LILRB4 signalling in leukaemia cells mediates T cell suppression and tumour infiltration.

Immune checkpoint blockade therapy has been successful in treating some types of cancer but has not shown clinical benefits for treating leukaemia1. This result suggests that leukaemia uses unique mechanisms to evade this therapy. Certain immune inhibitory receptors that are expressed by normal immune cells are also present on leukaemia cells. Whether these receptors can initiate immune-related primary signalling in tumour cells remains unknown. Here we use mouse models and human cells to show that LILRB4, an immunoreceptor tyrosine-based inhibition motif-containing receptor and a marker of monocytic leukaemia, supports tumour cell infiltration into tissues and suppresses T cell activity via a signalling pathway that involves APOE, LILRB4, SHP-2, uPAR and ARG1 in acute myeloid leukaemia (AML) cells. Deletion of LILRB4 or the use of antibodies to block LILRB4 signalling impeded AML development. Thus, LILRB4 orchestrates tumour invasion pathways in monocytic leukaemia cells by creating an immunosuppressive microenvironment. LILRB4 represents a compelling target for the treatment of monocytic AML.

[Interpretation of the reporting specifications for mixed methods systematic reviews].

The number of mixed methods systematic reviews (MMSRs) published internationally is increasing day by day, thanks to the continuous development and improvement of MMSRs methodological guidelines and reporting specification, which effectively promote the depth and breadth of evidence synthesis and integration results. However, the application of this method has yet to be popularized in China. With the continuous development of mixed methods research and evidence-based medicine in our country, the number of MMSRs will gradually increase. This paper aims to analyze the reporting specifications for MMSRs with cases to improve the quality of evidence integration and reporting standardization of domestic relevant researchers in MMSRs.

[Role of mitochondrial autophagy and the curative effect of rehmannia glutinosa leaves total glycoside capsules on nucleos(t)ide drug-induced renal injury].

Objective: To study the curative effect of rehmannia glutinosa leaves total glycoside capsules and the role of mitochondrial autophagy on nucleos(t)ide drug-induced renal injury. Methods: Adefovir dipivoxil (ADV) was used to construct a hepatitis B virus (HBV) transgenic mouse model for renal injury. Renal function was measured in each group at one and two weeks of modeling. Mitochondrial autophagy indicators were measured at two weeks of modeling in renal tissue. Transmission electron microscopy was used to detect mitochondrial autophagy phenomena in renal tissue. The model was established for two weeks. Mouse with renal injury were treated with rehmannia glutinosa leaves total glycoside capsules or isotonic saline for eight weeks by intragastric administration. Renal function was measured. Renal tissue morphology was observed. Mitochondrial autophagy indicators were detected in renal tissue. The protective effect of different concentrations of verbascoside (the main active ingredient of rehmannia glutinosa capsule) was observed on HK-2 cell damage induced by ADV. HK-2 cells were divided into control, ADV, and ADV plus verbascoside groups. The effects of verbascoside at different times and concentrations were observed on the HK-2 mitochondrial autophagy indicators. Fifty patients with chronic hepatitis B were collected who presented with renal injury after treatment with nucleos(t)ide analogs. The random number method was used to divide 29 cases into a control group that received conventional treatment. The treatment group of 21 cases was treated with rehmannia glutinosa leaves total glycoside capsules on the basis of the control group. Serum creatinine (Scr) and urinary protein were detected at eight weeks.The χ(2) test or t-test was used for statistical analysis. Results: Compared with the control group, two weeks of modeling in the ADV group induced renal function injury in HBV mice. The expression of autophagy indicators was higher in the renal tissue of the ADV group than that of the control group. Transmission electron microscopy had revealed mitochondrial autophagy in the renal tissue of the ADV group. Compared with the control group, the renal function of HBV mice treated with rehmannia glutinosa leaves total glycoside capsules improved for two months, and the expressions of autophagy indicators were down-regulated.Verbascoside promoted proliferation in ADV-damaged HK-2 cells, and the expression of autophagy indicators was down-regulated compared with the ADV alone group. In 50 patients with renal function injury, the urinary protein improvement was significantly superior in the treatment group than that in the control group, with eighteen and three cases being effective and ineffective in the treatment group and 12 and 17 cases being effective and ineffective in the control group, with a statistically significant difference (χ(2) = 9.975 0, P = 0.001 6). Serum creatinine was decreased in the treatment group compared with the control group, with 11 and 10 cases being effective and ineffective in the treatment group and 12 and 17 cases being effective and ineffective in the control group, with no statistically significant difference (χ(2) = 0.593 5, P = 0.441 1). Conclusion: Rehmannia glutinosa leaves total glycoside capsule can improve the nucleos(t)ide drug-induced renal function injury in chronic hepatitis B, possibly playing a role via inhibiting PINK1/Parkin-mediated mitochondrial autophagy.

