Effects of positive end-expiratory pressure on regional cerebral oxygen saturation in elderly patients undergoing thoracic surgery during one-lung ventilation: a randomized crossover-controlled trial.

BACKGROUND: A significant reduction in regional cerebral oxygen saturation (rSO2) is commonly observed during one-lung ventilation (OLV), while positive end-expiratory pressure (PEEP) can improve oxygenation. We compared the effects of three different PEEP levels on rSO2, pulmonary oxygenation, and hemodynamics during OLV. METHODS: Forty-three elderly patients who underwent thoracoscopic lobectomy were randomly assigned to one of six PEEP combinations which used a crossover design of 3 levels of PEEP-0 cmH2O, 5 cmH2O, and 10 cmH2O. The primary endpoint was rSO2 in patients receiving OLV 20 min after adjusting the PEEP. The secondary outcomes included hemodynamic and respiratory variables. RESULTS: After exclusion, thirty-six patients (36.11% female; age range: 60-76 year) were assigned to six groups (n = 6 in each group). The rSO2 was highest at OLV(0) than at OLV(10) (difference, 2.889%; [95% CI, 0.573 to 5.204%]; p = 0.008). Arterial oxygen partial pressure (PaO2) was lowest at OLV(0) compared with OLV(5) (difference, -62.639 mmHg; [95% CI, -106.170 to -19.108 mmHg]; p = 0.005) or OLV(10) (difference, -73.389 mmHg; [95% CI, -117.852 to -28.925 mmHg]; p = 0.001), while peak airway pressure (Ppeak) was lower at OLV(0) (difference, -4.222 mmHg; [95% CI, -5.140 to -3.304 mmHg]; p < 0.001) and OLV(5) (difference, -3.139 mmHg; [95% CI, -4.110 to -2.167 mmHg]; p < 0.001) than at OLV(10). CONCLUSIONS: PEEP with 10 cmH2O makes rSO2 decrease compared with 0 cmH2O. Applying PEEP with 5 cmH2O during OLV in elderly patients can improve oxygenation and maintain high rSO2 levels, without significantly increasing peak airway pressure compared to not using PEEP. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2200060112 on 19 May 2022.

Hollow CoZnSe@CN nanocage with enzymatic activity for determination of tetracycline using smartphone platforms and virtual reality revealing.

Antibiotic residues in the environment pose a serious threat to ecosystems and human health. Therefore, it is important to develop sensitive and rapid in situ detection methods. In this work, the designed nanozymes, with excellent four enzyme activities, were proved to be constituted of unique hollow nanocage structures (CoZnSe@CN HCs). Based on the peroxidase-like enzymes, a portable colorimetric sensor was constructed for the on-site determination of tetracycline (TC) in real samples. The linear range of TC detection was 0.1-100 µM, and the detection limit was 0.02 µM. At the same time, colorimetric detection and smartphones have also been combined for on-site colorimetric detection of TC. In-depth exploration of the detection mechanism showed that TC could be bound with the material, inhibiting the production of oxidized 3,3',5,5'-tetramethylbenzidine. The sensor was also used for the detection of TC in environmental soil and water samples. This study can provide an intelligent detection method for environmental monitoring.

Safety and Efficacy of OGT-Assisted Overlap Oesophagojejunostomy Versus the Traditional Overlap Method in Laparoscopic Total Gastrectomy for Gastric/Gastroesophageal Junction (G/GEJ) Tumours.

INTRODUCTION: Overlap guiding tube (OGT)-assisted overlap oesophagojejunostomy (EJS), which was first designed and reported by our team, has shown feasibility. However, its safety and efficiency have not yet been compared with the conventional overlap approach. METHODS: We retrospectively analysed the data of 155 gastric/gastroesophageal junction (G/GEJ) cancer patients who underwent laparoscopic total gastrectomy by conventional (conventional group, n = 83) or OGT-assisted (OGT group, n = 72) overlap methods at Nanfang Hospital. The anastomotic efficiency and surgical outcomes were compared between the two groups. RESULTS: The success rate of inserting an anvil fork into the oesophageal lumen at the first attempt in the OGT group was much higher than in the conventional group (86.7% vs. 97.2%, P = 0.019). Consistently, the duration of EJS (P < 0.001) in the OGT group was significantly shorter than that in the conventional group. Operatively, there was one case in which oesophageal pseudocanals developed; another case was converted to thoracoscopic surgery in the conventional group, but there were no such cases in the OGT group. In terms of postoperative recovery, the OGT group was superior to the conventional group. The incidence of postoperative complications (28.9% vs. 20.8%, P = 0.247) and the classification of complication severity (P = 0.450) were milder in the OGT group, although the difference was not statistically significant. Notably, the conventional group had four cases (4.8%) of oesophagojejunal anastomotic leakage (EJAL) and one case (1.2%) of anastomotic stenosis. In the OGT group, two patients (2.8%) developed EJAL, but none developed anastomotic stenosis or anastomotic bleeding. Neither group had any cases of unplanned secondary surgery or perioperative deaths. CONCLUSIONS: The OGT-assisted method reduced the surgical difficulty of overlap EJS with good safety. This study provides new perspectives for optimizing EJS.

