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Graphical abstract, Highlights • Skin cancer is a fatal public health concern rising continuously all over the world. • Several environmental and genetic risk factors are associated with cutaneous carcinogenesis. • Use of nanocarriers for targeted delivery of anticancer agents is the most advanced approach. • Polymeric structures are suitable for tumor selective delivery of drugs, genes and imaging agents. • Polymeric micro/nanostructures have successfully used for combination anticancer therapies., Background Skin cancer has been the leading type of cancer worldwide. Melanoma and non-melanoma skin cancers are now the most common types of skin cancer that have been reached to epidemic proportion. Based on the rapid prevalence of skin cancers, and lack of efficient drug delivery systems, it is essential to surge the possible ways to prevent or cure the disease. Aim of review Although surgical modalities and therapies have been made great progress in recent years, however, there is still an urgent need to alleviate its increased burden. Hence, understanding the precise pathophysiological signaling mechanisms and all other factors of such skin insults will be beneficial for the development of more efficient therapies. Key scientific concepts of review In this review, we explained new understandings about onset and development of skin cancer and described its management via polymeric micro/nano carriers-based therapies, highlighting the current key bottlenecks and future prospective in this field. In therapeutic drug/gene delivery approaches, polymeric carriers-based system is the most promising strategy. This review discusses that how polymers have successfully been exploited for development of micro/nanosized systems for efficient delivery of anticancer genes and drugs overcoming all the barriers and limitations associated with available conventional therapies. In addition to drug/gene delivery, intelligent polymeric nanocarriers platforms have also been established for combination anticancer therapies including photodynamic and photothermal, and for theranostic applications. This portfolio of latest approaches could promote the blooming growth of research and their clinical availability.

INTRODUCTION This study aimed to assess understanding of the potential risks associated with medical imaging among caregivers and adolescent patients in a paediatric emergency department (PED) in Singapore. METHODS A prospective convenience sample survey was performed involving adolescents and caregivers presenting to our PED from December 2015 to May 2016. The questionnaire examined demographic data, knowledge of imaging procedures and radiation risks, and expectations regarding information provided about medical radiation. RESULTS A total of 349 questionnaires were returned (caregivers 82.5%, adolescents 17.5%). A mean of 6.2 ± 2.4 (out of 11) questions were correctly answered. Those who had tertiary education fared better than those who did not (36.4% vs. 17.2% scoring above the mean, p = 0.001). Age, gender, history of previous imaging and imaging performed during the visit did not affect the score. Two-thirds of the participants did not associate medical radiation with any negative lifetime risk of cancers or know that different scans entailed differing amounts of radiation. Most were unaware that the radiation dose in medical imaging is adjusted to a child’s size. Among patients who underwent imaging, 90.1% received explanations on the need for scans, and 26.5% were informed of the risks involved. Almost all participants wished to be informed of imaging indications and risks. More preferred to learn this from physicians (75.6%) or technicians (51.6%) rather than through educational pamphlets (34.4%) or Internet resources (22.9%). CONCLUSION Awareness regarding medical radiation needs to be improved in our patient population. A mismatch exists between caregiver expectations and the actual procedure of disclosure of the risk associated with radiation.

Large interindividual variability and over-anticoagulation resulting bleeding complications due to narrow therapeutic index of warfarin has causes its pharmacodynamic activity to be highly variable. Studies shown that ethnicity, age and gender contribute to warfarin response variability. Good coagulation control of time in therapeutic range (TTR) > 75% was chosen to determine the average warfarin dose in atrial fibrillation (AF) among ethnicity, age and gender. Data from Warfarin Medication Therapy Adherence Clinic of selected Pulau Pinang hospitals were used for the analysis of average warfarin dose in AF among ethnicity, age and gender. Patients who fulfilled the inclusion criteria from 2015–2016 were followed up for a year. Five hundred and seventy-six patients were included. Two hundred and ten patients had good coagulation control of TTR > 75% with mean warfarin dose of 3.05 ± 1.25 mg. Only Chinese and Indian have significant difference in average warfarin dose with 2.86 ± 1.10 mg and 4.11 ± 1.40 mg, respectively (p = 0.008). Average warfarin dose was found not significantly different among gender and age. As for TTR achievement, 210 (36.4%) were able to achieve TTR > 75%, 134 patients achieved TTR 60%–75% and 232 patients has TTR < 60%. The median day to achieve three consecutive targeted international normalised ratio (INR) is 186.5 days for atrial fibrillation patient newly started on warfarin therapy in 2015 until 2016. Indian patients required a higher warfarin dose than Chinese patients. This study found that mean warfarin doses were not affected by age and sex.