[Technological development of robot-assisted radical prostatectomy].

The surgical outcomes of robot-assisted radical prostatectomy have shown remarkable improvement over the last two decades since its advent, due to advances in surgical concepts, techniques, and equipment. Today, ongoing research aims to compare the benefits and drawbacks of various surgical approaches, such as anterior, posterior, lateral, transvesical, and transperineal approaches, in terms of tumor control, functional recovery, and complication reduction in order to achieve the goal of pentafecta (no postoperative complications and negative surgical margins in addition to trifecta) to the maximum extent. It is imperative to explore and integrate novel technologies such as 5G remote surgery and artificial intelligence into the clinical practice of robot-assisted radical prostatectomy while ensuring patient safety, which has immense potential for substantial benefits to patients with prostate cancer.

[Functional outcomes of robot-assisted radical prostatectomy with preservation of pelvic stabilized structure and early elevated retrograde liberation of neurovascular bundle].

Objectives: To examine the functional outcomes of robot-assisted radical prostatectomy (RARP) with preservation of pelvic floor stabilized structure and early elevated retrograde liberation of the neurovascular bundle (PEEL). Methods: This study was a retrospective cohort study. Between June 1, 2022, and March 20, 2023, 27 cases of RARP with PEEL and 153 cases of RARP with preservation of pelvic floor stabilized structure (PPSS) were included in this study. All patients were males, aged (62.5±5.2) years (range: 50 to 73 years). There were 18 cases of ≤T2b stage and 9 cases of T2c stage. After 1∶1 propensity score matching, the postoperative functional outcomes of 27 cases of RARP with PEEL and 27 cases of RARP with PPSS were compared. All surgeries were performed by a single surgeon and included patients were clinically staged as cT1-2N0M0 without preoperative urinary incontinence or erectile dysfunction. In RARP with PEEL, the prostate was cut near the midline at the front when dissecting the neurovascular bundle, dissection was performed between the visceral layer of the pelvic fascia and the prostatic fascia, preserving the parietal layer and the visceral layer of the pelvic fascia, and the neurovascular bundle was retrogradely released from the apex. The cumulative probability curve was plotted using the Kaplan-Meier method and the Log-rank test was used to compare the differences in functional outcomes between the two groups. Univariate and multivariate analysis with the Cox proportional hazards model was used to compare postoperative urinary continence and sexual function. Results: The recovery time of continence and potency was significantly longer in the PPSS group than in the PEEL group (all P<0.05). The continence rate of the PEEL group was significantly higher than that of the PPSS group (92.59% vs. 68.10%, P=0.026) at 3 months after surgery. The potency rate of the PEEL group was also significantly higher than that of the PPSS group (40.70% vs. 15.10%, P=0.037) at 3 months after surgery. In the univariate analysis, compared to the PPSS technique, the PEEL technique was associated with a shorter recovery time of continence (HR=1.94, 95%CI: 1.08 to 3.48, P=0.027) and a shorter recovery time of potency (HR=2.06, 95%CI: 1.03 to 4.13, P=0.042). In the multivariate analysis, the PEEL technique was an independent prognosis factor for postoperative recovery of continence (HR=2.05, 95%CI: 1.01 to 4.17, P=0.047) and potency (HR=3.57, 95%CI: 1.43 to 8.92, P=0.007). All the cases of the PPSS group and the PEEL group were performed successfully with negative surgical margins. Conclusion: Compared with PPSS, PEEL may be more conducive to the recovery of urinary continence and sexual function after RARP.

Effect of pulmonary function on bone mineral density in the United States: results from the NHANES 2007-2010 study.

