QL1604 plus paclitaxel-cisplatin/carboplatin in patients with recurrent or metastatic cervical cancer: an open-label, single-arm, phase II trial.

OBJECTIVE: QL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer. METHODS: This was a multicenter, open-label, single-arm, phase II study. Patients with advanced cervical cancer and not previously treated with systemic chemotherapy were enrolled to receive QL1604 plus paclitaxel and cisplatin/carboplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by QL1604 maintenance treatment. RESULTS: Forty-six patients were enrolled and the median follow-up duration was 16.5 months. An 84.8% of patients had recurrent disease and 13.0% had stage IVB disease. The objective response rate (ORR) per Response Evaluation Criteria in Advanced Solid Tumors (RECIST) v1.1 was 58.7% (27/46). The immune ORR per immune RECIST was 60.9% (28/46). The median duration of response was 9.6 months (95% confidence interval [CI]=5.5-not estimable). The median progression-free survival was 8.1 months (95% CI=5.7-14.0). Forty-five (97.8%) patients experienced treatment-related adverse events (TRAEs). The most common grade≥3 TRAEs (>30%) were neutrophil count decrease (50.0%), anemia (32.6%), and white blood cell count decrease (30.4%). CONCLUSION: QL1604 plus paclitaxel-cisplatin/carboplatin showed promising antitumor activity and manageable safety profile as first-line treatment in patients with advanced cervical cancer. Programmed cell death protein 1 inhibitor plus chemotherapy may be a potential treatment option for the patient population who have contraindications or can't tolerate bevacizumab, which needs to be further verified in phase III confirmatory study. Trial RegistrationClinicalTrials.gov Identifier: NCT04864782.

Niche differentiation in microbial communities with stable genomic traits over time in engineered systems.

Microbial communities in full-scale engineered systems undergo dynamic compositional changes. However, mechanisms governing assembly of such microbes and succession of their functioning and genomic traits under various environmental conditions are unclear. In this study, we used the activated sludge and anaerobic treatment systems of four full-scale industrial wastewater treatment plants as models to investigate the niches of microbes in communities and the temporal succession patterns of community compositions. High-quality representative metagenome-assembled genomes revealed that taxonomic, functional, and trait-based compositions were strongly shaped by environmental selection, with replacement processes primarily driving variations in taxonomic and functional compositions. Plant-specific indicators were associated with system environmental conditions and exhibited strong determinism and trajectory directionality over time. The partitioning of microbes in a co-abundance network according to groups of plant-specific indicators, together with significant between-group differences in genomic traits, indicated the occurrence of niche differentiation. The indicators of the treatment plant with rich nutrient input and high substrate removal efficiency exhibited a faster predicted growth rate, lower guanine-cytosine content, smaller genome size, and higher codon usage bias than the indicators of the other plants. In individual plants, taxonomic composition displayed a more rapid temporal succession than functional and trait-based compositions. The succession of taxonomic, functional, and trait-based compositions was correlated with the kinetics of treatment processes in the activated sludge systems. This study provides insights into ecological niches of microbes in engineered systems and succession patterns of their functions and traits, which will aid microbial community management to improve treatment performance.

Evaluation of a new dynamic real-time visualization 25 kHz swept-source optical coherence tomography based biometer.

BACKGROUND: To evaluate the intraobserver repeatability and interobserver reproducibility of a newly developed dynamic real-time visualization 25 kHz swept-source optical coherence tomography (SS-OCT) based biometer (ZW-30, TowardPi Medical Technology Ltd, China) and compare its agreement with another SS-OCT based biometer (IOLMaster 700, Carl Zeiss Meditec AG, Jena, Germany). METHODS: Eighty-two healthy right eyes were enrolled in this prospective observational study. Measurements were repeated for three times using the ZW-30 and IOLMaster 700 in a random order. Obtained parameters included axial length (AL), central corneal thickness (CCT), aqueous depth (AQD), anterior chamber depth (ACD), lens thickness (LT), mean keratometry (Km), astigmatism magnitude (AST), vector J0, vector J45, and corneal diameter (CD). The within-subject standard deviation (Sw), test-retest (TRT) variability, coefficient of variation (CoV), and intraclass correlation coefficient (ICC) were adopted to assess the intraobserver repeatability and interobserver reproducibility. The double-angle plot was also used to display the distribution of AST. To estimate agreement, Bland-Altman plots were used. RESULTS: For the intraobserver repeatability and interobserver reproducibility, the Sw, TRT and CoV for all parameters were low. Meanwhile, the ICC values were all close to 1.000, except for the J45 (ICC = 0.887 for the intraobserver repeatability). The double-angle plot showed that the distribution of AST measured by these two devices was similar. For agreement, the Bland-Altman plots showed narrow 95% limits of agreements (LoAs) for AL, CCT, AQD, ACD, LT, Km AST, J0, J45, and CD (- 0.02 mm to 0.02 mm, - 7.49 µm to 8.08 µm, - 0.07 mm to 0.04 mm, - 0.07 mm to 0.04 mm, - 0.07 mm to 0.08 mm, - 0.16 D to 0.30 D, - 0.30 D to 0.29 D, - 0.16 D to 0.16 D, - 0.23 D to 0.13 D, and - 0.39 mm to 0.10 mm, respectively). CONCLUSIONS: The newly dynamic real-time visualization biometer exhibited excellent intraobserver repeatability and interobserver reproducibility. The two devices both based on the SS-OCT principle had similar ocular parameters measurement values and can be interchanged in clinical practice.

