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Objectives We performed a meta-analysis of studies examining the computed tomography (CT) features of adnexal torsion (AT). Methods We searched PubMed, Embase, Web of Science, and the Cochrane Library for studies involving the proportion of CT features in patients with AT and that used surgery as the reference test. Study quality was assessed using the Newcastle-Ottawa scale and the Agency for Healthcare Research and Quality tool. Results Twelve articles involving 483 patients were included. The pooled proportion of right-sided adnexal lesion was 54% (95% confidence interval [CI]: 49%–56%). The pooled proportions of the ovarian lesion histopathological types were: benign germ cell tumors, 33% (95% CI: 28%–37%); benign cystic lesions, 26% (95% CI: 21%–30%); benign epithelial neoplasms, 24% (95% CI: 20%–29%); sex cord-stromal tumors, 4% (95% CI: 2%–6%); borderline neoplasms, 3% (95% CI: 1%–6%); and hemorrhagic cysts, 2% (95% CI: 0%–3%). The pooled proportions of CT features were: Adnexal enlargement, 99% (95% CI: 98%–99%); adnexal with mass, 98% (95% CI: 97%–100%); twisted pedicle, 81% (95% CI: 78%–83%); mass with thickened wall, 77% (95% CI: 73%–81%); tubal thickening, 73% (95% CI: 68%–77%); abnormal location of adnexa, 69% (95% CI: 63%–75%), pelvic ascites, 43% (95% CI: 38%–49%); pelvic fat infiltration, 41% (95% CI: 34%–48%); uterine deviation, 37% (95% CI: 31%–42%); and lack of enhancement, 20% (95% CI: 14%–25%). Conclusion Adnexal enlargement, adnexal mass, and twisted pedicle may be the most important CT features for diagnosing AT.

BackgroundGiant cell tumors of the mobile spine invasion of the adjacent vertebrae are an ignored imaging finding.MethodsNine patients with giant cell tumors of the mobile spine with invasion of the adjacent vertebrae confirmed by pathology were enrolled. Eight patients had pure giant cell tumors (GCTs), while one patient also had an aneurysmal bone cyst. All patients underwent conventional computed tomography, three-dimensional reconstruction, and conventional magnetic resonance imaging, while seven patients also underwent post-contrast magnetic resonance imaging.ResultsAll patients showed GCTs of the mobile spine that arose from the vertebral body and extended to the vertebral arch. The tumors showed soft-tissue attenuation with no evidence of a mineralized matrix. Pathological fracture was seen in five patients. The margin of the original tumor showed partial sclerosis in four patients and involved an adjacent vertebral body with a sclerotic rim in two patients. The tumors showed a homogeneous and similar signal intensity to the normal spinal cord on T1WI (T1-weighted image) in five patients. The cystic area of the tumors was hyperintense on T2WI in the remaining four patients, while one patient showed hemorrhage that was hyperintense on T1WI. The solid components of the GCTs show marked enhancement in all cases, while the cystic area of the tumors was observed without enhancement on contrast-enhanced images in four patients. Bone destruction of the adjacent vertebral body showed a homogeneous signal on T1WI and T2WI and marked enhancement on contrast-enhanced images.ConclusionsGiant cell tumors of the mobile spine with invasion into adjacent vertebrae are an unusual imaging finding. Radiologists should be familiar with this imaging characteristic.

Cerebral venous sinus thrombosis (CVST) and subdural hematoma (SDH) are extremely rare in patients with systemic lupus erythematosus (SLE), and when conditions are severe, it can endanger the life of the patients. We report a case of a 44-year-old woman who was admitted to our hospital due to multiple paroxysmal headaches, dizziness, and seizures for 20 days. In the past 2 years, she had severe thrombocytopenia. Her brain computed tomography (CT) and magnetic resonance venography (MRV) demonstrated CVST and a SDH near the right parietal occipital lobe and left temporal parietal lobe. After admission, she was eventually diagnosed with SLE based on the seizures, thrombocytopenia, positive antinuclear antibodies, and anti-ds DNA antibodies. After treatment, the patient's headaches and symptoms completely disappeared, and the myodynamia of the left limbs improved to grade 4. Her platelet count rose to 199×109 /L. The second brain MRV and MRI demonstrated partial reopening of the right superior sagittal sinus, transverse sinus, and sigmoid sinus, and the improvement of bilaterally SDH, which revealed that the treatment with an anticoagulant, pulse methylprednisolone therapy, and intravenous gamma globulin was effective. We summarized possible mechanisms in this case, which can improve our understanding of CVST and SDH in SLE. And we consider that such patients should be treated as soon as possible, and the outcome can be good.

BACKGROUND The most common causes of outlet obstructive constipation (OOC) are rectocele and internal rectal prolapse. The surgical methods for OOC are diverse and difficult, and the postoperative complications and recurrence rate are high, which results in both physical and mental pain in patients. With the continuous deepening of the surgeon’s concept of minimally invasive surgery and continuous in-depth research on the mechanism of OOC, the treatment concepts and surgical methods are continuously improved. AIM To determine the efficacy of the TST36 stapler in the treatment of rectocele combined with internal rectal prolapse. METHODS From January 2017 to July 2019, 49 female patients with rectocele and internal rectal prolapse who met the inclusion criteria were selected for treatment using the TST36 stapler. RESULTS Forty-five patients were cured, 4 patients improved, and the cure rate was 92%. The postoperative obstructed defecation syndrome score, the defecation frequency score, time/straining intensity, and sensation of incomplete evacuation were significantly decreased compared with these parameters before treatment, and the differences were statistically significant (P < 0.05). The postoperative anal canal resting pressure and maximum squeeze pressure in patients decreased compared with before treatment, and the differences were statistically significant (P < 0.05). The initial and maximum defecation thresholds after surgery were significantly lower than those before treatment, and the differences were statistically significant (P < 0.05). The postoperative ratings of rectocele, resting phase, and defecation phase in these patients were significantly decreased compared with those before treatment, and the differences were statistically significant (P < 0.05). CONCLUSION The TST36 stapler is safe and effective in treating rectocele combined with internal rectal prolapse and is worth promoting in clinical work.

Sulcus vocalis is an indentation parallel to the edge of vocal fold, which may extend into the cover and ligament layer of the vocal fold or deeper. The effects of sulcus vocalis depth d on phonation and the vocal cord vibrations are investigated in this study. The three-dimensional laryngeal models were established for healthy vocal folds (0 mm) and different types of sulcus vocalis with the typical depth of 1 mm, 2 mm, and 3 mm. These models with fluid-structure interaction (FSI) are computed numerically by sequential coupling method, which includes an immersed boundary method (IBM) for modelling the glottal airflow, a finite-element method (FEM) for modelling vocal fold tissue. The results show that a deeper sulcus vocalis in the cover layer decreases the vibrating frequency of vocal folds and expands the prephonatory glottal half-width which increases the phonation threshold pressure. The larger sulcus vocalis depth makes vocal folds difficult to vibrate and phonate. The effects of sulcus vocalis depth suggest that the feature such as phonation threshold pressure could assist in the detection of healthy vocal folds and different types of sulcus vocalis.