Who consumes curative care expenditure of medical institutions in Beijing: a case study based on System of Health Accounts 2011.

BACKGROUND: China's health system is challenged by complex health problems experienced by different population groups and caused by multiple diseases. This study examined the distribution of curative care expenditure (CCE) of medical institutions in Beijing using beneficiary characteristics such as residency, gender, age, and disease. Suggestions are presented for the development of health policies. METHODS: A total of 81 medical institutions with approximately 80 million patients in Beijing, China, were selected via a multistage stratified cluster random sampling approach. Based on this sample, the System of Health Accounts 2011 was used to estimate the CCE of medical institutions. RESULTS: The CCE of medical institutions in Beijing was ¥246.93 billion in 2019. The consumption of patients from other provinces was ¥60.04 billion, accounting for 24.13% of the total CCE. The CCE of female consumption (52.01%/¥128.42 billion) exceeded that of male consumption (47.99%/¥118.51 billion). Almost half of the CCE (45.62%/¥112.64 billion) was consumed by patients aged 60 or above. Adolescent patients up to an age of 14 (including those aged 14) mainly chose secondary or tertiary hospitals for treatment. Chronic non-communicable diseases accounted for the largest share of CCE consumption, with circulatory diseases accounting for the highest proportion. CONCLUSIONS: This study identified significant differences in CCE consumption in Beijing according to region, gender, age, and disease. Currently, the utilization of resources in medical institutions is not reasonable, and the hierarchical medical system is not sufficiently effective. Therefore, the government needs to optimize the allocation of resources according to the needs of different groups and rationalize the institutional process and functions.

Medical insurance payment schemes and patient medical expenses: a cross-sectional study of lung cancer patients in urban China.

BACKGROUND: As the main cause of cancer death, lung cancer imposes seriously health and economic burdens on individuals, families, and the health system. In China, there is no national study analyzing the hospitalization expenditures of different payment methods by lung cancer inpatients. Based on the 2010-2016 database of insured urban resident lung cancer inpatients from the China Medical Insurance Research Association (CHIRA), this paper aims to investigate the characteristics and cost of hospitalized lung cancer patient, to examine the differences in hospital expenses and patient out-of-pocket (OOP) expenses under four medical insurance payment methods: fee-for-service (FFS), per-diem payments, capitation payments (CAP) and case-based payments, and to explore the medical insurance payment method that can be conducive to controlling the cost of lung cancer. METHOD: This is a 2010-2016, 7-year cross-sectional study. CHIRA data are not available to researchers after 2016. The Medical Insurance Database of CHIRA was screened using the international disease classification system to yield 28,200 inpatients diagnosed with lung cancer (ICD-10: C34, C34.0, C34.1, C34.2, C34.3, C34.8, C34.9). The study includes descriptive analysis and regression analysis based on generalized linear models (GLM). RESULTS: The average patient age was 63.4 years and the average length of hospital stay (ALOS) was 14.2 day; 60.7% of patients were from tertiary hospitals; and 45% were insured by FFS. The per-diem payment had the lowest hospital expenses (RMB7496.00/US$1176.87), while CAP had the lowest OOP expenses (RMB1328.18/US$208.52). Compared with FFS hospital expenses, per-diem was 21.3% lower (95% CI = -0.265, -0.215) and case-based payment was 8.4% lower (95% CI = -0.151, -0.024). Compared with the FFS, OOP expenses, per-diem payments were 9.2% lower (95% CI = -0.130, -0.063) and CAP was 15.1% lower (95% CI = -0.151, -0.024). CONCLUSION: For lung cancer patients, per-diem payment generated the lowest hospital expenses, while CAP meant patients bore the lowest OOP costs. Policy makers are suggested to give priority to case-based payments to achieve a tripartite balance among medical insurers, hospitals, and insured members. We also recommend future studies comparing the disparities of various diseases for the cause of different medical insurance schemes.

A dandelion-like nanomedicine via hierarchical self-assembly for synergistic chemotherapy and photo-dynamic cancer therapy.