Harmine ameliorates CCl4-induced acute liver injury through suppression of autophagy and inflammation.

CCl4-induced acute liver injury (ALI) is characterized by heightened autophagy, inflammation, and oxidative damage. Accumulating evidence suggests that harmine exerts beneficial effects in countering CCl4-induced ALI by mitigating inflammation and oxidative stress. However, the impact of autophagy on CCl4-induced ALI and the protective role of harmine remain unclear. This study aimed to investigate the potential protective effects of harmine against CCl4-induced ALI in mice by suppressing autophagy and inflammation. Male Kunming mice were orally administered harmine or bifendate for seven days. Subsequently, one hour after the final administration, the model group and treatment groups were intraperitoneally injected with CCl4 to induce ALI. The findings revealed that harmine significantly reduced the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum, and ameliorated the liver histopathological changes induced by CCl4. Furthermore, harmine diminished the levels of TNF-α and IL-6, restored the levels of glutathione (GSH) and superoxide dismutase (SOD), and suppressed the production of nitric oxide (NO) and malondialdehyde (MDA) in the liver. Mechanistically, harmine down-regulated LC3B II/I, p38 MAPK, TLR4, and NF-κB levels, while upregulating p62, Bcl-2, Beclin1, ULK1, and p-mTOR expression. In conclusion, harmine mitigated CCl4-induced ALI by inhibiting autophagy and inflammation through the p38 MAPK/mTOR autophagy pathway, the Bcl-2/Beclin1 pathway, and the TLR4/NF-κB pathway.

Bletilla striata polysaccharide attenuated the progression of pulmonary fibrosis by inhibiting TGF-ß1/Smad signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Bletilla striata, a traditional medicinal plant, has been utilized as a folk medicine for many years because of its superior biological activity in China. However, Bletilla striata polysaccharide (BSP) has received less attention, and its specific mechanism for ameliorating pulmonary fibrosis is completely unclear. AIMS OF THE STUDY: In this study, we aim to assess BSP on the treatment of PF and explore potential mechanisms. MATERIALS AND METHODS: BSP was successfully extracted and purified from Bletilla striata. The mechanisms were assessed in bleomycin-induced pulmonary fibrosis model and lung fibroblasts activated by transforming growth factor-ß1 (TGF-ß1). Histological analysis, immunofluorescence, Western blot and flow cytometry were used to explore the alterations after BSP intervention. RESULTS: The results in vivo showed an anti-PF effect of BSP treatment, which reduced pathogenic damages. Furthermore, TGF-ß1-induced abnormal migration and upregulated expression of collagen I (COL1A1), vimentin and α-smooth muscle actin (α-SMA) were suppressed by BSP in L929 cells. Moreover, the abnormal proliferation was retarded by inhibiting the cell cycle of G1 to S phase. Immunofluorescence assay showed that BSP activated autophagy and played an antifibrotic role by inhibiting the expression of p62 and phospho-mammalian target of rapamycin (p-mTOR). Last but not least, the suppression of TGF-ß1/Smad signaling pathway was critical for BSP to perform therapeutic effects in vitro and in vivo. CONCLUSION: The possible mechanisms were involved in improving ECM deposition, regulating cell migration and proliferation, and promoting cellular autophagy. Briefly, all of the above revealed that BSP might be a novel therapy for treating pulmonary fibrosis.

