Phase I study of MSB2311, a novel pH-dependent anti-PD-L1 monoclonal antibody, treating patients with advanced solid tumors and lymphoma.

MSB2311 is a novel pH-dependent humanized anti-programmed death-ligand 1 (PD-L1) monoclonal antibody. This phase I study primarily aimed to determine the maximum tolerated dose (MTD)/recommended phase 2 dose level (RP2D) of MSB2311 in patients with advanced solid tumors or lymphoma. MSB2311 was intravenously administered at 3, 10, and 20 mg/kg every 3 weeks (Q3W) and 10 mg/kg every 2 weeks (Q2W) using 3 + 3 design. During expansion phase, eligible patients with either PD-L1 overexpression, Epstein-Barr Virus positive, microsatellite instability high/mismatch repair deficient, or high tumor mutation burden tumors were treated at RP2D. A total of 37 Chinese patients were treated, including 31 with solid tumors and 6 lymphoma. No dose limiting toxicity was reported and MTD was not reached. The trial was expanded at 20 mg/kg Q3W or 10 mg/kg Q2W, both of which were determined as RP2D. Most common drug-related treatment-emergent adverse events were anemia (43.2%), aspartate aminotransferase increase (27.0%), proteinuria (21.6%), alanine aminotransferase increase and hypothyroidism (18.9% each), thyroid stimulating hormone increased and hyperglycemia (16.2% each). Out of 20 efficacy evaluable patients with biomarker positive solid tumors, 6 achieved confirmed partial response with the median duration of response of 11.0 months (95% CI 7.0-11.4) and 4 had stable disease, resulting an objective response rate of 30.0% (95% CI 11.9, 54.3) and disease control rate of 50.0% (95% CI 27.2, 72.8). One partial response was also observed among 6 patients with lymphoma. MSB2311 demonstrated a manageable safety profile and promising antitumor activity in patients with advanced solid tumors and lymphomas.

A compendium of mitochondrial molecular characteristics provides novel perspectives on the treatment of rheumatoid arthritis patients.

Rheumatoid arthritis (RA) is an autoimmune disease that exhibits a high degree of heterogeneity, marked by unpredictable disease flares and significant variations in the response to available treatments. The lack of optimal stratification for RA patients may be a contributing factor to the poor efficacy of current treatment options. The objective of this study is to elucidate the molecular characteristics of RA through the utilization of mitochondrial genes and subsequently construct and authenticate a diagnostic framework for RA. Mitochondrial proteins were obtained from the MitoCarta database, and the R package limma was employed to filter for differentially expressed mitochondrial genes (MDEGs). Metascape was utilized to perform enrichment analysis, followed by an unsupervised clustering algorithm using the ConsensuClusterPlus package to identify distinct subtypes based on MDEGs. The immune microenvironment, biological pathways, and drug response were further explored in these subtypes. Finally, a multi-biomarker-based diagnostic model was constructed using machine learning algorithms. Utilizing 88 MDEGs present in transcript profiles, it was possible to classify RA patients into three distinct subtypes, each characterized by unique molecular and cellular signatures. Subtype A exhibited a marked activation of inflammatory cells and pathways, while subtype C was characterized by the presence of specific innate lymphocytes. Inflammatory and immune cells in subtype B displayed a more modest level of activation (Wilcoxon test P < 0.05). Notably, subtype C demonstrated a stronger correlation with a superior response to biologics such as infliximab, anti-TNF, rituximab, and methotrexate/abatacept (P = 0.001) using the fisher test. Furthermore, the mitochondrial diagnosis SVM model demonstrated a high degree of discriminatory ability in distinguishing RA in both training (AUC = 100%) and validation sets (AUC = 80.1%). This study presents a pioneering analysis of mitochondrial modifications in RA, offering a novel framework for patient stratification and potentially enhancing therapeutic decision-making.

Melatonin Alleviates Copper Toxicity via Improving Copper Sequestration and ROS Scavenging in Cucumber.