Purpose The association between the process of postoperative pneumonia and lung cancer recurrence remains elusive in lung cancer surgery. Herein, the association between postoperative pneumonia and lung cancer recurrence was investigated, emphasizing the warning role of postoperative specific pneumonia in primary lung cancer resection patients. Methods The occurrence of postoperative pneumonia was assessed in 4–6 months (PPFS), 7–12 months (PPST), and lung cancer recurrence within 1 year (LRO) in 332 patients. The primary outcome was the development of PPST and LRO according to PPFS occurrence. The relevant risk factors of PPFS, PPST, and LRO were identified through multivariable regression analysis. Results During follow-up, 151 (45.48%) participants experienced PPFS. Irrespective of the existing postoperative pneumonia in 1–3 months (PPOT), PPFS significantly increased the risk of PPST (P < 0.01) and LRO (P < 0.01), and persistent PPST further increased the risk of LRO (P < 0.001). The generalized estimating equation identified chemotherapy as an independent risk factor for PPFS and PPST. Conclusion PPFS was associated with the increased risk of PPST and LRO. Postoperative pulmonary inflammation assessed 4 months post-surgery also significantly influenced LRO development, indicating a need for close follow-up of lung inflammatory conditions to improve patient outcomes., Graphical Abstract

Background: Primary breast angiosarcoma is a rare malignancy with non-specific clinical and radiological findings. Case Report: A 30-year-old lady presented with left breast pain and lumpiness for over one year. She has had several breast ultrasounds (US) and was treated for acute mastitis and abscess. Subsequently, in view of the rapid growth of the lump and worsening pain, she was re-investigated with US, elastography, digital breast tomosynthesis (DBT) and MRI. MRI raised the suspicion of angiosarcoma. The diagnosis was confirmed after biopsy and she underwent mastectomy. Discussion: Literature review on imaging findings of breast angiosarcoma, especially on MRI, is discussed. MRI features showed heterogeneous low signal intensity on T1 and high signal intensity on T2. Dynamic contrast enhancement (DCE) features included either early enhancement with or without washout in the delayed phase, and some reported central areas of non-enhancement. Conclusion: This case report emphasises on the importance of MRI in clinching the diagnosis of breast angiosarcoma, and hence, should be offered sooner to prevent diagnostic delay.

Objectives To analyse the patterns of transition of health burden for 110 causes of death by stratification of age, sex and geographic regions in Guangdong between 2005 and 2015. Methods We analysed the age-specific, sex-specific, region-specific mortality in Guangdong based on assembled databases. County-level surveillance data were calculated to inform city-level changes. Results The age-standardised mortality of all causes, non-communicable diseases (NCDs), communicable diseases, maternal diseases, neonatal diseases, malnutrition and injury declined progressively. Despite declining mortality of NCDs, the overall burden of disease was dominated by NCDs (ie, cerebrovascular disease, chronic obstructive pulmonary disease) that still accounted for 86.93% and 88.12% of death in 2005 and 2015, respectively. Considerable variations across geographic regions were observed (lowest in Pearl River Delta and highest in west Guangdong). There was a modest shift to transport injuries at younger ages and unintentional injuries in the elderly. Conclusions We have documented a dramatic change in the overall mortality and age-specific, sex-specific and cause-specific mortality in Guangdong province between 2005 and 2015. The significant burden of NCDs remains a major healthcare issue despite the notable progress in reducing mortality in Guangdong, China. Our findings highlight important unmet needs to refine healthcare services by taking into account the inequity of age, sex and geographic regions. Identification of the ‘treatable’ risk factors and improved disease surveillance should be continuously improved to minimised the overall and cause-specific mortality.