Tectoridin alleviates caerulein-induced severe acute pancreatitis by targeting ERK2 to promote macrophage M2 polarization.

Severe acute pancreatitis (SAP) is an inflammatory disease of the pancreas with a high mortality rate. Macrophages play a crucial role in the pathogenesis of pancreatitis. Tectoridin (Tec) is a highly active isoflavone with anti-inflammatory pharmacological activity. However, the role of Tec in the SAP process is not known. The purpose of this study was to investigate the therapeutic effect and potential mechanism of Tec on SAP. To establish SAP mice by intraperitoneal injection of caerulein and Lipopolysaccharide (LPS), the role of Tec in the course of SAP was investigated based on histopathology, biochemical indicators of amylase and lipase and inflammatory factors. The relationship between Tec and macrophage polarization was verified by immunofluorescence, real-time quantitative PCR and Western blot analysis. We then further predicted the possible targets and signal pathways of action of Tec by network pharmacology and molecular docking, and validated them by in vivo and in vitro. In this study, we demonstrated that Tec significantly reduced pancreatic injury in SAP mice, and decreased serum levels of amylase and lipase. The immunofluorescence and Western blot analysis showed that Tec promoted macrophage M2 polarization. Network pharmacology and molecular docking predicted that Tec may target ERK2 for the treatment of SAP, and in vivo and in vitro experiments proved that Tec inhibited the ERK MAPK signal pathway. In summary, Tec can target ERK2, promote macrophage M2 polarization and attenuate pancreatic injury, Tec may be a potential drug for the treatment of SAP.

Evaluation of a New All-in-One Optical Biometer and Comparison With a Validated Swept-source OCT Biometer.

PURPOSE: To assess agreement between a new all-in-one non-contact optical biometer based on optical low coherence reflectometry (SW-9000 µm Plus; Suoer) and a swept-source optical coherence tomography biometer (OA-2000; Tomey). METHODS: Each eye was scanned three times in a row by each device at random. The measured ocular parameters included central corneal thickness (CCT), anterior chamber depth (ACD), lens thickness (LT), axial length (AL), flat keratometry (Kf), steep keratometry (Ks), mean keratometry (Km), astigmatism, corneal diameter (CD), and pupil diameter (PD). The paired t test was used to show the differences between the SW-9000 and OA-2000. Bland-Altman plots and the 95% limits of agreement (LoA) were applied to assess the consistency of the measurements. RESULTS: Sixty eyes from 60 healthy participants were examined, with a mean spherical equivalent refraction of -5.58 ± 2.31 diopters and a mean age of 30.40 ± 6.07 years. The Bland-Altman plots showed high agreement for AL, ACD, LT, Kf, Ks, Km, astigmatism, and CD measurements (95% LoA: -0.06 to 0.04 mm, -0.10 to 0.06 mm, -0.12 to 0.11 mm, -0.30 to 0.29 D, -0.35 to 0.38 D, -0.29 to 0.30 D, -0.30 to 0.34 D, and -0.50 to 0.06 mm, respectively), whereas the agreement for CCT and PD were moderate (95% LoA: 7.12 to 20.43 µm, -0.75 to 1.19 mm, respectively). CONCLUSIONS: The new all-in-one non-contact biometer had high agreement with the OA-2000 biometer on the AL, ACD, LT, Kf, Ks, Km, astigmatism, and CD measurements. For most of the ocular parameters assessed, they were clinically interchangeable. [J Refract Surg. 2023;39(12):825-830.].

Development of Single-Segment Substitution Lines and Fine-Mapping of qSPP4 for Spikelets Per Panicle and qGW9 for Grain Width Based on Rice Dual-Segment Substitution Line Z783.

Single segment substitution line (SSSL) libraries are an ideal platform for breeding by design. To develop SSSLs-Xihui18 covering the whole genome, a novel rice chromosome segment substitution line (CSSL), Z783, carrying two substitution segments (average length of 6.55 Mb) on Chr.4 and Chr.9 was identified, which was a gap in the library previously. Z783 was developed from the progeny of recipient "Xihui18" (an indica restorer line) and donor "Huhan3" (a japonica cultivar) by advanced backcross combined molecular marker-assisted selection (MAS). It displayed multiple panicles and less spikelets and wide grains. Then, a F2 population derived from Xihui18/Z783 was used to map quantitative trait loci (QTLs) for yield-related traits by the mixed linear model method. Nine QTLs were detected (p < 0.05). Furthermore, three SSSLs were constructed by MAS, and all 9 QTLs could be validated, and 15 novel QTLs could be detected by these SSSLs by a one-way ANOVA analysis. The genetic analysis showed that qSSP4 for less spikelets and qGW9 for wide grain all displayed dominant gene action in their SSSLs. Finally, qSSP4 and qGW9 were fine-mapped to intervals of 2.75 Mb and 1.84 Mb, on Chromosomes 4 and 9, respectively. The results lay a solid foundation for their map cloning and molecular breeding by design.

