Tobacco smoking confers risk for severe COVID-19 unexplainable by pulmonary imaging.

BACKGROUND: COVID-19 is a new pneumonia. It has been hypothesized that tobacco smoking history may increase severity of this disease in the patients once infected by the underlying coronavirus SARS-CoV-2 because smoking and COVID-19 both cause lung damage. However, this hypothesis has not been tested. OBJECTIVE: Current study was designed to focus on smoking history in patients with COVID-19 and test this hypothesis that tobacco smoking history increases risk for severe COVID-19 by damaging the lungs. METHODS AND RESULTS: This was a single-site, retrospective case series study of clinical associations, between epidemiological findings and clinical manifestations, radiographical or laboratory results. In our well-characterized cohort of 954 patients including 56 with tobacco smoking history, smoking history increased the risk for severe COVID-19 with an odds ratio (OR) of 5.5 (95% CI: 3.1-9.9; P = 7.3 × 10-8 ). Meta-analysis of ten cohorts for 2891 patients together obtained an OR of 2.5 (95% CI: 1.9-3.3; P < 0.00001). Semi-quantitative analysis of lung images for each of five lobes revealed a significant difference in neither lung damage at first examination nor dynamics of the lung damage at different time-points of examinations between the smoking and nonsmoking groups. No significant differences were found either in laboratory results including D-dimer and C-reactive protein levels except different covariances for density of the immune cells lymphocyte (P = 3.8 × 10-64 ) and neutrophil (P = 3.9 × 10-46 ). CONCLUSION: Tobacco smoking history increases the risk for great severity of COVID-19 but this risk is achieved unlikely by affecting the lungs.

Transformation, migration and outcome of residual bodies in the seminiferous tubules of the rat testis.

Experiments were performed to study the transformation, migration and outcome of residual bodies (RBs) in the seminiferous tubules of the rat testes. One part of the testes from adult Sprague-Dawley rats was used to generate paraffin sections to observe RBs and RB precursors through specific staining, and the other part of the testes was used to generate ultrathin sections to observe RBs under a transmission electron microscope. Deep blue particles of different sizes were observed in some seminiferous tubules through specific staining for RBs and RB precursors. These particles first appeared in the seminiferous tubules at stage I of the spermatogenic cycle, and after spermiation, the particles travelled rapidly towards the deeper region of the seminiferous epithelium and soon appeared close to the basement membrane of the seminiferous tubule. All of the particles in the tubules disappeared at stage IX. Using transmission electron microscopy, components of different electron densities were observed in the RBs on the surface of the seminiferous epithelium, all of which gradually formed in the cytoplasm of spermatozoon in later stages of spermiogenesis. After the spermatozoa were released, the RBs in the epithelium travelled quickly to the edge of the tube and were gradually transformed into lipid inclusions. These lipid inclusions ultimately became lipidlike particles. The lipidlike particles were discharged into the interstitial tissue. RBs initiate their own digestive process before their formation during spermiation in the rat testes. After spermiation, the RBs transform into lipid inclusions and finally into lipidlike particles. These lipidlike particles can be eliminated from the seminiferous tubules.

HLA-B*13:01 and the dapsone hypersensitivity syndrome.

BACKGROUND: Dapsone is used in the treatment of infections and inflammatory diseases. The dapsone hypersensitivity syndrome, which is associated with a reported mortality of 9.9%, develops in about 0.5 to 3.6% of persons treated with the drug. Currently, no tests are available to predict the risk of the dapsone hypersensitivity syndrome. METHODS: We performed a genomewide association study involving 872 participants who had received dapsone as part of multidrug therapy for leprosy (39 participants with the dapsone hypersensitivity syndrome and 833 controls), using log-additive tests of single-nucleotide polymorphisms (SNPs) and imputed HLA molecules. For a replication analysis, we genotyped 24 SNPs in an additional 31 participants with the dapsone hypersensitivity syndrome and 1089 controls and performed next-generation sequencing for HLA-B and HLA-C typing at four-digit resolution in an independent series of 37 participants with the dapsone hypersensitivity syndrome and 201 controls. RESULTS: Genomewide association analysis showed that SNP rs2844573, located between the HLA-B and MICA loci, was significantly associated with the dapsone hypersensitivity syndrome among patients with leprosy (odds ratio, 6.18; P=3.84×10(-13)). HLA-B*13:01 was confirmed to be a risk factor for the dapsone hypersensitivity syndrome (odds ratio, 20.53; P=6.84×10(-25)). The presence of HLA-B*13:01 had a sensitivity of 85.5% and a specificity of 85.7% as a predictor of the dapsone hypersensitivity syndrome, and its absence was associated with a reduction in risk by a factor of 7 (from 1.4% to 0.2%). HLA-B*13:01 is present in about 2 to 20% of Chinese persons, 1.5% of Japanese persons, 1 to 12% of Indians, and 2 to 4% of Southeast Asians but is largely absent in Europeans and Africans. CONCLUSIONS: HLA-B*13:01 was associated with the development of the dapsone hypersensitivity syndrome among patients with leprosy. (Funded by the National Natural Science Foundation of China and others.).

