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Genomic changes in Mycoplasma pneumoniae caused by adaptation to environmental or ecologic pressures are poorly understood. We collected M. pneumoniae from children who had confirmed pneumonia in Taiwan during 2017–2020. We used whole-genome sequencing to compare these isolates with a worldwide collection of current and historical clinical strains for characterizing population structures. A phylogenetic tree for 284 strains showed that all sequenced strains consisted of 5 clades: T1–1 (sequence type [ST]1), T1–2 (mainly ST3), T1–3 (ST17), T2–1 (mainly ST2), and T2–2 (mainly ST14). We identified a putative recombination block containing 6 genes (MPN366‒371). Macrolide resistance involving 23S rRNA mutations was detected for each clade. Clonal expansion of macrolide resistance occurred mostly within subtype 1 strains, of which clade T1–2 showed the highest recombination rate and genome diversity. Functional characterization of recombined regions provided clarification of the biologic role of these recombination events in the evolution of M. pneumoniae.

BACKGROUND Medial displacement calcaneal osteotomy (MDCO) is frequently used for the surgical correction of flatfoot. This study aims to investigate the biomechanical effect of the different diagonal screw design on a novel-designed embedded calcaneal plate for MDCO using finite element analysis (FEA), mechanical test and digital image correlation (DIC) measurement. METHODS Four groups according to the varied implanted plate were set as control group (Group 1), non-diagonal screw (Group 2), one-diagonal screw (Group 3), and two-diagonal screws groups (Group 4). For FEA, A 450 N load was applied to on the anterior process of the calcaneus from top to bottom. Observational indices included the stress on the cortical and cancellous bone of the calcaneus surrounding the implant, the plate itself as well as screws, and the displacement of the overall structure. In addition, this study also used in vitro biomechanics test to investigate the stiffness of the structure after implantation, and used DIC to observe the displacement of the calcaneus structure after external force. RESULTS Under a simulated load in FEA, there are significant overall instability and high stress concentration on the calcaneal surrounding host bone and the plate/screws system, respectively, in group 2 compared with other groups. Regard to the mechanical testing with DIC system, significant increased rotation stability, maximum force and stiffness with the addition of diagonal screws. In comparison to Group 2, the increase of 112% and 157% in maximum force as well as 104% and 176% in stiffness were found in Group 3 and 4, respectively. CONCLUSION For reducing stress concentration and enhancing overall stability, more than one-diagonal screw design is recommended and two-diagonal screws design will be superior. This study provided biomechanical references for further calcaneal implants design to prevent clinical failure after MDCO.

BACKGROUND Laparoscopic cholecystectomy (LC) with associated procedures and endoscopic retrograde cholangiopancreatography (ERCP) have been the standard treatments for both common and rare biliary diseases. Mirizzi syndrome (MS) is a rare and complex biliary condition. We report our experience with MS treatment and investigate the value of laparoscopic procedures and ERCP in patient management. METHODS From 2004 to 2017, 100 consecutive patients with MS were diagnosed by ERCP and underwent surgery in a referral center. Sixty patients were treated with intended LC, and 40 patients were treated with open cholecystectomy (OC). The clinical manifestations, ERCP and associated procedures, surgical procedures, and postoperative outcomes were investigated. RESULTS The surgical mortality rate was 1%, while the surgical morbidity rate was 15%. The patients treated with intended LC suffered from less morbidity (5%). The percentage of postoperative residual biliary stones was 32% (n = 32), and only three patients underwent re-operation (laparotomy) for stone removal. The laparotomy conversion rate in the intended LC group was 16.7% (10/60). The length of hospitalization for the patients with successful LC was significantly shorter than that for the patients with conversion and intended OC. Csendes classification was a risk factor for conversion from LC to OC (type I vs types II to V, P

Diabetic wounds are a protracted complication of diabetes mainly characterised by chronic inflammation, obstruction of epithelialization, damaged blood vessels and collagen production (maturation), as well as neuropathy. As a non-coding RNA (ncRNA) that lack coding potential, long non-coding RNAs (lncRNAs) have recently been reported to play a salient role in diabetic wound healing. Here, this review summarises the roles of lncRNAs in the pathology and treatments of diabetic wounds, providing references for its potential clinical diagnostic criteria or therapeutic targets in the future.

