[Saikosaponin a alleviates pentylenetetrazol-induced acute epileptic seizures in mouse models of depression by suppressing microglia activation-mediated inflammation].

OBJECTIVE: To explore the inhibitory effect of saikosonin a (SSa) on pentylenetetrazol-induced acute epilepsy seizures in a mouse model of depression and explore the mechanism mediating this effect. METHODS: Male C57BL/6J mouse models of depression was established by oral administration of corticosterone via drinking water for 3 weeks, and acute epileptic seizures were induced by intraperitoneal injection of a single dose of pentylenetetrazole. The effect of intraperitoneal injection of SSa prior to the treatment on depressive symptoms and epileptic seizures were assessed using behavioral tests, epileptic seizure grading and hippocampal morphology observation. ELISA was used to detect blood corticosterone levels of the mice, and RTqPCR was performed to detect the pro- and anti-inflammatory factors. Microglia activation in the mice was observed using immunofluorescence staining. RESULTS: The mouse model of corticosterone-induced depression showed body weight loss and obvious depressive behaviors with significantly increased serum corticosterone level (all P < 0.05). Compared with those with pentylenetetrazole-induced epilepsy alone, the epileptic mice with comorbid depression showed significantly shorter latency of epileptic seizures, increased number, grade and duration of of seizures, reduced Nissl bodies in hippocampal CA1 and CA3 neurons, increased number of Iba1-positive cells, and significantly enhanced hippocampal expressions of IL-1ß, IL-10, TNF-α and IFN-γ. Pretreatment of the epileptic mice with SSa significantly prolonged the latency of epileptic seizures, reduced the number, duration, and severity of seizures, increased the number of Nissl bodies, decreased the number of Iba1-positive cells, and reduced the expression levels of IL-1ß, IL-10, TNF-α, and IFN-γ in the hippocampus (P < 0.05). CONCLUSION: Depressive state aggravates epileptic seizures, increases microglia activation, and elevates inflammation levels. SSA treatment can alleviate acute epileptic seizures in mouse models of depression possibly by suppressing microglia activation-mediated inflammation.

[MiR-132-3p negatively regulates CAMTA1 to promote Schwann cell proliferation and migration and alleviates I-125 seeds-induced exacerbation of facial nerve injury in rats].

OBJECTIVE: To investigate the regulatory effect of miR-132-3p on calmodulin-binding transcription activator 1 (CAMTA1) and Schwann cell activity in rats with facial nerve injury (FNI) treated with I-125 seeds. METHODS: Rat Schwann cells were irradiated with I-125 seeds and transfected with miR-132-3p mimic, miR-132-3p inhibitor or sh-CAMTA1. The expressions of S100B and ß-tubulin Ⅲ in the cells were detected with immunofluorescence assay, and the expressions of miR-132-3p and CAMTA1 protein were determined using RT-qPCR and Western blotting, respectively. EdU staining and Transwell assay were used to evaluate the changes in cell proliferation and migration ability. In a rat model of FNI, I-125 seeds were implanted into the facial tissues near the facial nerve 2 weeks before modeling, and miR-132-3p mimic was injected subcutaneously in the face after modeling. The pathologies of the facial nerve was assessed by HE, LFB and immunofluorescence staining. The targeting relationship between miR-132-3p and CAMTA1 was verified using StarBase v2.0 database and dual-luciferase reporter assay. RESULTS: Rat Schwann cells showed high expressions of S100B and ß-tubulin Ⅲ. I-125 seeds radiation significantly decreased miR-132-3p expression and repressed proliferation and migration of the cells (P < 0.001). Overexpression of miR-132-3p or CAMTA1 knockdown obviously enhanced proliferation and migration of the Schwann cells, while miR-132-3p knockdown produced the opposite effect. MiR-132-3p negatively regulated CAMTA1 expression. In the rat models of FNI, miR-132-3p injection significantly inhibited CAMTA1 expression and attenuated I-125 seeds-induced exacerbation of FNI. CONCLUSION: Overexpression of miR-132-3p suppresses CAMTA1 expression and promotes Schwann cell proliferation and migration to alleviate I-125 seeds-induced exacerbation of FNI in rats.