Blockade of Extracellular HMGB1 Suppresses Xenoreactive B Cell Responses and Delays Acute Vascular Xenogeneic Rejection.

Blockade of extracellular high mobility group box 1 (HMGB1) can significantly prolong murine cardiac allograft survival. Here, we determined the role of HMGB1 in xenotransplantation. Sprague-Dawley rat hearts were transplanted heterotopically into BALB/c mice. Xenografts without any treatment developed predominant acute vascular rejection within 6 days. Both passively released HMGB1 from xenografts and actively secreted HMGB1 from infiltrated immune cells were significantly increased after xenotransplantation. HMGB1-neutralizing antibody treatment significantly prolonged xenograft survival and attenuated pathologic damage, immune cell infiltration, and HMGB1 expression and release in the xenografts. Compared to control IgG treatment evaluated at study endpoint, treatment with HMGB1-neutralizing antibody markedly suppressed xenoreactive B cell responses, as evidenced by the significant inhibition of anti-rat antibody production and deposition in xenografts at Day 6 posttransplant. Furthermore, treatment with anti-HMGB1 antibody suppressed B cell activation and reduced IFN-γ and IL-17A production after xenotransplantation. These results demonstrate for the first time that HMGB1 plays an important role in mediating acute xenograft rejection. Thus, we have shown that neutralization of extracellular HMGB1 can significantly inhibit xenoreactive B cell responses and delay xenograft rejection in a rat-to-mouse model of xenotransplantation, uncovering new insights in the role of HMGB1 in transplantation.

Effect of curcumin on p38MAPK expression in DSS-induced murine ulcerative colitis.

The aim of this study was to determine the therapeutic effect of curcumin on dextran sulfate sodium-induced ulcerative colitis (UC) and to explore the related mechanism. Sixty mice were randomly divided into 6 groups. A group was the normal control group; B group was the model group; C group was the 1.5 mg/kg dexamethasone group based on the B group; and D, E and F groups were 15, 30, and 60 mg/kg curcumin groups, respectively, based on the B group. The mice were killed 7 days after treatment; the expression of TNF-α and MPO in colon tissue was determined with ELISA, and colon p-p38MAPK and p38MAPK mRNA expression was evaluated by immunohistochemistry and RT-PCR, respectively. In the C, D, E, and F groups, TNF-α and MPO levels significantly decreased (P < 0.05), and the expression of p-p38MAPK also significantly decreased (P < 0.01). The expression of p38MAPK mRNA in the C, D, E, and F groups decreased (P < 0.01), and there was a statistically significant difference between the E and F groups (P < 0.01). Curcumin had a therapeutic effect, which probably played a role in UC treatment by inhibiting the p38MAPK signaling pathway, thereby reducing the release of TNF-α.

Effects of the Zhikang capsule on healing of the flap after radical breast cancer surgery.