Aims Secondary bleeding and further hematoma expansion (HE) aggravate brain injury after intracerebral hemorrhage (ICH). The majority of HE results from hypertensive ICH. Previous study reported higher iron content in the brains of hypertensive patients. Iron overload exacerbates the risk of hemorrhagic transformation in thromboembolic stroke mice. Whether iron overload during the process of hypertension participates in secondary bleeding of hypertensive ICH remains unclear. Methods Hypertension was induced by continuous infusion of angiotensin II (Ang II) with an osmotic pump into C57BL/6 mice. ICH was simulated by intrastriatal injection of the liquid polymer Onyx‐18. Iron chelation and iron overload was achieved by deferoxamine mesylate or iron dextran injection. Secondary bleeding was quantified by measuring the hemoglobin content in the ipsilateral brain hemisphere. Results Ang II‐induced hypertensive mice showed increased iron accumulation in the brain and expanded secondary hemorrhage after ICH modeling. Moreover, iron chelation suppressed while iron overload aggravated secondary bleeding. Mechanistically, iron exacerbated the loss of contractile cerebral vascular smooth muscle cells (VSMCs), aggravated blood–brain barrier (BBB) leakage in Ang II‐induced hypertensive mice, and increased glial and MMP9 accumulation after ICH. Conclusion Iron overload plays a key role in secondary bleeding after ICH in Ang II‐induced hypertensive mice. Iron chelation during the process of Ang II‐induced hypertension suppresses secondary bleeding after ICH., Iron accumulation in the brain tissues of Ang II‐induced hypertensive mice might exacerbate the loss of contractile VSMCs, enhance perivascular inflammation and BBB leakage. These factors might lead to increased vascular fragility and increased vulnerability to rupture, ultimately causing more secondary bleeding and subsequent HE after ICH.

BACKGROUND The incidence of biliary events (BE) following percutaneous cholecystostomy (PC) in acute cholecystitis (AC) patients is high. Therefore, definitive laparoscopic cholecystectomy (LC) is recommended. We aimed to investigate the optimal timing of LC following PC with regard to the clinical course and pathological findings. METHODS All 744 AC patients with PC were included. The incidence and median number of BE were investigated with the concept of competing risks. The 344 patients with interval LC were divided into two groups based on the pathological findings of resected gallbladders: the acute/acute-and-chronic group (AANC group) (n = 221) and the chronic group (n = 123). A comparative analysis of the demographic data and perioperative outcomes was performed. RESULTS Among the 744 AC patients with PC, 142 patients experienced recurrent BE. The cumulative incidence of BE was 26.6%, and the median time to recurrence was 67.5 days. The PC-to-LC days of the chronic group were longer than those of the AANC group (73.51 vs 63.00, P

Acute cholecystitis and several gallbladder stone-related conditions, such as impacted common bile duct stones, cholangitis, and biliary pancreatitis, are common medical conditions in daily practice. An early cholecystectomy or drainage procedure with delayed cholecystectomy is the current standard of treatment based on published clinical guidelines. Cirrhosis is not only a condition of chronically impaired hepatic function but also has systemic effects in patients. In cirrhotic individuals, several predisposing factors, including changes in the bile acid composition, increased nucleation of bile, and decreased motility of the gallbladder, contribute to the formation of biliary stones and the possibility of symptomatic cholelithiasis, which is an indication for surgical treatment. In addition to these predisposing factors for cholelithiasis, systemic effects and local anatomic consequences related to cirrhosis lead to anesthesiologic risks and perioperative complications in cirrhotic patients. Therefore, the treatment of the aforementioned biliary conditions in cirrhotic patients has become a challenging issue. In this review, we focus on cholecystectomy for cirrhotic patients and summarize the surgical indications, risk stratification, surgical procedures, and surgical outcomes specific to cirrhotic patients with symptomatic cholelithiasis.

Background The coronavirus disease 2019 (COVID-19) pandemic profoundly impacts on mental health, yet it is still unclear whether COVID-19 distress makes people more vulnerable to suicidal behavior. The present study aims to examine the association between COVID-19 related psychological distress and risk for suicide attempt, and moderators of this association, among hotline callers. Methods This case-control study was conducted at the largest psychological support hotline in China. Hotline callers who sought help for psychological distress and reported whether or not they attempted suicide in the last 2 weeks (recent suicide attempt) were analyzed. The primary predictor of recent suicide attempt was the presence or absence of COVID-19 related psychological distress. Demographic variables and common risk and protective factors for suicidal behavior were also studied. Callers with COVID-19 related distress (COVID-19 callers) and those without such distress (non-COVID-19 callers) were compared on these variables. Recent suicide attempt was regressed on COVID-19 related distress and the other variables, and significant interaction terms of aforementioned predictors by COVID-19 related distress, to identify variables that moderate the association of COVID-19 related distress and recent suicide attempt. Results Among 7337 included callers, there were 1252 COVID-19 callers (17.1%) and 6085 non-COVID-19 callers (82.9%). The COVID-19 callers were less likely to report recent suicide attempt (n = 73, 5.8%) than the non-COVID-19 callers (n = 498, 8.2%, P = 0.005). The COVID-19 callers were also less likely to have high scores on depressive symptoms (22.6% vs 26.3%, P P P P = 0.021), and a trend that suicide attempt history was associated with two-thirds greater risk (P = 0.063) for recent suicide attempt, among COVID-19 callers than non-COVID-19 callers. Conclusions The COVID-19 calls are from individuals with lower suicide-related risk compared to more typical callers. Acute stressful life events provided a key context for suicide attempt in non-COVID-19 callers, i.e., more typical calls.

