Methods of Corneal Vertex Centration and Evaluation of Effective Optical Zone in Small Incision Lenticule Extraction.

Inappropriate small incision lenticule extraction (SMILE) centration methods can affect the decentration of the effective optical zone (EOZ) after operation, which can subsequently lead to the decline of postoperative visual quality. We aimed to provide an overview of corneal vertex (CV) centration methods and an evaluation of the size and decentration of the EOZ in SMILE. We described the CV centration methods for patients with myopia, myopic astigmatism, hyperopia, and large kappa angle. The measurement methods of the EOZ were evaluated from the aspects of corneal morphology and corneal refractive power. Additionally, we summarized the advantages and disadvantages of measuring decentration based on topographic mapping and intraoperative video-captured images. Finally, we discussed the relationship between the EOZ and visual quality. Based on our review, clinicians should consider the following when choosing CV centration methods and evaluating EOZ postoperatively. First, the tear film mark center or topographic map comparison method is preferred for the correction of myopia, low myopic astigmatism, hyperopia, and large kappa angle (>0.2 mm). Triple marking centration is recommended for high myopic astigmatism (-3.5 diopters). Second, the total corneal power better reflects the change in refractive power than the topographic method. The measurement of the area rather than the diameter of the total corneal refractive power is more suitable for the evaluation of non-circular EOZs after high myopia astigmatism (< -2.0 diopters). Third, for the evaluation of decentration, the tangential curvature difference map method is preferred as it is not influenced by offset pupils. Finally, a large EOZ after SMILE may improve patient tolerance to decentration.

Defective TiO2- x for High-Performance Electrocatalytic NO Reduction toward Ambient NH3 Production.

Synthesis of green ammonia (NH3 ) via electrolysis of nitric oxide (NO) is extraordinarily sustainable, but multielectron/proton-involved hydrogenation steps as well as low concentrations of NO can lead to poor activities and selectivities of electrocatalysts. Herein, it is reported that oxygen-defective TiO2 nanoarray supported on Ti plate (TiO2- x /TP) behaves as an efficient catalyst for NO reduction to NH3 . In 0.2 m phosphate-buffered electrolyte, such TiO2- x /TP shows competitive electrocatalytic NH3 synthesis activity with a maximum NH3 yield of 1233.2 µg h-1  cm-2 and Faradaic efficiency of 92.5%. Density functional theory calculations further thermodynamically faster NO deoxygenation and protonation processes on TiO2- x (101) compared to perfect TiO2 (101). And the low energy barrier of 0.7 eV on TiO2- x (101) for the potential-determining step further highlights the greatly improved intrinsic activity. In addition, a Zn-NO battery is fabricated with TiO2- x /TP and Zn plate to obtain an NH3 yield of 241.7 µg h-1  cm-2 while providing a peak power density of 0.84 mW cm-2 .

Expression and functional analysis of Niemann-Pick C2 gene in Phytoseiulus persimilis.

As a new protein class of semiochemical binding and transporting, Niemann-Pick proteins type C2 (NPC2) in arthropods have received more attentions in recent decade. However, the gene function has not been studied in phytoseiid mites with biocontrol potential. In the current study, we cloned a NPC2 gene PpNPC2a from the transcriptome of Phytoseiulus persimilis Athias-Henriot. By encoding 181 amino acids with a conserved ML domain, PpNPC2a was found a homolog of NPC2-1 in Galendromus occidentalis Nesbitt. We then measured the spatio-temporal expression of PpNPC2a in P. persimilis, and found the highest expression in female adults compared to other stages. Due to the tiny body size of predatory mites, we only examined tissue expressions in two sections: the anterior part (gnathosoma and the first pair of legs) and the posterior part (idiosoma without the first pair of legs). Higher transcription of PpNPC2a was found in the posterior part. To investigate the potential function of PpNPC2a in P. persimilis, we interfered gene expression in female adults by feeding dsRNA, which resulted in a decrease of relative expression by 59.1 and 78.2% after 24 and 72 h, respectively. Compared with the control, dsNPC2a-treated P. persimilis were insensitive to the scent of leaves or plants infested by spider mites, suggesting a role of PpNPC2a in response to plant volatiles. However, the dsNPC2a-interfered mites could still respond to four representative compounds of herbivore-induced plant volatiles, including 4,8,12-trimethyl-1,3,7,11-tridecatetraene (TMTT), methyl salicylate (MeSA), ß-caryophyllene and linalool. In short, our results indicated PpNPC2a may be involved in the chemosensory process of P. persimilis in response to whole-plant volatiles.

