Development and validation of a LASSO prediction model for cisplatin induced nephrotoxicity: a case-control study in China.

BACKGROUND: Early identification of high-risk individuals with cisplatin-induced nephrotoxicity (CIN) is crucial for avoiding CIN and improving prognosis. In this study, we developed and validated a CIN prediction model based on general clinical data, laboratory indications, and genetic features of lung cancer patients before chemotherapy. METHODS: We retrospectively included 696 lung cancer patients using platinum chemotherapy regimens from June 2019 to June 2021 as the traing set to construct a predictive model using Absolute shrinkage and selection operator (LASSO) regression, cross validation, and Akaike's information criterion (AIC) to select important variables. We prospectively selected 283 independent lung cancer patients from July 2021 to December 2022 as the test set to evaluate the model's performance. RESULTS: The prediction model showed good discrimination and calibration, with AUCs of 0.9217 and 0.8288, sensitivity of 79.89% and 45.07%, specificity of 94.48% and 94.81%, in the training and test sets respectively. Clinical decision curve analysis suggested that the model has value for clinical use when the risk threshold ranges between 0.1 and 0.9. Precision-Recall (PR) curve shown in recall interval from 0.5 to 0.75: precision gradually declines with increasing Recall, up to 0.9. CONCLUSIONS: Predictive models based on laboratory and demographic variables can serve as a beneficial complementary tool for identifying high-risk populations with CIN.

From Cd(SCN)2(CH4N2S)2 to Cd(SCN)2(C4H6N2)2: Controlling Sulfur Content in Thiocyanate Systems Significantly Improves the Overall Performance of UV Nonlinear Optical Materials.

Combining a strong second-order nonlinear optical (NLO) effect (>1×KH2PO4 (KDP)), a large band gap (>4.2 eV), and a moderate birefringence in ultraviolet (UV) NLO crystals remains a formidable challenge. Herein, Cd(SCN)2(C4H6N2)2, the first example of a thiocyanate capable of realizing a phase-matched UV NLO crystal material, is obtained by reducing the sulfur (S) content in the centrosymmetric (CS) structure of Cd(SCN)2(CH4N2S)2. Compared to the "shoulder-to-shoulder" one-dimensional (1D) chain of Cd(SCN)2(CH4N2S)2, Cd(SCN)2(C4H6N2)2 has a different sawtooth 1D chain structure. Cd(SCN)2(CH4N2S)2 has second harmonic generation (SHG) inertia with a band gap of 3.90 eV and a UV cutoff edge of 342 nm, however, it possesses a large birefringence (0.35@546 nm). In contrast, the symmetry center breaking of Cd(SCN)2(C4H6N2)2 leads to remarkably strong SHG intensity (10 times that of KDP). Furthermore, it has a wide band gap (4.74 eV), short UV cutoff edge (234 nm), and moderate birefringence capable of phase matching (0.17@546 nm). This research indicates that thiocyanates are a promising class of UV NLO crystal materials, and that modulation of the sulfur content of CS thiocyanates is an effective strategy for the development of UV NLO crystals with excellent overall performances.

From C4H7N2Ge0.4Sn0.6Br3 to C6H11N2Ge0.4Sn0.6Br3: Effective Modulation of the Second Harmonic Generation Effect and Optical Band Gap by Planar π-Conjugated Organic Cation Size.

In the search for nonlinear optical (NLO) materials with excellent overall performance, we have devoted ourselves to organic-inorganic hybrids consisting of anionic groups containing stereochemically active lone-pair (SCALP) electron cations and organic planar π-conjugated group cations. Accordingly, in this paper, two novel organic-inorganic hybrid metal halides, C4H7N2Ge0.4Sn0.6Br3 (I) and C6H11N2Ge0.4Sn0.6Br3 (II), have been synthesized. The powder second-harmonic technique shows that both C4H7N2Ge0.4Sn0.6Br3 and C6H11N2Ge0.4Sn0.6Br3 have moderately strong second-order nonlinear optical effects, which are about 2.03 (I) and 1.16 (II) times that of KH2PO4 (KDP), respectively. They also have different optical band gaps of 2.75 (I) and 2.88 eV (II) due to the different sizes of the organic cations, and their photoluminescent and thermal properties were also investigated. This work provides new structural insights for the design and modulation of organic-inorganic hybrid halide materials with multiple excellent optical properties.