Casp11 Deficiency Alters Subgingival Microbiota and Attenuates Periodontitis.

Periodontitis (PD) is the primary cause of tooth loss in adults. Porphyromonas gingivalis (P.g), a keystone pathogen, has been identified as a crucial contributor to this process. Pyroptosis activation in PD is acknowledged, with accumulating evidence underscoring the crucial role of Caspase-11 (described as Caspase-4/5 in humans)-mediated noncanonical pyroptosis. However, the mechanism behind its impact on PD remains unclear. In this study, we delved into the interplay between the Caspase-11-mediated noncanonical pyroptosis, subgingival microbiota alteration, and macrophage polarization. Clinical samples from PD patients revealed heightened expression of Caspase-4, gasdermin-D, and their active fragments, pointing to the activation of the noncanonical pyroptosis. Single-cell sequencing analysis linked Caspase-4 with gingival macrophages, emphasizing their involvement in PD. In vitro cell experiments confirmed that P.g-induced pyroptosis was activated in macrophages, with Casp11 deficiency attenuating these effects. In an experimental PD mouse model, Casp11 deficiency led to an alteration in subgingival microbiota composition and reduced alveolar bone resorption. Casp11-/- mice cohousing with wild-type mice confirmed the alteration of the subgingival microbiota and aggravated the alveolar bone resorption. Notably, Casp11 deficiency led to decreased M1-polarized macrophages, corresponding with reduced alveolar bone resorption, uncovering a connection between subgingival microbiota alteration, macrophage M1 polarization, and alveolar bone resorption. Taken together, we showed that Caspase-11 fulfilled a crucial role in the noncanonical pyroptosis in PD, potentially influencing the subgingival microbiota and linking to M1 polarization, which was associated with alveolar bone resorption. These findings underscored the pivotal role of the Caspase-11-mediated noncanonical pyroptosis in PD pathogenesis and may provide critical insights into potential therapeutic avenues for mitigating PD.

Changes in brain susceptibility in Wilson's disease patients: a quantitative susceptibility mapping study.

AIM: To assess changes in the susceptibility of the caudate nucleus (CN), putamen, and globus pallidus (GP) in patients with neurological and hepatic Wilson's disease (WD) by quantitative susceptibility mapping (QSM). MATERIAL AND METHODS: The brain MRI images of 33 patients diagnosed with WD and 20 age-matched controls were analysed retrospectively. All participants underwent brain T1-weighted, T2-weighted, and QSM imaging using a 1.5 T magnetic resonance imaging (MRI) machine. QSM maps were evaluated with the STISuite toolbox. The quantitative susceptibility levels of the CN, putamen, and GP were analysed using region of interest analysis on QSM maps. Differences among neurological WD patients, hepatic patients, and controls were determined. RESULTS: Susceptibility levels were significantly higher for all examined structures (CN, putamen and GP) in patients with neurological WD compared with controls (all p<0.05) and hepatic WD patients (all p<0.05). No statistically significant differences were found in susceptibility levels between patients with hepatic WD and controls (all p>0.05). CONCLUSION: The QSM technique is a valuable tool for detecting changes in brain susceptibility in WD patients, indicating abnormal metal deposition. Notably, the current findings suggest that neurological WD patients exhibit more severe susceptibility changes compared with hepatic WD patients. Therefore, QSM can be utilised as a complementary method to detect brain injury in WD patients.

[Preliminary application of recombinase -aided amplification in detection of Clonorchis sinensis metacercariae in freshwater fish].