Electrochemical Cross-Dehydrogenative Coupling of Isochroman and Unactivated Ketones.

An unprecedented electrochemical cross-dehydrogenative coupling reaction between isochroman and unactivated ketones to directly synthesize α-substituted isochromans has been developed. This strategy provides a facile and efficient procedure to the direct activation of C(sp3)-H bond adjacent to the O atom of isochroman. The method features high atom economy, chemical oxidant-free, and mild conditions, in which methanesulfonic acid (MsOH) acts as both electrolyte and catalyst, making the process more convenient and environmentally friendly. Gram-scale experiment and synthesis of antitumor active compounds demonstrate the great potential of this protocol for practical applications.

Correlated with better prognosis, CSTA inhibits metastasis of nasopharyngeal carcinoma cells via suppressing AKT signaling through promoting METTL3 degradation.

BACKGROUND: Metastasis is one of the main obstacles impeding the survival of nasopharyngeal carcinoma (NPC) patients, with the molecular mechanism underlying NPC metastasis still unclear. RESULTS: In this study, Cystatin A (CSTA) was found downregulated in NPC tissues with metastasis compared with those without metastasis. Shorter overall survival and distant metastasis-free survival were found in NPC patients with lower CSTA expression. Using functional assays, we found that CSTA prevented both the in vitro motility of NPC cells and their ability to metastasize in vivo. Transcriptome sequencing and western blot analysis revealed that CSTA inhibited the phosphorylation of AKT. Moreover, activating AKT using AKT agonist SG79 rescued the motility of CSTA-overexpressing NPC cells, whereas, treatment with AKT inhibitor MK2206 inhibited the motility of CSTA-knockdown NPC cells. Mechanically, immunoprecipitation coupled mass spectrometry found that CSTA interacted with the N6-adenosine-methyltransferase subunit METTL3 and promoted its ubiquitin-proteasome-mediated degradation following the upregulation of NKX3-1 and LHPP, which are negative regulators of AKT. Furthermore, knock-down of NKX3-1 and LHPP enhanced the motility of CSTA-overexpressing NPC cells. CONCLUSIONS: The inhibitory effect of CSTA upon NPC metastasis mainly depended on suppressing AKT signaling by the upregulation of NKX3-1 and LHPP expression resulting from the binding between CSTA and METLL3. Our study suggests that the CSTA-METLL3-NKX3-1/LHPP-AKT axis could be of therapeutic value for inhibiting NPC metastasis.

Polymorphisms of placental iodothyronine deiodinase genes in a rural area of Northern China with high prevalence of neural tube defects.

INTRODUCTION: We have reported that high total homocysteine (tHCY), and the coexistence of inadequate thyroid hormones in maternal serum increase the risk of fetal neural tube defects (NTDs). Placental iodothyronine deiodinases (DIOs: DIO1, DIO2, and DIO3) play a role in regulate the conversions between different forms of maternal thyroid hormones. This study hypothesized that single nucleotide polymorphisms (SNPs) in placental DIOs genes could be related to NTDs. METHODS: We performed a case-control study from 2007 to 2009 that included pregnant women from Lüliang, Shanxi Province, China. Nine distinct SNPs in DIOs genes were analyzed and placental samples were obtained from 83 pregnant women with NTDs fetuses and 90 pregnant women with normal fetuses. The nine SNPs were analyzed using the Cochran-Armitage test and the Fisher's exact test. RESULTS: There were no statistically significant differences between case and control in the nine SNPs of DIOs (P>0.05). CONCLUSIONS: The results of this study suggested that SNPs of DIOs genes in placenta among pregnant women has no statistically significant difference between the two groups, suggesting that other factors might be involved in metabolism of maternal thyroid hormone provided to fetuses, such as epigenetic modification of methylation and homocysteinylation and genomic imprinting in the placenta. Further those functional studies on placenta samples are necessary.