Objective To investigate the dosimetric impact of different collimator angle optimization methods in intensity‐modulated radiotherapy of gastric cancer. Methods A total of 10 gastric cases were retrospectively selected in this study. Three sets of plans were generated with different collimator angle optimization: setting the collimator angle to 0° (CL0), applying Eclipse automatic collimator angle optimization (CLA), and setting the collimator angle corresponding to the minimum X‐jaw gap (CLX). Different dosimetric metrics were applied in comparison of the target volume and normal tissues. Delivery efficiency was accessed in terms of control points, split fields, monitor units, and treatment time. All plans were verified using the 2‐D array MatriXX, and the γ‐index analysis was carried out by using different criteria. Results There was no significant difference in dosimetric comparison of planning target volume and organs at risk. Compared with CL0, Both CLA and CLX can significantly reduce control points, split fields, and monitor units, except that CLA increased treatment time. For dose verification, the γ passing rate showed a tendency of CLx > CLA > CL0. Conclusion For intensity‐modulated radiotherapy for gastric cancer, CLA and CLX can obtain comparable dosimetry distribution in respect to CL0. However, CLX can significantly increase the dose delivery efficiency and verification passing rates. It was suggested that CLx was beneficial in intensity‐modulated radiotherapy for gastric cancer.

Iron homeostasis disturbance has been implicated in Alzheimer’s disease (AD), and excess iron exacerbates oxidative damage and cognitive defects. Ferroptosis is a nonapoptotic form of cell death dependent upon intracellular iron. However, the involvement of ferroptosis in the pathogenesis of AD remains elusive. Here, we report that ferroportin1 (Fpn), the only identified mammalian nonheme iron exporter, was downregulated in the brains of APPswe/PS1dE9 mice as an Alzheimer’s mouse model and Alzheimer’s patients. Genetic deletion of Fpn in principal neurons of the neocortex and hippocampus by breeding Fpnfl/fl mice with NEX-Cre mice led to AD-like hippocampal atrophy and memory deficits. Interestingly, the canonical morphological and molecular characteristics of ferroptosis were observed in both Fpnfl/fl/NEXcre and AD mice. Gene set enrichment analysis (GSEA) of ferroptosis-related RNA-seq data showed that the differentially expressed genes were highly enriched in gene sets associated with AD. Furthermore, administration of specific inhibitors of ferroptosis effectively reduced the neuronal death and memory impairments induced by Aβ aggregation in vitro and in vivo. In addition, restoring Fpn ameliorated ferroptosis and memory impairment in APPswe/PS1dE9 mice. Our study demonstrates the critical role of Fpn and ferroptosis in the progression of AD, thus provides promising therapeutic approaches for this disease.

Objective To evaluate the effect of newly designed arthroscopic reconstruction of posterior cruciate ligament (PCL) using tibial tendon bolt. Methods The effects of embedded tendon pin were observed by X‐ray of knee joint. From October 2010 to September 2015, 51 PCL injury patients who met the inclusion criteria were enrolled in this retrospective study. The arthroscopically assisted reconstruction of the PCL with tibial tendon bolt was performed on all patients. Visual Analog Scale (VAS) pain score, Tegner activity score, Lysholm score, International Knee Documentation Committee (IKDC) assessment, posterior drawer test (PDT), and KT‐1000 activity score were evaluated preoperatively and at 1‐year postoperative and 3‐year postoperative. Results The preoperative, 1‐year postoperative, and 3‐year postoperative IKDC score (15.8% ± 14.8%, 89.6% ± 5.8%, and 86.8% ± 5.4%), Lysholm score (17.4 ± 10.7, 91.2 ± 2.8, and 88.2 ± 3.1), VAS score (5.8 ± 1.2, 1.3 ± 0.5, and 0.6 ± 0.5), Tegner activity score (1.2 ± 0.8, 8.1 ± 0.8, and 7.4 ± 0.8), and KT‐1000 score (15.6 ± 3.6, 4.5 ± 2.4, and 5.4 ± 1.8) were obtained. There were significant differences in these outcomes among preoperative, 1‐year postoperative, and 3‐year postoperative (all P, The application of tendon pin fixed by tibial inlay “8” shape tibial tunnel to reconstruct PCL was an effective, simple and safe surgical procedure for PCL injury.

Aims We have previously reported that nano-selenium quantum dots (SeQDs) prevented endothelial dysfunction in atherosclerosis. This study is to investigate whether amorphous SeQDs (A-SeQDs) increase endogenous tetrahydrobiopterin biosynthesis to alleviate pulmonary arterial hypertension. Results Both A-SeQDs and C-SeQDs were stable under physiological conditions, while the size of A-SeQDs was smaller than C-SeQDs by high resolution-transmission electron microscopy scanning. In monocrotaline-injected mice, oral administration of A-SeQDs was more effective to decrease pulmonary arterial pressure, compared to C-SeQDs and organic selenium. Further, A-SeQDs increased both nitric oxide productions and intracellular BH4 levels, upregulated dihydrofolate reductase activity in lungs, and improved pulmonary arterial remodeling. Gene deletion of dihydrofolate reductase abolished these effects produced by A-SeQDs in mice. Finally, the blood levels of tetrahydrobiopterin and selenium were decreased in patients with pulmonary arterial hypertension. Conclusion A-SeQDs increase intracellular tetrahydrobiopterin to prevent pulmonary arterial hypertension through recoupling endothelial nitric oxide synthase. Methods Two polymorphs of SeQDs and A-SeQDs, and a crystalline form of SeQDs (C-SeQDs) were prepared through self-redox decomposition of selenosulfate precursor. Mice were injected with monocrotaline to induce pulmonary arterial hypertension in vivo. Pulmonary arterial pressure was measured.

Treatment of acute pancreatitis (AP) and chronic pancreatitis (CP) remains problematic due to a lack of knowledge about disease-specific regulatory targets and mechanisms. The purpose of this study was to screen proteins related to endoplasmic reticulum (ER) stress and apoptosis pathways that may play a role in pancreatitis. Human pancreatic tissues including AP, CP, and healthy volunteers were collected during surgery. Humanized PRSS1 (protease serine 1) transgenic (PRSS1Tg) mice were constructed and treated with caerulein to mimic the development of human AP and CP. Potential regulatory proteins in pancreatitis were identified by proteomic screen using pancreatic tissues of PRSS1Tg AP mice. Adenoviral shRNA-mediated knockdown of identified proteins, followed by functional assays was performed to validate their roles. Functional analyses included transmission electron microscopy for ultrastructural analysis; qRT-PCR, western blotting, co-immunoprecipitation, immunohistochemistry, and immunofluorescence for assessment of gene or protein expression, and TUNEL assays for assessment of acinar cell apoptosis. Humanized PRSS1Tg mice could mimic the development of human pancreatic inflammatory diseases. EMC6 and APAF1 were identified as potential regulatory molecules in AP and CP models by proteomic analysis. Both EMC6 and APAF1 regulated apoptosis and inflammatory injury in pancreatic inflammatory diseases. Moreover, APAF1 was regulated by EMC6, induced apoptosis to injure acinar cells and promoted inflammation. In the progression of pancreatitis, EMC6 was activated and then upregulated APAF1 to induce acinar cell apoptosis and inflammatory injury. These findings suggest that EMC6 may be a new therapeutic target for the treatment of pancreatic inflammatory diseases.

Sepsis remains a major global concern and is associated with high mortality and morbidity despite improvements in its management. Markers currently in use have shortcomings such as a lack of specificity and failures in the early detection of sepsis. In this study, we aimed to identify key genes involved in the molecular mechanisms of sepsis and search for potential new biomarkers and treatment targets for sepsis using bioinformatics analyses. Three datasets (GSE95233, GSE57065, and GSE28750) associated with sepsis were downloaded from the public functional genomics data repository Gene Expression Omnibus. Differentially expressed genes (DEGs) were identified using R packages (Affy and limma). Functional enrichment of the DEGs was analyzed with the DAVID database. Protein-protein interaction networks were derived using the STRING database and visualized using Cytoscape software. Potential biomarker genes were analyzed using receiver operating characteristic (ROC) curves in the R package (pROC). The three datasets included 156 whole blood RNA samples from 89 sepsis patients and 67 healthy controls. Between the two groups, 568 DEGs were identified, among which 315 were upregulated and 253 were downregulated in the septic group. These genes were enriched for pathways mainly involved in the innate immune response, T-cell biology, antigen presentation, and natural killer cell function. ROC analyses identified nine genes—LRG1, ELANE, TP53, LCK, TBX21, ZAP70, CD247, ITK, and FYN—as potential new biomarkers for sepsis. Real-time PCR confirmed that the expression of seven of these genes was in accordance with the microarray results. This study revealed imbalanced immune responses at the transcriptomic level during early sepsis and identified nine genes as potential biomarkers for sepsis.