OBJECTIVE: To evaluate the performance of recombinase-aided amplification (RAA) assay in detection of Clonorchis sinensis metacercariae in freshwater fish samples, so as to provide insights into standardization and field application of this assay. METHODS: Wild freshwater fish samples were collected in the rivers of administrative villages where C. sinensis-infected residents lived in Jiangyan District, Xinghua County and Taixing County of Taizhou City, Jiangsu Province from June to September 2022. Genomic DNA was extracted from six freshwater fish specimens (5 g each) containing 0, 1, 2, 4, 8 and 16 C. sinensis metacercariae for fluorescent RAA assay, and the diagnostic sensitivity was evaluated. Fluorescent RAA assay was performed with genomic DNA from C. sinensis, Metorchis orientalis, Haplorchis pumilio and Centrocestus formosanus metacercariae as templates to evaluate its cross-reactions. In addition, the detection of fluorescent RAA assay and direct compression method for C. sinensis metacercariae was compared in field-collected freshwater fish samples. RESULTS: Positive amplification was found in fresh-water fish specimens containing different numbers of C. sinensis metacercariae, and fluorescent RAA assay was effective to detect one C. sinensis metacercaria in 5 g freshwater fish specimens within 20 min. Fluorescent RAA assay tested negative for DNA from M. orientalis, H. pumilio and C. formosanus metacercariae. Fluorescent RAA assay and direct compression method showed 5.36% (93/1 735) and 2.88% (50/1 735) detection rates for C. sinensis metacercariae in 1 735 field-collected freshwater fish samples, with a statistically significant difference seen (χ2 = 478.150, P < 0.001). There was a significant difference in the detection of C. sinensis metacercariae in different species of freshwater fish by both the direct compression method (χ2 = 11.20, P < 0.05) and fluorescent RAA assay (χ2 = 20.26, P < 0.001), and the detection of C. sinensis metacercariae was higher in Pseudorasbora parva than in other fish species by both the direct compression method and fluorescent RAA assay (both P values < 0.05). CONCLUSIONS: Fluorescent RAA assay has a high sensitivity for detection of C. sinensis metacercariae in freshwater fish samples, and has no cross-reactions with M. orientalis, H. pumilio or C. formosanus metacercariae. Fluorescent RAA assay shows a higher accuracy for detection of C. sinensis infections in field-collected freshwater fish than the direct compression method.

[Curcumol reverses temozolomide resistance in glioma cells by regulating the UTX/MGMT axis].

OBJECTIVE: To explore the mechanism through which curcumol reverses primary drug resistance in glioma cells. METHODS: The inhibitory effect of 10, 20, and 40 µg/mL curcumol were observed in human glioma cell lines A172 and U251. UTX-overexpressing glioma cells constructed by lentiviral transfection were treated with curcumol (40 µg/mL), temozolomide (TMZ; 10 µg/mL), or both, and the changes in cell viability, clone formation capacity and apoptosis were assessed using MTT assay, cell clone formation experiment, and flow cytometry; UTX activity in the cells was determined using a UTX detection kit, and the enrichment of UTX and H3K27me3 in the MGMT promoter region was detected with ChiP-qPCR. The protein expressions in glioma cells were detected using Western blotting and immunohistochemistry. In a nude mouse model bearing glioma xenografts, the effects of curcumol (20 mg/kg), TMZ (20 mg/kg) and their combination on tumor growth and expressions of UTX, H3K27me3 and MGMT were evaluated. RESULTS: Curcumol significantly inhibited the proliferation (P<0.05) and promoted apoptosis of cultured glioma cells (P<0.01). Curcumol, but not TMZ, produced significant inhibitory effect on tumor growth in the tumor-bearing mice (P<0.01). Curcumol significantly inhibited UTX activity and increased the expression level of H3K27me3 protein in the glioma cells. UTX overexpression obviously decreased H3K27me3 protein expression and reversed the effects of curcumol on glioma cell proliferation and apoptosis (P<0.01). Curcumol reduced the enrichment of UTX and H3K27me3 in the MGMT promoter region (P<0.05) and decreased MGMT protein expression, which was reversed by UTX overexpression. In both the in vivo and in vitro experiments, curcumol combined with TMZ significantly increased H3K27me3 protein expression in the glioma cells, reduced the expression of its downstream target gene MGMT, and enhanced TMZ sensitivity of the glioma cells. CONCLUSION: Curcumol can enhance glioma cell sensitivity to TMZ by regulating the UTX/MGMT axis.

[Application of augmented reality navigation combined with indocyanine green fluorescence imaging technology in the accurate guidance of laparoscopic anatomical segment 8 liver resection].