Repeatability and Interobserver Reproducibility of a Swept-Source Optical Coherence Tomography for Measurements of Anterior, Posterior, and Total Corneal Power.

INTRODUCTION: The aim of this work is to evaluate the intraobserver repeatability and interobserver reproducibility of corneal power measurements obtained with a swept-source optical coherence tomographer (CASIA 2, Tomey, Japan) in healthy subjects. METHODS: A total of 67 right eyes from 67 healthy subjects were enrolled. Two experienced observers measured each eye three times consecutively with the CASIA 2. Corneal power values were recorded as simulated keratometry, anterior, posterior, and total corneal power. Parameters were flattest keratometry (Kf), steepest keratometry (Ks), mean keratometry (Km), astigmatism magnitude, astigmatism power vectors J0 and J45. Intraobserver repeatability and interobserver reproducibility of the CASIA 2 were assessed by the within-subject standard deviation (Sw), test-retest repeatability (TRT), coefficients of variation (CoV), and intraclass correlation coefficients (ICCs). Double-angle plots were used for astigmatism vector analysis. RESULTS: The CASIA 2 had high repeatability for all corneal power values, with Sw values ≤ 0.17 diopters (D), TRT ≤ 0.46 D, and ICCs ranging from 0.866 to 0.998. Interobserver reproducibility was also high, showing all Sw values ≤ 0.10 D, TRT ≤ 0.27 D, and ICCs ≥ 0.944. The reproducibility of the average of three consecutive measurements (Sw 0.01-0.10 D, TRT 0.03-0.27 D, ICC 0.944-0.998) was higher than the reproducibility of single measurements (Sw 0.01-0.17 D, TRT 0.03-0.47 D, ICC 0.867-0.996). CONCLUSIONS: The CASIA 2 showed high intraobserver repeatability and interobserver reproducibility for anterior, posterior, and total corneal power measurements in 6.0-mm diameter area. In addition, we suggest that using the average of three consecutive measurements can improve reproducibility between observers, compared to single measurements only.

Comparison of a New Scheimpflug Camera and Swept-Source Optical Coherence Tomographer for Measurements of Anterior Segment Parameters.

INTRODUCTION: This study evaluated the differences and agreement between a new Scheimpflug camera (Scansys) and a swept-source anterior segment optical coherence tomographer (CASIA 2) for measurements of the anterior segment of the eye in normal subjects. METHODS: This prospective study included 84 eyes from 84 normal adult subjects who underwent three consecutive measurements with the Scansys and the CASIA 2 in random order. The mean keratometry (Km), astigmatism magnitude (AST), J0, and J45 vectors for both anterior and posterior corneal surfaces, central corneal thickness (CCT), thinnest corneal thickness (TCT), and anterior chamber depth (ACD) were obtained by both devices. The difference between these two devices was assessed using paired t test and violin plots. Bland-Altman plots and 95% limits of agreement (LoAs) were used to evaluate agreement. RESULTS: No statistically significant differences between the two devices were found for the anterior AST, anterior J45, and posterior J45 (P > 0.05). The remaining parameters were statistically significant (P ≤ 0.05), but the differences not clinically significant. The violin plots showed that the distribution and probability density of the measured parameters were similar for both devices. Bland-Altman plots revealed high agreement for the measured parameters between the Scansys and CASIA 2, with narrow 95% LoAs. CONCLUSIONS: In terms of assessing parameters for the anterior segment, our study indicated that Scansys and CASIA 2 generally showed significant agreement. The two devices used in this study's assessment of all the parameters can be used interchangeably in refractive analysis.

Genetic Effects Analysis of QTLs for Rice Grain Size Based on CSSL-Z403 and Its Dissected Single and Dual-Segment Substitution Lines.