BACKGROUND: Using standard vancomycin dosage in critically ill patients might lead to therapy failure and worse patient outcomes, augmented renal clearance (ARC) may be the leading risk factor. In this study, we comprehensively investigated the pharmacokinetics-pharmacodynamics (PK-PD) of vancomycin in critically ill patients with ARC, hoping to explore the precise and accurate dose adjustment method for vancomycin. METHODS: All critically ill patients tested for steady-state trough vancomycin serum concentrations during the recent 6 years in a tertiary level hospital were collected retrospectively and divided into ARC and non-ARC groups, respectively, according to creatinine clearance (CLcr). Serum vancomycin concentrations were measured by the fluorescence polarization immunoassay method. PK-PD parameters of vancomycin were recorded or calculated. The desired daily dose successful in achieving the lower target trough levels (10 mg/L) of vancomycin were investigated correspondingly. RESULTS: A total of 280 vancomycin concentrations were eligible for analysis. The ARC group (n=139) contained more male patients (64.7%) with average age and CLcr of 40 years old (P

Objective This study compared the dose verification results between plans created based on computed tomography (CT) scan and digital virtual phantom. Methods We retrospectively analyzed the treatment plan of 10 patients with head and neck cancer. CT scanned phantom and digital virtual phantom measured using Delta4 3‐D matrix were used to generate verification plans for each patient. The doses based on the effective measurement volume of the two phantoms were compared, and the verification results were analyzed using gamma index analysis. Results For the body, the minimum dose, the maximum dose, the average dose, and the total dose were 0.72 ± 0.46 cGy, 251.86 ± 49.83 cGy, 58.10 ± 10.93 cGy, and 154.67 ± 20.28 cGy, respectively, in the CT‐scan group, and 0.62 ± 0.36 cGy, 248.34 ± 48.59 cGy, 57.20 ± 10.77 cGy, and 151.57 ± 19.73 cGy, respectively in the Uniform group. The difference between the groups was significant (P 95%, but the Uniform group had a higher passing rate than the CT‐scan group. Conclusions Because the passing rate was higher in the Uniform group than in the CT‐scan group, it is recommended to use digital virtual phantom modules to generate verification plans in clinical practice.

Introduction Triterpene has attracted considerable interests because it exhibits anticancer effects. However, the effects of tripterine on hepatocellular carcinoma (HCC) are not well studied. In the current study, the mechanism of tripterine on HCC cells growth and metastasis was examined. Methods The inhibitory effect on the growth and aggressiveness in HCC cells was analyzed by Cell Counting Kit-8 (CCK-8), wound healing and Transwell assay. The levels of microRNA-532-5p (miR-532-5p) in HCC cells and tissues were measured using qRT-PCR. The expression of chemokine (C-X-C Motif) ligand 2 (CXCL2) was determined by Western blotting and immunohistochemistry (IHC). Luciferase reporter gene assay was used to validate the binding between miR-532-5p and CXCL2. The impact of tripterine on the growth and metastasis of HCC cells in vivo was analyzed using transplanted tumor model and experimental lung metastasis model, respectively. Results We found that tripterine inhibited HCC cells proliferation, migration ability and invasion. Under tripterine treatment, the level of miR-532-5p was strikingly raised, and overexpression of miR‑532-5p reduced cell viability and metastatic-related traits. In addition, we identified CXCL2 as a target of miR-532-5p in HCC. Rescue experiments indicated that overexpression of CXCL2 restored the migration and invasive capacity of HCC cells inhibited by miR-532-5p or tripterine treatment. Finally, the tumor growth and metastatic ability of HCC MHCC97H cell in vivo were also significantly restrained by tripterine. The expression of CXCL2 was distinctly decreased and miR-532-5p level was increased by tripterine in vivo. Conclusion In conclusion, tripterine inhibits the growth, migration ability and invasiveness of HCC cells through intervening miR-532-5p/CXCL2.

Objective The aim of this study was to investigate the changes of bile acids in the liver during hemorrhagic shock (HS) and their potential to attenuate liver injury via activation of SIRT1 (sirtuin 1)-FXR (farnesoid X receptor) signaling. Methods A Sprague-Dawley (SD) rat HS model was established, whereas HepG2 cells were hypoxically cultured to simulate HS in vitro. Liver bile acids (BA) were profiled with ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). FXR expression was detected by western blot and immunohistochemistry. The mRNA levels of SIRT1 and FXR were detected by polymerase chain reaction. Protein expression of SIRT1, FoxM1, NF-κB, acetyl-NF-κB, p53, and acetyl-p53 was analyzed by western blot. Hepatocyte apoptosis and proliferation were measured by TUNEL assay and Ki-67 staining, respectively. Serum and supernatant cytokines were analyzed using ELISA assays. Liver injury was also assessed. To investigate the possible mechanisms, SIRT1 agonist (SRT1720), SIRT1 inhibitor (EX527), and FXR inhibitor (Z-guggulsterone) were used. Results Tauroursodeoxycholic acid (TUDCA) in the liver decreased significantly after HS. SIRT1 and FXR expression was time-dependently downregulated by HS or hypoxia condition. TUDCA upregulated SIRT1-FXR activity, which inhibited expression and acetylation of NF-κB and p53 and increased FoxM1 expression, leading to decreased inflammatory response and apoptosis and increased proliferative capacity in hepatocytes, and attenuation of liver injury. EX527 pretreatment reversed the protective effect of TUDCA. Moreover, Z-guggulsterone supplementation decreased the protective effect of TUDCA in vitro. Conclusion TUDCA in the liver decreased during HS. TUDCA supplementation might attenuate HS-induced liver injury by upregulating SIRT1-FXR signaling.

Vocal cord diseases can cause irregular vibration of the vocal cords, resulting in abnormalities. Therefore, it is necessary to study abnormal vocal cords in a vocal cord model. Research that focus...

Background Aerobic vaginitis (AV) is a newly defined type of bacterial vaginitis, but its pathogenesis is not yet clear. Streptococcus anginosus appears as an emerging pathogen in recent case reports, and colonizes in vagina of patients with AV. In this study, we investigate the pathogenesis of S. anginosus in AV. Materials and methods (1) We collected 41 vaginal specimens from 21 healthy, fertile women with normal vaginal flora (NM), 10 with bacterial vaginosis (BV) and 10 with AV; their microbiome structure was analysed by 16S rRNA gene sequencing. (2) S. anginosus and vaginal epithelial cells were cocultured in vitro, and cytotoxicity was tested by an LDH kit. (3) The S. anginosus virulence gene sag was knocked out, and the cytotoxicity of the mutant in vaginal epithelial cells was tested. Results (1) The microbiome structure of AV was dramatically different from that of BV and NM. The predominant genera of the three groups were Streptococcus spp., Gardnerella spp. and Lactobacillus spp. Streptococcus spp. were significantly more abundant in AV than in BV (95% CI [0.1391, 0.8676], P

Thymic carcinoma (TC) is the most aggressive thymic epithelial neoplasm. TC patients with microsatellite instability, whole-genome doubling, or alternative tumor-specific antigens from gene fusion are most likely to benefit from immunotherapies. However, due to the rarity of this disease, how to prioritize the putative biomarkers and what constitutes an optimal treatment regimen remains largely unknown. Therefore, we integrated genomic and transcriptomic analyses from TC patients and revealed that frameshift indels in KMT2C and CYLD frequently produce neoantigens. Moreover, a median of 3 fusion-derived neoantigens was predicted across affected patients, especially the CATSPERB-TC2N neoantigens that were recurrently predicted in TC patients. Lastly, potentially actionable alterations with early levels of evidence were uncovered and could be used for designing clinical trials. In summary, this study shed light on our understanding of tumorigenesis and presented new avenues for molecular characterization and immunotherapy in TC.

