The efficacy and safety of hydroxychloroquine versus leflunomide in patients with IgA nephropathy: a single-center experience.

PURPOSE: To date, our understanding of IgA nephropathy (IgAN) pathophysiology has remained incomplete; therefore, treatment remains largely empiric, and the efficacy and safety of immunosuppressants remain controversial. We aimed to assess the efficacy and safety of hydroxychloroquine and leflunomide therapy in a retrospective cohort of patients with IgAN. METHODS: We screened the IgAN registration database in our department, and a total of 159 kidney patients with biopsy-confirmed IgAN were enrolled, with 57 patients receiving hydroxychloroquine plus a renin-angiotensin system inhibitor (hydroxychloroquine group), 52 patients receiving leflunomide plus a renin-angiotensin system inhibitor (leflunomide group), and 50 patients receiving only a renin-angiotensin system inhibitor (renin-angiotensin system inhibitor-only group). Changes in proteinuria, hematuria, and the estimated glomerular filtration rate (eGFR), as well as adverse events, were analyzed during the follow-up period. RESULTS: At the end of 6-month follow-up, proteinuria significantly decreased by 70.36 (57.54, 79.33)%, 57.29 (46.79, 67.29)% and 41.20 (25.76, 48.94)% in the hydroxychloroquine, leflunomide and renin-angiotensin system inhibitor-only groups, respectively, compared to baseline (all P values < 0.001). Hematuria significantly decreased by 71.07 (56.48, 82.47)% in the leflunomide group (P < 0.001). The eGFR improved by 3.72 ± 2.97%, 3.16 ± 2.00% and 1.91 ± 2.41%, respectively, in the hydroxychloroquine, leflunomide and renin-angiotensin system inhibitor-only groups, but without statistical significance. No serious adverse events occurred during the follow-up period. CONCLUSION: Both hydroxychloroquine combined with a renin-angiotensin system inhibitor and leflunomide combined with a renin-angiotensin system inhibitor were more effective than a renin-angiotensin system inhibitor alone in improving proteinuria in IgAN patients. Hydroxychloroquine was more effective in reducing proteinuria, and leflunomide showed superiority in reducing hematuria. Our results need to be verified in large-scale randomized controlled trials.

A human-specific insertion promotes cell proliferation and migration by enhancing TBC1D8B expression.

Human-specific insertions play important roles in human phenotypes and diseases. Here we reported a 446-bp insertion (Insert-446) in intron 11 of the TBC1D8B gene, located on chromosome X, and traced its origin to a portion of intron 6 of the EBF1 gene on chromosome 5. Interestingly, Insert-446 was present in the human Neanderthal and Denisovans genomes, and was fixed in humans after human-chimpanzee divergence. We have demonstrated that Insert-446 acts as an enhancer through binding transcript factors that promotes a higher expression of human TBC1D8B gene as compared with orthologs in macaques. In addition, over-expression TBC1D8B promoted cell proliferation and migration through "a dual finger" catalytic mechanism (Arg538 and Gln573) in the TBC domain in vitro and knockdown of TBC1D8B attenuated tumorigenesis in vivo. Knockout of Insert-446 prevented cell proliferation and migration in cancer and normal cells. Our results reveal that the human-specific Insert-446 promotes cell proliferation and migration by upregulating the expression of TBC1D8B gene. These findings provide a significant insight into the effects of human-specific insertions on evolution.

Quantitative analysis of optic disc changes in school-age children with ametropia based on artificial intelligence.

AIM: To explore changes in the optic disc and peripapillary atrophy (PPA) in school-age children with ametropia using color fundus photography combined with artificial intelligence (AI) technology. METHODS: Based on the retrospective case-controlled study, 226 eyes of 113 children aged aged 6-12y were enrolled from October 2021 to May 2022. According to the results of spherical equivalent (SE), the children were divided into four groups: low myopia group (66 eyes), moderate myopia group (60 eyes), high myopia group (50 eyes) and emmetropia control group (50 eyes). All subjects underwent un-aided visual acuity, dilated pupil optometry, best-corrected visual acuity (BCVA), intraocular pressure, ocular axis measurement and color fundus photography. RESULTS: The width of PPA, horizontal diameter ratio of PPA to the optic disc and area ratio of PPA to the optic disc were significantly different among the four groups (P<0.05). The width of the nasal and temporal neuroretinal rim, the roundness of the optic disc, the height of PPA, the vertical diameter ratio of PPA to the optic disc, and the average density of PPA in the high myopia group were significantly different compared with the other three groups (P<0.05). There were strong negative correlations between SE and area ratio of PPA to the optic disc (r=-0.812, P<0.001) and strong positive correlation between axial length (AL) and area ratio of PPA to the optic disc (r=0.736, P<0.001). CONCLUSION: In school-age children with high myopia, the nasal and temporal neuroretinal rims are narrowed and even lost, which have high sensitivity. The area ratio of the PPA to the optic disc could be used as an early predictor of myopia progression, which is of great significance for the development prevention and management of myopia.