Objective: To investigate the application value of augmented reality navigation combined with indocyanine green(ICG) fluorescence imaging technology in laparoscopic anatomical segment 8 liver resection. Methods: Clinical and pathological data from 8 patients with hepatocellular carcinoma located in segment 8 of the liver admitted to the First Department of Hepatobiliary Surgery,Zhujiang Hospital,Southern Medical University from October 2021 to October 2022 were collected restrospectively. Among them,there were 5 males and 3 females,aged between 40 and 72 years. During the operation,the self-developed laparoscopic augmented reality surgical navigation system was used to integrate the three-dimensional liver model with the laparoscopic scene,and ICG fluorescence imaging technology was used to guide the anatomical liver resection of segment 8. The predicted liver resection volume and actual liver resection volume,related surgical indicators and postoperative complications were analyzed. Results: Among the 8 patients, 4 underwent laparoscopic anatomical segment 8 liver resection,1 underwent laparoscopic anatomical ventral subsegment of segment 8 liver resection,2 underwent laparoscopic anatomical ventral subsegment combined with medial subsegment of segment 8 liver resection, and 1 underwent laparoscopic anatomical dorsal subsegment of segment 8 liver resection. All operations were completed under the guidance of augmented reality navigation combined with ICG fluorescence imaging,without conversion to open surgery. The operation time was (276.3±54.8)minutes(range:200 to 360 minutes). Intraoperative blood loss was (75.0±35.4)ml(range:50 to 150 ml). No blood transfusion was performed during the operation. The length of postoperative hospital stay was (7.6±0.8)days(range:7 to 9 days). There were no deaths or postoperative complications such as bleeding or biliary fistula during the perioperative period. Conclusion: Augmented reality navigation combined with ICG fluorescence imaging technology can guide the implementation of laparoscopic anatomical segment 8 liver resection.

Morin protects chicks with T-2 toxin poisoning by decreasing heterophil extracellular traps, oxidative stress and inflammatory response.

1. Fusarium tritici widely exists in a variety of grain feeds. The T-2 toxin is the main hazardous component produced by Fusarium tritici, making a serious hazard to poultry industry. Morin, belonging to the flavonoid family, can be extracted from mulberry plants and possesses anticancer, antioxidant and anti-inflammatory compounds, but whether morin protects chicks with T-2 toxin poisoning remains unclear. This experiment firstly established a chick model of T-2 toxin poisoning and then investigated the protective effects and mechanism of morin against T-2 toxin in chicks.2. The function of liver and kidney was measured by corresponding alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), blood urea nitrogen (BUN), creatinine (Cre) and uric acid (UA) kits. Histopathological changes were observed by haematoxylin-eosin staining. The status of oxidative stress was measured by MDA, SOD, CAT, GSH and GSH-PX kits. The mRNA levels of TNF-α, COX-2, IL-1ß, IL-6, caspase-1, caspase-3 and caspase-11 were measured by quantitative real-time PCR. Heterophil extracellular trap (HET) release was analysed by immunofluorescence and fluorescence microplate.3. The model with T-2 toxin poisoning in chicks was successfully established. Morin significantly decreased T-2 toxin-induced ALT, AST, ALP, BUN, Cre and UA, and improved T-2 toxin-induced liver cell rupture, liver cord disorder and kidney interstitial oedema. Oxidative stress analysis showed that morin ameliorated T-2 toxin-induced damage by reducing malondialdehyde (MDA), increasing superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and glutathione peroxidase (GSH-PX). The qRT-PCR analysis showed that morin reduced T-2 toxin-induced mRNA expressions of TNF-α, COX-2, IL-1ß, IL-6, caspase-1, caspase-3 and caspase-11. Moreover, morin significantly reduced the release of T-2 toxin-induced HET in vitro and in vivo.4. Morin can protect chicks from T-2 toxin poisoning by decreasing HETs, oxidative stress and inflammatory responses, which make it a useful compound against T-2 toxin poisoning in poultry feed.

[Comparison of the disease burden of schistosomiasis globally and in China and Zimbabwe].