Objectives: The present study explored the clinical characteristics and prognostic factors of epilepsy in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS).Methods: Thirty-four MELAS patients were included in the present study. They were diagnosed by clinical characteristics, genetic testing, muscle biopsy, and retrospective analysis of other clinical data. The patients were divided into three groups according to the effects of treatment after at least 2 years of follow-up.Results: Epilepsy was more common in male MELAS patients than in females (20/14). The age of onset ranged from 0.5 to 57 years, with an average of 22.6 years. Patients with epilepsy and MELAS had various forms of seizures. Focal seizures were the most common type affecting 58.82% of patients, and some patients had multiple types of seizures. The abnormal EEG waves were mainly concentrated in the occipital (69.57%), frontal (65.22%) and temporal lobes (47.83%). Overall, the prognosis of patients with epilepsy and MELAS was poor. Poor prognosis was associated with brain atrophy (P = 0.026), status epilepticus (P < 0.001), and use of anti-seizure medications with high mitochondrial toxicity (P = 0.015).Interpretation: Avoiding the application of anti-seizure medications with high mitochondrial toxicity, controlling seizures more actively and effectively, and delaying the occurrence and progression of brain atrophy as much as possible are particularly important to improve the prognosis of patients with MELAS and epilepsy.

Background The incidence of Candida bloodstream infections (BSIs), has increased over time. In this study, we aimed to describe the current epidemiology of Candida BSI in a large tertiary care hospital in Shanghai and to determine the risk factors of 28-day mortality and the impact of antifungal therapy on clinical outcomes. Methods All consecutive adult inpatients with Candida BSI at Ruijin Hospital between January 1, 2008, and December 31, 2018, were enrolled. Underlying diseases, clinical severity, species distribution, antifungal therapy, and their impact on the outcomes were analyzed. Results Among the 370 inpatients with 393 consecutive episodes of Candida BSI, the incidence of nosocomial Candida BSI was 0.39 episodes/1000 hospitalized patients. Of the 393 cases, 299 (76.1%) were treated with antifungal therapy (247 and 52 were treated with early appropriate and targeted antifungal therapy, respectively). The overall 28-day mortality rate was 28.5%, which was significantly lower in those who received early appropriate (25.5%) or targeted (23.1%) antifungal therapy than in those who did not (39.4%; P = 0.012 and P = 0.046, respectively). In multivariate Cox regression analysis, age, chronic renal failure, mechanical ventilation, and severe neutropenia were found to be independent risk factors of the 28-day mortality rate. Patients who received antifungal therapy had a lower mortality risk than did those who did not. Conclusions The incidence of Candida BSI has increased steadily in the past 11 years at our tertiary care hospital in Shanghai. Antifungal therapy influenced short-term survival, but no significant difference in mortality was observed between patients who received early appropriate and targeted antifungal therapy.

Purpose It has been reported that approximately 40% of ALI (acute lung injury) incidence resulted from sepsis. Paclitaxel, as a classic anti-cancer drug, plays an important role in the regulation of inflammation. However, we do not know whether it has a protective effect against CLP (cecal ligation and puncture)-induced septic ALI. Our study aims to illuminate the mitigative effects of paclitaxel on sepsis-induced ALI and its relevant mechanisms. Materials and methods The survival rates and organ injuries were used to evaluate the effects of paclitaxel on CLP mice. The levels of inflammatory cytokines were tested by ELISA. MUC1 siRNA pre-treatment was used to knockdown MUC1 expression in vitro. GO203 was used to inhibit the homodimerization of MUC1-C in vivo. The expression levels of MUC1, TLR 4 and p-NF-κB/p65 were detected by Western blot. Results Our results showed that paclitaxel improved the survival rates and ameliorated organ injuries especially lung injury in CLP-induced septic mice. These were accompanied by reduced inflammatory cytokines in sera and BALF (bronchoalveolar lavage fluid). We also found paclitaxel could attenuate TLR 4-NF-κB/p65 activation both in lung tissues of septic mice and LPS-stimulated lung type II epithelial cell line A549. At the upstream level, paclitaxel-upregulated expression levels of MUC1 in both in vivo and in vitro experiments. The inhibitory effects of paclitaxel on TLR 4-NF-κB/p65 activation were reversed in lung tissues of septic mice pre-treated with MUC1 inhibitor and in MUC1-knockdown A549 cells. Protection of paclitaxel on sepsis-induced ALI and decrease of inflammatory cytokines were also abolished by inhibition of MUC1. Conclusion Collectively, these results indicated paclitaxel could significantly alleviate acute lung injury in CLP-induced septic mice and LPS-stimulated lung type II epithelial cell line A549 by activating MUC1 and suppressing TLR-4/NF-κB pathway.

Sepsis is a syndrome characterized by systemic inflammatory response caused by infection or toxin, with high morbidity and mortality. Different infection microflora and environment have great influence on the occurrence, development and prognosis of sepsis, but individual genetic factors also play an extremely important role. It was reported that the polymorphisms of mannose-binding lectin 2 gene were closely relevant to the occurrence and development of sepsis, but the conclusions in different studies were inconsistent. Therefore, we performed this reviews on the relevance of mannose-binding lectin 2 gene polymorphisms and sepsis.

OBJECTIVE To evaluate the clinical significance of permanent 125 I prostate brachytherapy in patients with castration-resistant prostate cancer. METHODS A retrospective study of 45 patients with castration-resistant prostate cancer from the Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu, China was carried out. Patients were divided into two groups according to different treatments: 21 patients received endocrine therapy alone (control group), and 24 patients underwent brachytherapy combined with endocrine therapy (treatment group). Prostate-specific antigen progression-free survival, cancer-specific survival, overall survival and quality of life of the two groups were compared. RESULTS The median prostate-specific antigen progression-free survival and cancer-specific survival of the treatment group were 29 months (interquartile range 25-37 months) and 37 months (interquartile range 30-50 months), respectively. These were significantly longer than those of the control group (both P

Background No clinical study has investigated the use of ceftazidime-avibactam combination schemes with an in vitro non-susceptible antimicrobial that could be superior to ceftazidime-avibactam monotherapy against carbapenem-resistant Klebsiella pneumoniae. Methods We performed a retrospective cohort study at two tertiary hospitals in China for patients with carbapenem-resistant Klebsiella pneumoniae infection treated with ceftazidime-avibactam for at least 72 h. A Cox proportional hazards regression model was used to evaluate covariates that potentially affected 30-day mortality. Results Sixty-two patients were eligible for our study; 41 (66.1%) received ceftazidime-avibactam combination therapy and 21 (33.9%) received ceftazidime-avibactam monotherapy. The overall 30-day mortality was 33.9% (21 patients): 24.4% (10/41) and 47.6% (11/21), P = 0.028, in combination and monotherapy groups, respectively. Combination therapy was significantly associated with lower 30-day mortality (Hazard ratio, 0.167; 95% Confidence Interval, 0.060–0.465, P = 0.001). At the same time, a higher APACHE II score, use of vasoactive drugs and comorbidity of organ transplantation were considered factors that increased mortality. The propensity score showed no significant alterations with other variables after adding it to the final model. In the subgroup analysis, the protective effect was revealed when combined with carbapenems, tigecycline or fosfomycin were applied, and in the following subgroups of patients: with sepsis, with creatinine clearance > 50 mL/min, stayed in the intensive care unit ≤ 30 days or underwent mechanical ventilation. Conclusions Ceftazidime-avibactam combined with another in vitro non-susceptible antimicrobial, especially carbapenems, fosfomycin and tigecycline, could significantly decrease the 30-day mortality rate for critically ill patients with carbapenem-resistant Klebsiella pneumoniae infection. Further investigation should be carried out to confirm this conclusion and identify autofit antimicrobials in ceftazidime-avibactam combination schemes.