Integrated metabolomics and transcriptomic analysis reveals metabolic changes of flavor compounds of Camellia assamica host plant after parasitized by Viscumarticulatum.

Tea is one of the most popular beverages, it has many health benefits and flavor properties due to the presence of numerous secondary metabolites. Camellia assamica is also a main source of tea, which is mainly planted in the regions of southwest China. In this study, a non-targeted and targeted metabolomics analysis and sensory evaluation on tea leaves with and without mistletoe (Viscum articulatum) was carried out using liquid chromatography-mass spectrometry. RNA-seq-based transcriptomic analysis was conducted in parallel on the same samples, subsequently gene expression and metabolic differentiation were also investigated. Tea leaves with mistletoe presented much lower contents of (-)-catechin, (-)-epicatechin, (-)-gallocatechin gallate and (-)-epicatechin gallate, but significantly higher levels of free amino acids including Arg, Asp, GABA and Gln than that without mistletoe. Transcriptomic analysis also confirmed the main differentially expressed genes (DEGs) containing phenylpropanoid and flavonoid biosynthesis were down-regulated, but genes of amino acid biosynthesis were up-regulated. qRT-PCR analysis further revealed that the relative expression of CsCHS, CsC4H, CsANS, CsLAR, and CsF3H was hindered, while CsglyA and CsilvE expression was increased.

An Intraoperative Sub-Anesthetic Dose of Esketamine on Postoperative Depressive Symptoms in Perimenopausal Women with Breast Cancer Undergoing Modified Radical Mastectomy: Protocol for a Randomized, Triple-Blinded, Controlled Trial.

Background: Depressive symptoms are common among perimenopausal women with breast cancer having modified radical mastectomy. Esketamine exerts antidepressant effects. This study aims to assess whether an intraoperative sub-anesthetic dose of esketamine prevents postoperative depressive symptoms in these patients. Methods: In this randomized, triple-blinded, placebo-controlled trial, we will enroll 130 perimenopausal women (aged 45-60 years) with breast cancer undergoing unilateral modified radical mastectomy. Patients will be randomly assigned with a 1:1 ratio to receive either esketamine (0.25 mg/kg i.v.) or normal saline after anesthesia induction and before skin incision. The primary outcome is the incidence of depressive symptoms at day 30 postoperatively, assessed using the Beck's Depression Inventory (BDI). Secondary outcomes include incidence of depressive symptoms and BDI scores at day 1, 3, and 180 postoperatively, anxiety symptoms and scores at day 1, 3, 30, and 180 postoperatively, pain intensity and quality of recovery at day 1 and 2 postoperatively, nausea and vomiting within 48 hours postoperatively, length of postoperative hospital stay, and cancer-specific outcomes. Data will be analyzed in the modified intention-to-treat population. Discussion: This is the first trial to evaluate the effects of a sub-anesthetic dose of esketamine on depressive symptoms in perimenopausal women after modified radical mastectomy. The results of this study will help to improve their mental health and recovery after breast cancer surgery. Trial Registration: Chinese Clinical Trial Registry (ChiCTR2200064348).

Effect of rScO2-Guided Blood Pressure Management on Postoperative Complications in Elderly Patients After Major Noncardiac Surgery: Protocol for a Randomized Controlled Trial.

Background: Postoperative complications are common after major surgical procedures, leading to increased morbidity and mortality. Regional cerebral oxygen saturation (rScO2) reflects cerebral and global perfusion, and thus it can be used to guide hemodynamic management. We aim to explore the effect of rScO2-guided blood pressure management strategy on postoperative major complications in older adults who undergo major noncardiac surgery. Methods: This randomized controlled clinical trial includes a total of 400 elderly patients receiving major noncardiac surgery and general anesthesia. Patients will be randomized (1:1) to one of two blood pressure management groups: a standard care group (targeting mean arterial pressure >65 mmHg or within 20% of baseline value), and a rScO2-guided group (absolute value of rScO2 >60% or decrease in rScO2 <10% of baseline). The primary outcome is the composite outcome of major complications (including infectious, respiratory, neurologic, cardiovascular, renal, thromboembolic gastrointestinal, and surgical complications) and deaths within the first 7 days after surgery. Secondary outcomes include the individual components of the primary outcome by day 7 after surgery and 30-day mortality. Data will be analyzed in the modified intention-to-treat population. Discussion: This study will provide evidence for improving postoperative outcomes using the rScO2-guided blood pressure management among older adults who undergo major noncardiac surgery. Trial Registration: Chinese Clinical Trial Registry (Identifier: ChiCTR2200060816).