OBJECTIVE: To investigate the trends in the disease burden of schistosomiasis worldwide and in China, and Zimbabwe from 1990 to 2019, so as to provide insights into the formulation of the schistosomiasis control strategy in Zimbabwe. METHODS: Based on Global Burden of Disease Study 2019 (GBD 2019) data sources, the age-standardized prevalence, mortality, disability-adjusted life year (DALY) rate of schistosomiasis were compared in the world, China, and Zimbabwe and the trends in the disease burden of schistosomiasis from 1990 to 2019 were investigated using Joinpoint regression analysis. In addition, the associations between the burden of schistosomiasis worldwide and in China and Zimbabwe from 1990 to 2019 and socio-demographic index (SDI) were examined using Pearson correlation analysis. RESULTS: The age-standardized prevalence, mortality, and DALY rate of schistosomiasis were 1 804.95/105, 0.14/105 and 20.92/105 in the world, 707.09/105, 0.02/105 and 5.06/105 in China, and 2 218.90/105, 2.39/105 and 90.09/105 in Zimbabwe in 2019, respectively. The global prevalence, mortality, and DALY rate of schistosomiasis appeared a tendency towards a rise followed by a decline with age in 2019, while the prevalence and DALY rate of schistosomiasis appeared a tendency towards a sharp rise followed by a fluctuating decline in both China and Zimbabwe, and the mortality of schistosomiasis appeared a tendency towards a rise. The age-standardized prevalence [average annual percent change (AAPC) = -1.31%, -2.22% and -6.12%; t = -20.07, -83.38 and -53.06; all P values < 0.05)] and DALY rate of schistosomiasis (AAPC = -1.91%,-4.17% and -2.08%; t = -31.89, -138.70 and -16.45; all P values < 0.05) appeared a tendency towards a decline in the world, China and Zimbabwe from 1990 to 2019, and the age-standardized mortality of schistosomiasis appeared a tendency towards a decline in the world and China (AAPC = -3.46% and -8.10%, t = -41.03 and -61.74; both P values < 0.05), and towards a rise followed by a decline in Zimbabwe (AAPC = 1.35%, t = 4.88, P < 0.05). In addition, Pearson correlation analysis showed that the age-standardized prevalence (r = -0.75, P < 0.05), mortality (r = -0.73, P < 0.05), and DALY rate of schistosomiasis (r = -0.77, P < 0.05) correlated negatively with SDI in the world, China and Zimbabwe from 1990 to 2019. CONCLUSIONS: The disease burden of schistosomiasis appeared a remarkable decline in China from 1990 to 2019, and the prevalence of schistosomiasis showed a tendency towards a decline in Zimbabwe from 1990 to 2019; however, the mortality and DALY rate of schistosomiasis in Zimbabwe topped in the world. A schistosomiasis control strategy with adaptations to local epidemiology and control needs of schistosomiasis is needed to facilitate the elimination of schistosomiasis in Zimbabwe.

[A new understanding of wound repair after surgery for benign prostatic hyperplasia].

Benign prostatic hyperplasia (BPH) is one of the most common diseases in elderly men. Transurethral resection of prostate (TURP), as an important BPH treatment, is also the most effective way to relieve prostatic obstruction. However, postoperative complications, such as lower urinary tract symptoms (LUTS), infection, hematuria and bladder neck contracture, may still occur, which seriously impact the therapeutic effect and patients' quality of life. The wound healing after BPH surgery is closely associated with the occurrence of postoperative complications. Therefore, comprehensively understanding the influencing factors of wound healing and designing tailored interventions will be particularly important for reducing postoperative complications of BPH.

[Analysis of causes of graft loss in 135 kidney transplant recipients].

OBJECTIVE: To investigate the causes of graft loss in kidney transplant recipients. METHODS: We retrospectively analyzed the clinical data of 135 recipients with graft loss after renal transplantation in the Eighth Medical Center of Chinese PLA General Hospital from January 1, 2002 to January 1, 2022. RESULTS: A total of 135 kidney transplant recipients experienced graft failure. The causes of graft loss included graft rejection (70 cases, 51.8%), death of the recipients with functional graft (37 cases, 27.4%), surgical complications (12 cases, 8.9%), drug toxicity (4 cases, 3.0%), carbapenem-resistant Klebsiella pneumoniae infection (4 cases, 3.0%), polyoma BK virus-related nephropathy (3 cases, 2.2%), primary nonfunctioning kidney (2 cases, 1.5%), recurrence of primary disease (2 cases, 1.5%), and prerenal acute renal failure (1 case, 0.7%). CONCLUSION: The main cause of graft loss after renal transplantation is graft rejection, and the secondary cause is death of the recipient with functional graft, and other reasons can be rare.