Background The aim of this study was to evaluate the in vivo confocal microscopic morphology of corneal subbasal nerves and its relationship with clinical parameters in patients with primary Sjögren’s syndrome in China. Methods This was a case control study of 22 dry eye disease (DED) patients with primary Sjögren’s syndrome (pSS) and 20 control subjects with non-Sjögren dry eye disease (NSDE). Each patient underwent an evaluation of ocular surface disease using the tear film break-up time (TBUT), noninvasive tear film break-up time (NIKBUT), noninvasive tear meniscus height (NIKTMH), corneal staining (National Eye Institute scale, NEI), Schirmer I test, meibography, and corneal subbasal nerve analysis with in vivo confocal microscopy (IVCM). The right eye of each subject was included in this study. Results SS patients showed a shorter TBUT (P = 0.009) and Schirmer I test results (P = 0.028) than the NSDE group. However, there was no significant difference in NIKBUT between the two groups (P = 0.393). The nerve density of subbasal nerves, number of nerves and tortuosity of the SS group were significantly lower than those of the NSDE group (P = 0.001, P P = 0.039, respectively). In the SS group, the mean nerve length was correlated with age and the Schirmer I test (r = − 0.519, P = 0.013 and r = 0.463, P = 0.035, respectively). Corneal staining was correlated with nerve density and the number of nerves (r = − 0.534, P = 0.013 and r = − 0.487, P = 0.025, respectively). Conclusions Sjögren syndrome dry eye (SSDE) patients have more severe clinical dry eye parameters than non-Sjögren dry eye disease (NSDE) patients. Compared with NSDE patients, we found that SSDE patients showed decreased corneal subbasal nerve density and numbers.

Objective: This study assesses the prevalence of musculoskeletal (MSK) pain in patients attending primary care clinics in a medium-sized town in Malaysia and examines the interventions given for the symptoms and the level of the associated disabilities. Method: This investigation comprises a cross-sectional descriptive study of all patients visiting two primary care clinics aged 18 years and above. Patients presenting with joint pain answered a questionnaire assessing demographic data, disabilities (measured by the Stanford HAQ-DI), and treatment options. Results: Of 1,074 patients surveyed, 202 (18.8%) had MSK complaints. The mean age of those with MSK pain was 56.1 years. Incidence increased with age, reaching 78.8% of those over 48 years of age. The knee was the most common site of MSK pain (52.2%), with 20.3% requiring referral for specialist assessment. The median HAQ score was 0.375 and 89.6% of those surveyed had mild disability. Conclusion: MSK pain is a common problem among patients visiting primary care clinics. The most common site of MSK pain was the knee. On formal assessment, the majority of these patients exhibited mild disability. A significant proportion of patients still required specialist referral. This finding would suggest a need for further training on the management of MSK disease at the primary care level to avoid over-burdening the secondary care services.

Bladder cancer is one of the most common malignant tumors worldwide. Accordingly, its incidence and mortality are high. One of the characteristics of cancer is genomic instability. New studies suggest that long non-coding RNAs (lncRNAs) play an important role in maintaining genomic instability. This study aimed to identify a genomic instability-associated lncRNA signature to predict the outcome of patients with bladder cancer. We downloaded data for bladder cancer patients from The Cancer Genome Atlas database to obtain lncRNA expression profiles as well as somatic mutation profiles. Using the lncRNA computational framework, a genomic instability-related lncRNA signature (GIlncSig) was established and the prognostic value of this signature was assessed and validated. A five-lncRNA signature based on genomic instability (CFAP58-DT, MIR100HG, LINC02446, AC078880.3, and LINC01833) was obtained from 58 differentially expressed lncRNAs. Patients were divided into high-risk and low-risk groups, with the high-risk group having a substantially worse prognosis than the low-risk group. Univariate and multivariate Cox analyses indicated that GIlncSig may be an independent prognostic factor; this finding was subsequently validated. In addition, enrichment analysis indicated that GIlncSig is associated with genomic instability in bladder cancer. GIlncSig has a predictive value for the prognosis of bladder cancer patients and provides guidance for the clinical treatment of these patients.