Melatonin plays an important role in stress tolerance in plants. In this study, exogenous melatonin significantly alleviated the dwarf phenotype and inhibited the decrease of plant fresh weight induced by excess copper (Cu2+). Our results indicated that melatonin alleviated Cu2+ toxicity by improving Cu2+ sequestration, carbon metabolism and ROS (reactive oxygen species) scavenging, rather than by influencing the Cu2+ uptake under excess Cu2+ conditions. Transcriptome analysis showed that melatonin broadly altered gene expression under Cu2+ stress. Melatonin increased the levels of glutathione and phytochelatin to chelate excess Cu2+ and promoted cell wall trapping, thus keeping more Cu2+ in the cell wall and vacuole. Melatonin inhibited ROS production and enhanced antioxidant systems at the transcriptional level and enzyme activities, thus building a line of defense in response to excess Cu2+. The distribution of nutrient elements was recovered by melatonin which was disturbed by Cu2+. In addition, melatonin activated carbon metabolism, especially glycolysis and the pentose phosphate pathway, to generate more ATP, an intermediate for biosynthesis. Taken together, melatonin alleviated Cu2+ toxicity in cucumber via multiple mechanisms. These results will help to resolve the toxic effects of Cu2+ stress on plant growth and development. These results can be used for new strategies to solve problems associated with Cu2+ stress.

Antiproliferative and apoptosis-inducing activity of schisandrin B against human glioma cells.

BACKGROUND: Malignant glioma is the most devastating and aggressive tumour in the brain and is characterised by high morbidity, high mortality and extremely poor prognosis. The main purpose of the present study was to investigate the effects of schisandrin B (Sch B) on glioma cells both in vitro and in vivo and to explore the possible anticancer mechanism underlying Sch B-induced apoptosis and cell cycle arrest. METHODS: The anti-proliferative ability of Sch B on glioma cells were assessed by MTT and clony formation assays. Flow cytometric analysis was used to detect cell cycle changes. Apoptosis was determined by Hoechst 33342 staining and annexin V/PI double-staining assays. The mitochondrial membrane potential was detected by Rhodamine 123 staining. The in vivo efficacy of Sch B was measured using a U87 xenograft model in nude mice. The expressions of the apoptosis-related and cell cycle-related proteins were analysed by western blot. Student's t-test was used to compare differences between treated groups and their controls. RESULTS: We found that Sch B inhibited growth in a dose- and time-dependent manner as assessed by MTT assay. In U87 and U251 cells, the number of clones was strongly suppressed by Sch B. Flow cytometric analysis revealed that Sch B induced cell cycle arrest in glioma cells at the G0/G1 phase. In addition, Sch B induced glioma cell apoptosis and reduced mitochondrial membrane potential (ΔΨm) in a dose-dependent manner. Mechanically, western blot analysis indicated that Sch B induced apoptosis by caspase-3, caspase-9, PARP, and Bcl-2 activation. Moreover, Sch B significantly inhibited tumour growth in vivo following the subcutaneous inoculation of U87 cells in athymic nude mice. COCLUSIONS: In summary, Sch B can reduce cell proliferation and induce apoptosis in glioma cells and has potential as a novel anti-tumour therapy to treat gliomas.

Transplanted neural stem cells modulate regulatory T, γδ T cells and corresponding cytokines after intracerebral hemorrhage in rats.

The immune system, particularly T lymphocytes and cytokines, has been implicated in the progression of brain injury after intracerebral hemorrhage (ICH). Although studies have shown that transplanted neural stem cells (NSCs) protect the central nervous system (CNS) from inflammatory damage, their effects on subpopulations of T lymphocytes and their corresponding cytokines are largely unexplored. Here, rats were subjected to ICH and NSCs were intracerebrally injected at 3 h after ICH. The profiles of subpopulations of T cells in the brain and peripheral blood were analyzed by flow cytometry. We found that regulatory T (Treg) cells in the brain and peripheral blood were increased, but γδT cells (gamma delta T cells) were decreased, along with increased anti-inflammatory cytokines (IL-4, IL-10 and TGF-ß) and decreased pro-inflammatory cytokines (IL-6, and IFN-γ), compared to the vehicle-treated control. Our data suggest that transplanted NSCs protect brain injury after ICH via modulation of Treg and γδT cell infiltration and anti- and pro-inflammatory cytokine release.

