic intracranial hemorrhage, lower 90-day good prognosis rate, and higher 90-day mortality rate. Further, propensity score matching statistical analysis showed that patients in the low ASPECT score group had a significantly higher incidence of malignant brain edema after EVT treatment (40.0% vs. 17.6%, χ2=9.13, P=0.003), and a significantly lower 90-day good prognosis rate (24.7% vs. 41.6%, χ2=4.96, P=0.026), but there was no significant difference in the incidence of symptomatic intracranial hemorrhage and 90-day mortality between the two groups (40.3% vs. 26.0%, χ2=3.55, P=0.060). Among 102 patients with low ASPECT score, 22 (21.6%) patients had good prognosis and 80 (78.4%) had poor prognosis. Multivariate logistic regression analysis showed that history of atrial fibrillation (OR=4.478, 95%CI 1.186-16.913, P=0.027) was an independent risk factor for poor prognosis of EVT in patients with low ASPECT score, while good collateral circulation (grade 2 vs. grade 0: OR=0.206, 95%CI 0.051-0.842, P=0.028) was a protective factor for good prognosis of EVT in patients with low ASPECT score. Conclusions: Although the 90-day good prognosis rate of EVT treatment for patients with low ASPECT score was lower than that of the non-low ASPECT group, 21.6% patients still benefitted from EVT treatment, especially patients with non-atrial fibrillation and good collateral circulation. Future studies involving more patients are needed to validate our observations.

Heating, ventilation, and air-conditioning systems in healthcare: a scoping review.

Guidelines for heating, ventilation, and air-conditioning systems have been developed for different settings. However, there is a lack of up-to-date evidence providing concrete recommendations for the heating, ventilation, and air-conditioning systems of an isolation room, which is essential to appropriately guide infection control policies. To highlight the guidelines for heating, ventilation, and air-conditioning systems in isolation rooms to inform relevant stakeholders and policymakers. A systematic search was performed based on Joanna Briggs Methodology using five databases (CINAHL, Embase, Joanna Briggs Institute, Medline, and Web of Science) and websites. Eight articles published by government departments were included in this review. Most studies recommended controlled airflow without recirculation, 12 air changes per hour, high-efficiency particulate air filtrate to exhaust contaminated air from the airborne isolation room, humidity ≤60%, and temperature in the range of 18-30 °C. This review provides further evidence that there is a need for interdisciplinary collaborative research to quantify the optimum range for heating, ventilation, and air conditioning system parameters, considering door types, anterooms, and bed management, to effectively reduce the transmission of infection in isolation rooms.

Intravenous N-acetylcysteine in respiratory disease with abnormal mucus secretion.

OBJECTIVE: Evidence for the mucolytic and expectorant efficacy of intravenous (IV) N-acetylcysteine (NAC) is limited. This study aimed to evaluate in a large, multicenter, randomized, controlled, subject, and rater-blinded study whether IV NAC is superior to placebo and non-inferior to ambroxol in improving sputum viscosity and expectoration difficulty. PATIENTS AND METHODS: A total of 333 hospitalized subjects from 28 centers in China with respiratory disease (such as acute bronchitis, chronic bronchitis and exacerbations, emphysema, mucoviscidosis, and bronchiectasis) and abnormal mucus secretion were randomly allocated in a 1:1:1 ratio to receive NAC 600 mg, ambroxol hydrochloride 30 mg, or placebo as an IV infusion twice daily for 7 days. Mucolytic and expectorant efficacy was assessed by ordinal categorical 4-point scales and analyzed by stratified and modified Mann-Whitney U statistics. RESULTS: NAC showed consistent and statistically significant superiority to placebo and non-inferiority to ambroxol in change from baseline to day 7 in both sputum viscosity scores [mean (SD) difference 0.24 (0.763), p<0.001 vs. placebo] and expectoration difficulty score [mean (SD) difference 0.29 (0.783), p=0.002 vs. placebo]. Safety findings confirm the good tolerability profile of IV NAC reported from previous small studies, and no new safety concerns were identified. CONCLUSIONS: This is the first large, robust study of the efficacy of IV NAC in respiratory diseases with abnormal mucus secretion. It provides new evidence for IV NAC administration in this indication in clinical situations where the IV route is preferred.