This is a protocol for a prospective, randomized, controlled clinical trial to evaluate the use of intraoperative individualized regional cerebral oxygen saturation (rScO₂) optimization for blood pressure management in older adults undergoing major noncardiac surgery. The primary focus of this trial is the composite outcome of major complications (including infectious, respiratory, neurologic, cardiovascular, renal, thromboembolic gastrointestinal, and surgical complications) and deaths within the first 7 days after surgery. The secondary outcomes are the individual components of the primary outcome by day 7 after surgery and 30-day mortality. The findings of this trial will provide clinical evidence for the rScO₂-guided blood pressure management to improve postoperative outcomes in older patients who are scheduled for major noncardiac surgery.

Exploration of Artemisinin Against IgA Nephropathy via AKT/Nrf2 Pathway by Bioinformatics and Experimental Validation.

Background: Artemisinin (ART) is a safe and effective antimalarial drug. In recent years, antimalarial drugs have demonstrated a good therapeutic efficacy in IgA nephropathy, suggesting that this may become a new treatment option. Purpose: We aimed to evaluate the effect and mechanism of artemisinin in IgA nephropathy. Methods: In this study, CMap database was used to predict the artemisinin therapeutic effect for IgA nephropathy. A network pharmacology approach was applied to explore the unknown mechanism of artemisinin in IgA nephropathy. We used molecular docking to predict the binding affinity of artemisinin with the targets. A mouse model of IgA nephropathy was established to investigate the therapeutic effect of artemisinin on IgA nephropathy. In vitro, the cell counting Kit-8 assay was used to evaluate the cytotoxicity of artemisinin. Flow cytometry and PCR assays were used to detect the effects of artemisinin on oxidative stress and fibrosis in lipopolysaccharide (LPS)-stimulated mesangial cells. Western blot and immunofluorescence were used to detect the expression of pathway proteins. Results: CMap analysis showed artemisinin may reverse the expression levels of differentially expressed genes in IgA nephropathy. Eighty-seven potential targets of artemisinin in the treatment of IgA nephropathy were screened. Among them, 15 hub targets were identified. Enrichment analysis and GSEA analysis indicated that response to reactive oxygen species is the core biological process. AKT1 and EGFR had the highest docking affinity with artemisinin. In vivo, artemisinin could improve renal injury and fibrosis in mice. In vitro, artemisinin attenuated LPS-induced oxidative stress and fibrosis promoted AKT phosphorylation and Nrf2 nuclear translocation. Conclusion: Artemisinin reduced the level of fibrosis and oxidative stress with IgA nephropathy through the AKT/Nrf2 pathway, which provided an alternative treatment for IgAN.

Genetic characterization of human adenoviruses in patients using metagenomic next-generation sequencing in Hubei, China, from 2018 to 2019.

Objectives: This study aimed to characterize the genomic epidemiology of human adenoviruses (HAdVs) in Hubei, China, using metagenomic next-generation sequencing (mNGS). Methods: In total, 25 HAdV-positive samples collected from 21 pediatric patients were sequenced and subjected to mNGS using the NextSeq 550 and GenoLab M sequencing platforms. The metagenomic data were assembled de novo for molecular typing, phylogenetic and recombination analyzes. Results: We assembled 50 HAdV genomes, 88% (22/25) genomes from GenoLab M, and 84% (21/25) genomes from NextSeq 550 have perfect alignments to reference genomes with greater than 90%. The most fully assembled 25 genomes were categorized into 7 HAdV genotypes, the most abundant of which were HAdV-B3 (9/25) and HAdV-C2 (6/25). Phylogenetic analyzes revealed that the newly isolated HAdV-B3 strains diverged into separate clusters according to their genotypes. Vigilance is needed that HAdV-B3 isolates have begun to form new distinct clusters. High nucleotide identity was observed in the whole genome level within the same HAdV genotypes, while marked differences of three capsid genes across HAdV genotypes were noted. The high nucleotide diversity regions were concordant with the reported hypervariable regions. Further, three recombinant strains were identified: S64 and S71 originated from the parental strains HAdV-B14 and HAdV-B11, and S28 originated from HAdV-C1, HAdV-C5, and HAdV-CBJ113. GenoLab M and NextSeq 550 showed comparable performance with respect to data yield, duplication rate, human ratio, and assembly completeness. Conclusion: The sequencing quality and assembly accuracy showed that mNGS assembled genomes can be used for subsequently HAdV genotyping and genomic characterization. The high nucleotide diversity of capsid genes and high frequency of recombination events has highlighted the necessity for HAdV epidemiological surveillance in China.