Genetic polymorphisms of CYP2B6 is a risk of metabolic associated fatty liver disease in Chinese population.

BACKGROUND: The expression and activity of cytochrome P450 2B6 (CYP2B6) may be related to the metabolic associated fat liver disease (MAFLD). Since constitutive androstane receptor (CAR) is a classic transcriptional regulator of CYP2B6, and the single nucleotide polymorphisms (SNPs) of CYP2B6 and CAR are both associated with adverse reactions of efavirenz, we hypothesized that genetic polymorphisms of CAR might also result in additional interindividual variability in CYP2B6. This study was devoted to explore the association between CYP2B6 and CAR SNPs and susceptibility to MAFLD. MATERIALS AND METHODS: A total of 590 objects of study (118 with MAFLD and 472 healthy control) between December 2014 and April 2018 were retrospectively enrolled. Twenty-two selected SNPs in CYP2B6 and CAR were genotyped with a custom-designed 48-plex SNP Scan TM® Kit. The frequencies of the alleles, genotypes and genetic models of the variants were compared between the two groups. The odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were calculated. RESULTS: The T allele of rs3745274 in CYP2B6 was associated with a decreased risk for MAFLD (OR 0.610; 95% CI: 0.451-0.825, p = 0.001) which was still statistically significant after adjusting with Bonferroni method(p = 0.014) The allele, genotype and genetic model frequencies were similar in the two groups for the other twenty-one SNPs (all P > 0.05). There were no multiplicative or additive interactions between the SNPs. CONCLUSION: Our study revealed that rs3745274 variants in CYP2B6 is associated with susceptibility to MAFLD in the Han Chinese population.

TRPA1 promotes cisplatin-induced acute kidney injury via regulating the endoplasmic reticulum stress-mitochondrial damage.

BACKGROUND: Cisplatin is a widely used and effective chemotherapeutic agent against cancer. However, nephrotoxicity is one of the most common side effects of cisplatin, and it can proceed to acute kidney injury (AKI). Studies have reported that activation of transient receptor potential ankyrin-1 (TRPA1) mediates cisplatin-induced renal tubular cytotoxic injury. The aim of this study was to investigate the mechanism of TRPA1 in promoting cisplatin-induced AKI through modulation of the endoplasmic reticulum stress (ERS)-mitochondrial damage. METHODS: A cisplatin-induced HK-2 cell model in vitro and mouse model in vivo were established. The mechanism of TRPA1 promotes AKI was elucidated by H&E staining, TUNEL staining, transmission electron microscope (TEM), immunofluorescence, CCK-8 viability assays, flow cytometry, Western blotting, JC-1 assay, and enzyme linked immunosorbent assay (ELISA). RESULT: In vivo and in vitro, HC-030031 reduced cisplatin-induced Scr and BUN level elevations; improved cisplatin-induced renal tissue injury, apoptosis, and mitochondrial dysfunction; elevated the reduced ERS-associated proteins glucose-regulated protein 78 (GRP78), glucose-regulated protein 75 (GRP75), and C/EBP homologous protein (CHOP) levels induced by cisplatin; reduced the elevated optic atrophy 1 (OPA1), mito-fusion 1 (MFN1), and mito-fusion 2 (MFN2) protein levels, and elevated phospho-dynamin-related protein 1 (p-DRP1) and mitochondrial fission factor (MFF) protein levels. HC-030031 also reduced the mitochondria-associated endoplasmic reticulum membrane (MAM) structure. In addition, TRPA1 agonists also decreased cell proliferation, increased apoptosis, and triggered mitochondrial dysfunction and calcium overload in HK-2 cells via modulation of MAM. ERS inhibitors and GRP75 inhibitors reversed these changes caused by TRPA1 agonists. CONCLUSION: Our findings suggest that TRPA1 enhances cisplatin-induced AKI via modulation of ERS and mitochondrial damage.