This study aimed to investigate the effect and mechanism of trauma flap healing promoted by the Zhikang capsule after radical breast cancer surgery. The enrolled breast cancer patients were randomly divided into two groups: treatment and observation. The patients in the treatment group were treated with the Zhikang capsule in addition to the conventional dressing changes, while patients in the observation group underwent only the regular dressing changes. Serum samples of 98 breast cancer patients (with complete clinical data) who underwent modified radical mastectomy were collected and analyzed for expressions of transforming growth factor beta (TGF-ß) and basic fibroblast growth factor (bFGF). The drainage fluid amount and tissue necrosis rate were found to be lower in the treatment group than in the observation group. Moreover, bFGF expression in peripheral blood was higher in the treatment group than in the observation group. However, no significant difference was found between the two groups in the expression of TGF-ß in peripheral blood. In conclusion, Zhikang capsule is effective in promoting flap healing after radical breast cancer surgery, and the increase of bFGF expression in peripheral blood may be the underlying mechanism.

Role of alanine aminotransferase in the effects of urinary caffeine concentration and its primary metabolite concentration on cognitive function in older adults: Bayesian Kernel Machine regression analysis and mediation analysis.

OBJECTIVE: This study aimed to explore the role of alanine aminotransferase (ALT) in the effects of urinary caffeine and its primary metabolites on cognitive function in elderly people. MATERIALS AND METHODS: In this investigation, we meticulously curated a cohort from the 2011-2014 National Health and Nutrition Examination Survey (NHANES) database. Animal fluency emerged as the pivotal metric for assessing cognitive function within our study population. In order to navigate the intricacies of mixture analysis and circumvent potential complexities, we harnessed the power of Bayesian kernel machine regression (BKMR) models. This method allowed us to dissect the nuanced impacts of caffeine and its primary urinary metabolites on cognitive function. While accounting for caffeine and its metabolites, we analyzed the relationship between ALT and cognitive function through non-linear dynamics. Lastly, employing structural equation modeling, we probed the intriguing question of whether ALT mediates the influence of 3,7-dimethylxanthine on cognitive function. This comprehensive approach has unveiled a deeper understanding of the multifaceted interplay among these variables, offering invaluable insights into the determinants of cognitive function within our cohort. RESULTS: After meticulous adjustment for various covariates, our linear regression analysis unveiled a noteworthy finding: 3,7-dimethylxanthine demonstrated a significant positive correlation with cognitive function (p < 0.05). Importantly, within the BKMR model employed, 3,7-dimethylxanthine emerged as the most influential factor within the compound, with posterior inclusion probabilities of 0.995 and 0.939. Furthermore, our single-exposure effect model confirmed its presence at the 25th, 50th, and 75th percentile concentrations of other components within the compound. Interestingly, bivariate concentration curves indicated no interaction within the compound, underscoring the prominent impact of 3,7-dimethylxanthine on cognitive function. Subsequently, through a test of Restricted Cubic Splines (RCS), we revealed a non-linear relationship between ALT and cognitive function at the 10th, 50th, and 90th percentiles (p < 0.05), indicating a heightened risk of diminished cognitive function in the low ALT group. Employing structural equation modeling, we meticulously examined the mediating role of ALT in relation to 3,7-dimethylxanthine and cognitive function. However, our study results did not yield significant evidence of a mediating effect. This comprehensive analysis elucidates the intricate interplay between these variables, unveiling the subtle mechanisms governing cognitive function. CONCLUSIONS: In this study, a noteworthy positive correlation was observed between 3,7-dimethylxanthine and cognitive function. Additionally, a non-linear relationship was identified between ALT and cognitive function, with lower levels of ALT associated with a decline in cognitive function. The RCS trend suggested that higher levels of ALT may similarly lead to diminished cognitive performance. However, in our pursuit to ascertain potential mediation, we regrettably found no significant evidence supporting mediation among these factors involving ALT. This underscores the need for more comprehensive investigations and expanded clinical explorations into the intricate associations among these three pivotal elements.

Association of the interleukin-10 gene polymorphism (-1082A/G) with systemic lupus erythematosus: a meta-analysis.

