[Comparison of efficacy and safety between domestic immune checkpoint inhibitors and pembrolizumab in the treatment of driver gene-negative advanced non-small cell lung cancer].

Objective: To compare the efficacy and safety of domestic immune checkpoint inhibitors and pembrolizumab in the treatment of driver gene-negative advanced non-small cell lung cancer. Methods: A retrospective analysis was conducted on the data of 1 241 patients with driver gene-negative, unresectable stage ⅢB to Ⅳ non-small cell lung cancer who were treated at the Hunan Cancer Hospital from January 1, 2017 to October 1, 2022. All patients received monotherapy or combination therapy with domestic immune checkpoint inhibitors or pembrolizumab. Among the 1 241 patients, there were 1 066 males and 175 females, with an age range of 14 to 84 years and a median age of 62 years. Among them, 67 patients received monotherapy with domestic immune checkpoint inhibitors, 695 patients received combination therapy with domestic immune checkpoint inhibitors, 102 patients received monotherapy with pembrolizumab, and 377 patients received combination therapy with pembrolizumab. The efficacy and safety of domestic immune checkpoint inhibitors and pembrolizumab monotherapy or combination therapy were compared. Results: In the immune checkpoint inhibitor monotherapy group, the objective response rate (ORR) using domestic immune checkpoint inhibitors and pembrolizumab was 43.3%(29/67) and 44.1%(45/102), respectively, and the disease control rate (DCR) was 79.1%(53/67) and 84.3%(86/102), respectively, with no statistically significant differences (both P>0.05). In the immune combination therapy group, the ORR using domestic immune checkpoint inhibitors and pembrolizumab was 60.9%(423/695) and 62.9%(237/377), respectively, and the DCR was 92.9%(646/695) and 91.0%(343/377), respectively, with no statistically significant differences (both P>0.05). In the immune checkpoint inhibitor monotherapy group, the median progression-free survival (PFS) using domestic immune checkpoint inhibitors and pembrolizumab was 9.0 (95%CI: 3.0-15.0) months and 7.4 (95%CI: 4.8-9.8) months, respectively, with no statistically significant differences (P=0.660). The median overall survival (OS) was 27.0 (95%CI: 25.0-29.0) months and 22.0 (95%CI: 17.1-26.9) months, respectively, with no statistically significant differences (P=0.673). In the immune combination therapy group, the median PFS using domestic immune checkpoint inhibitors and pembrolizumab was 9.0 (95%CI: 8.2-9.8) months and 10.5 (95%CI: 9.0-12.0) months, respectively, with no statistically significant differences (P=0.186). The median OS was 24.0 (95%CI: 19.1-28.9) months and 26.0 (95%CI: 21.3-30.7) months, respectively, with no statistically significant differences (P=0.359). The incidence of grade 1-2 reactive capillary proliferation of the skin in the domestic immune checkpoint inhibitor group and pembrolizumab group was 14.0% (107/762) and 0, respectively. The incidence of grade≥3 reactive capillary proliferation of the skin was 1.0% (7/762) and 0, respectively, with statistically significant differences (both P<0.05). No statistically significant differences were observed in other adverse reactions (all P>0.05). Conclusions: The efficacy of domestically produced immune checkpoint inhibitors is comparable to that of pembrolizumab in the treatment of driver gene-negative advanced non-small cell lung cancer. There is little difference in safety, except for the specific difference in domestically produced immune checkpoint inhibitor, which has a unique risk of reactive cutaneous capillary endothelial proliferation.

[Infection status and Molecular types of Rhinovirus among Cases of Acute Respiratory Tract Infections in Luohe City, Henan Province, from 2017 to 2022].

Objective: To understand the infection status and molecular types of rhinovirus (RV) among cases of Acute Respiratory Infections (ARIs) in Luohe City, Henan Province, from 2017 to 2022. Methods: From October 2017 to June 2022, clinical and epidemiological data were collected from 2 270 cases of ARIs at Luohe Central Hospital in Henan Province. Throat swab specimens were obtained from these cases. Real-time quantitative polymerase chain reaction (qPCR) was used to screen for RV-positive specimens. Subsequently, the positive samples were subjected to nested reverse transcription polymerase chain reaction (nested RT-PCR) to amplify the full-length VP1 region. Using the MEGA software, along with 169 RV reference strains recommended by the International Committee on Taxonomy of Viruses, a phylogenetic tree was constructed to determine RV types. Results: Among the 2 270 cases of ARIs, there were 1 283 male cases (56.52%). The median age (Q1, Q3) was 3 (1, 6) years, with the population under 5 years old accounting for 68.59% (1 557/2 270). RV was detected in 137 cases (6.04%), of which 68 cases (49.64%) showed co-detection with other viruses, with the most common being co-detection with enterovirus, accounting for 14.60% (20/137). The RV detection rates in the age groups of 0~4 years, 5~14 years, 15~59 years, and≥60 years were 6.42% (100/1 557), 4.69% (21/448), 3.80% (6/158), and 9.35% (10/107), respectively, with no statistically significant differences (χ2=5.310, P=0.150). The overall detection rates of RV before (2017-2019) and during (2020-2022) the COVID-19 pandemic showed no statistically significant difference (χ2=1.823, P=0.177). A total of 109 VP1 sequences were obtained, including 62 types. Among them, RV-A, RV-B, and RV-C had 42, 3, and 17 types respectively. Conclusion: RV is one of the predominant pathogens in ARIs cases in Luohe City, Henan Province, from 2017 to 2022. Multiple types of RV co-circulate without any apparent dominant type.