Rice chromosomal segment substitution lines (CSSLs) are ideal materials for studying quantitative traits such as grain size. Here, a rice large-grain CSSL-Z403 was identified among progeny of the recipient Xihui18 and the donor Jinhui35 based on molecular marker-assisted selection. Z403 carried 10 substitution segments with average length of 3.01 Mb. Then, a secondary F2 population derived from a cross between Xihui18 and Z403 was used to map quantitative trait loci (QTL) for grain size. Six QTLs distributed on chromosomes 5, 6, 7, 9 and 12 were detected. Finally four single-segment substitution lines (SSSLs) and two dual-segment substitution lines (DSSLs) carrying these target QTLs were constructed, and 10 novel QTLs were identified by four SSSLs. The large grain of Z403 was controlled at least by qGWT5, qGWT7, qGWT9 and qGWT12, and its grain weight was influenced through grain length QTL such as qGL5, qGL6, qGL9 and qGL12, as well as grain width QTL such as qGW5, qGW7, qGW9 and qGW12. Among 16 QTLs, four QTLs including qGL6, etc., might be novel compared with the reported documents. Again, positive or less negative epistatic effects between two non-allelic QTLs (additive effect > 0) may assist screening the genotype with larger grain size in further selection.

Inter-examiner and intra-examiner reliability of optical coherence tomography angiography in vascular density measurement of retinal and choriocapillaris plexuses in healthy children aged 6-15 years.

Objective: This study aimed to test the inter-examiner and intra-examiner reliability of macular vascular density (VD) measurement of retinal and choriocapillaris plexuses in healthy children using optical coherence tomography angiography (OCTA). Materials and methods: Ninety-two school children were prospectively recruited. Macular OCTA images (6 × 6 mm2) were obtained thrice by two examiners using the RTVue-XR Avanti OCT system. The coefficient of variation (COV), intraclass correlation coefficient (ICC), and Bland-Altman plots were used to evaluate the repeatability and reproducibility. Results: Ninety participants aged 6-15 years were enrolled; two participants were excluded because of low-quality images. In the retina, the reproducibility and repeatability of VD became poorer from superficial to deep retinal capillary plexus (superficial: COV = 4.61-11.11%; intermediate: COV = 7.73-14.15%; deep: COV = 14.60-32.28%). For both reproducibility and repeatability, the ICC ranged from moderate to high (superficial plexus: ICC = 0.570-0.976; intermediate plexus: ICC = 0.720-0.968; deep plexus: ICC = 0.628-0.954). In the choroid, the inter-examiner reproducibility and intra-examiner repeatability of the VD measurement of choriocapillaris were excellent in the macula, fovea, parafovea, and perifovea (COV = 1.00-6.10%; ICC = 0.856-0.950). The parameters of the foveal avascular zone (FAZ) also showed significant reproducibility and repeatability (COV = 0.01-0.21%; ICC = 0.743-0.994). Conclusion: The VD measurements of the choriocapillaris and FAZ parameters using OCTA showed excellent inter-examiner and intra-examiner reliability in school children. The reproducibility and repeatability of the VD of three retinal capillary plexuses depended on the depth of the retinal capillary plexus.

Reliability and Agreement of an Integrated Platform for Intelligent Visual Function Measurement.

INTRODUCTION: Phoropters are widely accepted for clinical use in refraction examination and visual function assessment. This study assessed the reliability of the new Inspection Platform of Visual Function (IPVF) in comparison with the conventional equipment phoropter (TOPCON VT-10) in visual function assessment. METHODS: This prospective study enrolled 80 eyes of 80 healthy subjects. The horizontal phoria at distance and near (Phoria_D and Phoria_N, respectively) was measured with the von Graefe method, negative/positive relative accommodation (NRA/PRA) was measured with the positive/negative lens method, and accommodative amplitude (AMP) was measured with the minus lens method. Data of three consecutive measurements with each instrument were evaluated using the intraclass correlation coefficient (ICC) for repeatability, and the agreement of the two instruments was evaluated using a Bland-Altman plot. RESULTS: The ICCs of the three consecutive measurements for phoria, NRA/PRA, and AMP using the IPVF instrument were high (0.87-0.96), indicating high repeatability. The ICCs of the three consecutive measurements using the phoropter were high (0.914-0.983) for phoria, NRA, and AMP, indicating high repeatability, while that of PRA was 0.732 (between 0.4 and 0.75), indicating acceptable repeatability. The 95% limits of agreement of phoria, NRA/PRA, and AMP were narrow, indicating good agreement between the two instruments. CONCLUSION: The repeatability of both instruments was high, and the IPVF instrument was slightly better in terms of PRA repeatability than the phoropter. The agreement of phoria, NRA/PRA, and AMP measured by the new IPVF instrument and phoropter was also satisfactory.