The relationship between pulmonary function (PF) and bone mineral density (BMD) remains controversial. In the US population, we found a positive association between PF and BMD. Mixed variables such as age, gender, and race may influence this association. INTRODUCTION: Based on the data from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2010, this study explored whether there is a correlation between PF (1st second forceful expiratory volume as a percentage of expected value (FEV1(% predicted)), (one-second rate (FEV1/FVC)), and bone mineral density. METHODS: We evaluated the relationship between PF and BMD in 6327 NHANES subjects (mean age 44.51 ± 15.64 years) from 2007 to 2010. The bone mineral density of the whole femur was measured by dual-energy X-ray absorptiometry (DXA). After adjusting for a wide range of confounders, we examined the relationship between PF and total femur BMD using a multiple linear regression model. RESULTS: Correction of race, age, alcohol consumption, body mass index (BMI), height, poor income ratio (PIR), total protein, serum calcium, serum uric acid, cholesterol, serum phosphorus, blood urea nitrogen, FEV1(% predicted), and femur BMD were positively correlated (ß = 0.032, 95% CI: 0.010-0.054, P = 0.004). FEV1/FVC was positively correlated with spine BMD (ß = 0.275 95%CI: 0.102-0.448, P = 0.002). CONCLUSIONS: Our study shows that PF is positively associated with BMD in the US population. A variety of factors such as race and age influence this relationship. the relationship between PF and BMD needs to be further investigated, including specific regulatory mechanisms and confounding factors.

Expression of ICAM-1 and E-selectin in different metabolic obesity phenotypes: discrepancy for endothelial dysfunction.

OBJECTIVES: Endothelial dysfunction, the earliest vascular alteration, is a consequence of metabolic disorders associated with obesity. However, it is still unclear whether a proportion of obese individuals without metabolic alterations associated with obesity, defined as "metabolically healthy obesity (MHO)", exhibit better endothelial function. We therefore aimed to investigate the association of different metabolic obesity phenotypes with endothelial dysfunction. METHODS: The obese participants without clinical cardiovascular disease from the MESA (Multi-Ethnic Study of Atherosclerosis) were allocated to the different metabolic obesity phenotypes based on their metabolic status, including MHO and metabolically unhealthy obesity (MUO). Associations of metabolic obesity phenotypes with the biomarkers of endothelial dysfunction, including soluble intercellular adhesion molecule-1 (sICAM-1) and soluble E-selectin (sE-selectin), were evaluated using multiple linear regression models. RESULTS: Plasma levels of sICAM-1 and sE-selectin were respectively measured in 2371 and 968 participants. Compared to the non-obese participants, those with MUO were associated with higher concentrations of sICAM-1 (ß 22.04, 95% CI 14.33-29.75, P < 0.001) and sE-selectin (ß 9.87, 95% CI 6.00-13.75, P < 0.001) after adjusting for confounders. However, no differences were found for the concentrations of sICAM-1 (ß 0.70, 95% CI - 8.91 to 10.32, P = 0.886) and sE-selectin (ß 3.69, 95% CI - 1.13 to 8.51, P = 0.133) in the participants with MHO compared to the non-obese participants. CONCLUSIONS: Individuals with MUO were associated with elevated biomarkers of endothelial dysfunction, but the association with endothelial dysfunction was not found in those with MHO, indicating that the individuals with MHO might exhibit better endothelial function.

[Genetic diagnosis of microcephaly].

Objective: To explore the diagnostic value of chromosome karyotype analysis, chromosomal microarray analysis (CMA) and whole exome sequencing (WES) in microcephaly. Methods: A total of 9 cases of microcephaly fetuses diagnosed by prenatal ultrasound or children with microcephaly diagnosed after birth were selected from the Sixth Affiliated Hospital of Guangzhou Medical University from January 2014 to August 2022.Karyotype analysis and/or CMA were used to detect. The cases with negative karyotype analysis and CMA results were further sequenced by trio-based WES (Trio-WES). Then the coding genes contained in the pathogenic copy number variation (CNV) fragments were analyzed by gene ontology (GO) enrichment. The genes related to the development of the central nervous system contained in the pathogenic CNV and the pathogenic genes found by Trio-WES were combined for gene interaction network analysis. Results: In this study, 9 cases of microcephaly were recruited, with the time of diagnosis ranged from 23 weeks of gestation to 7 years after birth, and the head circumference of fetus or children ranged from 18.3 to 42.5 cm (-7SD to -2SD). Karyotype analysis was detected in all 9 cases and no abnormality result was found. Eight cases were detected by CMA, and one abnormal was found. Five cases were detected by Trio-WES, and two cases were detected with likely pathogenic genes. The GO enrichment analysis of the coding gene in the 4p16.3 microdeletion (pathogenic CNV) region showed that: in biological process, it was mainly concentrated in phototransduction, visible light; in terms of molecular function, it was mainly concentrated in fibroblast growth factor binding; in terms of cell components, it was mainly concentrated in rough endoplasmic reticulum. Gene interaction network analysis suggested that CDC42 gene could interact with CTBP1, HTT and ASPM gene. Conclusions: CMA could be used as a first-line detection technique for microcephaly. When the results of chromosome karyotype analysis and/or CMA are negative, Trio-WES could improve the detection rate of pathogenicity of microcephaly.