Direct B-H Functionalization of Icosahedral Carboranes via Hydrogen Atom Transfer.

The efficient and selective functionalization of icosahedral carboranes (C2B10H12) at the boron vertexes is a long-standing challenge owing to the presence of 10 inert B-H bonds in a similar chemical environment. Herein, we report a new reaction paradigm for direct B-H functionalization of icosahedral carboranes via B-H homolysis enabled by a nitrogen-centered radical-mediated hydrogen atom transfer (HAT) strategy. Both the HAT process of the carborane B-H bond and the resulting boron-centered carboranyl radical intermediate have been confirmed experimentally. The reaction occurs at the most electron-rich boron vertex with the lowest B-H bond dissociation energy (BDE). Using this strategy, diverse carborane derivatization, including thiolation, selenation, alkynylation, alkenylation, cyanation, and halogenation, have been achieved in satisfactory yields under a photoinitiated condition in a metal-free and redox-neutral fashion. Moreover, the synthetic utility of the current protocol was also demonstrated by both the scale-up reaction and the construction of carborane-based functional molecules. Therefore, this methodology opens a radical pathway to carborane functionalization, which is distinct from the B-H heterolytic mechanism in the traditional strategies.

Discovery of decreased ferroptosis in male colorectal cancer patients with KRAS mutations.

Aberrant tumor metabolism is a hallmark of cancer in which metabolic rewiring can support tumor growth under nutrient deficient conditions. KRAS mutations occur in 35-45% of all colorectal cancer (CRC) cases and are difficult to treat. The relationship between mutant KRAS and aberrant metabolism in CRCs has not been fully explored and could be a target for intervention. We previously acquired non-targeted metabolomics data from 161 tumor tissues and 39 normal colon tissues from stage I-III chemotherapy naïve CRC patients. In this study, we revealed that tumors from male patients with KRAS mutations only, had several altered pathways that suppress ferroptosis, including glutathione biosynthesis, transsulfuration activity, and methionine metabolism. To validate this phenotype, MC38 CRC cells (KRAS G13R ) were treated with a ferroptosis inducer; RAS-selected lethal (RSL3). RSL3 altered metabolic pathways in the opposite direction to that seen in KRAS mutant tumors from male patients confirming a suppressed ferroptosis metabolic phenotype in these patients. We further validated gene expression data from an additional CRC patient cohort (Gene Expression Omnibus (GEO), and similarly observed differences in ferroptosis-related genes by sex and KRAS status. Further examination of the relationship between these genes and overall survival (OS) in the GEO cohort showed that KRAS mutant tumors are associated with poorer 5-year OS compared to KRAS wild type tumors, and only in male patients. Additionally, high compared to low expression of GPX4, FTH1, FTL , which suppressed ferroptosis, were associated with poorer 5-year OS only in KRAS mutant tumors from male CRC patients. Low compared to high expression of ACSL4 was associated with poorer OS for this group. Our results show that KRAS mutant tumors from male CRC patients have suppressed ferroptosis, and gene expression changes that suppress ferroptosis associate with adverse outcomes for these patients, revealing a novel potential avenue for therapeutic approaches.

Identification of Diagnostic Markers in Synovial Tissue of Osteoarthritis by Weighted Gene Coexpression Network.