Nonstrabismic binocular dysfunctions (NBD) are common vision abnormalities. The relevant indicators involved in NBD are accommodative anomalies, convergence and divergence anomalies, and phoria. Convergence and divergence anomalies are disorders of binocular vision that result in either a failure of fusion or an inability to accurately integrate and stabilize retinal images from both eyes into a single representation. Phoria is the tendency of the eyes not to be directed towards the point of fixation, manifested in the absence or prevention of fusion. Measurement of accommodation and phoria are two particularly important components of comprehensive eye examination. Phoropter is widely used in ophthalmic clinics and optical stores for refraction examination and visual function assessment. It largely depends on the examiner's training, skill, and experience, which leads to high inter-examiner variability. In large-scale eye screening or busy hospital hours, examinees have to be inspected one by one using traditional instruments, which can be time consuming and tiring for optometrists, and can cause long queuing time for examinees. In this study, we evaluated the possibility of an alternative automatic diagnostic instrument for the assessment of binocular visual function. The platform is a new type of intelligent visual function inspection equipment with good reliability, and could be an alternative for clinicians to obtain visual function measurements with improved efficiency and fewer subjective errors. The use of this automatic instrument can avoid inter-examiner variability, helping to resolve the shortage problem of optometrists in China and offer a better testing service to eye examinees.

Repeatability and reproducibility of a new fully automatic measurement optical low coherence reflectometry biometer and agreement with swept-source optical coherence tomography-based biometer.

AIMS: To assess the repeatability and reproducibility of the ocular measurements obtained with the Suoer SW-9000 µm Plus, a new fully automatic biometer based on optical low coherence reflectometry (OLCR) biometer, and to compare them to those obtained by a swept-source optical coherence tomography (SS-OCT)-based biometer. METHODS: This prospective study consisted of 115 eyes of 115 healthy subjects. The measurements were taken by the two optical biometers in random order. The measured parameters were axial length (AL), central corneal thickness (CCT), aqueous depth (AQD), anterior chamber depth (ACD), mean keratometry (Km), lens thickness (LT) and corneal diameter (CD). To evaluate the intraobserver repeatability and interobserver reproducibility, the within-subject SD, test-retest variability, coefficient of variation (CoV) and intraclass correlation coefficient (ICC) were adopted. The Bland-Altman plot was drawn to assess the agreement. RESULTS: The repeatability and reproducibility of all parameters for the new device were excellent (ICC>0.960 and CoV<0.71%). The Bland-Altman plots showed high agreement between the OLCR-based and SS-OCT-based devices for AL, CCT, AQD, ACD, Km and LT, with narrow 95% limit of agreements (LoAs) (-0.08 mm to 0.06 mm, -15.91 µm to -1.01 µm, -0.09 mm to 0.09 mm, -0.09 mm to 0.08 mm, -0.47 D to 0.35 D, -0.05 mm to 0.16 mm, respectively) and moderate agreement for CD (95% LoA: -0.67 mm to -0.01 mm). CONCLUSIONS: The new Suoer SW-9000 µm Plus biometer showed excellent repeatability and reproducibility. All the parameters obtained by this biometer were similar to those measured by SS-OCT-based biometer.

(-)-Epicatechin gallate blocked cellular foam formation in atherosclerosis by modulating CD36 expression in vitro and in vivo.

Green tea is popular worldwide, so its main active ingredients have attracted people's attention. (-)-Epicatechin gallate (ECG) is the main active component of green tea polyphenols, which has good antioxidant activity, but its cardiovascular intervention is unknown. This study established in vitro and in vivo models of ox-LDL-induced macrophages and HFD-induced ApoE-/- mice to study the effects of ECG on atherosclerotic lesions. Firstly, the study confirmed that ECG has a therapeutic effect in different stages of atherosclerotic plaques. Subsequently, the results showed that the ox-LDL-induced release of pro-inflammatory mediators and the expression of the related protein CD86 in macrophages were inhibited by ECG. ECG blocked the formation of cellular foam by downregulating the expression of CD36 and LOX-1 proteins, thereby increasing SOD activity and reducing MDA production in cells. ECG also prevented ox-LDL-induced apoptosis, promoted macrophage migration, and increased plaque stability. The results confirmed that ECG attenuated ox-LDL-induced green fluorescence of ROS in macrophages by inhibiting the expression of related proteins in the NF-κB signaling pathway and activating the HO-1/Nrf2 signaling pathway. These results indicated that ECG has anti-oxidative stress and anti-inflammatory potential, and its molecular mechanism may be related to the inhibition of intracellular NF-κB signaling pathway proteins and activation of the HO-1/Nrf2 signaling pathway.