[The advances of allergen component detection in IgE-mediated food allergy].

There are many types in food allergy, and the most common is mediated by IgE. Currently, the diagnosis of food allergy mainly relied on skin prick test and serum specific IgE of allergen extract, which can not identify cross-sensitization. Component-resolved diagnosis (CRD) can identify the major allergen components and cross-components of food allergens, which plays an important role in dietary guidance, prognosis monitoring and diagnosis of special types of IgE-mediated food allergy. This article enumerates clinical characteristics of the IgE-mediated common food allergies, such as milk, egg and seafood allergy, and special type of food allergy, such as cat pork syndrome, oral allergy syndrome, α-gal syndrome and food-dependent exercise-induced anaphylaxis, summarizes the advances of CRD in these types of IgE-mediated food allergy, in order to provide an evidence for the diagnosis, treatment and prevention of IgE-mediated food allergy.

[Chinese expert consensus on management of dyslipidemia in the elderly].

Dyslipidemia is an important risk factor of atherosclerotic cardiovascular disease (ASCVD). Statins delay the occurrence and development of ASCVD, and reduce the risk of cardiovascular events and death. Due to safety concerns, there exist insufficient use of lipid-lowering agents and a high withdrawal rate of the agents in the elderly. To promote the prevention and treatment of ASCVD, this expert consensus is issued and focuses on the management of dyslipidemia of Chinese elderly basing on the clinical evidence of the use of lipid-lowering drugs by the elderly, and the lipid management guidelines and expert consensus recommendations at home and abroad.

[Research advances of metabolomics in early diagnosis of hepatocellular carcinoma].

Primary liver cancer is the second leading cause of death from malignant tumors in China, and hepatocellular carcinoma (HCC) is the main type. The disease stage at the time of HCC diagnosis largely determines the efficacy of subsequent treatment. Due to the HCC screening among high-risk population has not yet popularized, and the current diagnose method of early HCC is not satisfactory, the early HCC diagnosis rate is less than 30% in China. Metabolomics research emerging in recent years has promoted the research progress of HCC in many fields, such as elaborating the mechanism of occurrence and development, early prevention and diagnosis, exploring drug treatment targets. At the same time, a large number of serum metabolites with excellent sensitivity and specificity were discovered, which made up for the deficiency of traditional serological indicators and helped the early screening and early diagnosis of HCC. This review will summarize the studies on serum metabolomic markers of HCC in recent 5 years, explore the role of metabolomics in the early prediction and diagnosis of HCC and its application prospect.

[Effects of celastrol on autophagy and endoplasmic reticulum stress-mediated apoptosis in a mouse model of nonalcoholic fatty liver disease].