[Clinical follow-up analysis of multidisciplinary treatment of children with spinal muscular atrophy].

Objective: To analyze the follow-up and clinical effect of multidisciplinary treatment on the children with spinal muscular atrophy (SMA). Methods: The clinical data including nutritional status, respiratory function, bone health and motor function of 45 children with SMA who received multidisciplinary management 1-year follow-up in the Children's Hospital, Zhejiang University School of Medicine from July 2019 to October 2021 were retrospectively collected. Comparisons before and after management were performed using paired-samples t-test or Wilcoxon rank-sum test, etc. Results: The age of 45 patients (25 boys and 20 girls) was 50.4 (33.6, 84.0) months at the enrollment, with 6 cases of type 1, 22 cases of type 2, and 17 cases of type 3 respectively. After the multidisciplinary management, the cases of SMA patients with malnutrition decreased from 22 to 12 (P=0.030), the level of vitamin D were significantly increased ((45±17) vs. (48±14) nmol/L, t=-4.13, P<0.001). There was no significant difference in the forced vital capacity %pred, the forced expiratory volume at 1 second %pred, and the peak expiratory flow %pred ((76±19)% and (76±21)%, (81±18)% and (79±18)%, (81±21)% and (78±17)%; t=-0.24, 1.36, 1.21; all P>0.05). The Cobbs angle of scoliosis also improved significantly (8.0°(0°, 13.0°) vs. 10.0°(0°, 18.5°), Z=-3.01, P=0.003). The Hammersmith functional motor scale expanded scores of children with SMA type 2 and type 3 both showed significant elevation (11.0 (8.0, 18.0) vs. 11.0 (5.0, 18.5) scores, 44.0 (36.5, 53.0) vs. 44.0 (34.0, 51.5) scores, Z=2.44, 3.11, P=0.015, 0.002). Conclusion: Multidisciplinary management is beneficial for delaying the progression of the multi-system impairments of SMA patients, such as malnutrition, restrictive ventilation dysfunction and scoliosis.

[Association between metabolic risk factors and the hepatitis B reactivation of inactive HBsAg carriers in Jiangsu province: a cohort study].

Objective: To analyze the impact of metabolic risk factors on the epidemiological characteristics of the reactivation of inactive HBsAg carriers (IHC) and provide effective intervention measures to standardize the management of chronic hepatitis B infections. Methods: Based on the chronic hepatitis B infection cohort established in 2010 in Jiangsu province, six follow-up visits from 2012 to 2020 were conducted to analyze the characteristics and influencing factors of the hepatitis B reactivation of IHC and the impact of metabolic risk factors, including obesity, high blood pressure, diabetes and hyperglycemia. Results: From 2012 to 2020, 2 527 IHC and 17 730 person-years were observed during a median follow-up period of 7.0 person-years. Ninety-eight cases of hepatitis B reactivation, with a cumulative reaction rate, was 3.9%, and the incidence density was 5.53/1 000 person-years. Multivariate Cox proportional risk regression analysis showed that age and baseline HBV DNA were independent risk factors of HBV reactivation. Compared with the patients ≥60 years, 40-49 age group (aHR=2.16, 95%CI:1.20-3.90) and 20-29 age group (aHR=5.48, 95%CI:2.07-14.48) were significantly associated with hepatitis B reactivation. Compared with the HBV DNA negative patients at baseline, the risk of hepatitis B reactivation was higher in the group with low HBV DNA level 100-1 999 IU/ml (aHR=1.67, 95%CI:1.11-2.52). Stratification analysis results showed that compared with those without metabolic risk factors, in the ≥50 age group, patients with ≥2 metabolic risk factors showed adjusted HR of 2.73 (95%CI:1.08-6.96). Conclusions: The risk of hepatitis B being reactive is the persistent existence of IHC in communities in Jiangsu province, especially young adults, low-level HBV DNA carriers, and IHC with ≥2 metabolic risk factors. Follow-up for these IHC should be strengthened to reduce the risk of disease progression by antiviral treatment at the right time.