[Analysis of the effect of early subcutaneous specific immunotherapy on the levels of dust mite allergen-specific antibodies and polyunsaturated fatty acid metabolism].

Objective: To investigate the effects of subcutaneous immunotherapy (SCIT) on patients' immune markers and metabolic levels in the early stage of allergen treatment, and to gain insight into the role of SCIT in regulating immune responses and metabolic levels, so as to provide reference data for the further discovery of potential biomarkers. Methods: A longitudinal study was used to include 40 subjects who underwent SCIT with dust mite allergens in the Department of Pediatrics of the First Affiliated Hospital of Guangzhou Medical University between November 2017 and February 2022, including 20 subjects each of single mite subcutaneous immunotherapy (SM-SCIT) and double mite subcutaneous immunotherapy (DM-SCIT). In this study, levels of dust mite allergen-specific antibodies and polyunsaturated fatty acid metabolism were measured before and 12 months after treatment, while pulmonary function tests were performed. The therapeutic effects of the patients were followed up by visual analogue scale (VAS), asthma control test (ACT) and total medication scores (TMS). The results were statistically analyzed using t-test and Mann-Whitney U-test. Results: After 12 months of treatment with SCIT, both groups showed a significant decrease in total VAS score (SM-SCIT:Z=-2.298, P<0.05; DM-SCIT:Z=-3.411, P<0.001); total ACT score (SM-SCIT:Z=-2.054, P<0.05; DM-SCIT:Z=-2.014, P<0.05) and total medication scores (SM-SCIT:Z=-3.799, P<0.000 1; DM-SCIT:Z=-3.474, P<0.001) were significantly higher, in addition to significantly higher MMEF75/25 values in the DM-SCIT group (t=-2.253, P<0.05). There was no significant change in sIgE in the SM-SCIT group (P>0.05), and the sIgG4 levels of the Der p, Der f, p 1, p 2, f 2, and p 21 fractions were significantly elevated (Z=-2.651, -3.771, -2.949, -2.912, -2.725, -2.128, and -3.285, respectively, all P<0.05); The sIgE of Der p 2, f 2, p 7 and p 23 fractions(Z=-2.651, -3.771, -2.949, -2.912, -2.725, -2.128, -3.285, all P<0.05) and the sIgG4 levels of the Der p, Der f, p 1, p 2, f 1, f 2, p 10, p 21 and p 23 fractions (Z=-3.808, -3.845, -3.061, -2.688, -2.464, -3.211, -2.371, -2.091, -2.427, all P<0.05) of the DM-SCIT group were significantly elevated. Metabolomics analysis showed that arachidonic acid, docosahexaenoic acid, docosapentaenoic acid, eicosapentaenoic acid, 5, 9, 12-octadecatrienoic acid, 5(S)-hydroxylated eicosatetraenoic acid, and dihomo-gamma-linolenic acid were significantly elevated at the beginning of the treatment period after SM-SCIT treatment (Z of -2.191, -2.497, -1.988, -2.090, -2.19, -2.803, -2.073, all P<0.05); 5(S)-hydroxylated eicosatetraenoic acid showed elevated and alpha-linolenic acid, eicosadienoic acid, and eicosapentaenoic acid were significantly decreased in the DM-SCIT group after treatment (Z=-1.988, -2.090, -2.497, -1.988, respectively, all P<0.05). Correlation analysis showed that arachidonic acid was significantly negatively correlated with changes in dust mite-specific IgG4 (r=-0.499, P<0.05), and that alpha-linolenic acid, 5, 9, 12-octadecatrienoic acid, and eicosapentaenoic acid were positively correlated with the ΔsIgG4 of the dust mite der p 2 (r=0.451, 0.420, 0.474, respectively; all P<0.05). Conclusion: Significant changes in allergen-specific antibody levels and polyunsaturated fatty acid metabolism levels occur during SCIT, and the two may interact and influence each other.

[Exploration of detection methods for free silica with different crystal forms in dust].