The synergistic effect of chemotherapy and photo-dynamic therapy (PDT) is an effective way to improve the efficiency of tumor treatment. However, most synergistic therapeutic drugs have poor water solubility and stability, so it is difficult to achieve high therapeutic effects while avoiding the severe side effects. Herein, a unique dandelion-like nanomedicine (named as cRGDfk-CCPT-mCe6) was successfully synthesized using Ce6-loaded amphiphilic ß-cyclodextrins (ß-CD) doped lipid-based vesicles as the core (receptacle) and ß-CD modified camptothecin (CPT) pro-drug as the flyable dandelion seeds. The ß-CD modified CPT pro-drug was introduced into the core vesicles in succession via host-guest interaction between inter-molecular ß-CD and CPT, and cRGDfk peptides were further introduced as the outermost layer (stigma) to enhance the internalization into cancer cells. CPT interacted with ß-CD through glutathione (GSH)-cleavable disulfide bonds, which led to drug release in glutathione-rich cancer cells, just as spread of dandelion seeds in the wind. GSH consumption further disrupted the intracellular redox homeostasis of cancer cells through combined action of Ce6 with light irradiation and the synergistic anti-tumor effect was thus achieved, resulting in apoptosis of cancer cells. Therefore, the nanomedicine provides a facile and versatile anti-tumor strategy, as well as a persistent anti-cancer effects.

Impact of preoperative therapy on surgical outcomes of laparoscopic total gastrectomy for gastric/gastroesophageal junction cancer.

Objective: As laparoscopic surgery is widely applied for primarily treated gastric cancer (GC)/gastroesophageal junction cancer (GEJC) and gains many advantages, the feasibility of laparoscopic total gastrectomy (LTG) for GC/GEJC patients who have received preoperative therapy (PT) has come to the fore. This study aims to analyze the safety and feasibility of LTG after PT for GC/GEJC patients. Methods: We retrospectively analyzed the data of 511 patients with GC/GEJC undergoing LTG, of which 405 received LTG (LTG group) and 106 received PT+LTG (PT-LTG group) at Nanfang Hospital between June 2018 and September 2022. The surgical outcomes were compared between the two groups. Results: The surgical duration was significantly longer in the PT-LTG group (P<0.001), while the incidence of intraoperative complications (P=1.000), postoperative complications (LTG group vs. PT-LTG group: 26.2% vs. 23.6%, P=0.587), the classification of complication severity (P=0.271), and postoperative recovery was similar between two groups. Notably, the incidence of anastomotic complications of esophagojejunostomy was also comparable between the two groups (LTG group vs. PT-LTG group: 5.9% vs. 5.7%, P=0.918). The univariate and multivariate analysis confirmed that positive proximal margin [positive vs. negative: odds ratio (OR)=14.094, 95% confidence interval (95% CI): 2.639-75.260, P=0.002], rather than PT, has an impact on anastomotic complications after LTG (OR=0.945, 95% CI: 0.371-2.408, P=0.905). Conclusions: PT did not increase the surgical risk of LTG for GC/GEJC. Therefore, considering the positive effect of PT on long-term survival, the broader application of PT and LTG for GC/GEJC is supported by our findings.

Association of peripheral basophils with tumor M2 macrophage infiltration and outcomes of the anti-PD-1 inhibitor plus chemotherapy combination in advanced gastric cancer.

BACKGROUND: Although the anti-programmed death-1 (PD-1) inhibitor plus chemotherapy combination has been approved as the standard first-line treatment for advanced gastric cancer, a proportion of patients do not significantly benefit from this therapy. Who would respond poorly to this treatment and the underlying mechanisms of treatment failure are far from clear. METHODS: We retrospectively analyzed the associations between the peripheral basophils at baseline and clinical outcomes in 63 advanced gastric cancer patients treated with anti-PD-1 plus chemotherapy and 54 patients treated with chemotherapy alone. Immunohistochemistry and immunofluorescence staining in gastric cancer samples were utilized to investigate the basophil-related immunophenotype. RESULTS: The optimal cutoff of basophil count to distinguish responders to anti-PD-1 plus chemotherapy from non-responders was 20.0/µL. Compared with the low basophil group (≤ 20.0/µL, n = 40), the high basophil group (> 20.0/µL, n = 23) had a significantly lower objective response rate (ORR 17.4% vs. 67.5%, p = 0.0001), worse progression-free survival (median PFS 4.0 vs. 15.0 months, p = 0.0003), and worse overall survival (median OS not reached, p = 0.027). Multivariate analyses identified a basophil count of > 20.0/µL as an independent risk factor for a worse ORR (OR 0.040, 95% CI 0.007-0.241, p = 0.0004), worse PFS (HR 3.720, 95% CI 1.823-7.594, p = 0.0003) and worse OS (HR 3.427, 95% CI 1.698-6.917, p = 0.001). In contrast, there was no significant association between peripheral basophil counts and tumor response or survival in the chemotherapy-alone group (p > 0.05). In primary gastric cancer samples, we observed a correlation between higher peripheral basophil counts and the accumulation of tumor-infiltrating basophils (r = 0.6833, p = 0.005). Tumor-infiltrating basophils were found to be spatially proximate to M2 macrophages within TME and positively correlated with tumor M2 macrophage infiltration (r = 0.7234, p = 0.0023). The peripheral basophil counts also had a significant positive correlation with tumor-infiltrating M2 macrophage counts (r = 0.6584, p = 0.003). Further validation in tumor samples treated with the neoadjuvant anti-PD-1 inhibitor plus chemotherapy combination suggests that the peripheral basophils, tumor infiltration of basophils, and M2 macrophages were significantly more abundant in non-responders than in responders (p = 0.0333, p = 0.0007, and p = 0.0066, respectively). CONCLUSIONS: The peripheral basophil count was observed to be a potential biomarker of anti-PD-1 efficacy for advanced gastric cancer. Moreover, basophils may induce an immune-evasive tumor microenvironment by increasing M2 macrophage infiltration, which could be a potential immunotherapeutic target for advanced gastric cancer.