Rationale Hematoma expansion (HE) aggravates brain injury after intracerebral hemorrhage (ICH) and hypertension is a key contributor to HE. Plasma kallikrein (PK) is involved in hemorrhagic transformation in ischemic stroke mice. This study was conducted to explore the role of PK in HE in hypertensive ICH. Methods Hypertension was achieved by continuous infusion of angiotensin II (Ang II) with an osmotic pump in C57BL/6 mice. ICH was achieved by stereotactic intrastriatal injection of blood. PK-specific antibody and platelet glycoprotein VI (GPVI) agonists were administered to intervene in hematoma expansion. The hematoma volume was indicated by the erythrocyte components hemoglobin and carbonic anhydrase-1 in the ipsilateral brain hemisphere. Results Ang II-induced hypertensive mice showed enhanced hematoma expansion and worsened neurologic deficits after ICH modeling. Moreover, intrastriatal injection of blood from Ang II-treated mice into normal mice increased the area of secondary hemorrhage more than blood from untreated mice. Mechanistically, elevated PK was found in Ang II-infused mice whereas, inhibition of PK and administration of the GPVI agonist convulxin decreased hematoma expansion and improved neurologic deficits after ICH. Conclusions These findings suggest that PK inhibition and GPVI agonist treatment might serve as potential methods to intervene in HE after ICH.

Bacterial superinfection aggravates the disease of influenza. Streptococcus pneumoniae is the most common bacterial pathogen. Synergistic virulence has been demonstrated between influenza neuraminidase and pneumococcal NanA and NanB. NanC, the other pneumococcal neuraminidase infrequently present in clinical isolates, is not well characterized. In this study, we report that superinfection with a NanC-negative pneumococcus strain suppresses anti-influenza immunity and impairs viral clearance with higher TGF-β activation in mice. Bacterial load in the lungs also increases as the host immunity is suppressed. NanC-positive isogenic mutant reverses wild type S. pneumoniae–mediated immune suppression and facilitates virus clearance. However, it causes more severe disease as the augmented inflammation causes collateral damage. Both virus-mediated damage and immune response–mediated inflammation are important for pathogenesis of severe influenza. Inflammation may be more critical than virus-mediated damage in influenza with bacterial superinfection.

Objective To compare the clinical efficacy of the direct anterior approach in lateral decubitus position (L‐DAA) and supine position (S‐DAA) for unilateral total hip arthroplasty. Methods A retrospective study was conducted on 89 patients who underwent primary unilateral total hip arthroplasty in our department between August 2016 and December 2017. There were 46 patients who underwent L‐DAA and 43 patients who underwent S‐DAA. The body mass index (BMI), operation time, blood loss, preoperative Hb, first day and third day postoperative Hb, incision length, hospital stay, preoperative and postoperative Harris score, preoperative and postoperative visual analogue scale (VAS) score, radiological evaluation, intraoperative and postoperative complication, postoperative absolute length difference of lower extremity were recorded and analyzed. P 0.05). However, significant differences were detected in BMI, blood loss, first day and third day postoperative Hb, and operation time (P, Lateral decubitus position: A. Surgical position; B. hemostasis of the extrafemoral artery achieved; C. Grinding the acetabulum; D. Position of operation in femur and acetabulum; E. Reaming the femur and acetabulum; F. Length of incision. Supine position: G. Surgical position; H. Skin preparation and draping; I. Position of operation in femoral; J & K. Muscle protection retractors.

Background Suicide rates in China have declined substantially in the last two decades, however, the correlates of the decreases are still unclear. Methods Using hospital-based suicidal acts registry system in Meixian county, we reviewed all episodes of suicidal behaviors presented at hospitals from 2009 to 2014. The data was combined with the suicides reported in the same period by the county's Center for Disease Prevention and Control. Stratified by gender and method, age-standardized incidences of suicide death, suicide attempts, suicidal acts, as well as the case-fatalities of suicidal acts, were calculated. Joinpoint regression analysis was applied to test the time trends changes of the annual incidences and case-fatalities. Correlation coefficients between suicide rates and case-fatality were estimated. Results Age-standardized suicide rates among females declined by 20.4% per year, meanwhile, overall suicide rates were characterized by downward trend without statistical significance. The annual proportions of suicide deaths by pesticide self-poisoning ranged from 57.1% to 82.6%. There were positive or marginally positive correlations between suicide rates and case-fatalities of suicidal acts in gender- and method-specific groups (r values range from 0.77 to 0.89). Limitations Underreporting in the hospital-based registry system and misclassification in the death reporting system. Changes in other related factors are not yet accessible. Conclusion Suicide rates in females declined prominently in Meixian from 2009 to 2014, even though overall suicide rates remained steady. Pesticide ingestion were most common suicide method. Restriction of pesticide and reduction in the case-fatality are critical targets of suicide prevention in rural China.