[IL-1ß inhibitor sensitizes to olaparib in homologous recombination deficiency proficient ovarian cancer cells].

Objective: To investigate the inhibitory effect of combined strategy of poly adenosine diphosphate ribose polymerase (PARP) inhibitor and interleukin-1ß (IL-1ß) inhibitor on homologous recombination deficiency (HRD)-proficient ovarian cancer cells. Methods: (1) HRD-proficient ovarian cancer cell lines OVCAR3 and CAOV3 were treated with PARP inhibitor olaparib. Screening by RNA sequencing analysis, the expression level of IL-1ß was validated by enzyme-linked immunosorbent assay (ELISA) and western blot. (2) The dose-response curves of IL-1ß inhibitor diacerein were evaluated by cell counting kit-8 (CCK-8) assays in OVCAR3 and CAOV3 cells. CCK-8 assays were further applied to determine the viabilities of OVCAR3 and CAOV3 cells. (3) To evaluate the synergistic effects of olaparib and IL-1ß inhibitor in vivo, the transplanted ovarian cancer model was constructed. BALB/c-nude mice (n=16) were injected intraperitoneally with 1×107 OVACR3 cells labelled with luciferase (OVCAR3-Luc). Immunohistochemistry (IHC) assay was performed to determine nuclear antigen associated with cell proliferation (Ki-67) expression. (4) Blood routine tests, kidney and liver function tests were performed to analyze the toxic reaction of different drug treatments. The potential drug-induced injuries of vital organs including heart, liver, spleen, lungs and kidneys of nude mice were determined by hematoxylin-eosin (HE) staining. Results: (1) The RNA sequencing results showed that the mRNA level of IL-1ß was the most significantly increased among the 25 differentially expressed genes in OVCAR3 cells treated with olaparib, compared to the negative control group. Olaparib treatment significantly promoted the secretion and expression of IL-1ß protein in both OVACR3 and CAOV3 cells by ELISA [(36.2±3.5) and (49.5±3.5) pg/ml, respectively; all P<0.001] and western bolt (2.87±0.37 and 2.05±0.08, respectively; all P<0.01). (2) The half maximal inhibitory concentration (IC50) value of IL-1ß inhibitor was determined as follows: 75 µmol/L for OVACR3 cells and 100 µmol/L for CAOV3 cells. The treatments were divided into four groups including control group, olaparib monotherapy group, IL-1ß inhibitor monotherapy group and the combination therapy group. The cell viabilities of each group in OVCAR3 and CAOV3 were determined by CCK-8 assay. The data in each group were showed as follows for OVCAR3 and CAOV3 cells: (100.0±0.4)% and (100.0±3.5)% in control group; (63.1±6.2)% and (63.3±3.8)% in olaparib monotherapy group; (61.6±4.7)% and (63.8±3.5)% in IL-1ß inhibitor monotherapy group; and (32.9±5.2)% and (30.0±1.3)% in the combination therapy group. The viability assay showed that the combined strategy exhibited a significant inhibition effect on OVACR3 and CAOV3 cells, compared to the monotherapy group and the control group (all P<0.01). (3) All mice with transplanted tumors of HRD-proficient ovarian cancer cells were randomly divided into four groups, and treated with four different treatments as mentioned above, respectively. After 4 weeks (on day 29), the vivo fluorescence imaging were determined. The results showed that the amount of fluorescence of transplanted tumors was mostly decreased in the combination therapy group [(0.5±0.4)×1010 p/s], compared to the control group [(4.2±1.0)×1010 p/s] or the groups treated with any single drug [(3.1±0.9)×1010, (2.2±0.9)×1010 p/s; all P<0.05]. Mice were then sacrificed under anesthesia, and all transplanted tumors detached and weighed for further investigation. The weight of transplanted tumors was significantly decreased in the combination therapy group [(0.09±0.03) g], compared to that in control group [(0.25±0.05) g] or groups treated with any single drug [(0.17±0.03), (0.19±0.04) g; all P<0.05]. The measurement of the expression of Ki-67 showed that it was significantly decreased in the combination therapy group (0.33±0.10), compared to that in the control group (1.00±0.20) or monotherapy groups (0.76±0.07, 0.77±0.12; all P<0.05). (4) There were no significant differences of body weights, blood routine test, renal and liver function tests among mice with different treatments (all P>0.05). Moreover, no significant injuries were observed in the vital organs among the four groups. Conclusions: The combination of olaparib and IL-1ß inhibitor synergistically exhibits significant cytotoxicity in HRD-proficient ovarian cancer cells. Moreover, the blood routine and blood biochemistry results confirmed the biosafety of the combination of olaparib and IL-1ß inhibitor.