Osteoarthritis (OA) is a serious threat to human health. However, the etiology and pathogenesis of the disease are not fully understood. Most researchers believe that the degeneration and imbalance of articular cartilage, extracellular matrix, and subchondral bone are the fundamental causes of osteoarthritis. However, recent studies have shown that synovial lesions may precede cartilage, which may be an important precipitating factor in the early stage of OA and the whole course of the disease. This study aimed to conduct an analysis based on sequence data from the Gene Expression Omnibus (GEO) database to investigate the presence of effective biomarkers in the synovial tissue of osteoarthritis for the diagnosis and control of OA progression. In this study, the differentially expressed OA-related genes (DE-OARGs) in osteoarthritis synovial tissues were extracted in the GSE55235 and GSE55457 datasets using the Weighted Gene Co-expression Network Analysis (WGCNA) and limma. Least-Absolute Shrinkage and Selection Operator (LASSO) algorithm was used to select the diagnostic genes based on the DE-OARGs by glmnet package. 7 genes were selected as diagnostic genes including SAT1, RLF, MAFF, SIK1, RORA, ZNF529, and EBF2. Subsequently, the diagnostic model was constructed and the results of the Area Under the Curve (AUC) demonstrated that the diagnostic model had high diagnostic performance for OA. Additionally, among the 22 immune cells of the Cell type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) and the 24 immune cells of the single sample Gene Set Enrichment Analysis (ssGSEA), 3 immune cells and 5 immune cells were different between the OA and normal samples, respectively. The expression trends of the 7 diagnostic genes were consistent in the GEO datasets and the results of the real-time reverse transcription PCR (qRT-PCR). The results of this study demonstrate that these diagnostic markers have important significance in the diagnosis and treatment of OA, and will provide further evidence for the clinical and functional studies of OA.

Epidemiology and risk stratification of low-grade gliomas in the United States, 2004-2019: A competing-risk regression model for survival analysis.

Background: Understanding the epidemiology and prognostic factors of low-grade gliomas (LGGs) can help estimate the public health impact and optimize risk stratification and treatment strategies. Methods: 3 337 patients diagnosed with LGGs were collected from the Surveillance, Epidemiology, and End Results (SEER) dataset, 2004-2019. The incidence trends of LGGs were analyzed by patient demographics (sex, age, race, and ethnicity). In addition, a competing risk regression model was used to explore the prognostic factors of LGGs by patient demographics, tumor characteristics (histological subtypes, invasiveness, and size), treatment modality, and molecular markers (IDH mutation and 1p/19q codeletion). Results: LGGs occurred more frequently in male, non-Hispanic, and White populations. The incidence rate of mixed gliomas was stable from 2004 to 2013 and decreased dramatically to nearly zero until 2019. The risk of death increased 1.99 times for every 20-year increase in patient age, and 60 years is a predictive cut-off age for risk stratification of LGGs. Male patients showed poorer LGG-specific survival. Among the different subtypes, astrocytoma has the worst prognosis, followed by mixed glioma and oligodendroglioma. Tumors with larger size (≥5 cm) and invasive behavior tended to have poorer survival. Patients who underwent gross total resection had better survival rates than those who underwent subtotal resection. Among the different treatment modalities, surgery alone had the best survival, followed by surgery + radiotherapy + chemotherapy, but chemotherapy alone had a higher death risk than no treatment. Furthermore, age, invasiveness, and molecular markers were the most robust prognostic factors. Conclusion: This study reviewed the incidence trends and identified several prognostic factors that help clinicians identify high-risk patients and determine the need for postoperative treatment according to guidelines.

The diagnostic significance of cerebrospinal fluid cytology and circulating tumor DNA in meningeal carcinomatosis.