Glomerular deposition of fibrinogen predicts good prognosis of IgA nephropathy: a single-center cohort study.

PURPOSE: It has been proven that fibrinogen deposition exists in IgA nephropathy (IgAN), but its clinical significance has not been identified. We aim to investigate the clinical implication of fibrinogen deposition in evaluating the activity and prognosis of IgA nephropathy. METHODS: In this cohort, 935 adult IgAN patients were divided into 3 groups according to the intensity of glomerular fibrinogen deposition. Primary outcome refers to a composite event of either a ≥ 50% reduction in eGFR or ESRD (eGFR < 15 ml/min/1.73m2, dialysis, or renal transplantation). Factors associated with fibrinogen deposition and prognosis were identified. RESULTS: The results showed that the intensity of fibrinogen deposition was positively correlated with eGFR (P < 0.001), serum albumin (P = 0.041), and hemoglobin levels (P < 0.05), but negatively correlated with age (P = 0.04), serum fibrinogen levels (P < 0.001), serum C4 (P = 0.023), the proportion of patients with hypertension (P = 0.003), and the percentage of glomeruli sclerosis (P < 0.001). The prognostic analyses identified that fibrinogen deposition was an independent predictor for the progression of IgAN (P = 0.033). CONCLUSION: Our study indicated that the deposition of renal fibrinogen can predict the prognosis of IgAN with high reliability.

Investigation of the Internal Conditions of 213 Reprocessed Endoscopic Channels.

BACKGROUND AND AIMS: Studies have indicated that endoscope reprocessing failure might be attributed to internal damage or residual liquid in endoscopes. However, large-sample survey data on the internal conditions of endoscopic channels after reprocessing are lacking. This study used a borescope to investigate the internal cleanliness and damage of 213 endoscopic biopsy channels after reprocessing at the endoscopy center of the First Affiliated Hospital of Nanchang University, provided in theoretical basis for the efficacy of endoscope reprocessing and maintenance. METHODS: A borescope was used to observe and analyze the inside of the endoscopic biopsy channel of 213 reprocessed endoscopes (in accordance with the Chinese health industry standard "Regulation for cleaning and disinfection technique of flexible endoscope (WS 507-2016). Each endoscope was observed for at least 10 minutes, and the results were recorded and evaluated by 5 researchers independently. RESULTS: In all, 2504 images and 109 videos were recorded, and abnormal findings were classified into 10 categories: scratches (91.5%, 195/213), scratches with adherent peel (46.0%, 98/213), discolored areas (49.3%, 105/213), transparent drops (28.2%, 60/213), milky drops (23.9%, 51/213), white particles (46.9%, 100/213), attached materials (37.6%, 80/213), wear on metal parts (41.3%, 88/213), rust (23.9%, 51/213), and black spots (35.7%, 76/213). Among scratches, those in Teflon from 0-10 cm at the apex of the biopsy channel outlet and in metal from 0-5 cm at the biopsy channel inlet accounted for 58.4% (114/195) and 96.4% (188/195), respectively. CONCLUSIONS: Scratches were the most common form of damage in the endoscopic biopsy channels investigated and were related to the use of endoscopic accessories and cleaning brush materials. The incidence of other abnormalities gradually increased with the duration of use and began to increase significantly after 18 months. All abnormalities have a certain impact on the quality of endoscope reprocessing. We recommend that a borescope be used to check the inside of endoscopic biopsy channels regularly to determine the damage and cleaning conditions and that these channels be reprocessed, repaired, or replaced in a timely manner.

Variability of radiotherapy volume delineation: PSMA PET/MRI and MRI based clinical target volume and lymph node target volume for high-risk prostate cancer.