BACKGROUND: The prediction of severe acute pancreatitis (SAP) is the key to providing timely and targeted intensive care for acute pancreatitis (AP). The heart is one of multiple organs involved in the early stage of SAP, but the predictive ability of cardiac dysfunction for SAP remains elusive. We sought to determine if the serum levels of three cardiac indicators (CI) including N-terminal pro-brain natriuretic peptide (NT-proBNP), cardiac troponin I (cTNI), and creatine kinase myocardial band (CK-MB) at admission could predict the occurrence of SAP and the development of related organ failure (OF). METHODS: A retrospective, single-center cohort study was conducted on the files of patients presenting to the emergency intensive care unit and medical ward of a regional hospital in Shanghai. Patients diagnosed as having AP and who met the 2012 Atlanta guideline were admitted within 48 hours after disease onset. RESULTS: Of the 670 AP patients screened, 238 were enrolled into the study and divided into mild acute pancreatitis (MAP) (n=59), moderate severe acute pancreatitis (MSAP) (n=123), and SAP (n=56) groups. No significant difference was found in baseline age, gender, duration from disease onset to admission, comorbidity, or substance abuse. As the levels of three CIs were significantly higher in the SAP group than in the MAP and MSAP groups, the enrolled patients were regrouped into non-SAP and SAP groups for predictive evaluation. Multivariate analysis and nomogram modelling showed that CK-MB, but not cTNI or NT-proBNP predicted the occurrence of SAP [area under curve (AUC) =0.805, confidence interval (CI): 0.794–0.905]. Specifically, 89 patients with OF (Modified Marshall score ≥2) upon admission were selected and CK-MB was shown to predict (AUC =0.805, CI: 0.794–0.905) persistent OF (n=48, duration of OF >48 hours) compared to transient organ failure (TOF) (n=41, duration of OF

Background: There is no clinical study investigating if using CAZ-AVI combination schemes with an in vitro non-susceptible antimicrobial could be superior to CAZ-AVI monotherapy against CRKP clinically. Methods: We performed a retrospective, cohort study at two tertiary hospitals in China for patients with CRKP infection who treated by CAZ-AVI at least 72 hours. A Cox-proportional hazards regression model was set up to evaluate covariates which potentially affected 30-day mortality. Results: Sixty-two patients were eligible in our study, 41 (66.1%) received CZA-AVI combination therapy and 21 (33.9%) received CZA-AVI monotherapy. The overall 30-day mortality was 33.9% (21 patients): 24.4% (10/41) and 47.6% (11/21), P=0.028, in combination and monotherapy groups, respectively. Combination therapy was significantly associated with lower 30-day mortality (HR 0.167, 95%CI 0.060-0.465, P=0.001), while higher APACHE II score, use of vasoactive drug and comorbidity of organ transplantation were considered as factors on increasing mortality. The propensity score showed no significant alteration with other variables after adding it into the final model. In the subgroup analysis, the protective effect revealed when combination with carbapenems, tigecycline or fosfomycin were applied, and in the following subgroups of patients: with sepsis, with CrCl > 50 mL/min, stayed in ICU ≤30 days or underwent mechanical ventilation. Conclusions: CAZ-AVI combination with another in vitro non-susceptible antimicrobial, especially carbapenems, fosfomycin and tigecycline, could significantly decrease 30-day mortality rate for critically ill patients with CRKP infection. Further investigation should be carried out to confirm this conclusion and find out the autofit antimicrobials in CAZ-AVI combination schemes.

For patients with sepsis and septic shock, it remains controversial when to restrict fluid intake and achieve a negative fluid balance. The present study aimed to evaluate the effects of the fluid intake volume during the first 24 h as well as fluid balance for 7 days on the prognosis of sepsis or septic shock. A total of 337 patients diagnosed with sepsis or septic shock at Ruijin Hospital (Shanghai, China) were enrolled in the present retrospective study. Patients with a low fluid intake volume during the first 24 h (fluid intake, 28.1±10.6 ml/kg) had lower in-hospital mortality rates (18.0 vs. 27.3%, P=0.043) and a shorter duration of mechanical ventilation [0 (0-6) vs. 3 (0-11), P=0.025] than the high-fluid volume intake group (62.6±17.6 ml/kg). Furthermore, survivors exhibited a daily negative net fluid balance from the second day (48 h), whereas non-survivors had a daily positive net fluid balance for 7 days, where fluid balance volumes were significantly lower in survivors compared with those in non-survivors. Finally, binary logistic regression analysis was used to determine whether the mean daily fluid balance (P

To perform a comparison of the different stereotactic body radiotherapy (SBRT) plans between the Varian EDGE and CyberKnife (CK) systems for locally advanced unresectable pancreatic cancer. Fifteen patients with pancreatic cancer were selected in this study. The median planning target volume (PTV) was 28.688 cm3 (5.736–49.246 cm3). The SBRT plans for the EDGE and CK were generated in the Eclipse and Multiplan systems respectively with the same contouring and dose constrains for PTV and organs at risk (OARs). Dose distributions in PTV were evaluated in terms of coverage, conformity index (CI), new conformity index (nCI), homogeneity index (HI), and gradient index (GI). OARs, including spinal cord, bowel, stomach, duodenum and kidneys were statistically evaluated by different dose-volume metrics and equivalent uniform dose (EUD). The volume covered by the different isodose lines (ISDL) ranging from 10 to 100% for normal tissue were also analyzed. All SBRT plans for EDGE and CK met the dose constraints for PTV and OARs. For the PTV, the dosimetric metrics in EDGE plans were lower than that in CK, except that D99 and GI were slightly higher. The EDGE plans with lower CI, nCI and HI were superior to generate more conformal and homogeneous dose distribution for PTV. For the normal tissue, the CK plans were better at OARs sparing. The radiobiological indices EUD of spinal cord, duodenum, stomach, and kidneys were lower for CK plans, except that liver were higher. The volumes of normal tissue covered by medium ISDLs (with range of 20–70%) were lower for CK plans while that covered by high and low ISDLs were lower for EDGE plans. This study indicated that both EDGE and CK generated equivalent plan quality, and both systems can be considered as beneficial techniques for SBRT of pancreatic cancer. EDGE plans offered more conformal and homogeneous dose distribution for PTV, while the CK plans could minimize the exposure of OARs.