[Publication and citation analyses of Chinese Journal of Schistosomiasis Control from 2011 to 2020].

OBJECTIVE: To investigate the publications and citations of Chinese Journal of Schistosomiasis Control from 2011 to 2020, so as to provide insights into improving the journal quality and impact. METHODS: All publications were retrieved from 60 issues of 10 volumes of Chinese Journal of Schistosomiasis Control from 2011 to 2020, and publication and citation analyses were performed using a bibliometric method. RESULTS: A total of 1 867 articles were published in Chinese Journal of Schistosomiasis Control from 2011 to 2020, with the largest number in 2012 (220 publications) and the lowest in 2020 (135 publications), and original article (36.48%), control experience (17.14%) and control study (10.34%) were the three most common article type. The overall proportion of grant-supported articles was 59.08% (1 103/1 867), and the number of grant per article was (2.34±1.58) grants. The mean duration from submission to publication was (173.48±105.84) days per article, and there was a significant difference in the mean duration from submission to publication among years (F = 30.883, P < 0.01). Jiangsu Province (492 publications, 26.35%), Shanghai Municipality (264 publications, 14.14%) and Hubei Province (230 publications, 12.32%) were the three most productive provinces where the first author lived, and disease control and prevention institutions were the predominant affiliations of the first author (67.22%), with Jiangsu Institute of Schistosomiasis Control, National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, and Wannan Medical College as the three most productive affiliations. The number of authors was 5.94 authors per publication, and the proportion of co-authored publications was 95.45% in Chinese Journal of Schistosomiasis Control from 2011 to 2020. Journal article was the predominant type of cited (89.97%), and the mean number of citations was (15.70±11.56) citations per publication, with a significant difference in the mean number of citations per publication among years (F = 2.205, P < 0.05). The impact factors of Chinese Journal of Schistosomiasis Control ranged from 0.877 to 1.676 during the period from 2011 to 2020, and the overall Price index was 47.59%. CONCLUSIONS: Both the academic impact and national transmissibility of Chinese Journal of Schistosomiasis Control appeared a tendency towards a rise from 2011 to 2020. Seeking high-quality contributions, increasing interdisciplinary integration, shortening the duration from submission to publication, expanding the coverage of publication services and enhancing impact are the future priorities of the journal.

Ligature-Induced Periodontitis Drives Colorectal Cancer: An Experimental Model in Mice.

Periodontitis is a prevalent inflammatory oral disease associated with an increased risk of colorectal cancer. Experimental animal models are critical tools to investigate the effects and mechanisms of periodontitis on colorectal cancer. Several murine periodontitis models have been used in research, including oral gavage, periodontal pathogen injection, and ligature models. The role of experimental periodontitis caused by silk ligation in colorectal cancer remains unclear. In this study, we used an experimental periodontitis model on a colitis-associated colorectal cancer model and a spontaneous model, respectively. We observed the promotion of colorectal cancer in ligature-induced periodontitis mice compared to those control mice in 2 different models, as assessed by tumor number, tumor size, and tumor load. Since bacterial dysbiosis is an important feature of periodontitis, we next analyzed the oral and gut microbiomes using 16S ribosomal RNA gene sequencing. We found that the experimental periodontitis model reshaped the microbial community in the oral cavity and gut. In addition, we found a higher extent of programmed death 1 (PD-1)-positive CD8+ T-cell infiltration in tumor samples of the periodontitis group than in controls by immunofluorescence staining. Regarding the potential molecular mechanism, we transplanted the fecal microbiota of the periodontitis patient into mice and observed a tumor-promoting effect in the periodontitis group, assessed by tumor volume and tumor weight, together with a low level of INF-γ+ CD8+ T-cell infiltration in subcutaneous tumor mice. Taken together, we show that ligature-induced periodontitis model promotes colorectal cancer by microbiota remodeling and suppression of the immune response.