How do primary hospitals enact early response to the relaxation of COVID-19 prevention and control measures? the experience from Chengdu, China.

Due to the highly contagious nature of the Omicron variant of SARS-CoV-2 and its subvariants, a high rate of transmission was observed throughout Chengdu, China, within 2 weeks of the relaxation of COVID-19 measures on December 3, 2022, particularly in hospitals. Hospitals experienced different degrees of medical overcrowding during the first 2 weeks, with a high patient volume in the emergency departments and a significant lack of beds in the medical wards, particularly in the respiratory intensive care unit (ICU) and ICU. The authors' place of employment, Chengdu Jinniu District People's Hospital, is a tertiary B-level public hospital situated in the Jinniu District in northwest Chengdu. The hospital's emergency coordination and response efforts emphasized addressing patients' difficulties in obtaining medical care and hospitalization in the region and keeping the mortality rate of patients with pneumonia to a minimal level. It has been emulated by sister hospitals and was well received by the local populace and municipal government. The hospital made the following significant alterations and modifications to this emergency medical care: (1) immediate establishment of the General ICU (GICU), a temporary unit set up in emergency situations that had most of the functions of but was not as complete as the ICU and had a lower ratio of doctors to nurses; (2) dynamic adjustment of anesthesiologists and respiratory physicians jointly stationed in the GICU; (3) choice of nurses with extensive experience in internal medicine and allocation to the GICU according to a 2:3 ICU bed to nurse ratio; (4) emergency purchase or deployment of pneumonia-related treatment equipment; (5) implementation of the GICU resident rotation system; (6) "twinning" of internal medicine and other departments to add beds; and (7) implementation of uniform hospital bed allocation for inpatients.

Managers' attitudes toward gene-editing technology and companies' R&D investment in gene-editing: the case of Chinese seed companies.

The Chinese government has issued a series of new policies to make it easier to industrialize gene-edited crops. However, whether technological advantages will eventually translate into industrial advantages and whether farmers will soon have access to gene-edited varieties partly depends on seed companies' willingness to produce and sell gene-edited varieties to farmers and to invest in developing their own gene-edited varieties. This study utilizes data from a survey of 111 seed companies collected in 2019 before the implementation of new regulations. This study provides empirical evidence on whether gene-edited crops will be available to farmers. The results show that the number of companies conducting research on gene-edited crops is limited, mostly to large companies. Approximately 55% of seed company managers would consider developing and selling gene-edited crops modified by SDN-1 and SDN-2 site-directed nuclease genome editing without external genetic material, whereas 46% support crops modified by SDN-3, which require gene replacement or foreign deoxyribonucleic acid (DNA) insertion and are regulated as genetically modified organisms (GMOs). The regression results show that large companies and companies with well-educated researchers are more likely to support and develop gene-editing technology. Past GM investment experience and collaboration with public institutions in gene-editing research increases the probability of company investment in gene editing R&D. These results suggest that gene-edited cultivars are more likely to be produced and sold to farmers in the future than GMOs, and that gene-edited agricultural products could have a significant market share of the seed market in the future.

Combined electronic medical records and gene polymorphism characteristics to establish an anti-tuberculosis drug-induced hepatic injury (ATDH) prediction model and evaluate the prediction value.