Nano-Enhanced Phase Reinforced Magnesium Matrix Composites: A Review of the Matrix, Reinforcement, Interface Design, Properties and Potential Applications.

Magnesium matrix composites are essential lightweight metal matrix composites, following aluminum matrix composites, with outstanding application prospects in automotive, aerospace lightweight and biomedical materials because of their high specific strength, low density and specific stiffness, good casting performance and rich resources. However, the inherent low plasticity and poor fatigue resistance of magnesium hamper its further application to a certain extent. Many researchers have tried many strengthening methods to improve the properties of magnesium alloys, while the relationship between wear resistance and plasticity still needs to be further improved. The nanoparticles added exhibit a good strengthening effect, especially the ceramic nanoparticles. Nanoparticle-reinforced magnesium matrix composites not only exhibit a high impact toughness, but also maintain the high strength and wear resistance of ceramic materials, effectively balancing the restriction between the strength and toughness. Therefore, this work aims to provide a review of the state of the art of research on the matrix, reinforcement, design, properties and potential applications of nano-reinforced phase-reinforced magnesium matrix composites (especially ceramic nanoparticle-reinforced ones). The conventional and potential matrices for the fabrication of magnesium matrix composites are introduced. The classification and influence of ceramic reinforcements are assessed, and the factors influencing interface bonding strength between reinforcements and matrix, regulation and design, performance and application are analyzed. Finally, the scope of future research in this field is discussed.

Up-regulation of microRNA-183 reduces FOXO1 expression in gastric cancer patients with Helicobacter pylori infection.

The aim of the study is to detect the expression of FOXO1 mRNA and protein in samples from gastric cancer patients with Helicobacter pylori (H. pylori) infection, and to investigate the relationship between FOXO1 expression and miR-183 expression. Twenty-six gastric cancer patients with H. pylori infection and 26 gastric cancer patients without H. pylori infection were included into experimental group and control group, respectively. Tumor tissues and peripheral blood were collected from all subjects. QRT-PCR was used to determine the expression of miRNA and mRNA. Western blotting was carried out to measure protein expression. Dual luciferase reporter assay was used to identify direct interaction between miRNA and 3'-UTR of mRNA. Cell proliferation was examined by CCK-8 assay. FOXO1 mRNA and protein expression was down-regulated in gastric cancer patients, being possibly related to H. pylori infection. The expression of miR-183 in tumor tissues and serum from gastric cancer patients with H. pylori infection was elevated, and probably regulated the expression of FOXO1 by direct targeting. Stimulation by H. pylori up-regulated the expression of miR-183 in gastric cancer AGS cells, and reduced the levels of FOXO1 mRNA and protein. Inhibition of miR-183 elevated the expression of FOXO1 and suppressed the proliferation of AGS cells. The present study demonstrates that the expression of FOXO1 in tumor tissues and blood from gastric cancer patients with H. pylori infection is significantly down-regulated, and may be related to the up-regulation of miR-183. H. pylori may regulate FOXO1 expression through miR-183 to affect the pathological process of gastric cancer.

The Role of Lithium in the Aging Precipitation Process of Al-Zn-Mg-Cu Alloys and Its Effect on the Properties.