Identification and development of a five-gene signature to improve the prediction of mechanical ventilator-free days for patients with COVID-19.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is a highly contagious infectious disease caused by the newly discovered severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Severe COVID-19 infection causes complications in the respiratory tract, which results in pulmonary failure, thus requiring prolonged mechanical ventilation (MV). An increase in the number of patients with COVID-19 poses numerous challenges to the healthcare system, including the shortage of MV facilities. Despite continued efforts to improve COVID-19 diagnosis and treatment, no study has established a reliable predictive model for the risk assessment of deteriorating COVID-19 cases. MATERIALS AND METHODS: We extracted the expression profiles and clinical data of the GSE157103, GSE116560 and GSE21802 cohorts from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified as the intersection of the resulting differential genes as analysed via limma, edgeR and DESeq2 R packages. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using the R package 'clusterProfiler'. Variables closely related to MV were examined using univariate Cox regression analysis, and significant variables were subjected to least absolute shrinkage and selection operator regression (LASSO) analysis for the construction of a risk model. Kaplan-Meier analysis and receiver operating characteristic (ROC) curves were generated to verify the predictive values of the risk model. RESULTS: We identified 198 unigenes that were differentially expressed in COVID-19 samples. Moreover, a five-gene signature (BTN3A1, GPR35, HAAO, SLC2A6 and TEX2) was constructed to predict the ventilator-free days of patients with COVID-19. In our study, we used the five-gene signature to calculate the risk score (MV score) for each patient. The results revealed a statistical correlation between the MV score and the scores of the Acute Physiology and Chronic Health Evaluation and Sequential Organ Failure Assessment of patients with COVID-19. Kaplan-Meier analysis revealed that the number of ventilator-free days was significantly reduced in the low-MVscore group compared to the high-MVscore group. The ROC curves revealed that our model had a good performance, and the areas under the ROC curve were 0.93 (3-week ROC) and 0.97 (4-week ROC). The 'Limma' package analysis revealed 71 upregulated genes and 59 downregulated genes in the high-MV score group compared to the low-MV score group. These DEGs were mainly enriched in cytokine signalling in immune system and cellular response to cytokine stimulus. CONCLUSIONS: This study identified a five-gene signature that can predict the length of ventilator-free days for patients with COVID-19.

The lateral cervical stria approach to selective neck dissection: a preliminary study.

BACKGROUND: This study aims to propose a lateral cervical stria approach for selective neck dissection (SND) in patients of early-stage oral malignancies. MATERIAL AND METHODS: The lateral cervical stria approach was used in 11 patients undergoing SND between December 2020 and March 2022. The surgical incision was located in submandibular cervical stria, with a length of 5.0 cm. The ipsilateral SND was performed according to the pathological type, covering part or all of I-V levels. Perioperative variables including operation time, blood loss, drainage volume, number of lymph node as well as complications were assessed. The score of appearance using the University of Washington Quality of Life Questionnaire (UW-QOL) was recorded 6-month postoperatively. RESULTS: Direct closure of primary lesion was performed in ten patients and a forearm free flap reconstruction was used in one patient. No wound breakdown or infection was found in all cases. The mean operative time of SND was 157.63±27.39 min. The volume of intraoperative blood loss and postoperative drainage was 120.45±36.77 ml and 314.09±98.82 ml, respectively. The mean number of retrieved lymph nodes was 17.89±6.03 (ranging from 12 to 31). Postoperative complications included mild static lower lip deviation (n=1), shoulder discomfort (n=1) and mild auricular paraesthesia (n=1). The mean score of appearance was 86.36±13.06, with 100 scores in 5 patients and 75 scores in 6 patients. CONCLUSIONS: The lateral cervical stria approach for SND in early-stage oral malignancies is reliable, achieving to satisfactory functional and aesthetic outcomes.

Oral Pathobionts Promote MS-like Symptoms in Mice.

Dysbiotic oral microbiota has been associated with multiple sclerosis. However, the role and mechanism of oral microbiota in the development of multiple sclerosis are still elusive. Here, we demonstrated that ligature-induced periodontitis (LIP) aggravated experimental autoimmune encephalomyelitis (EAE) in mice, and this was likely dependent on the expansion of T helper 17 (Th17) cells. LIP increased the splenic richness of Enterobacter sp., which was able to induce the expansion of splenic Th17 cells and aggravate EAE in mice. LIP also led to enrichment of Erysipelotrichaceae sp. in the gut and increased Th17 cells in the large intestinal lamina propria of EAE mice. Fecal microbiota transplantation from EAE mice with LIP also promoted EAE symptoms. In conclusion, periodontitis exacerbates EAE, likely through ectopic colonization of oral pathobionts and expansion of Th17 cells.