[Annual review of bronchiectasis in 2021].

Bronchiectasis, a common chronic respiratory disease, is characterized by irreversible and abnormal bronchial dilatation due to multiple causes. In 2021, a series of significant research progress have been made in bronchiectasis, focusing on the mechanism, diagnosis, clinical phenotypes, treatment, comorbidities, etc. Several studies have shown that many mediators are involved in the pathogenesis of bronchiectasis, such as lipids, platelets, and respiratory microorganisms, providing new insights into the development of prevention and therapy targets of bronchiectasis. At the same time, an international expert consensus proposed radiological and clinical diagnosis criteria for inclusion of bronchiectasis patients in clinical trials. Moreover, the proposal of new phenotype, measurement tools and predictors on bronchiectasis, promote the process of individualized therapy for patients. Regarding the clinical trials on bronchiectasis, several important studies have been published, including tobramycin inhalation powder, airway clearance techniques, tiotropium bromide and so forth. In addition, researches on bronchiectasis comorbidities also have new findings. This review summarized the recent published literatures in order to help clinicians better understand bronchiectasis.

[Lipid metabolism in idiopathic pulmonary fibrosis].

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease of unknown etiology, which was characterized by irreversible lung function decrease and high mortality. Up till now, only two drugs, i.e. Pirfenidone and Nintedanib,have been approved by Food and Drug Administration (FDA) for therapy of IPF, and the treatment is less effective. Therefore, it is urgent to develop new therapeutic drugs. In recent years, studies had paid attention to lipid metabolism in IPF. In this review, we discussed recent major advances of lipid metabolism, biomarkers and clinical trials in IPF.

Pharmacokinetics of HupA-PLGA-NPs of different sizes in the mouse blood and brain determined by LC-MS/MS.