It is well known that the development of lightweight alloys with improved comprehensive performance and application value are the future development directions for the ultra-high-strength 7xxx series Al-Zn-Mg-Cu alloys used in the aircraft field. As the lightest metal element in nature, lithium (Li) has outstanding advantages in reducing the density and increasing the elastic modulus in aluminum alloys, so Al-Zn-Mg-Cu alloys containing Li have gained widespread attention. Furthermore, since the Al-Zn-Mg-Cu alloy is usually strengthened by aging treatment, it is crucial to understand how Li addition affects its aging precipitation process. As such, in this article, the effects and mechanism of Li on the aging precipitation behavior and the impact of Li content on the aging precipitation phase of Al-Zn-Mg-Cu alloys are briefly reviewed, and the influence of Li on the service properties, including mechanical properties, wear resistance, and fatigue resistance, of Al-Zn-Mg-Cu alloys are explained. In addition, the corresponding development prospects and challenges of the Al-Zn-Mg-Cu-Li alloy are also proposed. This review is helpful to further understand the role of Li in Al-Zn-Mg-Cu alloys and provides a reference for the development of high-strength aluminum alloys containing Li with good comprehensive properties.

Development Trend in Composition Optimization, Microstructure Manipulation, and Strengthening Methods of Die Steels under Lightweight and Integrated Die Casting.

In the general environment of lightweight automobiles, the integrated die-casting technology proposed by Tesla has become the general mode to better achieve weight reduction in automobiles. The die-casting mold required by integrated die-casting technology has the characteristics of large scale and complexity. Hence, higher requirements are put forward for the comprehensive performance of the die steel. Despite the stagnation in the progress of conventional strengthening methods, enhancing the performance of die steel has become increasingly challenging. Indeed, it necessitates exploring novel die steel and optimizing heat treatment and reinforcement technologies. This article summarizes and analyzes the development status of die steel and corresponding heat treatment and microstructure manipulation as well as strengthening methods and elaborates on an excellent nano-strengthening technology. Furthermore, this review will aid researchers in establishing a comprehensive understanding of the development status of die steel and the processes utilized for its strengthening. It will also assist them in developing die steel with improved comprehensive performance to meet the high demand for mold steel in the integrated die-casting technology of the new era.

Natural history of postoperative nonfunctioning pituitary adenomas: a systematic review and meta-analysis.

OBJECTIVE: Previous studies attempting to define the natural history of postoperative nonfunctioning pituitary adenomas (pNFPAs) were somewhat limited by selection bias and/or small numbers and/or lack of consistency among the study findings. The aim of this study was to scrutinize the literature in order to analyze the natural history of pNFPAs. METHODS: Electronic database including MEDLINE, PubMed and Cochrane CENTRAL were searched. The literature relating to the patients with pNFPAs without postoperative radiotherapy and pharmacotherapy was collected. Eligible studies reported on the rate of tumor recurrence, the tumor growth-free survival rate (TGFSR) at 5 and 10 years, and/or the residual tumor volume doubling time (TVDT). RESULTS: 19 studies met the criteria. The pNFPAs were divided into two groups: the pooled recurrence rate of group I without detectable residual tumor (371 patients) was 12% (95% CI 6-19%), the TGFSR at 5 and 10 years were 96% (95% CI 89-99%) and 82% (95% CI 65-94%), respectively. The pooled recurrence rate of group II with residual tumor (600 patients) was 46% (95% CI 36-56%), the TGFSR at 5 and 10 years were 56% (95% CI 41-71%) and 40% (95% CI 27-53%), respectively. The mean TVDT was 3.4 years (95% CI 2.4-4.5 years). CONCLUSIONS: pNFPAs, with or without detectable residual tumor, need stratification of treatment and radiological/endocrinological follow-up strategy. According to the TVDT, residual tumor regrowth is very slow, which permits an extensive and safe follow-up program for most patients.

[Half-gloving cordectomy: a modified procedure for concealed penis].