Supplemental material, sj-pdf-1-aim-10.1177_09645284211009533 for Acupuncture for experimental cerebral ischemia/reperfusion injury: a systematic review of methodology and reporting quality by Ya-nan Luo, Huan Tian, Zhi-gang Mei, Zhi-tao Feng, Song-bai Yang, Xian-yun Fu and Ya-guang Huang in Acupuncture in Medicine

Aberrant mechanical factor is one of the etiologies of the intervertebral disc (IVD) degeneration (IVDD). However, the exact molecular mechanism of spinal mechanical loading stress-induced IVDD has yet to be elucidated due to a lack of an ideal and stable IVDD animal model. The present study aimed to establish a stable IVDD mouse model and evaluated the effect of aberrant spinal mechanical loading on the pathogenesis of IVDD. Eight-week-old male mice were treated with lumbar spine instability (LSI) surgery to induce IVDD. The progression of IVDD was evaluated by μCT and Safranin O/Fast green staining analysis. The metabolism of extracellular matrix, ingrowth of sensory nerves, pyroptosis in IVDs tissues were determined by immunohistological or real-time PCR analysis. The apoptosis of IVD cells was tested by TUNEL assay. IVDD modeling was successfully produced by LSI surgery, with substantial reductions in IVD height, BS/TV, Tb.N. and lower IVD score. LSI administration led to the histologic change of disc degeneration, disruption of the matrix metabolism, promotion of apoptosis of IVD cells and invasion of sensory nerves into annulus fibrosus, as well as induction of pyroptosis. Moreover, LSI surgery activated Wnt signaling in IVD tissues. Mechanical instability caused by LSI surgery accelerates the disc matrix degradation, nerve invasion, pyroptosis, and eventually lead to IVDD, which provided an alternative mouse IVDD model.

Background: Bloodstream infection (BSI) has been one of the biggest headaches for clinicians, as it not only aggravates symptoms but also increases the length of stay, the cost of hospitalization, and the side effects caused by antibiotics. It is an urgent need for clinicians to develop timely and accurate methods to find microorganisms. Currently, the gold standard for diagnosing BSI is blood culture, but it takes three to eight days to produce results, and its positive rate is extremely low. Next-generation sequencing (NGS) has emerged as a better technology desperately needed by doctors and patients to diagnose BSI. Objectives: This study compared NGS and blood culture methods in clinical patients with BSI. Methods: In this study, blood culture and NGS were used to analyze the blood of patients with BSI in different departments of the First Affiliated Hospital of Kunming Medical University. Results: Next-generation sequencing detected 60 pathogens in 63 blood samples, while blood culture detected 15 pathogens in 336 blood samples from 63 patients who were clinically considered to be infected. Pathogens detected by NGS included bacteria, fungi, and viruses, while blood culture only found bacteria and fungi. The positive rates of blood culture diagnosis and NGS diagnosis in BSI patients were 23.8% (15/63) (CI: 13.3% - 34.3%) and 95% (60/63) (CI: 90% - 100%), respectively. Conclusions: Our results showed that NGS creates a new diagnostic platform for patients with BSI. Its wide detection range, high positive rate, and characteristics of rapid detection will benefit patients with BSI.

Background Renal cell carcinoma (RCC) is one of the most common malignant tumors originating from the renal parenchymal urinary epithelial system. Tripartite motif 47 (TRIM47) is a member of the TRIM family proteins, which has E3 ligase activity and has been demonstrated to be involved in the occurrence and prognosis of many tumors. The main purpose of this study is to explore the role and potential mechanism of TRIM47 in promoting malignant biological behavior of RCC. Materials and methods TRIM47 mRNA and protein levels in human renal cancer and paired normal adjacent tissues were detected by qRT-PCR and Western blot. The effects of TRIM47 knockdown and overexpression in renal cell carcinoma cells on cell proliferation, invasion and xenograft tumor growth in nude mice were analyzed. The molecular mechanism was explored by mass spectrometric exploration,Western blot and immunoprecipitation assays. Results TRIM47 promoted RCC cell proliferation in vitro and in vivo as an oncogene. Mechanistically, TRIM47 exerted an E3 ligase activity by interacting with P53 protein to increase its ubiquitination and degradation, which further promoted the malignant biological behavior of RCC. Conclusions Our study demonstrated that the TRIM47-P53 axis played a functional role in RCC progression and suggested a potential therapeutic target for RCC.

BACKGROUND Functional constipation (FC) is a common functional gastrointestinal disease with various clinical manifestations. It is a physical and mental disease, which seriously affects patient physical and mental health and quality of life. Biofeedback therapy is the treatment of choice for FC, especially outlet obstructive constipation caused by pelvic floor dysfunction. High-quality nursing is a new nursing model in modern clinical work and a new concept of modern nursing service. AIM To explore the effect of biofeedback combined with high-quality nursing in the treatment of FC. METHODS A total of 100 patients with FC admitted to our hospital from March 2015 to July 2019 were selected for clinical observation. These patients were randomly divided into two groups of 50: Experimental group (biofeedback combined with high-quality nursing treatment group) and control group (biofeedback group). RESULTS The constipation symptom score of the experimental group was significantly lower than that of the control group, and the difference was statistically significant (P < 0.05). The anal canal resting pressure and initial defecation threshold of the experimental group were significantly lower than those of the control group, and the maximum squeeze systolic pressure of the anal canal of the experimental group was significantly higher than that of the control group (P < 0.05). The Self-Rating Anxiety Scale and Zung’s Self-Rating Depression Scale scores of the two groups were significantly lower than before treatment. The Self-Rating Anxiety Scale and Self-Rating Depression Scale scores of the experimental group were significantly lower than those of the control group (P < 0.05). The patient satisfaction score of the experimental group was significantly higher than that of the control group (P < 0.05). CONCLUSION The application of biofeedback combined with high-quality nursing in the treatment of FC has significant advantages over pure biofeedback treatment, and it is worthy of promotion in clinical work.

To assess the psychological effects of the novel coronavirus disease (COVID-19) on medical staff and the general public. During the outbreak of COVID-19, an internet-based questionnaire included The Self-rating Depression Scale (SDS), Perceived Stress Scale (PSS-10), and Impact of Event Scale-Revised (IES-R) was used to assess the impact of the pandemic situation on the mental health of medical staff and general population in Wuhan and its surrounding areas. Among the 1493 questionnaires completed, 827 (55.39%) of these were men, and 422 (28.27%) of these were medical personnel. The results suggest that the outbreak of COVID-19 has affected individuals significantly, the degree of which is related to age, sex, occupation and mental illness. There was a significant difference in PSS-10 and IES-R scores between the medical staff and the general population. The medical staff showed higher PSS-10 scores (16.813 ± 4.87) and IES-R scores (22.40 ± 12.12) compared to members of the general population PSS-10 (14.80 ± 5.60) and IES-R scores (17.89 ± 13.08). However, there was no statistically significant difference between the SDS scores of medical staff (44.52 ± 12.36) and the general public (43.08 ± 11.42). In terms of the need for psychological assistance, 50.97% of interviewees responded that they needed psychological counseling, of which medical staff accounted for 65.87% and non-medical staff accounted for 45.10%. During the ongoing COVID-19 outbreak, great attention should be paid to the mental health of the population, especially medical staff, and measures such as psychological intervention should be actively carried out for reducing the psychosocial effects.

Background: Candida spp. are important opportunist pathogens causing bloodstream infections (BSIs). The present study aims to describe the current epidemiology of Candida BSI in a large Shanghai Tertiary-care Hospital from 2008 to 2018 and to identify the risk factors and the impact of antifungal therapy on clinical outcomes. Methods: From January 2008 to December 2018, all consecutive patients who developed Candida BSI at Ruijin Hospital were enrolled. Underlying diseases, clinical severity, species distribution, antifungal therapy, and its impact on the outcome were analyzed. Results: The incidence of nosocomial Candida BSI was 0.39 episodes/1000 hospitalized patients, and the overall 28-day mortality rate was 28.5%. Among the 393 cases of Candida BSI, 299 cases (76.1%) received antifungal therapy. 247 received early appropriate antifungal therapy (an appropriate drug with adequate dosage was started before the subsequent in vitro susceptibility results), and 52 received target antifungal therapy (appropriate target treatment started after susceptibility results, regardless of whether the inappropriate antifungal treatment has been initialed or not). The 28-day mortality rate was significantly lower in those who received early appropriate antifungal therapy or target antifungal therapy compared with those who did not receive antifungal therapy (25.5% and 23.1% vs. 39.4%,P = 0.012 and P = 0.046). In multivariate Cox regression analysis, age, chronic renal failure, mechanical ventilation, neutropenia were independent risk factors for the 28-day mortality rate, while antifungal therapy was a protective factor for short-term survival rate. Conclusions: The epidemiology of Candida BSI in Shanghai differed from that observed in Western countries. Antifungal therapy did influence the short-term survival, while there was no significant difference between the mortality for those who received early appropriate antifungal therapy and for those who received target antifungal therapy.