PURPOSE: A comparative retrospective study to assess the impact of PSMA Ligand PET/MRI ([68 Ga]-Ga-PSMA-11 and [18F]-F-PSMA-1007 PET/MRI) as a new method of target delineation compared to conventional imaging on whole-pelvis radiotherapy for high-risk prostate cancer (PCa). PATIENTS AND METHODS: Forty-nine patients with primary high-risk PCa completed the whole-pelvis radiotherapy plan based on PSMA PET/MRI and MRI. The primary endpoint compared the size and overlap of clinical target volume (CTV) and nodal gross tumour volume (GTVn) based on PSMA PET/MRI and MRI. The diagnostic performance of two methods for pelvic lymph node metastasis (PLNM) was evaluated. RESULTS: In the radiotherapy planning for high-risk PCa patients, there was a significant correlation between MRI-CTV and PET/MRI-CTV (P = 0.005), as well as between MRI-GTVn and PET/MRI-GTVn (P < 0.001). There are non-significant differences in the CTV and GTVn based on MRI and PET/MRI images (P = 0.660, P = 0.650, respectively). The conformity index (CI), lesion coverage factor (LCF) and Dice similarity coefficient (DSC) of CTVs were 0.999, 0.953 and 0.954. The CI, LCF and DSC of GTVns were 0.927, 0.284, and 0.32. Based on pathological lymph node analysis of 463 lymph nodes from 37 patients, the sensitivity, specificity of PET/MRI in the diagnosis of PLNM were 77.78% and 99.76%, respectively, which were higher than those of MRI (P = 0.011). Eight high-risk PCa patients who finished PSMA PET/MRI changed their N or M stage. CONCLUSION: The CTV delineated based on PET/MRI and MRI differ little. The GTVn delineated based on PET/MRI encompasses metastatic pelvic lymph nodes more accurately than MRI and avoids covering pelvic lymph nodes without metastasis. We emphasize the utility of PET/MRI fusion images in GTVn delineation in whole pelvic radiotherapy for PCa. The use of PSMA PET/MRI aids in the realization of more individual and precise radiotherapy for PCa.

The Effect of Brief Mindfulness Meditation on Suicidal Ideation, Stress and Sleep Quality.

OBJECTIVES: Suicide is the fourth leading cause of death for individuals aged 15-29 years, and early intervention on suicidal ideation and risk factors should be priortized. Brief mindfulness meditation (BMM) is convenient and cost-effective in improving physical and mental well-being, but less is known about its efficacy for suicidal ideation, stress and sleep quality. We investigated the effects of BMM on suicidal ideation, stress, and sleep quality for individuals with suicide risk. METHODS: Sixty-four college students with high suicidal ideation (aged 18-30 years) were randomly allocated to either a BMM (n = 32) or control group (n = 32). The BMM was based on Anapanasati and core mindfulness concepts. Sixty participants completed all scheduled sessions including pretest, one month of intervention or waiting, and posttest. Suicidal ideation was measured with the Beck Scale for Suicidal Ideation. Stress was evaluated using the Perceived Stress Scale and salivary cortisol levels. Sleep was measured using the Pittsburgh Sleep Quality Index and actigraphy accompanied with 7-day sleep diaries. RESULTS: Post-intervention, the BMM group showed significant decrease in suicidal ideation with a large effect size; the decrease showed a medium effect size in the control group. The BMM group, but not the control group, showed significant decrease in morning salivary cortisol and sleep latency, and improved sleep efficiency. CONCLUSIONS: BMM could help reduce suicidal ideation, stress, and sleep disturbance for individuals with high suicidal ideation and it may implicate effective suicide prevention strategy.

Pharmacodynamics of human interferon α1b against severe acute respiratory syndrome coronavirus 2 Omicron strain in vitro / 中国生物制品学杂志

@#Objective To evaluate the pharmacodynamics of human interferon(IFN)α1b against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Omicron strain in vitro.Methods Total four drugs human IFNα1b bulk,human IFNα1b eye drops,human IFNα1b spray and Remdesivir were detected for cytotoxicity by CCK-8 assay.The inhibitory effect of human IFNα1b on SARS-CoV-2 Omicron strains(BA.5/BA.2/BA.1)was determined by qPCR.Results Human IFNα1b bulk of the maximum concentration(1 × 107IU/mL)and Remdesivir of the maximum concentration(150 μmol/L)did not achieve half cytotoxicity to Vero cells;The median cytotoxicity concentrations(CC_(50))of human IFNα1b eye drops and human IFNα1b sprays were 29 958 and 37 550 IU/mL,respectively,showing toxicity to Vero cells.The median effective concentrations(EC_(50))of human IFNα1b against virus strains BA.1,BA.2 and BA.5 after incubation for 2 h in advance were 9.30,13.38 and 12.33 IU/mL and those of Remdesivir were 0.314 7,0.291 0 and0.300 3 μmol/L.When incubation with virus simultaneously,the EC_(50)of human IFNα1b to BA.1,BA.2 and BA.5 were19.68,10.91 and 18.84 IU/mL and those of the control drug Remdesivir were 0.320 5,0.274 4 and 0.304 1 μmol/L,respectively.Conclusion At the cell level in vitro,human IFNα1b of very low activity showed a good inhibitory effect on SARS-CoV-2 Omicron strain,which was expected to be a clinical specific drug for the treatment of SARS-CoV-2 Omicron strain infection.