Background Accumulating evidence has converged to suggest that childhood trauma may contribute to bipolar disorder (BD). This study aimed to investigate the patterns of childhood trauma among patients with bipolar I (BD-I) and bipolar II (BD-II) disorders, according to DSM-IV and in contrast with healthy volunteers. We also explored whether the relationship between childhood trauma and onset of bipolar disorder is mediated by immature defense mechanisms. Methods Participants were patients with BD-I (n=44) and BD-II (n = 42), and healthy controls (HCs, n = 43). Childhood traumatic experiences and defense mechanisms were assessed by the Childhood Trauma Questionnaire (CTQ) and the Defense Style Questionnaire (DSQ), respectively. Results BD patients experienced more severe childhood trauma than HCs. Physical neglect sub-score and total score of the CTQ had both direct and indirect effects on the diagnosis of BD-I, and an immature defense style mediated the indirect effects. The diagnosis of BD-II was mainly related to the physical neglect and emotional abuse subs-core and total score of the CTQ, as mediated by the immature defense mechanisms. BD-I and BD-II significantly differed in the emotional abuse sub-score of the CTQ. Conclusions Physical neglect sub-score and total score of the CTQ were associated with the diagnosis of BD (both BD-I and BD-II), as mediated by an immature defense style. Furthermore, emotional abuse might be an important risk factor for BD-II compared to BD-I. These findings may inform risk reduction and psychosocial intervention strategies to prevent and treat patients with bipolar disorders.

This paper elucidates that the AIDS/HIV incidence rate differences exist among different population and regions, especially among the old and college students. Due to the effect of age, the AIDS incidence peak in males aged 20–35 years and 50 years old both in Chongqing and Shenzhen, and the incidence rate and increasing spread in males was higher than that of females under period effect. In the local population in Chongqing and Shenzhen, the incidence rate of males in over 40, below and in the whole age groups are predicted to increase sharply in the future six years, while in females, the incidence rates among over 40-year-old and the whole age groups were predicted to increase as well. The incidence rate among homosexually transmitted patients reaches the peak in the 20–35, the incidence rate of patients transmitted through heterosexual reaches the peak around 50-year-old. Under the effect of period, AIDS/HIV incidence rate of patients transmitted through sexual routes showed an upward trend both in Chongqing and Shenzhen. The incidence rate of patients aged between 41 and 70 years old presents with an upward trend in the future six years. The results show great differences exist in the AIDS/HIV incidence between males and females, therefore it is necessary to take specific measures respectively.

Background To systematically investigate structural and functional abnormalities in subregions of the basal forebrain (BF) using structural and resting-state fMRI, and to examine their clinical relevance in short-term and chronic insomnia disorder (ID). Methods Thirty-four patients with short-term ID, 41 patients with chronic ID, and 46 healthy controls (HCs) were recruited. Grey matter volume and seed-based resting-state functional connectivity (RSFC) in each BF subregion (Ch1,2,3 and 4) were computed and compared among the three groups. Spearman correlation was used to estimate the relationships between MRI-based alterations and clinical variables. Results The short-term group exhibited lower RSFC with the bilateral striatum and bilateral Ch_4 than HCs and the chronic group. In the left Ch_4, subjects in the chronic group exhibited lower RSFC with the left middle cingulate cortex than HCs and the short-term group. The short-term group exhibited lower RSFC with the left parahippocampal gyrus (PHG) than HCs and the chronic group. The chronic group exhibited the highest RSFC with the left middle frontal gyrus (MFG), followed by HCs and the short-term group. In the right Ch_4, the chronic group exhibited the lowest RSFC with the right superior temporal gyrus, followed by HCs and the short-term group. Moreover, in the short-term group, negative correlations were found between the left Ch_4 and left MFG RSFC and Epworth Sleepiness Scale scores. Conclusions These findings suggest that the Ch_4 may be a key node for establishing diagnostic and categorical biomarkers of ID, which could be useful in developing more effective treatment strategies for insomnia.

We conducted a retrospective analysis of the clinical characteristics and dynamic variations of immune indexes in nine COVID-19 patients in Zigong, China. We used flow cytometry and enzyme-linked immunosorbent assays to measure the absolute levels of CD4 and CD8 lymphocytes and SARS-CoV-2 antibodies, respectively. We found that CRP, LDH, HBDH, CD4/CD8 and IgE levels were increased in 6/9 patients, while PA and the absolute numbers of CD4 and CD8 lymphocytes decreased in 7/9 patients. From disease onset through 63 days of follow-up, SARS-CoV-2 IgG levels were consistently higher than those of SARS-CoV-2 IgM, reaching peaks on days 28 and 13, respectively. IgM levels decreased to normal 35 days after disease onset, while IgG levels remained elevated through day 63. IgE levels varied similarly to SARS-CoV-2 IgM. Our results suggest that SARS-CoV-2 may elicit allergic immune responses in patients and that the levels of CRP, PA, LDH, and HBDH, as well as the absolute numbers of CD4 and CD8 lymphocytes could be used as early diagnostic markers of SARS-CoV-2 infection. Lastly, the dynamic variation of SARS-CoV-2 antibodies could guide the timing of blood collection for plasma exchange.