Panlongqi tablet suppresses adjuvant-induced rheumatoid arthritis by inhibiting the inflammatory reponse in vivo and in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Panlongqi Tablet is prepared with the ancestral secret recipe provided by Mr. Wang Jiacheng, a famous specialist in orthopedics and traumatology of China. The efficacy and safety of PLQT have been supported by years of clinical practice in the treatment of joint-related conditions. Has remarkable effect for treating rheumatoid arthritis (RA) clinically. However, its mechanism is not entirely clear. AIM OF THE STUDY: We aim to evaluate the anti-inflammatory activity of PLQT and explore its mechanism in adjuvant-induced arthritis (AA) mice and LPS-induced Human fibroblast-like synovial (HFLS) cells. MATERIALS AND METHODS: To this end, we analyzed the active ingredients in PLQT by HPLC-MS/MS. Furthermore, the anti-RA effect of PLQT was studied through proliferation, apoptosis, foot swelling, cytokine levels, immune organ index, histopathology and related signal pathways in LPS-induced HFLS cells and AA-treated mice. RESULTS: HPLC-MS/MS results showed that PLQT contained a variety of active compounds, such as epicatechin, imperatorin, hydroxysafflor yellow A and so on. PLQT significantly inhibited the abnormal proliferation of HFLS cells induced by LPS, promoted cell apoptosis. In AA-treated mice, PLQT alleviated RA symptoms by alleviating paw swelling, synovial hyperplasia, pannus formation, inflammatory cell infiltration, and inhibiting abnormal immune responses. The results showed that PLQT significantly decreased the expression of inflammatory mediators (IL-1ß, IL-6, IL-17) in vivo and in vitro, which may be related to the regulation of PI3K/Akt, MAPK and JAK/STAT signaling pathways. CONCLUSION: Based on serum pharmacology and in vivo pharmacology studies, PLQT may regulate RA symptoms by regulating inflammatory and immune response-related pathways, which is an effective method for the treatment of RA.

Universal Dynamics of Microbial Communities in Full-Scale Textile Wastewater Treatment Plants and System Prediction by Machine Learning.

The performance of full-scale biological wastewater treatment plants (WWTPs) depends on the operational and environmental conditions of treatment systems. However, we do not know how much these conditions affect microbial community structures and dynamics across systems over time and predictability of the treatment performance. For over a year, the microbial communities of four full-scale WWTPs processing textile wastewater were monitored. During temporal succession, the environmental conditions and system treatment performance were the main drivers, which explained up to 51% of community variations within and between all plants based on the multiple regression models. We identified the universality of community dynamics in all systems using the dissimilarity-overlap curve method, with the significant negative slopes suggesting that the communities containing the same taxa from different plants over time exhibited a similar composition dynamic. The Hubbell neutral theory and the covariance neutrality test indicated that all systems had a dominant niche-based assembly mechanism, supporting that the communities had a similar composition dynamic. Phylogenetically diverse biomarkers for the system conditions and treatment performance were identified by machine learning. Most of the biomarkers (83%) were classified as generalist taxa, and the phylogenetically related biomarkers responded similarly to the system conditions. Many biomarkers for treatment performance perform functions that are crucial for wastewater treatment processes (e.g., carbon and nutrient removal). This study clarifies the relationships between community composition and environmental conditions in full-scale WWTPs over time.

Agreement between a new optical low coherence reflectometry biometer and an anterior segment optical coherence tomographer.