Objective: To investigate the differences and applicability of free silica detection methods of different crystal forms in dust, and to provide a basis for the selection of various methods. Methods: From December 2021 to June 2022, dust samples from 20 enterprises in different industries in 18 cities in Henan Province were randomly selected as the investigation objects. X-ray diffraction (XRD) method was used to analyze the samples and classify the samples. Based on GBZ/T 192.4-2007 "Determination of Dust in the Air of Workplace-Part 4: Content of Free Silica in Dust", pyrophosphate method and infrared spectrophotometry were used for quantitative determination. The measured results were analyzed by paired sample t test to evaluate the advantages and disadvantages of the two methods and their applicable scope. Results: The XRD results of 20 dust samples could be divided into α, ß, γ crystal types and the mixed type of α and γ. There was no significant difference between pyrophosphate method and infrared spectrophotometry (P=0.180). The pyrophosphate method results of ß, γ and α, γ mixed crystalline free silica were significantly higher than those of infrared spectrophotometry, and the difference was statistically significant (P<0.001) . Conclusion: Pyrophosphate method and infrared spectrophotometry are suitable for α-type free silica, while pyrophosphate method is suitable for ß, γ and α, γ mixed crystalline free silica.

[Analysis of clinical and genetic variation in neonatal intrahepatic cholestasis caused by citrin deficiency].

Objective: To investigate the clinical phenotype and gene variation conditions in neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), so as to provide a basis for genetic counseling and clinical diagnosis and treatment of the family. Methods: 11 cases of neonatal intrahepatic cholestasis who visited the Children's Hospital Affiliated to Zhengzhou University between February 2019 and March 2021 were selected as the study subjects. High-throughput sequencing technology was used to detect the gene variation condition in 11 neonatal patients and 100 normal control neonates. The suspicious loci and family members were verified by Sanger sequencing and QPCR technology. Results: All 11 children with NICCD had different degrees of jaundice and liver damage symptoms, combined with coagulation dysfunction and anemia (n = 7), cardiac malformation (n = 2), elevated myocardial enzymes (n = 4), hyperlipidemia (n = 1), hyperkalemia (n = 1), persistent diarrhea (n = 3), developmental delay (n = 1). A total of 10 different types of SLC25A13 gene mutations were detected in 11 cases, including three frameshift mutations, two splicing changes, two missense mutations, one intron insertion, one nonsense mutation, and one heterozygous deletion. After reviewing literature and databases, c.1878delG(p.I627Sfs*73) and exon11 deletion were novel mutations that had not been reported at home or abroad. Conclusion: The clinical features of NICCD are non-specific, and genetic testing aids in the early and accurate diagnosis of the disease, providing an important basis for clinical treatment and genetic counseling for family members. In addition, the detection of novel mutation sites has enriched the SLC25A13 gene variation spectrum.

[Determination of cobalt and tungsten in human urine by inductively coupled plasma mass spectrometry].

Objective: To establish a inductively coupled plasma mass spectrometry method for the determination of trace cobalt and tungsten in human urine. Methods: The authors used 1% nitric acid solution as diluent in October-December 2021, the sample dilution factor and internal standard element were optimized by single factor rotation experiment, and the difference between the working curve and the standard curve was compared. Results: The method uses working curve to determine cobalt and tungsten in urine, the linear range of this method was 0.0~10.0 µg/L, the correlation coefficient was 0.999 9, the detection limits respectively were 0.005 µg/L (cobalt) and 0.09 µg/L (tungsten), the recoveries of samples respectively were 87.0%~100.2% (cobalt) and 89.4%~104.8% (tungsten), the relative standard deviations respectively were 0.4%~4.4% (cobalt) and 0.6%~3.8% (tungsten) . Conclusion: A simple and rapid method for determination of cobalt and tungsten in urine has been established. This method has the advantages of simple operation, high sensitivity, low detection limit and good stability. It is suitable for determination of cobalt and tungsten in urine of all kinds of people.

Chondrocyte apoptosis in temporomandibular joint osteoarthritis promotes bone resorption by enhancing chemotaxis of osteoclast precursors.

OBJECTIVE: This study aimed to explore the effect and mechanism of chondrocyte apoptosis on the chemotaxis of osteoclast precursors (OCPs) during bone destruction. DESIGN: The relationship between cartilage and bone destruction was verified with a rat temporomandibular joint osteoarthritis (TMJOA) model. The pan-caspase inhibitor Z-VAD-FMK (ZVAD) was applied to confirm the chemotactic effect of chondrocyte apoptosis on OCPs. Synthesis and release of the key chemokine CX3CL1 in apoptotic and non-apoptotic chondrocytes was assessed with IHC, IF, WB, and ELISA. The function of CX3CL1-CX3CR1 axis in the chemotaxis of OCPs was examined by CX3XR1 inhibitor AZD8797 (AZD) and si-CX3CL1. The regulatory effect of p38 MAPK on CX3CL1 release was verified by p38 inhibitor PH-797804. RESULTS: A temporal and spatial association between cartilage degradation and bone resorption was found in the TMJOA model. The caspase-dependent chondrocyte apoptosis promoted chemotaxis of OCPs, which can be restrained by ZVAD. CX3CL1 was significantly upregulated when chondrocytes underwent apoptosis, and it played a critical role in the recruitment of OCPs, blockage of CX3CL1-CX3CR1 axis resulted in less bone resorption in TMJOA. P38 MAPK was activated in apoptotic chondrocytes, and had a regulatory effect on the synthesis and release of CX3CL1. After inhibition of p38 by PH-797804, the chemotactic effect of apoptotic chondrocytes on OCPs was limited. CONCLUSIONS: This study indicates that apoptosis of chondrocytes in TMJOA enhances chemotaxis of OCPs toward osteoclast precursors through upregulation of the p38-CX3CL1 axis, thereby promoting the activation of local osteoclasts.