Increasing evidence suggests that long non-coding RNAs (lncRNAs) are of vital importance for various biological processes, and dysregulation of lncRNAs is frequently associated with various diseases such as psoriasis. LncRNAs modulate gene expression at the transcriptional, post-transcriptional, and translational levels; however, the specific regulatory mechanisms of lncRNAs in psoriasis remain largely unexplored. This review provides an overview of recent studies investigating mechanisms and functions of lncRNAs in psoriasis, especially focusing on the role of lncRNAs in keratinocytes, T cells, and dendritic cells.

To develop and validate a clinical nomogram for individualized predicting hematoma expansion (HE) in patients with Intracerebral Hemorrhage (ICH).A total of 1025 patients with ICH were retrospectively enrolled in the development cohort between 2010 and 2016. We identified and integrated significant factors for HE to build a nomogram. The model was subjected to validation with a separate cohort of 397 patients from the 2017-2019. The predictive accuracy and discriminative ability were measured by concordance index (C-index). The primary outcome was HE, defined as hematoma growth more than 6 mL or 33% increase in the volume.A total of 1025 patients were included for univariable analysis. HE occurred in 180 patients (17.6%). The time to initial CT (≤6h vs.6 h; p = 0.001), NIHSS score (0-4 vs. 5-14 vs. ≥15; p = 0.031), CTA spot sign (yes vs. no vs. absent; p = 0.018), hypodensities (p = 0.000), blend sign (p = 0.005), and INR (1.2 vs. ≥1.2; p = 0.009) were identified and entered into the nomogram. The calibration curves for probability of HE showed optimal agreement between nomogram prediction and actual observation. The C-index was 0.751. The validation cohort consisted of 397 patients and HE occurred in 78 patients (19.6%). The C-index was 0.743.We developed and validated a nomogram that can individually predict HE for ICH in Chinese populations. This practical prognostic nomogram may help clinicians make decision of clinical practice and design of clinical studies.

Dynamic functional connectivity (DFC) analysis can capture time‐varying properties of connectivity. However, studies on large samples using DFC to investigate transdiagnostic dysconnectivity across schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD) are rare. In this study, we used resting‐state functional magnetic resonance imaging and a sliding‐window method to study DFC in a total of 610 individuals (150 with SZ, 100 with BD, 150 with MDD, and 210 healthy controls [HC]) at a single site. Using k‐means clustering, DFCs were clustered into three functional connectivity states: one was a more frequent state with moderate positive and negative connectivity (State 1), and the other two were less frequent states with stronger positive and negative connectivity (State 2 and State 3). Significant 4‐group differences (SZ, BD, MDD, and HC groups; q, We identified three functional connectivity states across multiple psychiatric disorders and healthy controls: one was a more frequent state with weak connectivity, and the other two were less frequent states with strong connectivity. Dysconnectivity in the psychiatric patients was found nearly only in the weak connectivity state. Psychiatric patients spent less time in the weak connectivity state than HC patients.

Staged surgery (SS) and primary anastomosis (PA) are alternatives to emergency surgery in Crohn's disease (CD). This study aimed to compare postoperative patient outcomes and medical cost of SS and PA for CD emergencies.Consecutive patients with CD undergoing emergency surgery between December 1997 and January 2017 in three centers were included. The PA and SS groups were compared regarding patient outcomes including postoperative complications and surgical recurrence, as well as hospitalization costs.Altogether 96 (39.5%) patients underwent an emergency PA, and 147 (60.5%) underwent an emergency SS. The incidence of intra-abdominal septic complications (IASC) in the PA group was 15.6% compared with 7.5% in the SS group (P = 0.04). The length of hospitalization was longer (32.36 ± 1.76 d vs 19.33 ± 2.36 d, P0.01) and the hospitalization cost was higher in the SS group (USD 15 811.1 ± 1697.1 vs USD 8345.3 ± 919.5, P0.01) than the PA group. SS correlated with a lower surgical recurrence rate than PA (log-rank test, P = 0.04). Presence of diffuse peritonitis, perforating or colonic disease, decision of operation choice made by a senior consultant and more than two concurrent surgical indications were related to the need for SS in emergencies. Localized peritonitis, body mass index (18.5 kg/mSS can be performed with limited IASC and low surgical recurrence rates for surgical emergencies in CD, although it increases hospitalization costs and delays discharge.