Adjuvant chemotherapy improves survival in high-risk stage II colon cancer: a retrospective cohort study.

Background: The survival advantage of postoperative chemotherapy for high-risk stage II colon cancer (CC) patients remains unclear. Objectives: The purpose was to evaluate the survival of high-risk stage II CC cases treated with chemotherapy and to construct survival prediction models to predict the survival benefit from chemotherapy. Design: The study is a retrospective observational cohort study. Methods: Data on patients with stage II CC diagnosed from 2005 to 2019 who underwent radical surgery were obtained from the Surveillance, Epidemiology and End Results (SEER) database. A 1:1 propensity score matching (PSM) was applied to obtain two cohorts, chemotherapy versus no chemotherapy. A chi-square analysis was used to assess the differences before and after PSM in the above two groups. Kaplan-Meier survival analysis and Cox proportional hazards regression were applied to investigate the 5- and 10-year overall survival (OS) and cancer cause-specific survival (CSS). The predictive power of the constructed models was assessed by the concordance index (C-index) and calibration curves. Results: Of the 37,050 cases, 14,744 (39.8%) stage II CC were at high-risk and 29.2% of them received chemotherapy. Age, T stage, marital status, histologic grade, gender, and site independently influenced the reception of chemotherapy. The survival advantage of chemotherapy in the high-risk patients remained positive before and after PSM. The estimated 3, 5, and 10 years OS rates of chemotherapy group were 9.3, 10.7, and 15.6% higher than the nonchemotherapy group, respectively. Four nomograms predicting OS and CSS were established, with great discrimination (C-index between 0.627 and 0.691) and excellent calibration. Conclusion: Postoperative chemotherapy is beneficial for high-risk stage II CC patients, including the elderly patients (over 65 years of age). Our study developed nomograms to quantify the survival benefit of chemotherapy among high-risk stage II CC patients to develop personalized treatment recommendations and guide management decisions.

Survival nomograms for colorectal carcinoma patients with lung metastasis and lung-only metastasis, based on the SEER database and a single-center external validation cohort.

BACKGROUND: We analysed the survival of colorectal cancer (CRC) patients with lung metastasis and lung-only metastasis and determined the risk factors for lung metastasis in CRC patients. METHODS: Data from colorectal cancer patients with lung metastasis diagnosed from 2010 to 2015 were obtained from the SEER database. Survival was analysed using the Kaplan-Meier method and log-rank test, the Cox proportional hazards regression model, and a competing risk model. The predictive ability of the nomgram was assessed by the concordance index (C-index) and calibration curves. The data from the SEER database for the period 2016-2019 was used as an external validation set. The characteristics of 70 CRC patients treated at Shanghai East Hospital between 2016 and 2019 were retrospectively analysed and data from China was chosen as an external validation set. RESULTS: The median survival time for colorectal cancer patients with lung metastasis was 12 months, while this value was 24 months in patients with lung-only metastasis. Among all CRC patients with lung metastasis, age, grade, T stage, N stage, presence of liver, brain or bone metastasis, anatomic site and surgery were related to overall survival (OS). In CRC patients with lung-only metastasis, age, T stage, marital status, chemotherapy and surgery were independent prognostic factors affecting OS. Two nomograms predicting OS were established, with great discrimination (C-index between 0.67 and 0.81) and excellent calibration. Factors including age, race, sex, tumour grade, T stage, N stage, presence of liver, brain or bone metastasis, marital status, insurance status and anatomic location were related to the occurrence of lung metastasis in CRC patients. CONCLUSION: We developed two reliable clinical prediction models among CRC patients to predict the OS rates in patients with lung metastasis and lung metastasis only.

Alterations in whole-brain dynamic functional stability during memory tasks under dexmedetomidine sedation.