Objective: To investigate the effect of celastrol (CEL) on autophagy and endoplasmic reticulum stress-mediated apoptosis in a mouse model of nonalcoholic fatty liver disease (NAFLD). Methods: Eighteen male C57BL/6J mice were randomly divided into normal control (NC, n=6), high-fat diet (HFD, n=6) and celastrol group (HFD+CEL, n=6). The normal control group was fed with regular diet, and the high-fat diet and celastrol group were fed with high-fat diet for 12 weeks. After successful modeling, celastrol group were injected with 100 µg⋅kg-1⋅d-1 celastrol intraperitoneally for 4 weeks, and NC and HFD group were injected intraperitoneally with the same doses of normal saline. Serum concentrations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) were measured in mouse after 4-weeks of intervention. HE and Oil Red O staining were used to observe the pathomorphological changes and lipid droplet deposition in mouse liver, and the findings were scored according to NAFLD activity score (NAS). Western blot was used to detect the expression levels of liver microtubule associated protein 1 light chain 3 (LC3), P62, glucose-regulated protein 78 (GRP78), protein kinase R-like endoplasmic reticulum kinase (PERK), phosphorylated PERK (p-PERK), activated transcription factor 4 (ATF4), C/EBP homologous protein (CHOP), cleaved Caspase-3(cleaved caspase-3), B-cell lymphoma-2 (Bcl-2) and Bcl-2 related X protein (Bax).TUNEL staining was used to observe the apoptosis of hepatocytes. One-way analysis of variance was used for the intergroup comparison. Results: Serum levels of ALT (68.71±8.57) U/L, AST (209.63±28.64) U/L, TG (0.97±0.14) mmol/L, TC (4.12±0.64) mmol/L, and LDL -C (0.40±0.06) mmol/L were lower in celastrol group mouse than HFD group [(110.19±10.79) U/L, (399.72±73.47) U/L, (1.44±0.13) mmol/L, (5.65±0.54) mmol /L, (0.61±0.07) mmol/L] (P<0.05); while the serum HDL-C level (1.29±0.17) mmol/L was higher in celastrol than HFD group (0.72±0.13) mmol/L (P<0.05). HE and Oil Red O staining showed that lipid deposition and intralobular inflammation were apparent in the liver tissue of HFD group mouse, and the NAS score was significantly increased, while the hepatocyte steatosis and intralobular inflammation were alleviated after celastrol intervention, and the NAS score was decreased significantly (P<0.05). Compared with HFD group, the ratio of LC3II/I was significantly increased in the liver of celastrol group mouse, and the P62 was significantly decreased (P<0.05). Meanwhile, the expression level of GRP78, p-PERK/PERK , ATF4, and CHOP was significantly lower in celastrol than HFD group (P<0.05). In addition, the expressions of cleaved caspase-3 and Bax were significantly lower in celastrol than HFD group, and the expression of Bcl-2 was significantly increased (P<0.05). At the same time, the apoptosis rate of hepatocytes was also significantly lower in celastrol than HFD group (P<0.05). Conclusion: Celastrol can effectively alleviate the lipid deposition, protect hepatocytes and delay the progression of non-alcoholic fatty liver disease in mouse liver with non-alcoholic fatty liver disease. In addition, its mechanism of action may be related to the induction of autophagy, inhibition of endoplasmic reticulum stress PERK/ATF4/CHOP pathway and its mediated apoptosis.

[Diagnosis and treatment status of perioperative anemia in patients with gastrointestinal neoplasms: a multi-center study in Hubei Province].

Objective: To investigate the incidence and treatment of perioperative anemia in patients with gastrointestinal neoplasms in Hubei Province. Methods: The clinicopathological data of 7 474 patients with gastrointestinal neoplasms in 62 hospitals in 15 cities (state) of Hubei Province in 2019 were collected in the form of network database. There were 4 749 males and 2 725 females. The median age of the patients was 62 years (range: 17 to 96 years). The hemoglobin value of the first time in hospital and the first day after operation was used as the criterion of preoperative anemia and postoperative anemia. Anemia was defined as male hemoglobin <120 g/L and female hemoglobin <110.0 g/L, mild anemia as 90 to normal, moderate anemia as 60 to <90 g/L, severe anemia as <60 g/L. The t test and χ2 test were used for inter-group comparison. Results: The overall incidence of preoperative anemia was 38.60%(2 885/7 474), and the incidences of mild anemia, moderate anemia and severe anemia were 25.09%(1 875/7 474), 11.37%(850/7 474) and 2.14%(160/7 474), respectively. The overall incidence of postoperative anemia was 61.40%(4 589/7 474). The incidence of mild anemia, moderate anemia and severe anemia were 48.73%(3 642/7 474), 12.20%(912/7 474) and 0.47%(35/7 474), respectively. The proportion of preoperative anemia patients receiving treatment was 26.86% (775/2 885), and the proportion of postoperative anemia patients receiving treatment was 14.93% (685/4 589). The proportions of preoperative anemia patients in grade ⅢA, grade ⅢB, and grade ⅡA hospitals receiving treatment were 26.12% (649/2 485), 32.32% (85/263), and 29.93% (41/137), and the proportions of postoperative anemia patients receiving treatment were 14.61% (592/4 052), 22.05% (73/331), and 9.71% (20/206). The proportion of intraoperative blood transfusion (16.74% (483/2 885) vs. 3.05% (140/4 589), χ²=434.555, P<0.01) and the incidence of postoperative complications (17.78% (513/2 885) vs. 14.08% (646/4 589), χ²=18.553, P<0.01) in the preoperative anemia group were higher than those in the non-anemia group, and the postoperative hospital stay in the preoperative anemia group was longer than that in the non-anemia group ((14.1±7.3) days vs. (13.3±6.2) days, t=5.202, P<0.01). Conclusions: The incidence of perioperative anemia in patients with gastrointestinal neoplasms is high. Preoperative anemia can increase the demand for intraoperative blood transfusion and affect the short-term prognosis of patients. At present, the concept of standardized treatment of perioperative anemia among gastrointestinal surgeons in Hubei Province needs to be improved.