[Effect of metformin combined with intermittent fasting on endoplasmic reticulum stress after cerebral ischemia-reperfusion in mice].

Objective: To explore the effect of metformin combined with intermittent fasting on endoplasmic reticulum stress after cerebral ischemia-reperfusion injury in mice. Methods: One hundred 10-Week-old healthy KM mice of SPF grade, weighing 25-28 g, were divided into 5 groups by the random number table method: sham group, focal cerebral ischemia group (I/R group), intermittent fasting group (IF group), metformin group (Met group), metformin+intermittent fasting group (Met+IF group). In IF group, food was provided ad libitum from 8∶00 to 16∶00 daily, but the mice were fasted for the rest of the time. In Met group, the mice underwent intraperitoneal injection of metformin (10 mg/kg). In Met+IF group, the mice received the same eating method as the IF group and the same method of metformin injection as Met Group. In Sham group, I/R group and IF group, the mice were intraperitoneally injected with equal volume of normal saline. Mice in all groups were not restricted to drinking water. Random plasma glucose and body weight changes in mice during preconditioning were monitored, and a focal cerebral ischemia-reperfusion model was established 14 days later. The cerebral infarction volume was measured after 1 hour of ischemia and 24 hours of reperfusion. The brain tissues of mice were subjected to Western blot to detect the contents of endoplasmic reticulum stress-related proteins, including glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), and apoptosis proteins (Caspase-3 and Cleaved-caspase 3). Results: After different interventions, there was no significant difference in random plasma glucose changes among the four groups (all P<0.05). The blood glucose level of the mice in the Met+IF group was lower than the sham group, I/R group, IF group and Met group (all P<0.05). GRP78/ß-actin in sham group, I/R group, IF group, Met group, IF+Met group were 0.48±0.05, 1.35±0.10, 0.94±0.05, 0.70±0.14, 0.41±0.37, respectively; CHOP/ß-actin were 0.27±0.04, 1.03±0.03, 0.72±0.04, 0.63±0.04, 0.44±0.01, respectively; Caspase-3/ß-actin were 0.51±0.04, 1.04±0.04, 0.83±0.03, 0.76±0.03, 0.63±0.05, respectively; Cleaved-Caspase-3/ß-actin were 0.17±0.06, 1.01±0.20, 0.75±0.06, 0.51±0.12, 0.29±0.08, respectively, with statistically significant differences (all P<0.001). The counts of GRP78-positive cells in the hippocampus immunohistochemistry in the sham group, I/R group, IF group, Met group, and IF+Met group were 53±5, 192±11, 162±12, 140±10, 114±13, respectively, while the counts of CHOP-positive cells were 35±4, 177±12, 120±12, 100±7, 69±10, respectively, with statistically significant differences (all P<0.001). The relative volume of cerebral infarction in I/R group, IF group, Met group and IF+Met group were 0, 0.333±0.046, 0.258±0.023, 0.116±0.039, 0.111±0.039, respectively, and there were statistically significant differences (all P<0.001). Conclusion: Both Metformin and intermittent fasting can alleviate endoplasmic reticulum stress after cerebral ischemia and reperfusion in mice, and the combination of the two has a better effect.

Hepatic transcriptome perturbations in dairy cows fed different forage resources.

BACKGROUND: Forage plays critical roles in milk performance of dairy. However, domestic high-quality forage such as alfalfa hay is far from being sufficient in China. Thus, more than 1 million tons of alfalfa hay were imported in China annually in recent years. At the same time, more than 10 million tons of corn stover are generated annually in China. Thus, taking full advantage of corn stover to meet the demand of forage and reduce dependence on imported alfalfa hay has been a strategic policy for the Chinese dairy industry. Changes in liver metabolism under different forage resources are not well known. Thus, the objective of the present study was to investigate the effect of different forage resources on liver metabolism using RNAseq and bioinformatics analyses. RESULTS: The results of this study showed that the cows fed a diet with corn stover (CS) as the main forage had lower milk yield, DMI, milk protein content and yield, milk fat yield, and lactose yield than cows fed a mixed forage (MF) diet (P <  0.01). KEGG analysis for differently expressed genes (DEG) in liver (81 up-regulated and 423 down-DEG, Padj ≤0.05) showed that pathways associated with glycan biosynthesis and metabolism and amino acid metabolism was inhibited by the CS diet. In addition, results from DAVID and ClueGO indicated that biological processes related to cell-cell adhesion, multicellular organism growth, and amino acid and protein metabolism also were downregulated by feeding CS. Co-expression network analysis indicated that FAM210A, SLC26A6, FBXW5, EIF6, ZSCAN10, FPGS, and ARMCX2 played critical roles in the network. Bioinformatics analysis showed that genes within the co-expression network were enriched to "pyruvate metabolic process", "complement activation, classical pathway", and "retrograde transport, endosome to Golgi". CONCLUSIONS: Results of the present study indicated that feeding a low-quality forage diet inhibits important biological functions of the liver at least in part due to a reduction in DMI. In addition, the results of the present study provide an insight into the metabolic response in the liver to different-quality forage resources. As such, the data can help develop favorable strategies to improve the utilization of corn stover in China.