Survival analysis of elderly patients over 65 years old with stage II/III gastric cancer treated with adjuvant chemotherapy after laparoscopic D2 gastrectomy: a retrospective cohort study.

BACKGROUND: The benefits of adjuvant chemotherapy for elderly patients with gastric cancer (GC) remain unknown because elderly patients are underrepresented in most clinical trials. This study aimed to evaluate the effectiveness and complications of adjuvant chemotherapy in patients > 65 years of age after laparoscopic D2 gastrectomy. METHODS: This was a single-center retrospective cohort study of elderly patients (> 65 years) with stage II/III GC who underwent curative laparoscopic D2 gastrectomy with R0 resection between 2004 and 2018. The adjuvant chemotherapy regimens included monotherapy (oral capecitabine) and doublet chemotherapy (oral capecitabine plus intravenous oxaliplatin [XELOX] or intravenous oxaliplatin, leucovorin, and 5-fluorouracil [FOLFOX]). The data were retrieved from a prospectively registered database maintained at the Department of General Surgery in Nanfang Hospital, China. The patients were divided as surgery alone and surgery plus adjuvant chemotherapy (chemo group). The overall survival (OS), disease-free survival (DFS), chemotherapy duration, and toxicity were examined. RESULTS: There were 270 patients included: 169 and 101 in the surgery and chemo groups, respectively. There were 10 (10/101) and six (6/101) patients with grade 3+ non-hematological and hematological adverse events. The 1-/3-/5-year OS rates of the surgery group were 72.9%/51.8%/48.3%, compared with 90.1%/66.4%/48.6% for the chemo group (log-rank test: P = 0.018). For stage III patients, the 1-/3-/5-year OS rates of the surgery group were 83.7%/40.7%/28.7%, compared with 89.9%/61.2%/43.6% for the chemo group (log-rank test: P = 0.015). Adjuvant chemotherapy was significantly associated with higher OS (HR = 0.568, 95%CI: 0.357-0.903, P = 0.017) and DFS (HR = 0.511, 95%CI: 0.322-0.811, P = 0.004) in stage III patients. CONCLUSIONS: This study suggested that adjuvant chemotherapy significantly improves OS and DFS compared with surgery alone in elderly patients with stage III GC after D2 laparoscopic gastrectomy, with a tolerable adverse event profile.

Apatinib induced ferroptosis by lipid peroxidation in gastric cancer.

BACKGROUND: Apatinib, a competitive inhibitor of VEGFR2, has anti-angiogenesis and anticancer activities through different mechanisms, but it still cannot fully explain the drug efficacy of apatinib. Ferroptosis, associated with lethal lipid peroxidation, has emerged to play an important role in cancer biology, however, the exact role of ferroptosis in apatinib-mediating anticancer treatment are still not clear. METHODS: The effects of (1S, 3R)-RSL3 and apatinib were evaluated in different GC cell lines and in normal human gastric epithelial cells. Further, the effects of apatinib and inhibition of antioxidant defense enzyme glutathione peroxidase (GPX4) on cell viability, cell death, glutathione (GSH) levels, lipid ROS production, cellular malondialdehyde (MDA) levels and protein expression were evaluated in vitro as well as in a mouse tumor xenograft model. The expression level of GPX4 in GC tissues and paracancerous tissues was measured by immunohistochemistry. RESULTS: (1S, 3R)-RSL3 selectively killed GC cells, but not normal cells. Apatinib induced ferroptosis in GC cells by decreasing cellular GSH levels and increasing lipid peroxidation levels. This effect was blocked by co-incubation with ferrostatin-1, liproxstatin-1, GSH, or vitamin E. Further investigation revealed that apatinib down-regulated GPX4 expression via inhibition of the transcription factors Sterol regulatory element-binding protein-1a (SREBP-1a). Besides, we found that multi-drug resistant GC cells were vulnerable to apatinib-induced GPX4 inhibition. CONCLUSIONS: In summary, we show that apatinib could induce the lipid peroxidation through GPX4 mediated by SREBP-1a, then negatively regulate the GC cell, even the multi-drug-resistant GC cell, ferroptosis.