Background: Anti-tuberculosis drug-induced hepatic injury (ATDH) lacks specific diagnostic markers. The characteristics of gene polymorphisms have been preliminarily used for the risk classification of ATDH, and the activation of Pregnane X receptor/aminole-vulinic synthase-1/forkhead box O1 (PXR/ALAS1/FOXO1) axis is closely related to ATDH. Therefore, we consider combining general clinical features of the electronic medical record, laboratory indications, and genetic features of key genes in this axis for predictive model construction to help early clinical diagnosis and treatment. Methods: The general characteristics derived from the Hospital Information System (HIS) medical record system, the biochemical tests and hematology tests were detected by Roche automatic biochemical immunoassay analyzer cobas8000 and Sysmex automatic hemocytometer XE2100. The single nucleotide polymorphisms (SNPs) genotyping work was conducted with a custom-designed 48-plex SNP scan® TM Kit. A total of 746 cases were included which were divided into training set and validation set according to the ratio of 3:2 randomly. Taking the occurrence of confirmed ATDH as the outcome variable, lasso regression and logistic regression were used to identify the predictors preliminarily. alanine aminotransferase, aspartate aminotransferase, monocyte, uric acid, albumin, fever, the polymorphisms of rs4435111 (FOXO1) and rs3814055 (PXR) were chosen from all variables to combine the predictive model. The goodness of fit, predictive efficacy, discrimination, and consistency, and clinical decision curve analysis was used to assess the clinical applicability of the models. Results: The best model had a discriminant efficacy C-index of 0.8164, a sensitivity of 34.25%, specificity of 97.99%, a positive predictive value of 78.13% and negative predictive value of 87.69%, the two-tailed value of Spiegelhalter Z test of consistency test S:P =0.896, maximum absolute difference Emax =0.147, and average absolute difference Eave =0.017. In the validation set, performance was close. The clinical decision curve showed the clinical applicability of the prediction model when the prediction risk threshold was between 0.1 and 0.8. Conclusions: The ATDH prediction model was constructed using a machine learning approach, combining general characteristics of the study population, laboratory indications, and SNP features of PXR and FOXO1 genes with good fit and certain predictive value, and has potential and value for clinical application.

Effect of Baking Temperature and Time on Advanced Glycation End Products and Polycyclic Aromatic Hydrocarbons in Beef.

ABSTRACT: Beef is an important red meat that contains essential nutrients for human growth and development. Baking is a popular beef cooking method. Temperature and time play key roles in the final quality of beef. How temperature and time affect the changes of nutrients and the formation of harmful products in beef is not clear. The purpose of this study was to measure the content of water, fat, protein, ash, nitrite, total volatile base nitrogen, advanced glycation end products (AGEs) and their precursors, and polycyclic aromatic hydrocarbons (PAHs) at different temperatures (150, 190, 230, 270, and 310°C) for 20 min and at 190°C for different times (10, 20, and 30 min), so as to discuss the effect of different temperatures and times on beef nutrients and harmful products. The results showed that the moisture content of beef decreased with increased baking temperature and time, resulting in the increase of the relative content of fat, protein, and ash. The content of total volatile base nitrogen increased continuously. Compared with the control group, the content of glyoxal in beef decreased, whereas the content of methylglyoxal, pentosidine, and fluorescent AGEs increased, indicating the continuous accumulation of AGEs in beef. A total of 13 PAHs were identified by gas chromatography-mass spectrometry. The concentrations of 13 PAHs in beef increased with increases in baking temperature and time. The concentrations of BkP and BaP, which are the most carcinogenic to humans, were 0.36 and 0.35 µg/kg in raw meat, respectively; these were increased by high temperature and long baking times. After beef was baked at 270 and 310°C for 20 min, the concentration of BkP increased to 9.49 and 5.66 µg/kg, respectively, and the concentration of BaP increased to 5.45 and 4.42 µg/kg, respectively. After baking at 190°C for 30 and 40 min, the concentration of BkP increased to 4.81 and 24.20 µg/kg, respectively, and the concentration of BaP increased to 3.85 and 17.79 µg/kg, respectively.

Income and social support related with mental health during COVID-19 outbreak in China.

ABSTRACT: To investigate psychological response of Chinese public during the regular prevention and control of Corona Virus Disease 2019 (COVID-19), and explore the relationship among income loss, social support and mental health.Five hundred twenty-six participants were randomly selected by snowball sampling method. Chinese version of Perceived Psychological Stress Scale, Perceived Social Support Scale, self-rating anxiety scale, and the PTSD Checklist for DSM-5 were used to measure the levels of psychological stress, social support, anxiety, and post-traumatic stress disorder (PTSD) symptoms. Demographic variables, income loss and income satisfaction during the outbreak period were also collected.The prevalence rate of anxiety, PTSD symptoms and stress problems were 19.8%, 23.8%, and 24.7% respectively. Multiple Regression Analysis illustrated that social support associated with stress, anxiety and PTSD after controlling demographic variables; for non-student samples, stress, anxiety, and PTSD were corelated with change in income and social support.During the regular prevention and control of COVID-19, social support might help reducing stress, anxiety, and PTSD symptoms. In addition to social support, change of income level was also an important factor for mental health. This study suggested the importance of maintaining a steady income after acute outbreak of COVID-19.