LIM kinase 1 (LIMK1) and p21-activated kinase 4 (PAK4) are often over-expressed in breast tumors, which causes aggressive cancer phenotypes and unfavorable clinical outcomes. In addition to the well-defined role in regulating cell division, proliferation and invasion, the two kinases promote activation of the MAPK pathway and cause endocrine resistance through phosphorylating estrogen receptor alpha (ERα). PAK4 specifically phosphorylates LIMK1 and its functional partners, indicating possible value of suppressing both kinases in cancers that over-express PAK4 and/or LIMK1. Here, for the first time, we assessed the impact of combining LIMK1 inhibitor LIMKi 3 and PAK4 inhibitor PF-3758309 in preclinical breast cancer models. LIMK1 and PAK4 pharmacological inhibition synergistically reduced the survival of various cancer cell lines, exhibiting specific efficacy in luminal and HER2-enriched models, and suppressed development and ERα-driven signals in a BT474 xenograft model. In silico analysis demonstrated the cell lines with reliance on LIMK1 were the most prone to be susceptible to PAK4 inhibition. Double LIMK1 and PAK4 targeting therapy can be a successful therapeutic strategy for breast cancer, with a unique efficiency in the subtypes of luminal and HER2-enriched tumors.

Utilizing publicly available ribonucleic acid sequencing data, we identified SCUBE1 as a BMPR2-related gene differentially expressed between induced pluripotent stem cell-endothelial cells derived from pulmonary arterial hypertension (PAH) patients carrying pathogenic BMPR2 mutations and control patients without mutations. Endothelial SCUBE1 expression was decreased by known triggers of PAH, and its down-regulation recapitulated known BMPR2-associated endothelial pathophenotypes in vitro. Meanwhile, SCUBE1 concentrations were reduced in plasma obtained from PAH rodent models and patients with PAH, whereas plasma concentrations were tightly correlated with hemodynamic markers of disease severity. Taken together, these data implicate SCUBE1 as a novel contributor to PAH pathogenesis with potential therapeutic, diagnostic, and prognostic applications.

Background:Late-life depression issues in developing countries are challenging because of understaffing in mental health. Cognitive behavioural therapy (CBT) is effective for treating depression.Aim:This pilot trial examined the adherence and effectiveness of an eight-session adapted CBT delivered by trained lay health workers for older adults with depressive symptoms living in rural areas of China, compared with the usual care.Method:Fifty with screen-positive depression were randomly assigned to the CBT arm or the care as usual (CAU) arm. The primary outcomes were the session completion of older adults and changes in depressive symptoms, assessed using the Geriatric Depression Scale (GDS).Results:The majority (19/24) of participants in the CBT arm completed all sessions. Mixed-effect linear regression showed that the CBT reduced more GDS scores over time compared with CAU.Conclusion:Lay-delivered culturally adapted CBT is potentially effective for screen-positive late-life depression.

Background Koelreuteria henryi Dummer is an indigenous plant in Taiwan. The species has been used in traditional folk medicine for the promotion of liver functions and for treating malaria and urethritis. The present study investigated the antioxidant activity of the flower extract of Koelreuteria henryi Dummer. The extraction conditions were optimized by the contents of total phenolic acids and total flavonoids, and antioxidant activity assays. Moreover, an in vitro study for investigating antioxidant activity of K. henryi flower extract was demonstrated by hydrogen peroxide (H2O2)-induced apoptosis. Results K. henryi flower extracted for 150 min showed high contents of total phenolic acids and total flavonoids. In an in vitro model, L929 cells were pretreated with K. henryi flower extract, and then treated with H2O2 to induce oxidative damage. Results demonstrated that H2O2-induced apoptosis was inhibited by the treatment of 200 μg/ml K. henryi flower extract through the mitochondria-mediated pathway and mitogen-activated protein kinase (MAPK) pathway. The caspase 8/9 activity and expression of p-p38 and pERK were repressed by K. henryi flower extract. In addition, the prevention of H2O2-induced apoptosis by K. henryi flower extract activated the nuclear factor-erythroid 2-related factor (Nrf2) stress response pathway to transcript heme oxygenase 1 (HO-1). Also, K. henryi flower extract prevented H2O2-induced apoptosis through HO-1 production, as evident by the use of HO-1 inhibitor. Conclusions The present study demonstrated that K. henryi flower extract could inhibit the H2O2-induced apoptosis in L929 cells through the activation of the Nrf2/HO-1 pathway. How to cite: Tsai WC, Chang HC, Yin HY, et al. The protective ability and cellular mechanism of Koelreuteria henryi Dummer flower extract against hydrogen peroxide-induced cellular oxidative damage. Electron J Biotechnol 2020;47. https://doi.org/10.1016/j.ejbt.2020.07.006 .

Marchiafava-Bignami disease (MBD) is a rare neurological disease, and is characterized by callosal lesions consisting of necrosis and demyelination. Posterior reversible encephalopathy syndrome (PRES) is a clinical syndrome, and refers to a disorder with reversible subcortical vasogenic brain edema, predominantly involving the bilateral parieto-occipital regions. Never before had articles reported that the two diseases occurred simultaneously. We report a 49-year-old male alcoholic with both MBD and PRES who had a good prognosis after correct diagnosis and timely treatment.