OBJECTIVE: To search for a simple surgical procedure for the treatment of concealed penis that may have better effect and less complications. METHODS: We used a modified surgical method in the treatment of 58 patients with concealed penis aged from 3 to 15 (mean 6.8) years. The operation was simplified and involved the following steps: wholly unveiling the penis glans, half-degloving the foreskins, cutting off all the adhesive fibers up to the penile suspensory ligaments, and liberating the external penis. RESULTS: The operation was successful in all the patients, with the operative time of 15 -45 (mean 33) minutes, hospital stay of 2 - 5 (mean 3.5) days, but no complications except mild foreskin edema in 5 cases. The external penis was prolonged from 0.5 - 2.8 (mean 1.4) cm preoperatively to 3.2 - 8.5 (mean 3.9) cm postoperatively. The patients were followed up for 1 -3 years, all satisfied with the length and appearance of the penis, and their sexual and reproductive functions were normal. CONCLUSION: The modified surgical procedure for concealed penis is simple and effective, with desirable outcomes, few postoperative complications and no damage to sexual and reproductive functions.

Potential role of 25(OH)D insufficiency in the dysfunction of glycolipid metabolism and cognitive impairment in patients with T2DM.

Purpose: To investigate the changes of plasma 25(OH)D levels in type 2 diabetes mellitus (T2DM) patients and explore its role in the dysfunction of glucose and lipid metabolism and cognition. Methods: One hundred and thirty-two T2DM patients were enrolled and the demographic and clinical data were collected. The plasma concentration of 25(OH)D was detected and the patients were divided into two groups including a Vitamin D insufficient (VDI) group and a normal VD group according to the clinical diagnostic criterial of VDI with the plasma 25(OH)D level less than 29 ng/mL. The glycolipid metabolic and routine blood biochemical indices were detected, the plasma concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), soluble myeloid soluble trigger receptor 1 (sTREM1) were measured. The cognitive function was assessed using the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A). The depressive symptomatology was assessed using the Center for Epidemiological Survey Depression Scale (CES-D). Sleep quality was assessed using the Pittsburgh sleep quality index (PSQI). Results: There were 70 T2DM patients with VDI (70/132, 53.03%) in this study. The plasma concentrations of glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), postprandial blood glucose (PBG), IL-6, and sTREM1 were remarkably increased in T2DM patients with VDI as compared with that with the normal VD, accompanied with an elevated BRIEF-A scores. There was no significant difference between groups with regard to the indices of blood lipid, liver function, and scores in CES-D and PSQI. Moreover, results of Pearson correlation test showed that the plasma 25(OH)D levels were negatively correlated with HbA1c, FPG, PBG, CRP, IL-6, sTREM1, CES-D sum scores, and PSQI sum scores, but positively correlated with the plasma levels of Serum creatinine (Scr). Furthermore, result of Receiver Operating Characteristic (ROC) curve analysis showed a predictive role of VDI levels in discriminating T2DM patients with higher cognitive impairments, with the sensitivity and specificity being 62.12% and 62.12%, respectively. Conclusion: VDI is harmful for T2DM patients with a significant relation with the hyperglycosemia and cognitive dysfunction.

Efficacy and safety of bevacizumab plus chemotherapy in Chinese patients with metastatic colorectal cancer: a randomized phase III ARTIST trial.

The efficacy and safety of bevacizumab with modified irinotecan, leucovorin bolus, and 5-fluorouracil intravenous infusion (mIFL) in the first-line treatment of metastatic colorectal cancer (mCRC) has not been well evaluated in randomized clinical trials in Chinese patients. We conducted a phrase III trial in which patients with previously untreated mCRC were randomized 2:1 to the mIFL [irinotecan (125 mg/m(2)), leucovorin (20 mg/m(2)) bolus, and 5-fluorouracil intravenous infusion (500 mg/m(2)) weekly for four weeks every six weeks] plus bevacizumab (5 mg/kg every two weeks) group and the mIFL group, respectively. Co-primary objectives were progression-free survival (PFS) and 6-month PFS rate. In total, 214 patients were enrolled. Our results showed that addition of bevacizumab to mIFL significantly improved median PFS (4.2 months in the mIFL group vs. 8.3 months in the bevacizumab plus mIFL group, P < 0.001), 6-month PFS rate (25.0% vs. 62.6%, P < 0.001), median overall survival (13.4 months vs. 18.7 months, P = 0.014), and response rate (17% vs. 35%, P = 0.013). Grades 3 and 4 adverse events included diarrhea (21% in the mIFL group and 26% in the bevacizumab plus mIFL group) and neutropenia (19% in the mIFL group and 33% in the bevacizumab plus mIFL group). No wound-healing complications or congestive heart failure occurred. Our results suggested that bevacizumab plus mIFL is effective and well tolerated as first-line treatment for Chinese patients with mCRC. Clinical benefit and safety profiles were consistent with those observed in pivotal phase III trials with mainly Caucasian patients.