Objective: The objective of this research is to investigate the clinical application value of cerebrospinal fluid (CSF) cytology and circulating tumor DNA (ctDNA) in lung adenocarcinoma (LUAD) meningeal metastasis-meningeal carcinomatosis (MC), and to further explore the possible molecular mechanisms and drug treatment targets of LUAD meningeal metastasis by next-generation sequencing (NGS). Methods: We retrospectively analyzed LUAD with MC in 52 patients. CSF cytology was carried out using the slide centrifugation precipitation method and May-Grüwald-Giemsa (MGG) staining. Tumor tissue, plasma and CSF ctDNA of some MC patients were detected by NGS. Results: Of the 52 MC patients, 46 (88.46%) were positive for CSF cytology and 34 (65.38%) were positive for imaging, with statistically significant differences in diagnostic positivity (P < 0.05). In 32 of these patients, CSF cytology, cerebrospinal fluid ctDNA, plasma ctDNA and MRI examination were performed simultaneously, and the positive rates were 84.38, 100, 56.25, and 62.50% respectively, the difference was statistically significant (P < 0.001). Analysis of the NGS profiles of tumor tissues, plasma and CSF of 12 MC patients: the mutated gene with the highest detection rate was epidermal growth factor receptor (EGFR) and the detection rate were 100, 58.33, and 100% respectively in tumor tissues, plasma and CSF, and there were 6 cases of concordance between plasma and tissue EGFR mutation sites, with a concordance rate of 50.00%, and 12 cases of concordance between CSF and tissue EGFR mutation sites, with a concordance rate of 100%. In addition, mutations not found in tissue or plasma were detected in CSF: FH mutation, SETD2 mutation, WT1 mutation, CDKN2A mutation, CDKN2B mutation, and multiple copy number variants (CNV), with the most detected being CDKN2A mutation and MET amplification. Conclusion: CSF cytology is more sensitive than traditional imaging in the diagnosis of meningeal carcinomatosis and has significant advantages in the early screening and diagnosis of MC patients. CSF ctDNA can be used as a complementary diagnostic method to negative results of CSF cytology and MRI, and CSF ctDNA can be used as an important method for liquid biopsy of patients with MC, which has important clinical significance in revealing the possible molecular mechanisms and drug treatment targets of meningeal metastasis of LUAD.

Exosome-mediated inhibition of microRNA-449a promotes the amplification of mouse retinal progenitor cells and enhances their transplantation in retinal degeneration mouse models.

Inherited and age-related retinal degenerations are the commonest causes of blindness without effective treatments. Retinal progenitor cells (RPCs), which have the multipotency to differentiate into various retinal cell types, are regarded as a promising source of cell transplantation therapy for retinal degenerative diseases. However, the self-limited expansion of RPCs causes difficulty in cell source supply and restrict its clinical treatment. In this work, we found that inhibition of microRNA-449a (miR-449a) in RPCs can promote proliferation and inhibit apoptosis of RPCs, partially through upregulating Notch signaling. Further optimization of transduction miR-449a inhibitor into RPCs by endothelial cell-derived exosomes can promote the survival of RPCs transplanted in vivo and reduce cell apoptosis in retinal degeneration mouse models. In summary, these studies have shown that exosome-miR-449a inhibitor can effectively promote the expansion of RPCs in vitro and enhance transplanted RPCs survival in vivo, which might provide a novel intervention strategy for retinal degenerations in the future.

Tcf21 Alleviates Pancreatic Fibrosis by Regulating the Epithelial-Mesenchymal Transformation of Pancreatic Stellate Cells.

BACKGROUND AND AIMS: The activation of pancreatic stellate cells (PSCs) plays a key role in the occurrence and development of chronic pancreatitis (CP) and pancreatic fibrosis, which is related to the process of epithelial-mesenchymal transition (EMT). This study was designed to investigate the effect and mechanism of Tcf21 (one of tumor suppressor genes) on pancreatic inflammation and fibrosis in vivo and in vitro. METHODS: C57BL/6 male mice were intraperitoneally injected with caerulein for 6 weeks to establish CP animal model. Fixed pancreatic tissue paraffin-embedded sections were used for immunohistochemistry staining of Tcf21, fibrosis-related markers (α-SMA), interstitial markers (Vimentin) and epithelial markers (E-cadherin). Western blotting and qRT-PCR assay were performed to analyze the change of expression of the above markers after stimulation of TGF-ß1 or overexpressed Tcf21 lentivirus transfection in human pancreatic stellate cells (HPSCs). RESULTS: The pancreatic expression of α-SMA and Vimentin of CP mice significantly increased, while the expression of Tcf21 and E-cadherin significantly decreased. TGF-ß1 could promote activation and EMT process of HPSCs, and inhibited the expression of Tcf21. Overexpression of Tcf21 could significantly down-regulate the expression of α-SMA, Fibronectin and Vimentin, and up-regulated the expression of ZO-1 of HPSCs. Cell Counting Kit-8 assay and scratch wound-healing assay results showed that overexpression of Tcf21 could significantly inhibit the cell migration and proliferation of HPSCs. CONCLUSIONS: Overexpression of Tcf21 could significantly alleviate the activation, proliferation, migration of PSCs by regulating the EMT process. Tcf21 had a potential prospect of a new target for CP therapy.