Background Taraxacum species (commonly known as dandelion) used as herbal medicine have been reported to exhibit an antiproliferative effect on hepatoma cells and antitumor activity in non-small-cell lung cancer cells. Although several investigations have demonstrated the safety of Taraxacum officinale, the safety of tissue-cultured plants of T. formosanum has not been assessed so far. Therefore, the present study examines the safety of the water extract of the entire plant of tissue cultured T. formosanum based on acute and subacute toxicity tests in rats, as well as the Ames tests. Results No death or toxicity symptoms were observed in the acute and subacute tests. The results of the acute test revealed that the LD50 (50% of lethal dose) value of the T. formosanum water extract for rats exceeded 5 g/kg bw. No abnormal changes in the body weight, weekly food consumption, organ weight, or hematological, biochemical, and morphological parameters were observed in the subacute toxicity test. Thus, the no observed adverse effect level (NOAEL) of T. formosanum water extract was estimated to be higher than 2.0 g/kg. Finally, the results of the Ames test revealed that T. formosanum water extract was not genotoxic at any tested concentration to any of five Salmonella strains. Conclusions The water extract of tissue-cultured T. formosanum was non-toxic to rats in acute and subacute tests and exhibited no genotoxicity to five Salmonella strains. How to cite: Tsai WC, Chang HC, Tseng YH, et al. Toxicity evaluation of water extract of tissue-cultured Taraxacum formosanum by acute, subacute administration, and Ames test. Electron J Biotechnol 2020;45. https://doi.org/10.1016/j.ejbt.2020.04.001

We aim to assess the surgical outcomes of our novel hysteropexy procedure, laparoscopic long mesh surgery (LLMS) with augmented round ligaments. Twenty-five consecutive women with stage II or greater main uterine prolapse defined by the POP quantification staging system were referred for LLMS. Long mesh is a synthetic T-shaped mesh, with the body fixed at the uterine cervix and the two arms fixed along the bilateral round ligaments. The clinical evaluations performed before and 6 months after surgery included pelvic examinations, urodynamic studies, and questionnaires for urinary and sexual symptoms. After a follow-up time of 12 to 24 months, the anatomical reduction rate was 92% (23/25) for the apical compartment. The average operative time was 65.4 ± 28.8 minutes. No major complications were recognized during LLMS. The lower urinary tract symptoms and scores on the questionnaires improved significantly after the surgery, except urgency urinary incontinence and nocturia. Neither voiding nor storage dysfunction was observed after the operations. All of the domains and total Female Sexual Function Index (FSFI) scores of the 15 sexually active women did not differ significantly after LLMS. The results of our study suggest that LLMS is an effective, safe, and time-saving hysteropexy surgery for the treatment of apical prolapse.

Codeine-containing cough syrup (CCS) is considered as one of the most popular drug of dependence among adolescents because of its inexpensiveness and easy availability. However, its relationship with neurobiological effects remains sparsely explored. Herein, we examined how high-impulse behaviours relate to changes in the brain structural networks. Forty codeine-containing cough syrup dependent (CCSD) users and age-, gender-, and number of cigarettes smoked per day -matched forty healthy control (HC) subjects underwent structural brain imaging via MRI. High-impulse behaviour was assessed using the 30-item self-rated Barratt Impulsiveness Scale (BIS-11), and structural networks were constructed using diffusion tensor imaging and AAL-90 template. Between-group topological metrics were compared using nonparametric permutations. Benjamin–Hochberg false discovery rate correction was used to correct for multiple comparisons (P

Thioredoxin-interacting protein (TXNIP) is a multifunctional protein that functions in tumor suppression, oxidative stress, and inflammatory responses. However, how TXNIP functions during microbial infections is rarely reported. In this study, we demonstrate that Brucella infection decreased TXNIP expression to promote its intracellular growth in macrophages by decreasing the production of NO and reactive oxygen species (ROS). Following Brucella abortus infection, TXNIP knockout RAW264.7 cells produced significantly lower levels of NO and ROS, compared with wild-type RAW264.7 cells. Inducible NO synthase (iNOS) inhibitor treatment reduced NO levels, which resulted in a dose-dependent restoration of TXNIP expression, demonstrating that the expression of TXNIP is regulated by NO. In addition, the expression of iNOS and the production of NO were dependent on the type IV secretion system of Brucella. Moreover, Brucella infection reduced TXNIP expression in bone marrow–derived macrophages and mouse lung and spleen. Knocked down of the TXNIP expression in bone marrow–derived macrophages increased intracellular survival of Brucella. These findings revealed the following: 1) TXNIP is a novel molecule to promote Brucella intracellular survival by reducing the production of NO and ROS; 2) a negative feedback–regulation system of NO confers protection against iNOS-mediated antibacterial effects. The elucidation of this mechanism may reveal a novel host surveillance pathway for bacterial intracellular survival.