[Comparative study of decentration, tilt and visual quality after implantation of aspherical intraocular lenses].

Objective: To compare the difference of decentration and tilt among 4 kinds of aspherical intraocular lenses (IOLs), and to analyze their objective visual quality. Methods: Prospective non-randomized controlled clinical trial. Age-related cataract patients who planned to undergo phacoemulsification and IOL implantation in the Affiliated Hospital of North Sichuan Medical College from April to June in 2020 were divided into ZCB00 group, SN60WF group, A1-UV group, and AO group according to IOL types. Thirty right eyes and thirty left eyes were selected in each group. Before operation and at 1 day, 1 week and 1 month postoperatively, decentration and tilt values were measured by a new swept-source anterior-segment optical coherence tomography device (CASIA2), and wavefront aberrations, objective scatter index (OSI), modulation transfer function cut off frequency (MTF cut off) and Strehl ratio (SR) were also examined. Values of decentration, tilt and visual quality compared among 4 groups were took from the right eye. One-way analysis of variance was used for inter-group comparison, and repeated measurement one-way analysis of variance was used for intra-group comparison. Data between right eyes and left eyes from all the individuals were compared by independent sample t-test. Results: A total of 181 patients (240 eyes) were enrolled, and 169 patients (224 eyes) completed the follow-up (114 right eyes and 110 left eyes). There were 77 males and 92 females, with an age of (69±9) years. There was no significant difference in gender, age, axial length, decentration and tilt of crystalline lens and IOL power among 4 groups (all P>0.05). At 1 day, 1 week and 1 month postoperatively, there was significant difference in decentration value among 4 groups (F=7.11, 6.12, 4.66; all P<0.05). For further pairwise comparison, the decentration value of SN60WF group was higher than that of the other 3 groups at 1 day and 1 week postoperatively, and the decentration value of SN60WF group was (0.259±0.101) mm at 1 month postoperatively, which was higher than that of ZCB00 group (0.177±0.099) mm and AO group (0.163±0.122) mm, and the differences were statistically significant (using SNK-q test, both P<0.05). The IOL tilt value in the ZCB00 group, SN60WF group, A1-UV group, and AO group at 1 month postoperatively were (4.806±1.129)°, (5.080±1.309)°, (4.586±1.338)°, (5.112±1.406)°, respectively. No significant difference in tilt value among 4 groups was found at any time after surgery (all P>0.05). In each group, there was no significant difference in decentration and tilt value at different postoperative time points (all P>0.05). At 1 month postoperatively, there was no significant difference in decentration and tilt at horizontal and vertical directions respectively among 4 groups (all P>0.05), and in each group, there was no significant difference in decentration and tilt value between right eyes and left eyes (all P>0.05), and IOLs tended to tilt towards the inferonasal or inferotemporal direction in both eyes. With 4-mm and 6-mm pupil diameter, there was significant difference in internal (F=131.32, 85.17) and ocular (F=46.64, 47.55) spherical aberration among 4 groups (all P<0.01). For further pairwise comparison, the spherical aberration of AO group was higher than that of the other 3 groups, and the difference was statistically significant (using SNK-q test, all P<0.05). There was no significant difference in OSI, MTF cut off and SR among 4 groups (all P>0.05). Conclusions: The four types of IOLs show decentration and tilt in varying degrees after implantation in the capsular bag, but this difference do not lead to clinical significance. Human eyes have tolerance to mild decentration and tilt of aspheric IOLs, showing good visual quality.

Linoleic acid and α-linolenic acid inhibit conjugative transfer of an IncX4 plasmid carrying mcr-1.

AIMS: The aim of this study was to determine the effects of unsaturated fatty acids on clinical plasmids. METHODS AND RESULTS: Two unsaturated fatty acids, linoleic acid (LA) and α-linolenic acid (ALA) at final concentration 0, 0·03, 0·3 and 3 mmol l-1 , respectively, were used to assess the effects on conjugative transfer of a mcr-1-harbouring plasmid pCSZ4 (IncX4) in conjugation experiment. The inhibitory mechanisms were analysed by molecular docking and the gene expression of virB11 was quantitated by qRT-PCR. Target plasmid diversity was carried out by TrwD/VirB11 homology protein sequence prediction analysis. Our results showed that LA and ALA inhibit plasmid pCSZ4 transfer by binding to the amino acid residues (Phe124 and Thr125) of VirB11 with dose-dependent effects. The expression levels of virB11 gene were also significantly inhibited by LA and ALA treatment. Protein homology analysis revealed a wide distribution of TrwD/VirB11-like genes among over 37 classes of plasmids originated from both Gram-negative and Gram-positive bacteria. CONCLUSIONS: This study demonstrates representing a diversity of plasmids that may be potentially inhibited by unsaturated fatty acids. SIGNIFICANCE AND IMPACT OF THE STUDY: Our work reported here provides additional support for application of curbing the spread of multiple plasmids by unsaturated fatty acids.