Mean nocturnal baseline impedance: Influencing factors and diagnostic value in gastroesophageal reflux disease.

BACKGROUND: At present, there are few studies related to mean nocturnal baseline impedance (MNBI), esophageal dynamic reflux monitoring, high-resolution esophageal manometry (HRM) parameter indexes, and its diagnostic value in gastroesophageal reflux disease (GERD). OBJECTIVE: To analyze the factors influencing MNBI and examine the diagnostic value of MNBI in GERD. METHODS: A retrospective analysis on 434 patients with typical reflux symptoms who underwent gastroscopy, 24-hour multichannel intraluminal impedance and pH monitoring (MII/pH) and HRM. They were divided into the conclusive evidence group (103 cases), borderline evidence group (229 cases), and exclusion evidence group (102 cases) according to the level of diagnostic evidence of GERD based on the Lyon Consensus. We analyzed the differences in MNBI, esophagitis grade, MII/pH and HRM index among the groups; the correlation between MNBI and the above indexes and its influence on MNBI; and to evaluate the diagnostic value of MNBI in GERD. RESULTS: There were significant differences in MNBI, Acid Exposure Time (AET) 4%, DeMeester score, and total reflux episodes among the three groups (P< 0.001). EGJ contractile integral (EGJ-CI) of the conclusive evidence group and the borderline evidence group was significantly lower than that in the exclusion evidence group (P< 0.001). MNBI was significantly and negatively correlated with age, BMI, AET 4%, DeMeester score, total reflux episodes, EGJ classification, esophageal motility abnormalities, and esophagitis grade (all P< 0.05), and significantly and positively correlated with EGJ-CI (P< 0.001). Age, BMI, AET 4%, EGJ classification, EGJ-CI, and esophagitis grade had significant effects on MNBI (P< 0.05); MNBI was used to diagnose GERD with a diagnostic cutoff of 2061 Ω, and AUC was 0.792 (sensitivity 74.9%, specificity 67.4%); MNBI was used to diagnose exclusion evidence group with a diagnostic cutoff of 2432 Ω, AUC was 0.774 (sensitivity 67.6%, specificity 72%). CONCLUSION: AET, EGJ-CI, and esophagitis grade are the most important influence factors of MNBI. MNBI has good diagnostic value in identifying conclusive GERD.

Update on the genetic diversity and population structure of Echinococcus granulosus in Gansu Province, Tibet Autonomous Region, and Xinjiang Uygur Autonomous Region, Western China, inferred from mitochondrial cox1, nad1, and nad5 sequences.

The identification of additional Echinococcus granulosus sensu lato (s.l.) complex species/genotypes in recent years raises the possibility that there might be more variation among this species in China than is currently understood. The aim of this study was to explore intra- and inter-species variation and population structure of Echinococcus species isolated from sheep in three areas of Western China. Of the isolates, 317, 322, and 326 were successfully amplified and sequenced for cox1, nad1, and nad5 genes, respectively. BLAST analysis revealed that the majority of the isolates were E. granulosus s.s., and using the cox1, nad1, and nad5 genes, respectively, 17, 14, and 11 isolates corresponded to Elodea canadensis (genotype G6/G7). In the three study areas, G1 genotypes were the most prevalent. There were 233 mutation sites along with 129 parsimony informative sites. A transition/transversion ratio of 7.5, 8, and 3.25, respectively, for cox1, nad1, and nad5 genes was obtained. Every mitochondrial gene had intraspecific variations, which were represented in a star-like network with a major haplotype with observable mutations from other distant and minor haplotypes. The Tajima's D value was significantly negative in all populations, indicating a substantial divergence from neutrality and supporting the demographic expansion of E. granulosus s.s. in the study areas. The phylogeny inferred by the maximum likelihood (ML) method using nucleotide sequences of cox1-nad1-nad5 further confirmed their identity. The nodes assigned to the G1, G3, and G6 clades as well as the reference sequences utilized had maximal posterior probability values (1.00). In conclusion, our study confirms the existence of a significant major haplotype of E. granulosus s.s. where G1 is the predominant genotype causing of CE in both livestock and humans in China.