OBJECTIVE: The interleukin-10 (IL-10) gene polymorphism (-1082A/G) has been shown to be associated with systemic lupus erythematosus (SLE), but findings are not consistent across studies. The aim of our meta-analysis was to assess the association between the -1082A/G polymorphism in the IL-10 gene and SLE. METHODS: We searched all publications on the association between the IL-10 (-1082A/G) polymorphism and SLE in PubMed, Elsevier Science Direct, Chinese Biomedical Literature Database (CBM), Chinese National Knowledge Infrastructure (CNKI) and Wanfang (Chinese). Meta-analysis was conducted using software Stata version 10.1. Meta-odds ratios (ORs) and 95% confidence intervals (CIs) based on fixed-/random-effects models depended on Cochran's Q-statistic and I(2) values. RESULTS: A total of 17 studies with 2396 cases and 3653 controls were included in this meta-analysis. Meta-analysis was performed for genotypes GG versus AA, GG + AG versus AA, GG versus AG + AA, and G allele versus A allele. Significant differences were found in genotype distribution between SLE and normal controls in whole-population GG versus AA (OR = 1.428, 95% CI = 1.006-2.208). Similar results were detected in the dominant genetics effect of the G allele (OR = 1.202, 95% CI = 1.030-1.403). No significant association was found in allele distribution in whole-population G versus A (OR = 1.125, 95% CI = 0.998-1.269). In subgroup analysis by ethnicity, significant association was found when GG + AG versus AA was performed in a European population (OR = 1.240, 95% CI = 1.022-1.503) and GG versus AG + AA was performed in an Asian population (OR = 3.596, 95% CI = 1.389-9.311). Significant association was found between genotype distribution in Asians (OR = 4.491, 95% CI = 1.552-13.000). Publication year was detected as the source of heterogeneity. In the stratified analysis by publication year, the pooled OR was 1.049 (95% CI = 0.940-1.171; P (heterogeneity) = 0.431; I(2) ( )= 0.4%) in subgroup 1 (publication years 1999-2004). No significant association was found between the IL-10 (-1082 G) allele and SLE in subgroup 1 (Z = 0.85, p = 0.431). In subgroup 2 (publication years 2005-2011), the pooled OR was 1.327 (95% CI = 1.125-1.565; P (heterogeneity) = 0.143; I(2) ( )= 35.8%). Significant association was found between the IL-10 (-1082 G) allele and SLE (Z = 3.36, p = 0.001). CONCLUSIONS: This meta-analysis demonstrates the association between the IL-10 (-1082A/G) polymorphism and SLE. However, further studies are needed for a definitive conclusion.

A nomogram predicting the outcome of gallbladder cancer patients with different target organ metastases.

OBJECTIVE: Gallbladder cancer (GBC) is a highly aggressive malignancy that is associated with a high mortality rate globally. Unfortunately, distant metastases are often detected at the time of diagnosis. Therefore, we investigated the survival outcomes of gallbladder cancer patients with different metastases targeting organs, analyzed their prognosis, and explored their hidden clinical value. PATIENTS AND METHODS: Through data screening, a total of 398 patients with GBC with different target organ metastases were analyzed retrospectively, including patients with solitary bone metastasis, solitary liver metastasis, solitary lung metastasis, and multiple organ metastases. The survival results of different variables were plotted as Kaplan-Meier survival curves. Univariate and multivariate Cox regression models were used to screen study variables and identify independent prognostic factors. Finally, a nomogram was established to systematically evaluate the prognosis of patients with multiple organ metastasis. RESULTS: In the patient cohort, thirteen (3.3%) had solitary bone metastasis, 290 (72.9%) had solitary liver metastasis, 22 (5.5%) had solitary lung metastasis, and 73 (18.3%) had multiple organ metastases (including liver, lung, bone and brain metastases). Multivariate Cox analysis showed that the overall survival (OS) of patients with solitary lung metastasis was significantly better than that of patients with other organ metastasis (p = 0.038), while the difference in tumor cancer-specific survival (CSS) of this factor was not statistically significant (p > 0.05). Surgery and chemotherapy were independent prognostic protective factors for OS and CSS. The OS-related models exhibited a C-index of 0.74 (95% CI: 0.71-0.77), while the CSS-related models showed a slightly lower C-index of 0.73 (0.70-0.76). Both the OS- and CSS-related clinical prediction models had good accuracy. CONCLUSIONS: This study shows that different target organ metastases may affect the OS of patients with distant metastatic GBC. Patients receiving palliative surgery, primary site resection, radical surgery, and chemotherapy have significant survival benefits in terms of OS and CSS.