[Perioperative safety and feasibility of simultaneous off-pump coronary artery bypass grafting with non-cardiac surgical procedures of moderate-to-severe severity].

Objective: To examine the perioperative safety and feasibility of simultaneous off-pump coronary artery bypass grafting (OPCAB) with non-cardiac surgical procedures of moderate-to-severe severity. Methods: The perioperative results of 54 patients underwent simultaneous OPCAB with non-cardiac surgical procedures from September 2013 to January 2019 at Department of Cardiac Surgery, Peking University First Hospital were assessed retrospectively. There were 46 males and 8 females, aging (65.8±8.8) years (range: 41 to 85 years). All simultaneous non-cardiac surgical procedures, including vascular (n=1), thoracic (n=26), general (n=12) and urologic surgical procedures (n=15), were assessed to be of moderate-to-severe grade by operative severity scoring system. Perioperative results were compared between the OPCAB patients who underwent simultaneous non-cardiac surgical procedures (n=54) and 1∶2 matched patients who underwent isolated OPCAB performed most recently by the same cardiac team with similar procedures accordingly (n=108), using t test, Mann-Whitney U test, χ2 test or Fisher exact test. Results: All baseline factors were matched between the two groups, with no significant difference on European system for cardiac operative risk evaluation (EuroSCORE) Ⅱ (1.185(0.758)% vs. 1.215(0.905)%, Z=‒0.036, P=0.972). No perioperative death was observed in the two groups. Although patients underwent simultaneous non-cardiac surgical procedures showed prolonged operation duration time ((324.9±97.1) minutes vs. (166.7±36.7) minites, t=11.564, P<0.01) and increased intraoperaive blood loss ((462.2±269.6) ml vs. (304.5±177.8) ml, t=3.866, P<0.01), primary postoperative complications, including perioperative myocardial infarction, atrial fibrillation, perioperative stroke, acute renal failure, wound infection, and bleeding reoperation did not show significant differences between the two groups (all P>0.05), while total blood transfusion volume, mechanical ventilation time and intensive care unit residence time also showed no significant differences between the two groups (all P>0.05). Conclusion: Simultaneous OPCAB with non-cardiac surgical procedures of moderate-to-severe severity in patients with operative indications are safe and feasible, and are not associated with increased postoperative risks when compared with isolated OPCAB.

Short communication: Decrease of lipid profiles in cow milk by ultra-high-temperature treatment but not by pasteurization.

Triglyceride (TG) and fatty acid profiles of raw (RM), pasteurized (PM, 85°C for 15 s), and indirect UHT-treated (UM, 135°C for 15 s) cow milk were investigated by a lipidomics approach. Ninety-four TG were identified and all were present at significantly lower concentrations in UM than in RM or PM, and free fatty acid contents were significantly higher in UM than in RM and PM, indicating that TG lipolysis occurred to a greater degree in UM than in RM and PM. In addition, UM contained significantly fewer unsaturated fatty acids (14 types) than those in RM and PM, including C14:1n-5, C15:1n-5, C16:1n-7, C17:1n-7, C18:1n9 cis, C18:2n-6 cis, C18:3n-3, C18:3n-6, C20:1, C20:2, C20:3n-6, C20:3n-3, C20:4n-6, and C20:5n-3. However, we detected no significant differences between RM and PM in these fatty acids. In conclusion, UHT treatment, but not pasteurization, caused loss of the nutritional quality and bioactivity of cow milk lipid profiles.

[Short-term effect of sodium zirconium cyclosilicate on potassium lowering in chronic kidney disease patients with hyperkalemia].