Longitudinal associations between specific types/amounts social contact and cognitive function among middle-aged and elderly Chinese: A causal inference and longitudinal targeted maximum likelihood estimation analysis.

BACKGROUND: Social contact has demonstrated associations with cognitive function, while the literature on the effect of specific social relationship subdomains on cognitive function is limited. This study aimed to examine the causal effects of specific types/amounts of social contact on cognitive function among middle-aged and elderly Chinese. METHODS: A total of 38,883 middle-aged and elderly adults from the China Health and Retirement Longitudinal Study were involved. Social contact in this study included interaction with families, taking care of grandchildren, interaction with friends, and participation in three types of social activities. We performed the linear mixed-effects model analysis with propensity score approach and the longitudinal targeted maximum likelihood-based estimation analysis after adjusting for potential covariates and confounders. RESULTS: Interaction with families, caring for grandchildren, interaction with friends and participation in social activities were all associated with cognitive z-scores. Participants who interacted with families "2-3 times a week" and "once a week" versus "almost every day" had higher cognitive z-scores. Those who interacted with friends and participated in social activities "almost every week" versus "almost daily" had higher cognitive z-scores. LIMITATIONS: The assessment of cognition was biased against people with poor education due to elements of language and mathematical testing, and against those with visual impairment. CONCLUSIONS: Social contact was associated with better cognitive function among middle-aged and elderly Chinese. Social contact "1-3 times a week" was optimal for cognitive function. More social contact in middle-aged and elderly Chinese led to less cognitive decline in later life than in their inactive peers.

Clinical effects of Chemotherapy combined with Immunotherapy in patients with advanced NSCLC and the effect on their nutritional status and immune function.

Objectives: To evaluate the clinical effects of chemotherapy combined with immunotherapy in patients with advanced non-small-cell lung cancer (NSCLC) and the effect on their nutritional status and immune function. Methods: Total 120 patients with advanced NSCLC admitted to Affiliated Hospital of Hebei University from May 2019 to October 2021 were randomly divided into two groups (n= 60, respectively). Patients in the control group were treated by chemotherapy with cisplatin-paclitaxel (TP) alone: 120 mg/m2 paclitaxel was used on d1; and 25mg/m2 cisplatin (CDDP) was used for more than two hour, once every 14 days, for three consecutive three cycles. Patients in the study group were additionally given 200 mg sindilizumab by intravenous drip, once every three weeks. The contrastive analysis of clinical effects, the incidence of adverse reactions, improvement of the nutrient index and the changes in levels of CD3+, CD4+, CD8+, and CD4+/CD8+ in T-lymphocyte subsets was performed between the two groups. Result: The overall response rate (ORR) was 80% and 61% in the study group and the control group, respectively; and the difference was statistically significant (p=0.03); the contrast analysis of the incidence of post-treatment adverse drug reactions (ADRs) in patients in the two groups suggested that the incidence of adverse reactions was 33.3% and 45% in the study group and the control group, respectively; and the difference was not statistically significant (p=0.19). After the treatment, the improvement of hemoglobin, albumin, serum iron and ferritin levels in the study group was more significant than that in the control group; and the difference was statistically significant (p < 0.05). After the treatment, the levels of CD3+, CD4+ and CD4+/CD8+ in the study group were much higher than those in the control group; and the difference was statistically significant (p < 0.05). Conclusion: Chemotherapy combined with immunotherapy is effective in treating patients with advanced NSCLC without increasing the incidence of adverse reactions, and can significantly improve their nutritional status and T-lymphocyte function. This therapeutic regimen is of much higher clinical value than the chemotherapy-only regimen.

Clinical Efficacy of Chemotherapy Regimen Combined with Levofloxacin in Patients with Pulmonary Tuberculosis Complicated with Type-2 Diabetes.