Background Evidence implying that metabolism reprogramming plays an important role in the regulation of sepsis is increasing; however, whether it has a similar role in septic organ dysfunction remains unclear. Here we provide evidence to support a new role of uncoupling protein-2 (UCP2)-regulated Warburg effect, i.e., aerobic glycolysis, in promoting mitochondrial injury in the kidney. Methods To imitate sepsis condition, male C57BL/6 mice were operated by the cecal ligation puncture (CLP) in vivo, whereas a normal human kidney cell line (HK-2) was treated with lipopolysaccharide (LPS) in vitro. UCP2 siRNA pretreatment was performed to knock down UCP2 expression in vitro. The glycolysis metabolite was detected by liquid chromatography/tandem mass spectrometry (LC-MS) in vivo and detected by commercial kits in vitro. Oxidative phosphorylation (OXPHOS) level and glycolysis level were monitored by measuring the oxygen consumption rate (OCR, indicative of respiration) and extracellular acidification rate (ECAR, indicative of glycolysis) in vitro. Exogenous lactate was supplied to stimulate HK-2 cells and indicators of mitochondrial dysfunction were also assessed. Results Aerobic glycolysis is enhanced in septic tubular epithelial cells, and the glycolysis inhibitor 2-deoxyglucose (2-DG) can partially restore mitochondrial membrane potential (MMP or ΔΨm) and decrease the reactive oxygen species (ROS) production. With the knockdown of ucp2, the aerobic glycolysis level upregulates, and mitochondrial injury increases. Conclusions These results provide insights on a new mechanism of metabolic regulation of mitochondrial injury and the importance of targeting aerobic glycolysis for the treatment of septic acute kidney injury.

Objective This study was performed to explore the association of the high-resolution computed tomography (HRCT) score with ventilator weaning and 28-day mortality of patients with acute respiratory distress syndrome (ARDS). Method In total, 197 patients treated for ARDS from October 2004 to December 2015 were retrospectively analyzed. Univariate analysis and multifactor regression analysis were used to determine the relationship of the HRCT score with ventilator weaning and 28-day mortality. Curve-fitting analysis and threshold analysis were further used to explore the association of the HRCT score with ventilator weaning and 28-day mortality. Results The multifactor regression analysis showed that the HRCT score was significantly associated with a lower rate of ventilator weaning and a higher risk of 28-day mortality in patients with ARDS. HRCT scores of 257.0 and 243.2 were the thresholds for ventilator weaning and 28-day mortality, respectively. When the HRCT score was below the threshold, every 1-point increase in the HRCT score was associated with a 4.6% decrease in the ventilator weaning rate and a 4.6% increase in the 28-day mortality rate. Conclusion The HRCT score was associated with ventilator weaning and 28-day mortality with a threshold of 257.0 and 243.2 points, respectively.

The sterile inflammatory response is one of the key mechanisms leading to hepatic ischemia-reperfusion injury. Melatonin has been shown to prevent organ injuries, but its roles in the inflammatory response after hepatic ischemia-reperfusion injury have not been fully explored, especially in late ischemia-reperfusion injury. The present study aimed to investigate the roles and possible mechanisms of melatonin in the inflammatory response after hepatic ischemia-reperfusion injury.Sixty Sprague-Dawley rats were randomly divided into a sham group, ischemia-reperfusion injury group (I/R group), and melatonin-treated group (M + I/R group). The rats in the I/R group were subjected to 70% hepatic ischemia for 45 min, followed by 5 or 24 h of reperfusion. The rats in the M + I/R group were injected with melatonin (10 mg/kg, intravenous injection) 15 min prior to ischemia and immediately before reperfusion. Serum and samples of ischemic liver lobes were harvested for future analysis, and the 7-day survival rate was assessed after hepatic ischemia-reperfusion surgery.In comparison with the I/R group, the M + I/R group showed markedly decreased expression levels of inflammatory cytokines (IL-6 and TNF-α) and numbers of apoptotic hepatocytes (P 0.05). Immunoblotting showed that the expression levels of IL-6, p-NF-κBp65/t-NF-κBp65 and p-IκB-α/t-IκB-α in the M + I/R group were significantly lower than those in the I/R group, and immunofluorescence staining showed that the expression level of p-NF-κBp65 in the M + I/R group was lower than that in the I/R group (P 0.05). The 7-day survival rates were 20% in the I/R group and 50% in the M + I/R group (P 0.05).Melatonin downregulated the activity of the NF-κB signaling pathway in the early and late stages of hepatic ischemia-reperfusion injury, alleviated the inflammatory response, protected the liver from ischemia-reperfusion injury, and increased the survival rate.

Background Sjogren syndrome (SS) is a chronic and systemic autoimmune disease characterized by lymphocytic infiltration of the exocrine glands. And histoplasmosis is an invasive mycosis caused by the saprophytic dimorphic fungus H. capsulatum. In patients with primary SS (PSS), disseminated histoplasmosis (DH) is extremely rare. Case summary We report a 37-year-old female patient admitted to our hospital with exacerbating fatigue, somnolence, and pancytopenia as the main symptoms. She was eventually diagnosed with DH based on pancytopenia, splenomegaly, and findings of bone marrow smears. The atypical clinical symptoms made the diagnosis process more tortuous. Unfortunately, she died of respiratory failure on the day the diagnosis was confirmed. Conclusion We present a rare and interesting case of DH in a PSS patient. This case updates the geographic distribution of histoplasmosis in China, and expands the clinical manifestations of DH in PSS, highlighting the significance of constantly improving the understanding of PSS with DH.

Background Whole body vibration (WBV) is a non-pharmaceutical therapy that has been widely incorporated into clinical practice for musculoskeletal disorders, including low back pain (LBP). Intervertebral disc (IVD) degeneration (IVDD) is clinically associated with LBP and is known as the main cause for LBP. However, cumulative evidence also suggested WBV might have an adverse impact on IVDs. Moreover, previous studies have been focusing on the effects of WBV on healthy mice, rather than those suffering from IVDD. Thus, uncertainties still exist concerning the effects of WBV on IVDs undergoing IVDD. This study was aiming to evaluate the effects of WBV intervention on the development and progression of IVDD mouse model induced by lumbar spine instability (LSI) surgery. Methods LSI surgery, by resecting the lumbar 3 rd -5 th spinous processes along with the supraspinous and interspinous ligaments, was conducted in 10-week-old male mice which then received WBV treatment (1 h per day, 5 days per week, at 3 Hz with peak acceleration at 0.4 g) or sham treatment. The progression of IVDD was evaluated by MRI, μCT and histological analyses after WBV treatment. The matrix metabolism, distribution of sensory nerves, pyroptosis in IVDs tissues were determined by immunohistological analysis or real-time PCR. The apoptosis of IVD cells was detected by TUNEL assay. Results LSI surgery was successful in producing IVDD modeling. WBV caused decreases in IVD height and annulus fibrosus (AF) score, as well as increased numbers of apoptotic cells in IVD tissues. WBV contributed to sensory innervation into AF and upregulation of Adamts5 and MMP3 expression in IVDD mice received LSI surgery. In addition, WBV treatment triggered earlier activation of Wnt/β-catenin signaling in IVDD mice with WBV treatment compared with those without WBV treatment. Unexpectedly, WBV significantly attenuated Caspase-1 and IL-1β expression in AF. Conclusions Collectively, our findings demonstrate that WBV treatment may worsen the development of ongoing IVDD. Decrease of IL-1β expression after WBV intervention may partially account for patient self-reported pain relief after WBV treatment in some previous trials. This study may help us better understand the effects of WBV intervention on patients experiencing LBP resulting from the degeneration of lumbar IVDs.