Purpose: This study aimed to explore the neurological effects of dexmedetomidine-induced sedation on memory using functional stability, a whole-brain voxel-wise dynamic functional connectivity approach. Methods: A total of 16 participants (10 men) underwent auditory memory task-related fMRI in the awake state and under dexmedetomidine sedation. Explicit and implicit memory tests were conducted 4 h after ceasing dexmedetomidine administration. One-sample Wilcoxon signed rank test was applied to determine the formation of explicit and implicit memory in the two states. Functional stability was calculated and compared voxel-wise between the awake and sedated states. The association between functional stability and memory performance was also assessed. Results: In the awake baseline tests, explicit and implicit memory scores were significantly different from zero (p < 0.05). In the tests under sedation, explicit and implicit memory scores were not significantly different from zero. Compared to that at wakeful baseline, functional stability during light sedation was reduced in the medial prefrontal cortex, left angular gyrus, and right hippocampus (all clusters, p < 0.05, GRF-corrected), whereas the left superior temporal gyrus exhibited higher functional stability (cluster p < 0.05, GRF-corrected). No significant associations were observed between functional stability and memory test scores. Conclusions: The distribution and patterns of alterations in functional stability during sedation illustrate the modulation of functional architecture by dexmedetomidine from a dynamic perspective. Our findings provide novel insight into the dynamic brain functional networks underlying consciousness and memory in humans.

Comparative Study on Medicinal Natures (qi) of Black Ginseng, Red Ginseng, and Ginseng Leaves Based on Typical Deficiency-Heat Syndrome Rat Model.

To elucidate the medicinal nature of black ginseng (BG) by comparison of the effects of four Chinese herbs with different medicinal natures on the deficiency-heat syndrome rat model which was established by intragastric administration of traditional Chinese drugs with hot nature, the appearance indexes, biochemical indexes, and pathological sections of thyroid and stomach were examined. In addition, the seven short-chain fatty acids (SCFAs) in rat feces were also determined by headspace gas chromatography-mass spectrometry to reveal the action mechanism of the drugs with different natures. Results indicated that all the 4 drugs could exhibit similar actions in regulating the biochemical indexes of triiodothyronine (T3), thyroxine (T4), thyrotropin-releasing hormone (TRH), thyroid-stimulating hormone (TSH), and corticosterone (CORT) representing the hypothalamus-pituitary-thyroid (HPT) and hypothalamus-pituitary-adrenal (HPA) axes of the animal. However, cold-natured cortex phellodendri (HB) and ginseng leaves (GLs) showed stronger downregulation of the AChE activity of the nervous system. Red ginseng (RG) and BG tested exhibited stronger upregulation of the liver Na+-K+-ATPase activity. Principal component analysis (PCA) showed that GLs are similar to those of HB which belongs to the cold-nature drug, whereas BG showed closer to RG which attributes to a warm-nature drug. Thus, BG could be ascribed to a warm-nature drug. Further research disclosed that RG and BG mainly regulated the acetic acid and GL and HB primarily modulated the isovaleric acid and hexanoic acid in rat feces, which could be the features of drugs with warm or cold nature on the regulation of SCFAs in rats. It is for the first time that the medicinal nature of BG and its effect on the SCFAs were examined.

DNA methylation in polycystic ovary syndrome: Emerging evidence and challenges.

Polycystic ovary syndrome (PCOS) is a disease related to reproductive endocrine abnormalities in women of reproductive age, often accompanied by metabolic diseases such as hyperandrogenemia, insulin resistance and dyslipidemia. However, the etiology and mechanism of PCOS are still unclear. In recent years, more and more studies have found that epigenetic factors play an important role in PCOS. DNA methylation is the most widely studied epigenetic modification. At present, changes of DNA methylation have been found in serum, ovarian, hypothalamus, skeletal muscle, adipose tissue of PCOS patients, and these changes are closely related to insulin resistance, lipid metabolism and follicular development of PCOS. Although the current research on DNA methylation in PCOS is not in-depth, it indicated up a good direction for future research on the etiology and mechanism of PCOS. This review discussed the relationship between DNA methylation and PCOS. It is expected to help accelerate the application of DNA methylation in the diagnosis and treatment of PCOS.

Biodegradable PTX-PLGA-coated magnesium stent for benign esophageal stricture: An experimental study.