Anatomical characteristics and significance of the metopism and Wormian bones in dry adult-Chinese skulls.

BACKGROUND: This study aimed to investigate the incidence, topographical distribution, morphology, and interrelationship of the metopism and Wormian bones (WBs) in dry adult-Chinese skulls. MATERIALS AND METHODS: In this study, 285 dried adult-Chinese skull specimens from the Department of Anatomy at the Southern Medical University were examined. The incidence of different types of metopism and WBs were recorded. The length of the metopic suture was measured using a flexible ruler. Additionally, the lengths and widths of the WBs were measured using a vernier calliper. RESULTS: The incidence of metopism and WBs in Chinese adults were estimated at 10.18% (29/285) and 63.86% (182/285), respectively. The metopism always accompanied WBs (26/29, 89.66%), but the WBs did not necessarily accompany metopism (26/182, 14.29%). The locations of the WBs in the order of decreasing incidence were the lambdoid suture (78.57%, 143/182), pterion (34.62%, 63/182), asterion (12.09%, 22/182), lambda (8.24%, 15/182), sagittal suture (4.95%, 9/182), and Inca bone (3.85%, 7/182). These locations differed in topographical distribution and morphological patterns. CONCLUSIONS: Chinese adults differ in incidence of metopism and WBs from adults of other races, indicating racial differences. The characteristics of WBs vary depending on the cranial site of occurrence. The metopism always accompanies WBs, but the WBs do not necessarily accompany metopism.

Early strategy vs. late initiation of renal replacement therapy in adult patients with acute kidney injury: an updated systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: The optimal time to start renal replacement therapy (RRT) for acute kidney injury (AKI) remains controversial. We aim to compare the effects of early vs. delayed RRT initiation on clinical outcomes in adult patients with AKI. MATERIALS AND METHODS: PubMed, Embase, Cochrane Library, Web of Science, Chinese Biomedical Literature Database, ClinicalTrials.gov, and the International Clinical Trial registry platform were systematically searched from inception to 7 August 2022. The review included randomized clinical trials (RCTs) comparing early and delayed initiation of RRT in AKI patients. The selected primary outcomes were short-term and long-term mortality. Secondary outcomes included RRT dependency, intensive care unit (ICU) length of stay, hospital length of stay, mechanical ventilator-free days, vasoactive agents-free days, RRT-free days, and adverse events. RESULTS: Overall, 15 RCTs, including 5,625 patients, were analyzed. Early RRT showed no survival benefit when compared to the delayed therapy (28-or 30-day mortality: RR, 1.01, 95% CI: 0.94-1.08, p = 0.87; 60-day mortality: RR, 0.87, 95% CI: 0.71-1.06, p = 0.16; 90-day mortality: RR, 1.00, 95% CI: 0.88-1.13, p = 0.97; in-hospital mortality: RR, 1.05, 95% CI: 0.88-1.24, p = 0.58; ICU mortality: RR, 1.00, 95% CI: 0.91-1.10, p = 0.98). The delayed RRT did not lead to a higher risk of RRT dependency, ICU, or hospital length of stay than the early RRT. Similarly, early initiation of RRT did not lead to longer ventilator-free, vasoactive agent-free, and RRT-free days. However, early RRT initiation was associated with more adverse events. CONCLUSIONS: Our study suggested that early RRT initiation was not associated with survival benefits or better clinical outcomes and increased the risk of RRT-associated adverse events. Current evidence does not support the use of early RRT for AKI patients without urgent indications.

Comparison of laparoscopic common bile duct exploration and endoscopic retrograde cholangiopancreatography combined with laparoscopic cholecystectomy for patients with gallbladder and common bile duct stones a meta-analysis of randomized controlled trials.