High levels of regulatory T cells in blood are a poor prognostic factor in patients with diffuse large B-cell lymphoma.

OBJECTIVES: Host immunity likely plays a role in preventing progression of diffuse large B-cell lymphoma (DLBCL). Analysis of host immune cells may provide useful information for assessing prognosis or possibly clinical management. METHODS: Peripheral blood samples from 77 patients with DLBCL and 30 healthy volunteers were analyzed using flow cytometry immunophenotyping. CBC counts, T-cell subsets, and dendritic cells (DCs) were detected, and the results were correlated with clinicopathologic characteristics. RESULTS: Compared with healthy volunteers, patients with DLBCL had significantly higher leukocyte and monocyte counts (P < .001); higher percentages of neutrophils (P < .001), "natural" regulatory T cells (Tregs; CD3+Foxp3+, P < .001), and immature DCs (CD83-CD1a+, P = .005); and lower percentages of lymphocytes (P < .001) and helper T cells (P = .038). In univariate analysis, high neutrophil counts (≥6,000/µL, P = .014) and "induced" Tregs (CD4+CD25+, P = .026) were poor survival factors along with high International Prognostic Index scores (P < .001) and other high-risk clinical parameters. In multivariate analysis, high Tregs retained significance. Suppression of lymphocytes correlated with poor clinical factors; higher natural Tregs correlated with a lower CD4+/CD8+ ratio (P = .035) and more immature DCs (P = .055). CONCLUSIONS: Changes in blood immune cells occur in patients with DLBCL. The results also support a suppressive role of Tregs in adaptive immunity and correlate with poor-risk prognostic factors.

Effects of naphthalene quinonoids on the induction of oxidative DNA damage and cytotoxicity in calf thymus DNA and in human cultured cells.

The purpose of this study was to examine the differences in the induction of DNA damage and cytotoxic effects by quinonoid derivatives of naphthalene in calf thymus DNA (ct-DNA) and in human T47D breast cancer cells. Results indicated that copper(II) and NADPH were essential for causing oxidant-mediated aldehydic DNA lesions (ADLs), including abasic sites and aldehydic base/sugar lesions, in ct-DNA exposed to 1,2-naphthalenediol (NCAT), 1,4-naphthalenediol (NHQ), 1,2-naphthoquinone (1,2-NQ), and 1,4-naphthoquinone (1,4-NQ). The ADLs induced by naphthalene quinonoids in ct-DNA decrease in the rank order NCAT congruent with 1,2-NQ > NHQ >> 1,4-NQ. Results from the analyses in cells indicated that after 1.5-5 h of exposure all naphthalene quinonoids induced a cytotoxic response in T47D cells at concentrations 10-100 microM or above, where NHQ and 1,4-NQ were approximately 5-10 times more efficient than NCAT and 1,2-NQ in the induction of cell death. In addition, NHQ, 1,2-NQ, and 1,4-NQ were not able to produce measurable levels of ADLs in cells at concentrations up to 1.25 mM, whereas NCAT (0.75-1.25 mM) induced a significant increase in the number of ADLs in T47D cells after 1.5 h of exposure when compared to control. The specific type of ADLs induced by NCAT is resistant to cellular excision repair pathway. Results from the measurements of reactive oxygen species (ROS) indicated that all naphthalene quinonoids induced increases in ROS formation in T47D cells. The induction of ROS formation in cells by naphthalene quinonoids decreases in the rank order 1,4-NQ congruent with 1,2-NQ > NHQ > NCAT. Overall, results from our investigation suggest that naphthalene quinonoids cause cell death at concentrations well below the concentrations at which they induce the formation of ADLs, perhaps by altering intracellular redox status.