High pressure homogenization inactivation of Escherichia coli and Staphylococcus aureus in phosphate buffered saline, milk and apple juice.

High pressure homogenization (HPH) offers new opportunities for food pasteurization/sterilization. Escherichia coli and Staphylococcus aureus suspended in phosphate buffered saline (PBS) buffer, milk and apple juice at initial concentration of ~106 log10 CFU per ml were subjected to HPH treatments up to 200 MPa with inlet temperatures at 4-40°C. After HPH at 200 MPa with the inlet temperature at 40°C, the count of E. coli suspended in PBS, milk and apple juice reduced by 3·42, 3·67 and 3·19 log10 CFU per ml respectively while the count of S. aureus decreased by 2·21, 1·02 and 2·33 log10 CFU per ml respectively suggesting that S. aureus was more resistant. The inactivation data were well fitted by the polynomial equation. Milk could provide a protective effect for S. aureus against HPH. After HPH at 200 MPa with the inlet temperature at 20°C, the cell structure of E. coli was destroyed, while no obvious damages were found for S. aureus.

[Efficacy analysis of retroperitoneal laparoscopic selective renal artery branch occlusion and nephron sparing surgery for ≥ T1b stage renal carcinoma].

Objective: To investigate the safety and efficacy of retroperitoneal laparoscopic selective renal artery branch occlusion with nephron sparing surgery in patients with renal carcinoma of stage ≥ T1b. Methods: From July 2016 to September 2020, 35 patients with renal cancer ≥T1b underwent retroperitoneoscopic nephron sparing surgery in the First Affiliated Hospital of Shenzhen University. The surgical methods were retroperitoneoscopic nephron sparing surgery with total renal artery occlusion (group A) or selective renal artery branch occlusion (group B). Operation time, heat ischemia time, blood transfusion rate, positive margin rate, intraoperative blood loss, postoperative complications and length of hospital stay were compared between the two groups, and the total glomerular filtration rate (GFR) and the single-nephron glomerular filtration rate (sGFR) of the offected kidneys were compared between the two groups before, 3 months after and 12 months after surgery. Results: Among the 35 patients, 19 were male and 16 were female, aged (55.7±8.4) years and the body mass index is (24.6±3.1) kg/m2. The tumor diameter was (54.7±10.3) mm. The difference was statistically significant of operative time between group A and B [(103.5±14.3) vs (123.2±14.1) min,P=0.003]. There were no significant differences in thermal ischemia time, blood transfusion rate, positive margin, intraoperative blood loss, incidence of postoperative complications and length of hospital stay between the two groups (all P>0.05). The decrease of renal sGFR in the group A was significantly higher than group B at 3 months and 12 months after surgery [(23.1±3.6) vs (29.1±7.1) ml/min;(25.9±4.7) vs (30.7±7.2),both P<0.05]. Conclusion: Retroperitoneal laparoscopic selective renal artery branch occlusion and neon-sparing surgery for patients with ≥ T1b stage renal carcinoma is a safe and effective surgical method, which can well protect the renal function of patients in the early postoperative stage without increasing intraoperative blood loss and postoperative complications.

[Distribution and metabolism of toxicants in rats with phenol burn].

Objective: To study the distribution and metabolism of toxicants in rats after phenol burn. Methods: In February 2019, SPF-grade healthy SD male rats were transdermally exposed to 6 mg/kg phenol to create a 5% body surface burn model of rats. High performance liquid chromatography was used to determine phenol content in rat plasma and kidney tissues after 0.25, 0.75, 2, 4, 8, 16, and 32 h, respectively. The kinetic parameters of phenol were calculated by DAS 2.0 software, and the kidney targeting of phenol was evaluated. Results: The area under the blood concentration-time curve at 0-8 h (AUC(0-8)) of the rat after phenol burn was (28.741±6.485) µg/ml·h, and the area under the blood concentration-time curve from 0 to infinite time (AUC(0-∞)) was (30.354±6.424) µg/ml·h, half-life (t(1/2)) was (2.111±0.632) h, peak concentration (C(max)) was (16.287±4.870) µg/ml, mean residence time (MRT) was (1.854±0.148) h. The target efficiency (DTE) of rat kidney was 2.91. Conclusion: Phenol burn rats have fast percutaneous absorption, rapid elimination of phenol, and have high clearance rate, short MRT, and weak substance accumulation. Phenol has relatively obvious selectivity to the kidneys.