Impact of Beijing healthcare reform on the curative care expenditure of outpatients with noncommunicable diseases based on SHA2011 and interrupted time series analysis.

BACKGROUND: To analyse the changes in curative care expenditure (CCE) associated with noncommunicable diseases (NCDs) before and after the Beijing healthcare reform, thus providing a reference for the healthcare system. METHODS: A total of 60 medical institutions were selected using multistage stratified cluster random sampling in Beijing, China. The records of approximately 100 million outpatients with NCDs in 2016-2018 were extracted. System of Health Accounts 2011 (SHA2011) was used to estimate the CCE. The segmented regression model was established to observe both the instant change and the slope change of intervention in interrupted time series analysis (ITSA). The study was conducted from December 2019 to May 2020 in Beijing, China. RESULTS: From SHA2011, we found that the CCE for outpatients with NCDs in Beijing were 58.59, 61.46 and 71.96 billion RMB in 2016, 2017 and 2018, respectively. The CCE continued to rise at all hospital levels, namely, tertiary, secondary, and community-level hospitals. However, the proportion of CCE in tertiary hospitals decreased. From ITSA, we can also conclude that the CCE showed a significant increasing trend change at the three hospital levels after the intervention. The drug proportion showed a significant decreasing trend change in secondary and tertiary hospitals. CONCLUSIONS: Beijing healthcare reform does have an impact on the CCE of NCDs.

Polysaccharide-enhanced ARGET ATRP signal amplification for ultrasensitive fluorescent detection of lung cancer CYFRA 21-1 DNA.

An ultrasensitive fluorescence biosensor for detecting cytokeratin fragment antigen 21-1 (CYFRA 21-1) DNA of non-small cell lung carcinoma (NSCLC) is designed using polysaccharide and activator regenerated by electron transfer atom transfer radical polymerization (ARGET ATRP) signal amplification strategy. Thiolated peptide nucleic acid (PNA) is fixed on magnetic nanoparticles (MNPs) by a cross-linking agent and hybridized with CYFRA 21-1 DNA. Hyaluronic acid (HA) is linked to PNA/tDNA heteroduplexes in the form of carboxy-Zr4+-phosphate. Subsequently, multiple 2-bromo-2-methylpropionic acid (BMP) molecules are linked with HA to initiate ARGET ATRP reaction. Finally, a large number of fluorescein o-acrylate (FA) monomers are polymerized on the macro-initiators, and the fluorescence signal is significantly amplified. Under optimal conditions, this biosensor shows a significant linear correlation between the fluorescence intensity and logarithm of CYFRA 21-1 DNA concentration (0.1 fM to 0.1 nM), and the limit of detection is as low as 78 aM. Furthermore, the sensor has a good ability to detect CYFRA 21-1 DNA in serum samples and to recognize mismatched bases. It suggests that the strategy has broad application in early diagnosis by virtue of its high sensitivity and selectivity. Graphical abstract A novel and highly sensitive fluorescence biosensor for quantitatively detecting CYFRA 21-1 DNA via dual signal amplification of hyaluronic acid and ARGET ATRP reaction was developed. This proposed method has a low detection limit, wide detection range, high selectivity, and strong anti-interference.

Electrochemical CYFRA21-1 DNA sensor with PCR-like sensitivity based on AgNPs and cascade polymerization.