Purpose: To perform a comprehensive comparison of the different stereotactic body radiotherapy (SBRT) plans between the Varian EDGE and CyberKnife (CK) systems for pancreas cancer.Materials and methods: Fifteen patients with pancreas cancer were selected in this study. The median planning target volume (PTV) was 28.688cm 3 (5.736 to 49.246 cm 3 ). The SBRT plans for the EDGE and CK were generated in the Eclipse and Multiplan systems respectively with the same contouring and dose constrains for PTV and organ at risk (OAR). Dose distributions in PTV were evaluated in terms of coverage, conformity index (CI), new conformity index (nCI), homogeneity index (HI), and gradient index (GI). OARs, including spinal cord, bowel, stomach, duodenum and kidneys were statistically evaluated by different dose-volume metrics and equivalent uniform dose (EUD) . The volume covered by the different isodose lines (ISDL) ranging from 10% to 100% for normal tissue were also analyzed.Results: All SBRT plans for EDGE and CK met the clinical requirement for PTV and OARs. . For the PTV, the dosimetric metrics in EDGE plans were lower than that in CK, except that D 99 and GI were slightly higher. The EDGE plans with lower CI , nCI and HI were superior to offer the better conformity and homogeneity for PTV. For the normal tissue, the CK plans were better at OARs sparing. The radiobiological indices EUD of spinal cord, duodenum, stomach, and kidneys were lower for CK plans, except that liver were higher. The volumes of normal tissue covered by medium ISDLs (with range of 20%~70%) were lower for CK plans while that covered by high and low ISDLs were lower for EDGE plans.Conclusions: This study indicated that both EDGE and CK generated equivalent plan quality, and both systems can be considered as beneficial techniques for SBRT of pancreas cancer. EDGE plans offered the better conformity and homogeneity of dose distributions for PTV, while the CK plans could minimize the exposure of OARs.

Since December 2019, increasing attention has been paid to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic in Wuhan, China. SARS-CoV-2 primarily invades the respiratory tract and lungs, leading to pneumonia and other systemic disorders. The effect of SARS-CoV-2 in transplant recipients has raised significant concerns, especially because there is a large population of transplant recipients in China. Based on the current epidemic situation, this study reviewed publications on this virus and coronavirus disease 2019 (COVID-19), analyzed common features of respiratory viral pneumonias, and presented the currently reported clinical characteristics of COVID-19 in transplant recipients to improve strategies regarding the diagnosis and treatment of COVID-19 in this special population.

Ferroptosis is a new type of cell death that was discovered in recent years and is usually accompanied by a large amount of iron accumulation and lipid peroxidation during the cell death process; the occurrence of ferroptosis is iron-dependent. Ferroptosis-inducing factors can directly or indirectly affect glutathione peroxidase through different pathways, resulting in a decrease in antioxidant capacity and accumulation of lipid reactive oxygen species (ROS) in cells, ultimately leading to oxidative cell death. Recent studies have shown that ferroptosis is closely related to the pathophysiological processes of many diseases, such as tumors, nervous system diseases, ischemia-reperfusion injury, kidney injury, and blood diseases. How to intervene in the occurrence and development of related diseases by regulating cell ferroptosis has become a hotspot and focus of etiological research and treatment, but the functional changes and specific molecular mechanisms of ferroptosis still need to be further explored. This paper systematically summarizes the latest progress in ferroptosis research, with a focus on providing references for further understanding of its pathogenesis and for proposing new targets for the treatment of related diseases.

We applied three 16S rRNA sequencing protocols on vaginal microbiome samples, to evaluate whether they produce unbiased estimation of vaginal microbiome composition. We modified the 27F primer (hereafter denoted as 27F’). Using vaginal samples from 28 healthy women and 10 women with bacterial vaginosis, we sequenced three 16S rRNA sequencing protocols, i.e., 27F-338R, 27F’-338R and 341F-806R protocols, naming after their PCR primer sets, to test whether the sequencing results are consistent with the clinical diagnostics, morphology and qPCR results. First, the 27F primer would not align withGardnerlla vaginalisvery well, leading to poor amplification of such species. By modifying the primer sequences, the modified 27F primer (27F’) was able to amplifyGardnerlla vaginalisvery well. Second, the DNA sequence of characteristic speciesLactobacillus crispatusis identical withLactobacillus garrinarum, leading to biased estimation of abundance ofLactobacillus crispatuswhen using V3-V4 as PCR target region; in contrast, such bias did not occur when using V1-V2 as a target region. Third, optimized 27F’-338R avoided above-mentioned biases and restored the well-established community state types (CSTs) clustering.ImportanceVaginal microbiome has profound effects on the health of women and their newborns. Our study found that two well-established 16S rDNA sequencing protocols led to systementical biased estimation of characteristic species of vaginal microbiome. Subsequent analysis proved that the PCR primer fetching efficacy and target region identity were major contributor for such bias. With carefully selected target region and optimized PCR primer set, we were able to eliminate such biases and provide accurate estimation of vaginal microbiome, which showed high consistency with clinical diagnostics. We modified the 27F primer (27F’). Using the optimized PCR primer set of 27F’ and 338R to target the V1-V2 hyper-variable region, our 16S rRNA sequencing correctly evaluate the composition of vaginal microbiome.

Research focused on transforming growth factor β (TGFβ) signaling in osteoblast is gradually increasing, whereas literature is rare in terms of fluorosis. This work aimed to investigate how TGFβ signaling participated in regulation of the osteoblast by different doses of fluoride treatment. Bone marrow stem cells (BMSCs) were developed into osteoblastic cells and exposed to 1, 4, and 16 mg/L F− with and without 10 ng/mL of TGFβ. Cell viability and differentiation state of osteoblast under different settings were measured by means of cell counting kit and analysis of alkaline phosphatase (ALP) activity as well as formation of mineral nodules. Real-time PCR was utilized to test expression of ALP and Runt-related transcription factor 2 (Runx2) at gene level. The gene expression of TGFβ signaling effectors was also investigated, such as TGFβ receptors (TβRs), smad3, and mitogen-activated protein kinases (MAPK). Results demonstrated that fluoride treatment exhibited action on osteoblast viability and osteogenic differentiation and upregulated expression of TβR2, smad3, and MAPK in this process. Administration of TGFβ strengthened ALP activity but attenuated formation of mineral nodules. Co-treatment of TGFβ and low-dose fluoride increased ALP activity compared to same dose of single fluoride treatment, whereas it inhibited mineral nodule formation. Administration of TGFβ reversed the suppression of high-dose fluoride on osteogenic differentiation of BMSCs. Taken together, studies revealed that TβR2 acted as a target for fluoride and TGFβ treatment on BMSCs, and smad3 and MAPK were involved in the mechanism of fluoride regulating osteogenic differentiation. Together, our data indicated that TGFβ receptor-mediated signaling through smad3 and MAPK was required for modulation of fluoride on osteoblast viability and differentiation, and activating TβR2-smad3 signaling pathway reversed suppression of osteoblasts differentiation by high dose of fluoride treatment.