OBJECTIVE: This study aimed to compare the efficacy and safety of laparoscopic common bile duct exploration (LCBDE) and endoscopic retrograde cholangiopancreatography (ERCP) combined with laparoscopic cholecystectomy (LC) to determine which one provides a better outcome for patients with gallbladder and common bile duct stones. MATERIALS AND METHODS: An electronic literature search was undertaken using Embase, Medline, PubMed, and Cochrane Library databases up to April 2022. For quality assessment of included studies, randomized controlled trials (RCTs) were assessed by utilizing the Jadad scale. The primary outcome includes surgical success rate, retained stone rate, stone clearance rate, major morbidity, and mortality. The second outcome includes conversion to open surgery rate, postoperative pancreatitis, bile leakage, cholangitis, hemorrhage, pneumonia, and surgical-site infection. RESULTS: 14 randomized controlled trials with 2,181 patients were included. No significant difference was seen between the two groups in terms of surgical success, stone clearance, retained stones, operation time, and total morbidity. LC-LCBDE had higher rate of bile leakage [relative risk (RR): 4.52; 95% confidence interval (CI): 2.19-9.31] and lower rate of postoperative pancreatitis (RR: 0.25; 95% CI: 0.13-0.46), cholangitis (RR: 0.17; 95% CI: 0.05-0.67), and hemorrhage (RR: 0.18; 95% CI: 0.07-0.42). CONCLUSIONS: Both LC+LCBDE and LC+ERCP are safe, effective, and minimal-invasive treatments for concomitant gallbladder and CBD stones. LC-LCBDE was associated with comparable effects compared with LC+ERCP in terms of surgical success rate, stone clearance rate, retained stones rate, operation time, and total morbidity. At the same time, LC-LCBDE had a higher rate of bile leakage and a lower rate of postoperative pancreatitis, cholangitis, and hemorrhage.

Emotional responses of piglets under long-term exposure to negative and positive auditory stimuli.

The stress caused by sound is inevitable. The stress caused by noise and the positive effects of music can affect the endocrine of animals and their welfare. In this study, a total of 72 hybrid piglets (Large White × Duroc × Min pig) were randomly divided into 3 groups, including music (Mozart K.448, 60-70 dB), noise (recorded mechanical noise, 80-85 dB), and control (natural background sound, <40 dB) groups. S-IgA (secretory immunoglobulin A), IL-6 (interleukin-6), IL-8 (interleukin-8), and positive emotion-related behaviors were used as indicators to discuss whether noise induced stress and inflammation in piglets or whether music could have positive effects. Six hours of auditory exposure were given daily (10:00-16:00), which lasted for 56 days. Behavioral responses of the piglets were observed, and the concentrations of salivary S-IgA and serum IL-6 and IL-8 were measured. The results showed that the concentration of S-IgA increased in the noise and control groups on the 57th day (P < 0.05); S-IgA concentration in the music group was unchanged after long-term music exposure. The concentrations of IL-6 and IL-8 showed that long-term noise exposure might lead to stress and inflammation in piglets. Tail-wagging and play behaviors of the piglets in the music group were significantly greater than those in the noise and control groups, which implied that long-term music exposure improved the emotional state of the piglets in a restricted and barren environment.

A pilot randomized controlled trial of dual-plasmid HBV DNA vaccine mediated by in vivo electroporation in chronic hepatitis B patients under lamivudine chemotherapy.

A DNA vaccine against the hepatitis B virus (HBV), enhanced by IL-2/IFN-γ fusion protein expression from a plasmid construct and mediated by in vivo electroporation, was evaluated in a total of 39 HBeAg-positive patients with chronic hepatitis B (CHB). The six of 39 patients with a serum alanine aminotransferase (ALT) value of 1-2 times upper limit of normal (ULN) were assigned to the open-label arm (Group01) receiving vaccine monotherapy; the remaining 33 patients with an ALT of more than two times ULN were enroled to the randomized and controlled arm (Group02) receiving lamivudine (LAM) monotherapy (LAM+placebo) or combined therapy (LAM+DNA vaccine) in 1:2 ratio. In Group01, a significant elevation of HBV-specific IFN-γ-secreting T-cell counts in comparison with baseline was observed. In Group02, the proportion of patients with HBV DNA suppression was higher with LAM+DNA vaccine than with LAM monotherapy at each visit time point after the final injection of DNA vaccine at week 36, revealing a significant difference between the two groups (P = 0.03) at week 60. The incidence of dual-site mutations of rtM204/I/S+rtL180M was significantly lower (P = 0.03) with an identified lower virological breakthrough (VBT) rate (P = 0.03) in patients receiving LAM+DNA vaccine than LAM monotherapy, accompanied with a significant higher positive T-cell response rate in patients receiving LAM+DNA vaccine (P = 0.03). In conclusion, this study provides evidence that HBV DNA vaccination is safe and immunologically effective, and that the HBV-specific T-cell responses induced by DNA vaccination under LAM chemotherapy showed a correlation with the suppression of viral replication in patients with CHB.