Objective: To investigate the efficacy of sodium zirconium cyclosilicate on emergency correction of hyperkalemia in chronic kidney disease patients. Methods: Patients with chronic kidney disease who were admitted to the Department of Nephrology of the First Affiliated Hospital of Zhengzhou University from May to June 2020 were selected. Those who had hyperkalemia and took sodium zirconium cyclosilicate powder were finally included. The patient's clinical data and laboratory results were collected. Results: A total of 24 results were included from 21 patients. The age of patients was (48.9±13.5) years old. Fourteen patients were male, and 7 patients were female. After 2 hours of administration, the venous potassium level decreased from (5.85±0.52) mmol/L to (5.15±0.43) mmol/L (P<0.001, n=21), with an average decline of (0.71±0.43) mmol/L. Meanwhile, the arterial potassium level decreased from (5.50±0.40) mmol/L to (4.88±0.33) mmol/L (P<0.001, n=10), with an average decline of (0.62±0.29) mmol/L. Based on the initial venous potassium level, the patients were further divided into three groups. The average potassium decrease in<5.5 mmol/L group (4 patients), 5.5-<6.0 mmol/L group (11 patients) and ≥6.0 mmol/L group (6 patients) was (0.46±0.26) mmol/L, (0.62±0.38) mmol/L and (1.04±0.45) mmol/L, respectively. There was statistically significant difference of potassium reduction among the three groups (P=0.045). Moreover, the extent of potassium reduction was positively correlated with baseline venous potassium level (r=0.603, P=0.004, n=21). The study did not reveal any treatment-related adverse event. Conclusion: Sodium zirconium cyclosilicate powder can rapidly and effectively reduce the serum potassium level in chronic kidney disease patients with hyperkalemia.

Two sphingomyelin synthase homologues regulate body weight and sphingomyelin synthesis in female brown planthopper, N. lugens (Stål).

Although sphingomyelins known to be are lipid constituents of the plasma membrane in vertebrates, much remains obscure about the metabolism of sphingomyelins in insects. With ultra performance liquid chromatography-time-of-flight-tandem mass spectrometry analysis, we revealed for the first time that sphingomyelins are abundant in Nilaparvata lugens (Stål), the brown planthopper (BPH), and their biosynthesis is carried out by sphingomyelin synthase-like protein 2 (SMSL2), which is homologous to sphingomyelin synthase-related protein (SMSr). Unlike other insect species, high concentrations of sphingomyelins rather than ceramide phosphoethanolamines exist in the BPH. Two putative genes, which are homologous to SMSr, are named Nilaparvata lugens SMS-like 1 (NlSMSL1) and 2 (NlSMSL2). Knockdowns of both NlSMSL2 and NlSMSL1 were conducted but only the first decreased concentrations of sphingomyelins in the BPH, indicating that NlSMSL2 plays a role in the biosynthesis of sphingomyelins. Real-time quantitative PCR analysis revealed both NlSMSL1 and NlSMSL2 are highly expressed in BPH adults, with NlSMSL1 specifically highly expressed in reproductive organs (ovaries and testes) whereas NlSMSL2 was highly expressed in the malpighian tubules. The knockdown of NlSMSL1 or NlSMSL2 increased BPH female body weight but not that of males, suggesting sex-specific roles for SMSLs in influencing BPH body weight. The results suggest that NlSMSL2 catalyses the synthesis of sphingomyelins and maintains female BPH body weight through alteration of sphingolipid content.

Differentiation of focal organising pneumonia and peripheral adenocarcinoma in solid lung lesions using thin-section CT-based radiomics.

AIM: To evaluate the predictive role of radiomics based on computed tomography (CT) in discriminating focal organising pneumonia (FOP) from peripheral lung adenocarcinoma (LA). MATERIALS AND METHODS: Institutional research board approval was obtained for this retrospective study. One hundred and seventeen patients with FOP and 109 patients with LA who underwent thin-section CT from January 2011 to August 2017 were reviewed systematically and analysed. The clinical and radiological features were established as model A and multi-feature-based radiomics as model B. The diagnostic performance of model A, model B, and model A+B were evaluated and compared via receiver operating characteristic (ROC) curve analysis and logistic regression analysis. RESULTS: Sex, symptoms, necrosis, and the halo sign were identified as independent predictors of LA. The area under the ROC curve (Az value), accuracy, sensitivity, and specificity of model A were 0.839, 75.7%, 82.6%, and 69.2% respectively. Model B showed significantly higher accuracy than model A (83.6% versus 75.7%, p=0.032). The top four best-performing features, WavEnLH_s-3, WavEnHH_s-3, Teta3, and Volume, performed as independent factors for discriminating LA. Regression analysis indicated that model B had superior model fit than model A with Akaike information criterion (AIC) values of 73.6% versus 59.1%, respectively. Combining model A with model B is useful in achieving better diagnostic performance in discriminating FOP from LA: the Az value, accuracy, sensitivity, and specificity were 0.956, 87.6%, 85.3%, and 89.7% respectively. CONCLUSIONS: Radiomics based on CT exhibited better diagnostic accuracy and model fit than clinical and radiological features in discriminating FOP from LA. Combination of both achieved better diagnostic performance.

Determination of sulbactam in raw bovine milk by isotope dilution-ultra-high-performance liquid chromatography-tandem mass spectrometry.