Aims Hypertension is a leading cause of cerebral small vessel disease (CSVD). Currently, treatments for CSVD are limited. Nicotinamide riboside (NR) can protect against vascular injury and cognitive impairment in neurodegenerative diseases. In this study, the protective effects of NR against angiotensin ‐ (Ang ‐)–induced CSVD were evaluated. Methods To explore the effects of NR in CSVD, C57BL/6 mice were infused with Ang ‐, and NR was added to the food of the mice for 28 days. Then, short‐term memory, blood‐brain barrier (BBB) integrity, and endothelial function were detected. Arteriole injury and glial activation were also evaluated. Results Our data showed that mice infused with Ang ‐ exhibited decreased short‐term memory function and BBB leakage due to decreased claudin‐5 expression and increased caveolae‐mediated endocytosis after 28 days. Furthermore, Ang ‐ decreased the expression of α‐smooth muscle actin (α‐SMA) and increased the expression of proliferating cell nuclear antigen (PCNA) in arterioles and decreased the expression of neurofilament 200 (NF200) and myelin basic protein (MBP) in the white matter. These CSVD‐related damages induced by Ang ‐ were inhibited by NR administration. Moreover, NR administration significantly reduced glial activation around the vessels. Conclusion Our results indicated that NR administration alleviated Ang ‐–induced CSVD by protecting BBB integrity, vascular remodeling, neuroinflammation, and white matter injury (WMI)–associated cognitive impairment.

Acinetobacter baumannii emerged as one of the most important pathogens that causes nosocomial infections due to its increased multidrug resistance. Identifying capsular epidemiology in A. baumannii can aid in the development of effective treatments and preventive measures against this emerging pathogen. Here we established a wzc-based method, and combined it with wzy-PCR to determine capsular types of A. baumannii causing nosocomial bacteraemia collected at two medical centres in Taiwan from 2015 to 2017. Among the 237 patients with A. baumannii bacteraemia, 98 (41.4%) isolates were resistant to carbapenems. Four prevalent capsular types (KL2, KL10, KL22, and KL52) accounted for 84.7% of carbapenem-resistant A. baumannii (CRAB) and 12.2% of non-CRAB. The rate of pneumonia, intensive care unit admission, APACHE II score, and Pitt bacteraemia score were higher in patients with KL2/10/22/52 infection than in those with non-KL2/10/22/52 infection. Patients with KL2/10/22/52 infection and patients with CRAB infection have a higher cumulative incidence of attributable and all-cause in-hospital 30-day mortality. On multivariate analysis, appropriate empirical antimicrobial therapy within 24 h was associated with a lower risk of 30-day attributable mortality in the KL2/10/22/52 isolates (odds ratio = 0.19, 95% CI: 0.06–0.66, p = 0.008) but not in non-KL2/10/22/52 isolates. Early recognition of carbapenem resistance-associated capsular types may help clinicians to promptly implement appropriate antimicrobial therapy for improving the outcomes in patients with CRAB bacteraemia.

The novel coronavirus disease 2019 (COVID-19) infection broke out in December 2019 in Wuhan, and rapidly overspread 31 provinces in mainland China on 31 January 2020. In the face of the increasing number of daily confirmed infected cases, it has become a common concern and worthy of pondering when the infection will appear the turning points, what is the final size and when the infection would be ultimately controlled. Based on the current control measures, we proposed a dynamical transmission model with contact trace and quarantine and predicted the peak time and final size for daily confirmed infected cases by employing Markov Chain Monte Carlo algorithm. We estimate the basic reproductive number of COVID-19 is 5.78 (95%CI: 5.71–5.89). Under the current intervention before 31 January, the number of daily confirmed infected cases is expected to peak on around 11 February 2020 with the size of 4066 (95%CI: 3898–4472). The infection of COVID-19 might be controlled approximately after 18 May 2020. Reducing contact and increasing trace about the risk population are likely to be the present effective measures.

Incidence of invasive pneumococcal disease caused by antimicrobial-resistant Streptococcus pneumoniae types not included in pneumococcal conjugate vaccines has increased, including a penicillin- and meropenem-resistant serotype 15A-ST63 clone in Japan. During 2013-2017, we collected 206 invasive pneumococcal isolates in Taiwan for penicillin and meropenem susceptibility testing. We found serotypes 15B/C-ST83 and 15A-ST63 were the most prevalent penicillin- and meropenem-resistant clones. A transformation study confirmed that penicillin-binding protein (PBP) 2b was the primary meropenem resistance determinant, and PBP1a was essential for high-level resistance. The rate of serotype 15B/C-ST83 increased during the study. All 15B/C-ST83 isolates showed an ermB macrolide resistance genotype. Prediction analysis of recombination sites revealed 12 recombination regions in 15B/C-ST83 compared with the S. pneumoniae Spain23F-ST81 genome. Pneumococcal clones rapidly recombine to acquire survival advantages and undergo local expansion under the selective pressure exerted by vaccines and antimicrobial drugs. The spread of 15B/C-ST83 is alarming for countries with high antimicrobial pressure.