MRCP Combined With CT Promotes the Differentiation of Benign and Malignant Distal Bile Duct Strictures.

OBJECTIVE: To determine whether contrast-enhanced computed tomography (CT) can promote the identification of malignant and benign distal biliary strictures (DBSs) compared to the use of magnetic resonance cholangiopancreatography (MRCP) alone and to identify imaging findings of malignant DBSs. MATERIALS AND METHODS: A total of 168 consecutive patients with confirmed DBSs were reviewed. MRCP alone and MRCP combined with CT images were blindly analyzed by two radiologists (e.g., stricture pattern, margins), and malignant or benign DBSs were identified based on surgical findings, endoscopy findings, or follow-up. The diagnostic accuracy of the two reviewers using MRCP alone and MRCP combined with CT were evaluated. MRCP and CT features of malignant and benign DBSs were compared using multiple logistic regression analysis to identify independent malignant risk factors. RESULTS: MRCP combined with CT examination could improve the diagnostic accuracy, which increased from 70.2% to 81.5% in Doctor A and from 85.1% to 89.3% in Doctor B. The multiple logistic regression model revealed that stricture length [odds ratio (OR) 1.070, P=0.016], angle of the DBS (OR 1.061, P<0.001), double duct sign (OR 4.312, P=0.003) and low density in the arterial phase (OR 0.319, P=0.018) were associated with malignant DBS. A scoring model incorporating these four factors was established; at a threshold value of 1.75, and the sensitivity and specificity for the detection of malignant DBSs were 73.5 and 85.9%, respectively. CONCLUSIONS: Compared to the use of MRCP alone, MRCP combined with contrast-enhanced CT can improve the accuracy of DBS diagnosis. The scoring model accurately predicts malignant DBSs and helps make treatment decisions.

Predicting intraventricular hemorrhage growth with a machine learning-based, radiomics-clinical model.

We constructed a radiomics-clinical model to predict intraventricular hemorrhage (IVH) growth after spontaneous intracerebral hematoma. The model was developed using a training cohort (N=626) and validated with an independent testing cohort (N=270). Radiomics features and clinical predictors were selected using the least absolute shrinkage and selection operator (LASSO) method and multivariate analysis. The radiomics score (Rad-score) was calculated through linear combination of selected features multiplied by their respective LASSO coefficients. The support vector machine (SVM) method was used to construct the model. IVH growth was experienced by 13.4% and 13.7% of patients in the training and testing cohorts, respectively. The Rad-score was associated with severe IVH and poor outcome. Independent predictors of IVH growth included hypercholesterolemia (odds ratio [OR], 0.12 [95%CI, 0.02-0.90]; p=0.039), baseline Graeb score (OR, 1.26 [95%CI, 1.16-1.36]; p<0.001), time to initial CT (OR, 0.70 [95%CI, 0.58-0.86]; p<0.001), international normalized ratio (OR, 4.27 [95%CI, 1.40, 13.0]; p=0.011), and Rad-score (OR, 2.3 [95%CI, 1.6-3.3]; p<0.001). In the training cohort, the model achieved an AUC of 0.78, sensitivity of 0.83, and specificity of 0.66. In the testing cohort, AUC, sensitivity, and specificity were 0.71, 0.81, and 0.64, respectively. This radiomics-clinical model thus has the potential to predict IVH growth.

Expression of D2RmRNA isoforms and ERmRNA isoforms in prolactinomas: correlation with the response to bromocriptine and with tumor biological behavior.