We developed a sensitive and selective isotope dilution ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the determination of sulbactam residue in raw bovine milk. Sulbactam and internal standard, sulbactam-d5, were extracted from raw bovine milk via liquid-liquid extraction and enriched with strong anion exchange solid-phase extraction cartridges and finally analyzed by using UPLC-MS/MS with multiple reaction monitoring mode. The method was validated according to European regulations. The calibration curve showed good linearity, with a correlation coefficient of 0.9998. Decision limit and detection capability of sulbactam were determined by matrix calibration curve and were 0.0445 and 0.0517 µg/L, respectively. The recoveries of sulbactam in fortified raw bovine milk ranged from 72.1 to 91.5%, with the intra- and interday relative standard deviations ranging from 3.0 to 18.9%. Furthermore, the developed method was applied to analyzing real raw bovine milk samples collected from dairy farms in Beijing, China. Sulbactam was not determined in all samples. The proposed method could ultimately serve as a methodological foundation for the determination of sulbactam in different types of raw milk and dairy products.

[Study on the association of dietary patterns of Shaanxi women of childbearing age during pregnancy with adverse pregnancy outcomes from 2010 to 2012].

Objective: To analyze the types of dietary patterns of women during pregnancy in Shaanxi and their association with adverse pregnancy outcomes. Methods: Data were derived from a cross-sectional program named "The prevalence and risk factors of birth defects in Shaanxi Province" from July to November in 2013. A multi-stage stratified random sampling method was used to extract 15 980 women of childbearing age who met the inclusion exclusion criteria from Shaanxi Province. The questionnaire obtained information such as the pregnancy outcome and the food intake of the study subjects during pregnancy. The dietary pattern was extracted by factor analysis, and the each dietary pattern of subjects were divided into T(1)-T(3) groups according to the factor score. The effects of each dietary pattern on major adverse pregnancy outcomes were estimated by unconditional logistic regression model. Results: Four dietary patterns were established:vegetarian pattern, balanced pattern, traditional pattern, and processing pattern. The multivariate logistic regression model results showed that compared with the vegetarian pattern T(2) group, the T(1) group had lower risk of low birth weight (OR=0.56, 95%CI: 0.41-0.83), and the T(3) group had higher risk of low birth weight in offspring (OR=2.32, 95%CI: 1.59-3.89); compared with the traditional pattern T(2) group, the T(3) group had higher risk of premature (OR=2.62, 95%CI: 1.58-5.01); compared with the balanced pattern T(2) group, the T(3) group had a lower risk of spontaneous abortion (OR=0.73, 95%CI: 0.36-0.89); compared with the processing pattern T(2) group, the T(3) group had a higher risk of spontaneous abortion (OR=1.97, 95%CI: 1.36-3.34) and higher risk of stillbirth (OR=2.96, 95%CI: 1.49-6.26), and the T(1) group had a lower risk of stillbirths in offspring (OR=0.52, 95%CI: 0.33-0.83). Conclusion: The women of childbearing age in Shaanxi have different dietary patterns, and there may be a correlation between dietary patterns and adverse pregnancy outcomes.

A metabolomics approach to characterize raw, pasteurized, and ultra-high temperature milk using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry and multivariate data analysis.

We developed a metabolomics workflow using ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry to determine the effect of thermal treatment on milk composition and metabolites based on multivariate data analysis. We analyzed raw, pasteurized, and UHT milk samples. The samples were first centrifuged to remove the fat layer and mixed with methanol to precipitate proteins. Subsequently, the supernatant was analyzed by ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry in electrospray negative mode. Mass spectral data were acquired in MSE mode, a technique whereby both precursor and fragment mass spectral are simultaneously acquired by alternating between low and high collision energy (CE) during a single analytical run, to enable metabolite identification. Based on multivariate data analysis, these markers were significantly affected by thermal treatment. Among the 8 potential markers, we identified 7 oxylipids (9-hydroxydecanoic acid, 12-hydroxydodecanoic acid, 2-hydroxymyristic acid, 3-hydroxytetradecanoic acid, 5-hydroxyeicosatetraenoic acid, 3-hydroxyhexadecanoic acid, and 10-hydroxyoctadecanoic acid) and 1 phospholipid (LysoPE, hexadecanoyl-lysophosphatidylethanolamine). The oxylipids seemed to be adequate for distinguishing UHT milk from raw and pasteurized milk. The structures of the 8 potential markers were identified and characterized using informatics software. Our metabolomics workflow provides a fast approach for the identification of various types of milk.

Quantitative evaluation of diffusion-kurtosis imaging for grading endometrial carcinoma: a comparative study with diffusion-weighted imaging.