Anatomical observation and significance of the parietal foramen in Chinese adults.

BACKGROUND: This study aimed to investigate the incidence, number, diameter, and relative location of the parietal foramen (PF) as well as communication of intracranial and extracranial orifices and their direction, and sagittal suture morphology and length. MATERIALS AND METHODS: A total of 280 dry Chinese adult skull specimens from the Department of Anatomy, Southern Medical University, were observed and measured. The occurrence rate and quantity of the PF near the sagittal suture were recorded. The aperture of the PF, the vertical distance between PF and sagittal suture, and the linear distance between PF and lambda were measured using a Vernier calliper. The length of the sagittal suture was measured by a flexible ruler; the direction and communication of intracranial and extracranial orifices were detected using a probe. RESULTS: The total incidence of the PF was 82.86%, slightly higher on the right side than on the left side. The single-foramen type was the most prevalent. The mean diameter of the PF on the left and right sides were 1.02 ± 0.72 mm and 1.07 ± 0.67 mm, respectively, and the diameter of the PF on the sagittal suture was 1.77 ± 0.44 mm. The mean vertical distance between the PF and the sagittal suture was 5.90 ± 2.78 mm and 5.85 ± 2.75 mm on the left and right sides, respectively. The shape of the sagittal suture in the PF area was primarily dentate shaped, with an average arc length of χ = 124.36 ± 7.76 mm, of which the majority were completely healed type. The intracranial and extracranial communication was 39.97%, and the majority of the PF were anteromedial direction. CONCLUSIONS: The current study provided an anatomical basis for imaging diagnosis and neurosurgery by investigating the incidence, diameter, and relative location of the PF and intracranial and extracranial communication and direction.

Complement inhibition enables renal allograft accommodation and long-term engraftment in presensitized nonhuman primates.

Protection against humoral injury mediated by donor-specific antibodies (DSA), also known as accommodation, may allow for long-term allograft survival in presensitized recipients. In the present study, we determined the role of complement in renal allograft accommodation in donor skin-presensitized nonhuman primates under conventional immunosuppression. Donor skin allografts were transplanted to presensitized recipients 14 days prior to renal transplantation. Renal allografts not receiving any immunosuppressive treatment developed accelerated rejection with predominantly humoral injury, which was not prevented using conventional cyclosporine (CsA) triple therapy. Inhibition of complement activation with the Yunnan-cobra venom factor (Y-CVF) successfully prevented accelerated antibody-mediated rejection and resulted in successful accommodation and long-term renal allograft survival in most presensitized recipients. Accommodation in this model was associated with the prevention of the early antibody responses induced against donor antigens by complement inhibition. Some antiapoptotic proteins and complement regulatory proteins, including Bcl-2, CD59, CD46 and clusterin, were upregulated in the surviving renal allografts. These results suggest that the complement inhibition-based strategy may be valuable alternative in future clinical cross-match positive or ABO-incompatible transplantation.

MiR-150 suppressed cell viability, invasion and EMT via HMGA2 in oral squamous cell carcinoma.

OBJECTIVE: Oral squamous cell carcinoma (OSCC) accounts for 90% of head and neck cancers, and its 5-year overall survival is very poor. MiR-150 is usually downregulated and acts as tumor suppressor in multiple cancers. The aim of our study is to explore the functions of miR-150 in OSCC. PATIENTS AND METHODS: Expressions of miR-150 and HMGA2 mRNA in OSCC tissues and cells were analyzed by qRT-PCR. Methyl Thiazolyl Tetrazolium (MTT) and transwell assays were conducted to assess the cell viability and invasive abilities. Western blot was conducted to assess the protein levels of epithelial-mesenchymal transition (EMT) markers. Luciferase reporter assay was carried out to verify miR-150 directly binding to HMGA2 in SCC25 cells. RESULTS: MiR-150 was low expressed and HMGA2 was highly expressed in OSCC tissues and cells. Downregulation of miR-150 or upregulation of HMGA2 predicted poor prognosis of OSCC patients. MiR-150 overexpression inhibited the abilities of viability, invasive and the EMT by targeting HMGA2 in OSCC cells. HMGA2 was a target gene of miR-150 and its expression was regulated by altering the expression of miR-150 in OSCC cells. HMGA2 reversed partial roles of miR-150 on cell viability and invasion in OSCC. CONCLUSIONS: MiR-150 impaired cell viability, invasion and EMT via binding to HMGA2 of OSCC. Our research demonstrates that miR-150 plays a critical role in the progression of OSCC. miR-150 might be a candidate molecular marker and a novel therapy target for OSCC patients.