OBJECTIVE: Huperzine A, which was extracted from a Chinese herb, is a reversible and selective inhibitor of acetylcholinesterase (AChE), which is used as an anti-Alzheimer's drug that exerts evident pretreatment effects against exposure to organophosphate chemical warfare agents or pesticides. The aims of this study were to establish an LC-MS/MS method for the detection of HupA in biological samples and to investigate the pharmacokinetics of HupA polylactic-co-glycolic acid nanoparticles (HupA-PLGA-NPs) with different diameters in mice. MATERIALS AND METHODS: The proposed LC-MS/MS method was established by optimizing the MS conditions and validating the specificity, linear range, lower limit, precision, accuracy, matrix effects, absolute recovery, and sample stability of the method. ICR mice were divided into three treatment groups: the HupA control group, the 46.4-nm HupA-PLGA-NP group and the 208.5-nm HupA-PLGA-NP group. All the mice in the three groups were administered 0.5 mg/kg HupA via the tail vein. The pharmacokinetic parameters in plasma and the brain were detected by LC-MS/MS. Pharmacokinetic parameters were analyzed using PKS pharmacokinetic software, and the relative bioavailability and brain-targeted drug targeting efficiency (DTE) were also calculated. RESULTS: The distributions of HupA-PLGA-NP groups showed marked changes compared with that of HupA in mice in vivo, and the particle size of nanodrugs exerted a significant effect on the pharmacokinetic parameters in mice. The half-life (T1/2) values in plasma of the 46.4- and 208.5-nm HupA-PLGA-NPs were 1.53- and 1.96-fold longer than that of the HupA at the same dose. The bioavailabilities of the two nanoparticles were 1.93- and 2.19-fold higher than that of HupA, respectively. In the brain, the Tmax values of the two HupA-PLGA-NPs of different sizes was 1.25 h, which was clearly longer than that of HupA (0.5 h), and the corresponding T1/2 values were 12.53 h and 8.47 h, which were 1.82- and 1.23-fold higher than that of HupA (6.89 h). In addition, the brain targeting index of the 46.40-nm HupA-PLGA-NPs was 1.48, which revealed an evident brain-targeting effect. CONCLUSIONS: The LC-MS/MS method has the advantages of good specificity, high sensitivity and needing a low sample amount and is economical and particularly suitable for determining the drug content in plasma and brain samples. The NP size is associated with the distribution patterns of nanodrugs. Therefore, a particular NP size can be selected to maximize the pharmacodynamics effects and control the toxicity of nanodrugs.

[The effects of robotic-assisted versus laparoscopic-assisted radical right hemicolectomy on short-term outcome and long-term prognosis based on propensity score matching].

Objective: To compare the short-term and long-term outcomes between robotic-assisted and laparoscopic-assisted radical right hemicolectomy in patients with adenocarcinoma of the right colon. Methods: Retrospective review of a prospectively collected database identified 288 right colon cancer patients who underwent either robotic-assisted (n=57) or laparoscopic-assisted right hemicolectomy (n=231) between October 2014 and October 2020 at Department of Gastrointestinal Surgery, the Affiliated Hospital of Qingdao University. There were 161 males and 127 females, aging (60.3±12.8) years (range: 17 to 86 years). After propensity score matching as 1∶4 between robotic-assisted and laparoscopic-assisted right hemicolectomy, there were 56 cases in robotic group and 176 cases in laparoscipic group. Perioperative outcomes and overall survival were compared between the two groups using t test, Wilcoxon rank sum test, χ2 test, Fisher exact test, Kaplan-Meier method and Log-rank test, respectively. Results: The total operative time was similar between the robotic and laparoscopic group ((206.9±60.7) minutes vs. (219.9±56.3) minutes, t=-1.477, P=0.141). Intraoperative bleeding was less in the robotic group (50 (20) ml vs. 50 (50) ml, Z=-4.591, P<0.01), while the number of lymph nodes retrieved was significantly higher (36.0±10.0 vs. 29.0±10.1, t=4.491, P<0.01). Patients in robotic group experienced significantly shorter hospital stay, shorter time to first flatus, and defecation (t: -2.888, -2.946, -2.328, all P<0.05). Moreover, the overall peri-operative complication rate was similar between robotic and laparoscopic group (17.9% vs. 22.7%, χ²=0.596,P=0.465). The 3-year overall survival were 92.9% and 87.9% respectively and the 3-year disease-free survival rates were 83.1% and 82.6% with no statistical significance between the robotic and laparoscopic group (P>0.05). Conclusions: Compared to laparoscopic-assisted right hemicolectomy, robot-assisted right hemicolectomy could improve some short-term clinical outcomes. The two procedures are both achieving comparable survival.