In this work, a new method of CYFRA21-1 DNA (tDNA) detection based on electrochemically mediated atom transfer radical polymerization (e-ATRP) and surface-initiated reversible addition-fragmentation chain transfer polymerization (SI-RAFT) cascade polymerization and AgNP deposition is proposed. Firstly, the peptide nucleic acid (PNA) probe is captured on a gold electrode by Au-S bonds for specific recognition of tDNA. After hybridization, PNA/DNA strands provide high-density phosphate groups for the subsequent ATRP initiator by the identified carboxylate-Zr4+-phosphate chemistry. Then, a large number of monomers are successfully grafted from the DNA through the e-ATRP reaction. After that, the chain transfer agent of SI-RAFT and methacrylic acid (MAA) are connected by recognized carboxylate-Zr4+-carboxylate chemistry. Subsequently, through SI-RAFT, the resulting polymer introduces numerous aldehyde groups, which could deposit many AgNPs on tDNA through silver mirror reaction, causing significant amplification of the electrochemical signal. Under optimal conditions, this designed method exhibits a low detection limit of 0.487 aM. Moreover, the method enables us to detect DNA at the level of PCR-like and shows high selectivity and strong anti-interference ability in the presence of serum. It suggests that this new sensing signal amplification technology exhibits excellent potential of application in the early diagnosis of non-small cell lung cancer (NSCLC). Graphical abstract Electrochemical detection principle for CYFRA21-1 DNA based on e-ATRP and SI-RAFT signal amplification technology.

Analysis of the effect of liraglutide on glycemic variability in patients with type 2 diabetes.

The efficacy of liraglutide in the treatment of glycemic variability in type 2 diabetic patients remains to be fully elucidated. Some studies evaluated the efficacy and safety of liraglutide in glycemic variability, and this meta-analysis was performed to evaluate the accuracy of the results of existing studies on the efficacy of liraglutide. We conducted a comprehensive search for all relevant studies published in PubMed, EMBASE, Cochrane Library, and China Academic Journal Full-Text Database from the beginning of 2011 to October 31, 2019. The mean ± SD and 95% confidence interval were used for evaluation, and subgroup and sensitivity analysis were carried out. Publication bias was estimated by funnel plots and Egger's tests. A total of 16 studies were included in the meta-analysis involving 492 participants. MAGE (mean amplitude of glycemic excursion), LAGE (largest amplitude of glycemic excursions), SD (standard deviation of blood glucose), and MODD (mean of daily differences) were collected to reflect the variability of blood glucose. The glycemic variability indexes of patients before and after treatment with liraglutide were compared. Patients with treatment had lower glycemic variability compared with patients receiving treatment of liraglutide. Compared with the patients before the treatment, the patients after the treatment had a smaller glycemic variability (MAGE: I2 = 92%, p < 0.01, Z = 11.91, p < 0.01, MD = -2.78, 95%CI: -3.24 - -2.32; LAGE: I2 = 76%, p = 0.08, Z = 9.94, p < 0.01, MD = -2.20, 95%CI: -2.59 - -1.81; MODD: I2 = 74%, p = 0.002, Z = 14.03, p < 0.01, MD = -0.90, 95%CI: -1.02 - -0.77; SD: I2 = 93%, p < 0.01, Z = 3.62, p < 0.01, SMD = -1.77, 95%CI: -2.73 - -0.81). Sensitivity analysis showed that our results were reliable and no evidence of significant publication bias was detected. The results of this study suggest that patients with type 2 diabetes treated with liraglutide are associated with lower glycemic variability.

[Change pattern and correlation analysis of macroscopic characteristics, active components and rancidness degrees of Armeniacae Semen Amarum in deterioration process].

To discuss the effect of deterioration on the quality of Armeniacae Semen Amarum by observing the changes of macroscopic characteristics, active components and rancidness degrees of Armeniacae Semen Amarum in deterioration process. The traditional macroscopic identification was used to observe, identify and classify the morphologic and organleptic characteristics of Armeniacae Semen Amarum. The contents of amygdalin and fatty oil(two representatives of active components) were detected by HPLC and general rule 0713 in Chinese Pharmacopoeia, respectively. Acid value and peroxide value of the samples were selected as the representative indices of different rancidness degrees, and the general rule 2303 was adopted as the method for quantitative analysis. Then principal component analysis(PCA), partial least square analysis discrimination analysis(PLS-DA) were further utilized to establish the discriminative models of samples with different rancidness degrees, and also to screen out the largest contribution factors. In sensory evaluation, Armeniacae Semen Amarum samples were divided into three groups: non-rancid, slightly-rancid, and noticeably-rancid. The color of seed coat, cotyledon and surface of noticeably-rancid samples was deepened, and the odor differed much from non-rancid samples. Average content of amygdalin and fatty oil in non-rancid samples was 4.12% and 67.77%, respectively, both meeting the requirements of Chinese Pharmacopoeia; and decreased to some extent in slightly-rancid samples. However, the content of amygdalin sharply dropped to 0.074% in noticeably-rancid samples. The acid value and peroxide value were increased significantly with the intensifying of the rancidness degree, from only 1.363 and 0.016 74 in non-rancid samples to 1.865 and 0.023 70 in slightly-rancid samples, even doubled in noticeably-rancid samples(2.167 and 0.033 82). The discriminative models established by PCA and PLS-DA could complete the task of distinguishing the non-rancid samples from noticeably-rancid ones. The contribution degree of amygdalin content as one of the input attributes of discriminative model was higher than 1. Rancidness affected the quality of Armeniacae Semen Amarum, resulting in appearance changes, decrease in content of active components, and increase in acid value and peroxide value. Obviously, noticeably-rancid samples were non-conforming to Chinese Pharmacopoeia and no longer suitable for medicinal use. Rancidness can significantly reduce the quality of Armeniacae Semen Amarum, and even could possibly produce toxicity, which should attach more attention.