Macrophages promote cell proliferation in colorectal cancer via IL-1ß-mediated downregulation of miR-28-3p.

Infiltration of macrophages is associated with tumor progression and poor prognosis in multiple malignancies, but the underlying mechanisms by which macrophages contribute to colorectal cancer (CRC) have not yet been elucidated. The purpose of this study was to discuss the potential mechanisms of macrophages in CRC. The MTT assay was used to assess cell viability. The expression of the proliferation-related marker PCNA was detected by Western blot analysis. The 10 most important factors (PDGF, VEGF, TNFα, bFGF, IL-8, TGF-ß, IFN-γ, SPARC, IL-1ß and IL-6) secreted by macrophages were knocked down by RNA interference (RNAi), and the mRNA expression levels of these 10 factors were analyzed by qRT-PCR. The effect of these factors on cell proliferation was assessed by the MTT assay. The miRNAs regulated by IL-1ß in CRC cells were identified by miRNA microarray and qRT-PCR analyses. The proliferation ability of miR-28-3p inhibitor on CRC cells was detected by colony formation assay. The association of IL-1ß and miR-28-3p expression with the clinicopathological characteristics in patients with CRC was analyzed by TCGA RNA-seq data. As a result, macrophages promoted the proliferation of CRC cells in a time- and number-dependent manner, and these effects were associated with the upregulation of PCNA and the macrophage-secreted cytokine IL-1ß, which had the most significant effect on CRC cell proliferation. Furthermore, downregulation of miR-28-3p was induced by IL-1ß in CRC cells. The miR-28-3p inhibitor promoted the proliferation in CRC cells. Moreover, upregulation of IL-1ß expression or downregulation of miR-28-3p expression was associated with poor survival in patients with CRC. Therefore, these data demonstrated that macrophages promoted CRC cell proliferation via IL-1ß-mediated downregulation of miR-28-3p.

Capacitation IVM improves cumulus function and oocyte quality in minimally stimulated mice.

PURPOSE: Oocyte in vitro maturation (IVM) is a patient-friendly reproductive technology but lower success rates than IVF have limited its uptake. Capacitation-IVM (CAPA-IVM) is an innovative new IVM system currently undergoing clinical evaluation. This study aimed to determine temporal effects of the pre-IVM phase of CAPA-IVM on cumulus function and oocyte developmental competence in mildly-stimulated mice. METHODS: Immature cumulus oocyte complexes (COCs) derived from mildly stimulated (23 h PMSG) 28-day-old mice underwent pre-IVM for 0-24 h in medium containing c-type natriuretic peptide (CNP), E2, FSH and insulin, prior to IVM (CAPA-IVM). The effect of pre-IVM duration on cumulus cell function and embryo development post-CAPA-IVM/IVF was assessed. RESULTS: Day 6 blastocyst rate increased incrementally with increasing pre-IVM duration: 40.6 ± 2.0%, 45.8 ± 1.2%, 52.2 ± 3.5%, 53.3 ± 5.9%, and 59.9 ± 2.5% for 0, 2, 6, 12, and 24 h pre-IVM, respectively (P < 0.01). DNA content/COC, a measure of cumulus cell proliferation, was significantly higher with 24 h pre-IVM group compared to 0, 2, or 6 h pre-IVM (P < 0.001). Pre-IVM for 24 h significantly increased cumulus expansion and mRNA expression of matrix genes Has2 and Tnfaip6 and Areg relative to no pre-IVM control (P < 0.01). Cumulus-oocyte gap-junctional communication (GJC) was maintained throughout 24 h pre-IVM (P < 0.0001), and GJC loss was slowed during the subsequent IVM phase, whilst meiotic resumption was accelerated (P < 0.05). Pre-IVM increased COC ATP and ADP content (P < 0.05), but not AMP, ATP/ADP, and energy charge. CONCLUSION: The pre-IVM phase of CAPA-IVM improves the quality of IVM oocytes in a temporally dependent manner and significantly influences cumulus cell function including increased cell proliferation, cumulus expansion, and prolonged cumulus-oocyte GJC.