LINC00958/miR-3174/PHF6 axis is responsible for triggering proliferation, migration and invasion of endometrial cancer.

OBJECTIVE: To reveal the role of LINC00958 in the progression of endometrial cancer (EC) and the underlying molecular mechanism. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was conducted to detect relative level of LINC00958 in EC specimens and cell lines. Its prognostic potential in EC was analyzed by Kaplan-Meier method. After in vitro knockdown of LINC00958, cell proliferative, migratory and invasive abilities in KLE and Ishikawa cells were evaluated by Cell Counting Kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU) and transwell assay. Dual-Luciferase reporter assay was carried out to identify the LINC00958/miR-3174/PHF6 axis, and their expression interaction was determined by Pearson correlation test. The role of miR-3174 in influencing LINC00958-induced phenotype changes of EC cells was determined through rescue experiments. RESULTS: LINC00958 was abnormally upregulated in EC specimens and cell lines, which was unfavorable to the prognosis of EC. Knockdown of LINC00958 reduced proliferative, migratory and invasive rates in KLE and Ishikawa cells. MiR-3174 shared a binding site in the 3'-untranslated region (3'-UTR) to that of LINC00958, which was lowly expressed in EC specimens and negatively linked to LINC00958 level. Overexpression of miR-3174 partially abolished the role of LINC00958 in accelerating the malignant phenotypes of EC cells. PHF6 was the downstream target of miR-3174 and it was upregulated in EC specimens. CONCLUSIONS: LINC00958 is upregulated in EC specimens, which is a prognostic factor of EC. It stimulates EC to proliferate, migrate and invade through the miR-3174/PHF6 axis.

Glycyrrhizin improves inflammation and apoptosis via suppressing HMGB1 and PI3K/mTOR pathway in lipopolysaccharide-induced acute liver injury.

OBJECTIVE: Acute liver injury (ALI) is mainly characterized by the symptom of metabolic disorders, homeostasis unbalance, and loss of liver function. There are no effective treatment methods at present stage except the liver transplantation. Effective treatment for early ALI is of great significance for the treatment of liver injury thereof. Glycyrrhizin (GL) is a promising inhibitor of the high-mobility group box-1 gene (HMGB1) which is expressed much higher in an inflammatory injury. However, it is not clear whether GL improves ALI via the inhibition of HMGB1. The present study is to probe the function and mechanism of glycyrrhizin on acute liver injury. MATERIALS AND METHODS: The expression of HMGB1 and inflammation in liver macrophages were analyzed. Lipopolysaccharide (LPS) was used in stimulating the macrophages to activate inflammatory response and recombined human HMGB1 was used to resist the function of GL to explore whether GL acted via the target of HMGB1. Then, LPS injection was utilized to induce ALI in mice, and then we evaluated GL treatment in ALI model. RESULTS: The results showed that the expressions of HMGB1 and inflammatory factors were markedly increased in LPS-activated liver macrophages. GL inhibited the progress of macrophages inflammation by restraining HMGB1, and the administration of GL could reverse the effects of LPS-induced ALI in mice. Moreover, PI3K/mTOR pathway was significantly suppressed by GL application. CONCLUSIONS: These results suggest that GL prevents inflammation in liver macrophages via inhibition of HMGB1. GL restrains inflammation and cell apoptosis by inhibiting HMGB1 via PI3K/mTOR signaling pathway in ALI. GL may become a novel drug for the therapy of ALI in the future.