[Discrimination of Armeniacae Semen Amarum from different processed products and various rancidness degrees by electronic nose and support vector machine].

This study was aimed to develop a simple, rapid and reliable method for identifying Armeniacae Semen Amarum from different processed products and various rancidness degrees. The objective odor information of Armeniacae Semen Amarum was obtained by electronic nose. 105 batches of Armeniacae Semen Amarum samples were studied, including three processed products of Armeniacae Semen Amarum, fried Armeniacae Semen Amarum and peeled Armeniacae Semen Amarum, as well as the samples with various rancidness degrees: without rancidness, slight rancidness, and rancidness. The discriminant models of different processed products and rancidness degrees of Armeniacae Semen Amarum were established by Support Vector Machine(SVM), respectively, and the models were verified based on back estimation of blind samples. The results showed that there were differences in the characteristic response radar patterns of the sensor array of different processed products and the samples with different rancidness degrees. The initial identification rate was 95.90% and 92.45%, whilst validation recognition rate was 95.38% and 91.08% in SVM identification models. In conclusion, differentiation in odor of different processed and rancidness degree Armeniacae Semen Amarum was performed by the electronic nose technology, and different processed and rancidness degrees Armeniacae Semen Amarum were successfully discriminated by combining with SVM. This research provides ideas and methods for objective identification of odor of traditional Chinese medicine, conducive to the inheritance and development of traditional experience in odor identification.

Prognostic value and nomograms of proximal margin distance in gastric cancer with radical distal gastrectomy.

OBJECTIVE: The proximal margin (PM) distance for distal gastrectomy (DG) of gastric cancer (GC) remains controversial. This study investigated the prognostic value of PM distance for survival outcomes, and aimed to combine clinicopathologic variables associated with survival outcomes after DG with different PM distance for GC into a prediction nomogram. METHODS: Patients who underwent radical DG from June 2004 to June 2014 at Department of General Surgery, Nanfang Hospital, Southern Medical University were included. The first endpoints of the prognostic value of PM distance (assessed in 0.5 cm increments) for disease-free survival (DFS) and overall survival (OS) were assessed. Multivariate analysis by Cox proportional hazards regression was performed using the training set, and the nomogram was constructed, patients were chronologically assigned to the training set for dates from June 1, 2004 to January 30, 2012 (n=493) and to the validation set from February 1, 2012 to June 30, 2014 (n=211). RESULTS: Among 704 patients with pTNM stage I, pTNM stage II, T1-2, T3-4, N0, differentiated type, tumor size ≤5.0 cm, a PM of (2.1-5.0) cmvs. PM≤2.0 cm showed a statistically significant difference in DFS and OS, while a PM>5.0 cm was not associated with any further improvement in DFS and OSvs. a PM of 2.1-5.0 cm. In patients with pTNM stage III, N1, N2-3, undifferentiated type, tumor size >5.0 cm, the PM distance was not significantly correlated with DFS and OS between patients with a PM of (2.1-5.0) cm and a PM≤2 cm, or between patients with a PM >5.0 cm and a PM of (2.1-5.0) cm, so there were no significant differences across the three PM groups. In the training set, the C-indexes of DFS and OS, were 0.721 and 0.735, respectively, and in the validation set, the C-indexes of DFS and OS, were 0.752 and 0.751, respectively. CONCLUSIONS: It is necessary to obtain not less than 2.0 cm of PM distance in early-stage disease, while PM distance was not associated with long-term survival in later and more aggressive stages of disease because more advanced GC is a systemic disease. Different types of patients should be considered for removal of an individualized PM distance intra-operatively. We developed a universally applicable prediction model for accurately determining the 1-year, 3-year and 5-year DFS and OS of GC patients according to their preoperative clinicopathologic characteristics and PM distance.

Tumor Necrosis Factor-α Is Required for Mast Cell-Mediated Host Immunity Against Cutaneous Staphylococcus aureus Infection.