BACKGROUND: To assess agreement of measurements between a new optical low coherence reflectometry (OLCR) biometer (SW-9000, Suoer, Tianjin, China) and a spectral-domain optical coherence tomographer (SD-OCT)/Placido topographer (MS-39, CSO, Florence, Italy) in healthy subjects. METHODS: A total of 66 right eyes from 66 healthy subjects were enrolled in this prospective study. Three consecutive measurements were randomly obtained with both devices by the same experienced operator to assess agreement. Bland-Altman plots and 95% limits of agreement (LoA) were used to verify the agreement between the devices. Results are presented as mean ± standard deviation (SD). RESULTS: The SD-OCT/Placido tomographer showed high agreement with the OLCR biometer for all parameters included in this study. The mean differences of central corneal thickness (CCT), anterior chamber depth (ACD), aqueous depth (AQD), mean keratometry (Km) and corneal diameter (CD) were 2.21 ± 2.67 µm (P < 0.001), - 0.10 ± 0.03 mm (P < 0.001), - 0.10 ± 0.04 mm (P < 0.001), - 0.01 ± 0.22 D (P = 0.773) and 0.20 ± 0.16 mm (P < 0.001), respectively. This implies that the inter-device difference in Km was not statistically significant, while the differences in CCT, ACD, AQD, CD were statistically but not clinically significant. The 95% LoAs of CCT, ACD, AQD, Km and CD were - 3.01 to 7.44 µm, - 0.16 to - 0.05 mm, - 0.18 to - 0.03 mm, - 0.45 to 0.43 D, and - 0.12 to 0.51 mm, respectively. CONCLUSIONS: For CCT, ACD, AQD, Km, and CD in healthy subjects, the new OLCR biometer has high agreement with the SD-OCT/Placido tomographer and can be used interchangeably due to the narrow range of 95% LoAs.

Solid fuel derived PM2.5 induced oxidative stress and according cytotoxicity in A549 cells: The evidence and potential neutralization by green tea.

PM2.5 (particulate matter with aerodynamic diameter ≤ 2.5 µm) is a well-known cytotoxic pollutant that capable to induce severe intracellular oxidative stress while the underlying mechanisms remain unclear. Herein, 4 types of PM2.5 derived from solid fuel burning were selected as stimuli in A549 cells exposure model to evaluate their effects on oxidative stress and inflammatory responses. Although resulting in different responses in cell viability, all PM2.5 exhibited over 50 % higher oxidative stress than control group, expression as intracellular reactive oxygen species, malondialdehyde and superoxide dismutase levels. The Pearson's correlation results indicated that cations (e.g., Ca2+), heavy metals (e.g., Cr and Pb), nPAHs (nitro-polycyclic aromatic hydrocarbons, e.g., 6-nitrochrysene) and oPAHs (oxygenated PAHs, e.g., 9-fluorenone) were the main functioning toxics (r > 0.6). A key finding was the dual-directional regulation function of ECG (epicatechin gallate), that is, it could either increase the low A549 cell viabilities in coal combustion PM2.5 group or reduce them in charcoal PM2.5 group (P < 0.05). The dual-directional effects were likely because ECG can activate Nrf2 oxidation signaling pathway then inhibit the inflammatory signaling pathway NF-κB accordingly. Therefore, evidences indicated cytotoxicity of solid fuel derived PM2.5 were mainly caused by oxidative stress, which was proved to be reversed by green tea, providing a potential therapy method to PM2.5 and other hazards.

The first Chinese National Union of Real-world Gynaecological Oncology Research and Patient Management Platform: A retrospective study.

OBJECTIVE: To produce high-quality, real-world evidence for oncologists by collating scattered gynaecologic oncology (GO) medical records in China. DESIGN: Retrospective study. SETTING: The National Union of Real-world Gynaecological Oncology Research and Patient Management Platform (NUWA platform). SAMPLE: Patient-centred data pool. METHODS: The NUWA platform integrated inpatient/outpatient clinical, gene and follow-up data. Data of 11 456 patients with ovarian cancer (OC) were collected and processed using 91 345 electronic medical records. Structured and unstructured data were de-identified and re-collated into a patient-centred data pool using a predefined GO data model by technology-aided abstraction. MAIN OUTCOME MEASURES: Recent treatment pattern shifts towards precision medicine for OC in China. RESULTS: Thirteen first-tier hospitals across China participated in the NUWA platform up to 7 December 2021. In total, 3504 (30.59%) patients were followed up by a stand-alone patient management centre. The percentage of patients undergoing breast cancer gene (BRCA) mutation tests increased by approximately six-fold between 2017 and 2018. A similar trend was observed in the administration rate of poly(ADP-ribose) polymerase inhibitors as first-line treatment and second-line treatment after September 2018, when olaparib was approved for clinical use in China. CONCLUSION: The NUWA platform has great potential to facilitate clinical studies and support drug development, regulatory reviews and healthcare decision-making.