Objective: To evaluate the clinical efficacy of a chemotherapy regimen combined with levofloxacin in patients with pulmonary tuberculosis complicated with Type-2 diabetes. Methods: Total 80 patients with pulmonary tuberculosis complicated with Type-2 diabetes admitted to Baoding People's Hospital from January, 2019 to January, 2022 were randomly divided into two groups: the experimental group and the control group, with 40 cases in each group. Patients in the control group were given the conventional 2HRZE/10HRE regimen, while those in the experimental group were given the chemotherapy regimen 2HRZEL/6HRE combined with levofloxacin. Sixty four slice spiral CT was used for chest plain scan before and after treatment, respectively, to evaluate the absorption of lesions based on the range of lung lesions; Venous blood was drawn to detect the changes of oxidative stress indicators, the incidence of adverse drug reactions and the negative conversion rate of sputum tuberculosis bacteria in the two groups. Results: After treatment, the efficacy of the experimental group was 90%, which was significantly higher than that of the control group (67.5%), with a statistically significant difference (p=0.01). After treatment, CD3+, CD4+, CD4+/CD8+ and other indicators in the experimental group were significantly higher than those in the control group, with a statistically significant difference (CD3+, p=0.01; CD4+, p=0.01; CD4+/CD8+, p=0.00), while CD8+ did not change significantly (p=0.92); The incidence of adverse reactions was 52.5% in the experimental group and 47.5% in the control group, with no statistically significant difference (p=0.66); The negative conversion rate of patients in the experimental group was significantly higher than that in the control group at one month, three months and six months after treatment, with a statistically significant difference (p<0.05). Conclusion: Chemotherapy combined with levofloxacin is a safe and effective regimen for patients' pulmonary tuberculosis complicated with Type-2 diabetes, boasting a variety of benefits such as improved clinical efficacy, ameliorated cellular immune status, a high negative conversion rate of sputum tuberculosis bacteria, and no significant increase in adverse reactions.

Sex-Specific Bioaccumulation, Maternal Transfer, and Tissue Distribution of Legacy and Emerging Per- and Polyfluoroalkyl Substances in Snakes (Enhydris chinensis) and the Impact of Pregnancy.

The effects of sex and pregnancy on the bioaccumulation and tissue distribution of legacy and emerging per- and polyfluoroalkyl substances (PFASs) in Chinese water snakes were investigated. The bioaccumulation factor of PFASs showed a positive correlation with their protein-water partition coefficients (log KPW), and steric hindrance effects were observed when the molecular volume was > 357 Å3. PFAS levels in females were significantly lower than those in males. The chemical composition of pregnant females was significantly different from that of non-pregnant females and males. The maternal transfer efficiencies of perfluorooctane sulfonic acid were higher than those of other PFASs, and a positive correlation between the maternal transfer potential and log KPW was observed for other PFASs. Tissues with high phospholipid content exhibited higher concentrations of ∑PFASs. Numerous physiological changes occurred in maternal organ systems during pregnancy, leading to the re-distribution of chemicals among different tissues. The change in tissue distribution of PFASs that are easily and not-so-easily maternally transferred was in the opposite direction. The extent of compound transfer from the liver to the egg determined tissue re-distribution during pregnancy.

[Corrigendum] ND­09 inhibits chronic myeloid leukemia K562 cell growth by regulating BCR­ABL signaling.

Subsequently to the publication of this paper, the authors have realized that an error was made during the compilation of Fig. 2A as it appeared on p. 4. Essentially, the partial Q2­3 images of the '1.56 µm' group were inadvertently copied across to the Q2­3 images of the '3.12 µm' group, leading to the cell number of the Q2­3 quadrant being the same for both the 1.56 µm and the 3.12 µm groups, and also leading the total cell number of the 3.12 µm group being calculated as 106.97%, which was clearly incorrect (the total percentage should have added up to 100%). The corrected version of Fig. 2, showing the correct data for the Q2­3 images in the '3.12 µm' group, is shown on the next page. Note that this error did not significantly affect the results or the conclusions reported in this paper, and all the authors agree with the publication of this Corrigendum. The authors are grateful to the Editor of Oncology Reports for allowing them this opportunity to publish a corrigendum, and apologize to the readership for any inconvenience caused. [Oncology Reports 46: 136, 2021; DOI: 10.3892/or.2021.8087].