AIM: To evaluate the diagnostic performance of histogram analysis of diffusion kurtosis magnetic resonance imaging (DKI) and standard diffusion-weighted imaging (DWI) in discriminating tumour grades of endometrial carcinoma (EC). MATERIALS AND METHODS: Seventy-three patients with EC were included in this study. The apparent diffusion coefficient (ADC) value from standard DWI, apparent diffusion for Gaussian distribution (Dapp), and apparent kurtosis coefficient (Kapp) from DKI were acquired using a 3 T magnetic resonance imaging (MRI) system. The measurement was based on an entire-tumour analysis. Histogram parameters (Dapp, Kapp, and ADC) were compared between high-grade (grade 3) and low-grade (grade 1 and 2) tumours. The diagnostic performance of imaging parameters for discriminating high- from low-grade tumours was analysed using a receiver operating characteristic curve (ROC). RESULTS: The area under the ROC curve (AUC) of the 10th percentile of Dapp, 90th percentile of Kapp and 10th percentile of ADC were higher than other parameters in distinguishing high-grade tumours from low-grade tumours (AUC=0.821, 0.891 and 0.801, respectively). The combination of 10th percentile of Dapp and 90th percentile of Kapp improved the AUC to 0.901, which was significantly higher than that of the 10th percentile of ADC (0.810, p=0.0314) in differentiating high- from low-grade EC. CONCLUSION: Entire-tumour volume histogram analysis of DKI and standard DWI were feasible for discriminating histological tumour grades of EC. DKI was relatively better than DWI in distinguishing high-grade from low-grade tumour in EC.

Short communication: Microbiological quality of raw cow milk and its association with herd management practices in Northern China.

Contamination of raw milk with bacterial pathogens is potentially hazardous to human health. The aim of this study was to evaluate the total bacteria count (TBC) and presence of pathogens in raw milk in Northern China along with the associated herd management practices. A total of 160 raw milk samples were collected from 80 dairy herds in Northern China. All raw milk samples were analyzed for TBC and pathogens by culturing. The results showed that the number of raw milk samples with TBC <2 × 106 cfu/mL and <1 × 105 cfu/mL was 146 (91.25%) and 70 (43.75%), respectively. A total of 84 (52.50%) raw milk samples were Staphylococcus aureus positive, 72 (45.00%) were Escherichia coli positive, 2 (1.25%) were Salmonella positive, 2 (1.25%) were Listeria monocytogenes positive, and 3 (1.88%) were Campylobacter positive. The prevalence of S. aureus was influenced by season, herd size, milking frequency, disinfection frequency, and use of a Dairy Herd Improvement program. The TBC was influenced by season and milk frequency. The correlation between TBC and prevalence of S. aureus or E. coli is significant. The effect size statistical analysis showed that season and herd (but not Dairy Herd Improvement, herd size, milking frequency, disinfection frequency, and area) were the most important factors affecting TBC in raw milk. In conclusion, the presence of bacteria in raw milk was associated with season and herd management practices, and further comprehensive study will be powerful for effectively characterizing various factors affecting milk microbial quality in bulk tanks in China.

Combination of histidine, lysine, methionine, and leucine promotes ß-casein synthesis via the mechanistic target of rapamycin signaling pathway in bovine mammary epithelial cells.

The ratio of different AA in the diets of cows is vital to improve milk protein yield. ß-Casein is one of the important milk proteins with high nutritive value. However, the suitable ratio of essential amino acids (EAA) for the expression of ß-casein in the immortalized bovine mammary epithelial cell line is not fully characterized. This study employed response surface methodology to determine the optimal ratio of His, Lys, Met, and Leu on ß-casein expression level in vitro and clarified the effect of the 4 EAA on ß-casein via the mechanistic target of rapamycin (mTOR) signaling pathway. A central composite design containing 5 axial points per EAA and 28 combinations of the 4 EAA was used in our study. The results of response surface methodology and the changes of the mTOR-related signaling proteins were determined by western blot. The results showed that ß-casein level was significantly affected by all 4 EAA (R2 = 0.71). The optimum conditions for ß-casein expression are found to be 5.47 mM of His, 7.48 mM of Lys, 1.17 mM of Met, and 8.21 mM of Leu (His:Lys:Met:Leu = 5:6:1:7) in the designed scope of concentration. The interaction of Leu and Met significantly affected ß-casein expression (P < 0.01). The phosphorylation of mTOR (Ser2481), regulatory associated protein of target of rapamycin (Ser792), ribosomal protein S6 kinase 1 (Thr389), ribosomal protein S6 (Ser235/236), and eukaryotic elongation factor 2 (Thr56) was increased with the supplementation of either single EAA or an optimal combination of EAA. However, the phosphorylation of eukaryotic initiation factor 4E binding protein 1 (Thr37) was decreased with the addition of Lys, Met, or Leu alone. Furthermore, the phosphorylation (P) of eIF2α (Ser51) was decreased when Met was supplemented alone. Under the optimal mixture of 4 EAA, the phosphorylation of mechanistic target of rapamycin complex 1 signaling proteins was significantly greater than the single EAA supplementations and the expression of ß-casein was 98% as high as the positive control (i.e., medium with all AA). A similar trend was found with P-ribosomal protein S6 kinase 1 and P-ribosomal protein S6. In conclusion, the extracellular concentrations of His, Lys, Met, and Leu at a ratio of 5:6:1:7 maximized ß-casein expression in the immortalized bovine mammary epithelial cell line may occur via activation of the mechanistic target of rapamycin complex 1 signaling pathway.