Invasive prolactinomas are more likely to be resistant to drug therapy but the mechanism of this is still unknown. The objective of this study was to analyze the different expression of ERmRNA and D2RmRNA isoforms in prolactinomas responsive and resistant to dopamine agonist (DA), and to discuss the correlation of such gene expression with tumor biological behavior. A prospective study of 20 consecutive patients who harbored prolactinomas was designed. Patients were classified as responsive (14 cases) or resistant (six cases) according to their clinical and biochemical response to bromocriptine. Tumor tissue samples were examined by means of QRT-PCR analysis. Median D2SmRNA expression in responsive patients was about 2.5-fold that in resistant ones (13.5 +/- 10.4 and 5.4 +/- 2.4, respectively, P = 0.09). No significant difference was found between D2LmRNA expression levels (P = 0.77). However, there was a significant difference between D2S/D2LmRNA ratios for responsive and resistant tumors (P = 0.012). A significant difference was not found between these two groups in levels of ERalphamRNA and ERbetamRNA expression (P = 0.20 and 0.06, respectively). D2SmRNA expression was significantly different for invasive and noninvasive tumors (6.2 +/- 3.6 vs. 17.0 +/- 11.2, respectively, P = 0.02). The D2S/D2L ratio is related to the responsiveness of prolactinomas to DA medication, in which D2SmRNA plays an important role. Lower expression of D2SmRNA in invasive tumor patients suggests that invasive prolactinomas may be more likely to be resistant to DA medication.

[Natural history study of postoperative residual non-functioning pituitary adenomas].

OBJECTIVE: To observe the postoperative residual non-functioning pituitary adenomas (PR-NFPAs) without postoperative radiotherapy and to analyze the natural history of PR-NFPAs' growth in order to provide a basis for selecting appropriate strategies of clinical treatment. METHODS: We evaluated the natural history of 20 patients with PR-NFPAs who did not receive postoperative radiotherapy and drug therapy. Through MRI images, the residual tumor volumes of those patients were serially measured. We further calculated the monthly growth rate and the tumor volume doubling time (TVDT) and analyzed the correlations between the patient age, gender, volume of residual tumor, cavernous sinus (CS) invasion and TVDT. RESULTS: All patients received observation alone. Among which, 17 adenomas increased in volume and 3 remained unchanged during a follow-up period of 7 months to 17 years (mean 3.90 yr). The mean patient age was 41.8 years. As to 17 patients with tumor regrowth, the tumor volume at the beginning of MRI observation period was 4.73 cm(3) and tumor volume at the last MRI observation was 16.98 cm(3). During the mean 4-year follow-up period, the average monthly growth rate of PR-NFPAs was 7.87% and the mean TVDT was 724 days. Such factors as patient age, gender, volume of residual tumor and CS invasion did not affect the TVDT of PR-NFPAs. CONCLUSION: The tumor growth rate of PR-NFPAs is not significantly correlated with the patient gender, age, volume of residual tumor and CS invasion. In conjunctions with the volume of PR-NFPAs and the distance between residual adenoma and optic chiasm, we should take the TVDT into consideration and determine the appropriate and safe follow-up period.

Association of IGF1R polymorphisms (rs1546713) with susceptibility to age-related cataract in a Han Chinese population.