Background: Mast cells (MCs) play a key role in immune process response to invading pathogens. Methods: This study assessed the involvement of MCs in controlling Staphylococcus aureus infection in a cutaneous infection model of MC-deficient (KitW-sh/W-sh) mice. Results: KitW-sh/W-sh mice developed significantly larger skin lesions after the cutaneous S. aureus challenge, when compared to wild-type (WT) mice, while MC dysfunction reduced the inflammation response to S. aureus. The levels of tumor necrosis factor (TNF)-α in skin tissues were significantly decreased in KitW-sh/W-sh mice upon infection. Moreover, the exogenous administration of MCs or recombinant TNF-α effectively restored the immune response against S. aureus in KitW-sh/W-sh mice via the recruitment of neutrophils to the infected site. These results indicate that the effects of MC deficiency are largely attributed to the decrease in production of TNF-α in cutaneous S. aureus infection. In addition, S. aureus-induced MC activation was dependent on the c-kit receptor-activated phosphoinositide 3-kinase (PI3K)/AKT/P65-nuclear factor (NF-κB) pathway, which was confirmed by treatment with Masitinib (a c-kit receptor inhibitor), Wortmannin (a PI3K inhibitor), and pyrrolidine dithiocarbamate (a NF-κB inhibitor), respectively. Conclusions: The present study identifies the critical role of MCs in the host defense against S. aureus infection.

ImmunoScore Signature: A Prognostic and Predictive Tool in Gastric Cancer.

OBJECTIVE: We postulated that the ImmunoScore (IS) could markedly improve the prediction of postsurgical survival and chemotherapeutic benefits in gastric cancer (GC). SUMMARY BACKGROUND DATA: A prediction model for GC patients was developed using data from 879 consecutive patients. METHODS: The expression of 27 immune features was detected in 251 specimens by using immunohistochemistry, and a 5-feature-based ISGC was then constructed using the LASSO Cox regression model. Testing and validation cohorts were included to validate the model. RESULTS: Using the LASSO model, we established an ISGC classifier based on 5 features: CD3invasive margin (IM), CD3center of tumor (CT), CD8IM, CD45ROCT, and CD66bIM. Significant differences were found between the high-ISGC and low-ISGC patients in the training cohort in 5-year disease-free survival (45.0% vs. 4.4%, respectively; P <0.001) and 5-year overall survival (48.8% vs. 6.7%, respectively; P <0.001). Multivariate analysis revealed that the ISGC classifier was an independent prognostic factor. A combination of ISGC and tumor, node, and metastasis (TNM) had better prognostic value than TNM stage alone. Further analysis revealed that stage II and III GC patients with high-ISGC exhibited a favorable response to adjuvant chemotherapy. Finally, we constructed 2 nomograms to predict which patients with stages II and III GC might benefit from adjuvant chemotherapy after surgery. CONCLUSIONS: The ISGC classifier could effectively predict recurrence and survival of GC, and complemented the prognostic value of the TNM staging system. Moreover, the ISGC might be a useful predictive tool to identify stage II and III GC patients who would benefit from adjuvant chemotherapy.

Laparoscopy-assisted colectomy as an Oncologically safe alternative for patients with stage T4 Colon Cancer: a propensity-matched cohort study.

BACKGROUND: It is still controversial whether laparoscopy-assisted colectomy (LAC) is suitable for patients with stage T4 colon cancer. This study aimed to compare the short- and long-term outcomes of LAC and open colectomy (OC) for patients with pathologic T4 colon cancer. METHODS: Data of eligible patients with colon cancer in our institution from March 2004 to September 2014 were retrospectively reviewed. The patients were followed up to September 2016. Propensity score matching was performed to control the bias. RESULTS: Two hundred and forty two patients were selected by propensity score matching, with 121 patients in the LAC group and 121 in the OC group. Mean operating time and rate of intraoperative blood transfusion were similar between two groups. In LAC group, shorter time to first flatus and first liquid intake were observed in patients with pT4b stage disease, but not for patients with pT4a stage disease. Less blood loss and shorter length of postoperative hospital stay were examined in LAC group, including pT4a and pT4b stages. Conversion was required in 9.1% (11 out of 121) cases. DFS and OS were similar between LAC and OC groups. The 5-year DFS rate was 64.2% for pT4a stage and 35.5% for pT4b stage in LAC group, and 62.9% and 33.7% in OC group for pT4a (p = 0.374) and pT4b (p = 0.385) stage respectively. For 5-year OS rates, two groups did not differ in pT4a stage (LAC 69.2% vs. OC 66.0%, p = 0.151) and pT4b stage (LAC 37.5% vs. OC 38.1%, p = 0.510). CONCLUSIONS: Laparoscopic colectomy appears to be safe for selected patients with pT4 colon cancer in centres with expertise in minimally invasive surgery.