Biodegradable stents can degrade step by step and thereby avoid secondary removal by endoscopic procedures in contrast to metal stents. Herein, a biodegradable composite stent, a magnesium (Mg)-based braided stent with a surface coating of poly (lactic-co-glycolic acid) (PLGA) containing paclitaxel (PTX), was designed and tested. By adding this drug-loaded polymer coating, the radial force of the stent increased from 33 Newton (N) to 83 N. PTX was continuously released as the stent degraded, and the in vitro cumulative drug release in phosphate-buffered saline for 28 days was 115 ± 13.5 µg/mL at pH = 7.4 and 176 ± 12 µg/mL at pH = 4.0. There was no statistically significant difference in the viability of fibroblasts of stent extracts with different concentration gradients (P > 0.05), while the PTX-loaded stents effectively promoted fibroblast apoptosis. In the animal experiment, the stents were able to maintain esophageal patency during the 3-week follow-up and to reduce the infiltration of inflammatory cells and the amount of fibrous tissue. These results showed that the PTX-PLGA-coated Mg stent has the potential to be a safe and effective approach for benign esophageal stricture. STATEMENT OF SIGNIFICANCE: We designed a biodegradable composite stent, having poly (lactic-co-glycolic acid) (PLGA) containing paclitaxel (PTX) coated the surface of the magnesium (Mg)-based braided stent. We evaluated in vitro and in vivo characteristics of the Mg esophageal stent having a PLGA coating plus a variable concentration of PTX in comparison with the absence of PTX PLGA coating. The PTX PLGA stents exerted higher radial force than stents without coating, degraded more quickly in an acid medium, and effectively promoted fibroblast apoptosis in vitro experiments. In a rabbit model of caustic-induced esophageal stricture, there was an increased lumen and decreased inflammation of the esophageal wall in the animals stented with PTX-PLGA versus the sham group, indicating a potential approach for benign esophageal stricture.

Analysis of Macular Retinal Thickness and Microvascular System Changes in Children with Monocular Hyperopic Anisometropia and Severe Amblyopia.

OBJECTIVE: To study the changes of macular retinal thickness and microvascular system in children with monocular hyperopic anisometropia and severe amblyopia using optical coherence tomography angiography (OCTA) and to explore the value of OCTA in the diagnosis and treatment of amblyopia. METHODS: Thirty-two children with monocular hyperopic anisometropia and severe amblyopia who were treated in the Department of Ophthalmology of the First Affiliated Hospital of Gannan Medical College from January 2020 to December 2020 were included in the study. Eyes with amblyopia (n = 32) served as the experimental group, and the contralateral healthy eyes (n = 32 eyes) served as the control group. All children underwent comprehensive ophthalmological examination including slit lamp, eye position, visual acuity, optometry, eye movement, intraocular pressure, ocular axis, and fundus examination to rule out organic lesions. Macular 6 mm × 6 mm scans were performed on both eyes of all subjects by the same experienced clinician using an OCTA instrument. After ImageJ processing, the vessel density, inner layer, and full-layer retinal thickness (RT) of superficial retinal capillary plexus (SCP) were obtained. All data were analyzed by SPSS21.0 software, and a paired t-test was used for comparison between groups. P < 0.05 was considered to indicate statistical significance. RESULTS: The vessel densities of macular SCP in the amblyopia and control groups were 47.66 ± 2.36% and 50.37 ± 2.24% in the outer superior, 49.19 ± 2.64% and 51.44 ± 2.44% in the inner inferior, 49.63 ± 2.51% and 51.41 ± 3.03% in the outer inferior, and 45.56 ± 3.44% and 50.44 ± 3.52% in the outer temporal regions, respectively. The vessel density of macular SCP in the amblyopia group was significantly lower than that in contralateral healthy eyes in the outer superior, inner inferior, outer inferior, outer temporal, and central regions. There was no significant difference between the two groups in the inner superior, inner nasal, outer nasal, and inner temporal regions. The macular RT in the amblyopia group and the control group is 90.38 ± 6.09 µm and 87.56 ± 5.55 µm in the outer temporal, respectively. The RT in the macular inner layer in the outer temporal region of the amblyopia group was thicker than that of the control group (P < 0.05). There was no significant difference in the other eight regions between the two groups. The whole macular RT in the amblyopia group was thicker than that in the control group in nine regions, and the central area of macular RT in the amblyopia and control groups was 229.06 ± 6.70 µm and 214.50 ± 10.36 µm, respectively. CONCLUSION: The OCTA results showed the overall RT of macula in 9 areas in the amblyopia group was thicker than that in the control group, which could show that the macular retinal thickness can be a potential way to distinguish the children with monocular hyperopic anisometropia and severe amblyopia.