Effect of Resistance Exercise Orders on Health Parameters in Trained Older Women: A Randomized Crossover Trial.

PURPOSE: This study aimed to compare the effects of four resistance exercise orders on muscular strength, body composition, functional fitness, cardiovascular risk factors, and mental health parameters in trained older women. METHODS: The intervention lasted 63 wk. Sixty-one physically independent women (>60 yr) after completing a 12-wk resistance training (RT) preconditioning phase were randomized into four different exercise orders groups to perform 12 wk of RT: multijoint to single-joint and upper- to lower-body, single-joint to multijoint and upper- to lower-body, multijoint to single-joint and lower- to upper-body, and single-joint to multijoint and lower- to upper-body. This was followed by a 12-wk detraining period and another 12-wk RT in which exercise orders were crossed over between MJ-SJ and SJ-MJ conditions. Body composition (dual-energy x-ray absorptiometry), muscular strength (one-repetition maximum tests), functional fitness (gait speed, walking agility, 30-s chair stand, and 6-min walk tests), cardiovascular risk factors (glucose, triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, C-reactive protein, advanced oxidation protein product, total radical-trapping antioxidant parameter, and nitric oxide), depressive (Geriatric Depression Scale) and anxiety symptoms (Beck Anxiety Inventory), and cognitive performance (Montreal Cognitive Assessment, Trail Making, verbal fluency, and Stroop test) were analyzed. RESULTS: After the final training period, all groups presented significant improvements ( P < 0.05) in almost all analyzed variables (muscular strength, body composition, functional tests, blood biomarkers, and mental health parameters), without significant difference among exercise orders. CONCLUSIONS: Our results suggest that RT exercise orders in which MJ, SJ, upper, or lower-body exercises are performed first have similar effects on health parameters in trained older women.

[Linagliptin improves diabetic kidney disease in rats by promoting mitochondrial biogenesis through the AMPK/PGC-1α/TFAM pathway].

OBJECTIVE: To investigate whether linagliptin improves diabetic kidney disease (DKD) by promoting mitochondrial biosynthesis via activating adenosine monophosphate activated protein kinase/peroxisome proliferator-activated receptor gamma coactivator 1α/mitochondrial transcription factor A (AMPK/PGC-1α/TFAM) pathway. METHODS: With 6 male SD rats feeding normal chow as the control group, 16 SD rat models of DKD induced by intraperitoneal injection of 45 mg/kg STZ and high-fat and high-glucose feeding for 4 weeks were randomized into DKD model group and linagliptin treatment group. The rats in the latter two groups were subjected to daily intragastric administration of vehicle or 5 mg/kg linagliptin (dissolved in 5 g/L sodium carboxymethylcellulose, final concentration of 2 mg/mL) for 12 weeks with further high-fat and high-glucose feeding. After the treatments, the rats were sacrificed and blood samples from the abdominal aorta and kidney tissues were collected for testing blood glucose, liver function and lipid metabolism; HE, PAS, Masson, Sirius red staining and electron microscopy were used to observe renal tissue damage. Renal expressions of transforming growth factor ß1 (TGF-ß1), fibronectin (FN) and collagen I (Col I) were detected by immunohistochemistry, and the changes in membrane potential (ΔψM) and ATP enzyme content were analyzed to assess mitochondrial damage; The expressions of AMPK/PGC-1α/TFAM pathway proteins were detected using Western blotting. RESULTS: Compared with DKD model rats, the rats receiving linagliptin treatment showed significantly decreased blood glucose level (P < 0.01) and improved proteinuria (P < 0.05) with obviously alleviated renal ultrastructural damage and fibrosis, increased ATPase content and ΔψM (P < 0.0001), and enhanced renal expressions of P-AMPK/AMPK, PGC-1α and TFAM (P < 0.05). CONCLUSIONS: Linagliptin improves proteinuria and renal fibrosis in rat models of DKD possibly by activating the AMPK/PGC-1α/TFAM pathway to promote mitochondrial biosynthesis.