AIM: To explore the susceptible association between the insulin-like growth factor-1 receptor (IGF1R) single nucleotide polymorphism (SNP) and age-related cataract (ARC), and investigate the underlying mechanisms in human lens epithelium (HLE) cells. METHODS: Totally 1190 unrelated participants, comprising 690 ARC patients and 500 healthy individuals in Han Chinese population were recruited and genotyped for target SNP. The χ 2-test was used to detect genotypic distribution between the patient and control groups and the logistic regression was performed to adjust the age and gender. Meanwhile, different biological experimental methods, such as cell counting kit 8 (CCK-8) assay, flow cytometry, quantitative real time polymerase chain reaction (Q-PCR) and Western blot, were used to detect cell viability, cell cycle progression and apoptosis in HLE cells or IGF1R knockdown HLE cells. RESULTS: The rs1546713 in IGF1R gene was identified (P=0.046, OR: 1.606, 95%CI: 1.245-2.071), which shown a significant relevance with ARC risk under the dominant model. The results demonstrated that IGF1R knockdown inhibited cell proliferation by inducing cell cycle arrested at S phase and promoting apoptosis. Mechanistically, the cell cycle blocked at S phase was linked with the alterations of cyclin A, cyclin B, cyclin E and P21. The pro-apoptosis function of IGF1R may related with stimulating the activation of Caspase-3 and altering the expression levels of apoptotic proteins, including Bcl-2, Bax and Caspase-3. CONCLUSION: This study first report that IGF1R polymorphisms may affect susceptibility to ARCs in Han Chinese population and provide new clues to understand the pathogenic mechanism of ARCs. Notably, IGF1R is likely a potential target for ARC prevention and treatment.

Characteristics of Renal Function in Patients Diagnosed With COVID-19: An Observational Study.

Objective: The aim of the study was to analyze the characteristics of renal function in patients diagnosed with COVID-19. Methods: In this retrospective, single-center study, we included all confirmed cases of COVID-19 in a tertiary hospital in Guangdong, China from January 20, 2020 to March 20, 2020. Blood and urine laboratory findings related to renal function were summarized, and the estimated glomerular filtration rate (eGFR) and endogenous creatinine clearance (Ccr) were also calculated to assess the renal function. Results: A total of 12 admitted hospital patients were diagnosed with COVID-19, included 3 severe cases, and 9 common cases. Serum creatinine (Scr) was not abnormally elevated in all of the patients, and blood urea nitrogen (BUN) was abnormally elevated in only 25.0% of the patients. However, compared with the recovery period, the patient's Scr and BUN increased significantly in peak of disease (p-scr = 0.002 & p-bun < 0.001). By observing the fluctuations in Scr and BUN from admission to recovery, it was found that the peak of Scr and BUN appeared within the first 14 day of the course of the disease. Urinary microprotein detection indicated that the abnormally elevated rates of urine microalbumin (UMA), α1-microglobulin (A1M), urine immunoglobulin-G (IGU), and urine transferring (TRU) standardized by urinary creatinine in peak of disease were 41.7, 41.7, 50.0, and 16.7%, respectively. The abnormal rates of the calculated eGFR and Ccr were 66.7 and 41.7%. Conclusion: Scr and BUN were generally increased during the course of COVID-19. Detection of urinary microproteins and application of multiple indicators assessment could be helpful for discovering abnormal renal function in patients with COVID-19. However, the evidence is limited due to the small sample size and observational nature. Additional studies, especially large prospective cohort studies, are required to confirm these findings.

[Prevention of poor incision healing after total knee arthroplasty].

OBJECTIVE: To investigate the causes of poor incision healing after total knee arthroplasty(TKA) and to propose active preventive and therapeutic measures. METHODS: Total 284 patients undergoing unilateral TKA from September 2016 to June 2018 were enrolled in the study and divided into control group and observation group. Firstly, 150 patients with unilateral TKA from September 2016 to June 2017 were retrospectively analyzed and included in the control group. There were 41 males and 109 females, with an average age of(63.5±7.2) years old. The causes of poor incision healing were discussed about patients themselves and surgical techniques. After analyzing, improvement measures were proposed. Total 134 patients with TKA from July 2017 to June 2018 were included in the observation group. There were 36 males and 98 females, with an average age of(62.4±8.9) years old. The patients in the observation group were treated with improved treatment strategies. RESULTS: Nine patients(6%) had poor incision healing in the control group and 1 patient (0.75%) had poor incision healing in the observation group. The incidence of poor incision healing was significantly different between the two groups (χ²=5.750, P<0.01). CONCLUSIONS: In order to prevent the poor incision healing after TKA, perioperative management and the operation techniques including stable, accurate, rapid and clean skills should be improved, leading to reduce the complications of incision and improve the recovery rate of patients.