Gary Benson,1 Tim Morton,2 Huw Thomas,3 Xin Ying Lee4 1Northern Ireland Haemophilia Comprehensive Care Centre and Thrombosis Unit, Belfast City Hospital, Belfast, UK; 2DRG, Bicester, UK; 3Biopharm, Novo Nordisk Ltd, Gatwick, UK; 4Biopharm Access, Novo Nordisk A/S, Søborg, DenmarkCorrespondence: Xin Ying LeeNovo Nordisk A/S, Vandtårnsvej 114, Søborg DK-2860, DenmarkTel +45 30777030Email xlee@novonordisk.comBackground: The standard of care for patients with hemophilia A is prophylaxis with factor VIII (FVIII) therapies. Extended half-life (EHL) FVIII products offer a reduced infusion burden compared with standard FVIII treatments. However, comparative evidence between EHLs is lacking.Objective: To develop a pharmacodynamic–pharmacokinetic decision model to predict comparative bleed outcomes of adolescents and adults with hemophilia A receiving treatment with various EHL FVIII therapies, capturing differences in cumulative bleeding episodes, breakthrough bleed resolution and resource costs, as well as quality-adjusted life years (QALYs).Methods: The patient population from the pathfinder 2 Phase III clinical trial was used to understand the link between FVIII levels and annual bleeding rates (ABRs). Pharmacokinetic/pharmacodynamic modeling was subsequently applied to estimate FVIII levels for four EHL FVIII treatments (turoctocog alfa pegol [Esperoct®], rurioctocog alfa pegol [Adynovi®], efmoroctocog alfa [Elocta®], and damoctocog alfa pegol [Jivi®]) to predict comparative ABRs. FVIII consumption costs (due to prophylactic treatment and breakthrough bleed resolution) and resource costs, as well as QALYs, were subsequently estimated from a UK NHS perspective over a 70-year time horizon.Results: Turoctocog alfa pegol prophylaxis resulted in 8– 19% fewer cumulative bleeding episodes versus comparators in the base case scenario. Assuming parity in annual prophylaxis costs, turoctocog alfa pegol prophylaxis reduced the cost of product and resource use to resolve a breakthrough bleed by 9– 25% versus comparators. Prophylaxis with turoctocog alfa pegol was also associated with the most QALYs, representing a discounted QALY gain of 0.35– 1.05 compared with the other treatments.Conclusion: Using a pharmacodynamic–pharmacokinetic decision model, turoctocog alfa pegol prophylaxis was associated with fewer cumulative bleeds, as well as lower product and resource costs related to resolving a breakthrough bleed and most QALYs versus comparators.Keywords: hemophilia A, prophylaxis, factor VIII, FVIII, cost-effectiveness model, turoctocog alfa pegol, Esperoct&reg

To evaluate the functional and structural outcomes of intravitreal conbercept monotherapy using a "3 + pro re nata (PRN)" regimen in treatment-naïve subjects with polypoidal choroidal vasculopathy (PCV) up to 12 months.Thirty subjects (30 eyes) with PCV participated in this interventional, retrospective study. All subjects received intravitreal injections of 0.5 mg (0.05 ml) conbercept using a "3 + PRN" regimen for 12 months. The changes in best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) parameters, polyp lesion area, and regression rate were evaluated at baseline, month 3, and month 12.At the study end-point, BCVA improved significantly from 52.80 ± 17.17 ETDRS letters at baseline to 62.20 ± 18.96 letters (P 0.001), with a mean gain of 9.40 ± 14.97 letters. The central retinal thickness (CRT) significantly reduced from 454.93 ± 147.31 μm at baseline to 308.73 ± 106.80 μm (P 0.001) at end-point, and the total macular volume (TMV) decreased from 9.51 ± 1.04 mmIntravitreal conbercept using the "3 + PRN" regimen was effective in the treatment of PCV.

Comparing the incidence of major cardiovascular events and severe microvascular complications in patients with type 2 diabetes mellitus: A systematic review and meta-analysis

Background There has been ongoing research impetus to uncover novel blood-based diagnostic and prognostic biomarkers for Alzheimer’s disease (AD), vascular dementia (VaD), and related cerebrovascular disease (CEVD)-associated conditions within the spectrum of vascular cognitive impairment (VCI). Sphingosine-1-phosphates (S1Ps) are signaling lipids which act on the S1PR family of cognate G-protein-coupled receptors and have been shown to modulate neuroinflammation, a process known to be involved in both neurodegenerative and cerebrovascular diseases. However, the status of peripheral S1P in AD and VCI is at present unclear. Methods We obtained baseline bloods from individuals recruited into an ongoing longitudinal cohort study who had normal cognition (N = 80); cognitive impairment, no dementia (N = 160); AD (N = 113); or VaD (N = 31), along with neuroimaging assessments of cerebrovascular diseases. Plasma samples were processed for the measurements of major S1P species: d16:1, d17:1, d18:0, and d18:1, along with pro-inflammatory cytokines interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF). Furthermore, in vitro effects of S1Ps on cytokine expression were also studied in an astrocytoma cell line and in rodent primary astrocytes. Results Of the S1Ps species measured, only d16:1 S1P was significantly reduced in the plasma of VaD, but not AD, patients, while the d18:1 to d16:1 ratios were increased in all cognitive subgroups (CIND, AD, and VaD). Furthermore, d18:1 to d16:1 ratios correlated with levels of IL-6, IL-8, and TNF. In both primary astrocytes and an astroglial cell line, treatment with d16:1 or d18:1 S1P resulted in the upregulation of mRNA transcripts of pro-inflammatory cytokines, with d18:1 showing a stronger effect than d16:1. Interestingly, co-treatment assays showed that the addition of d16:1 reduced the extent of d18:1-mediated gene expression, indicating that d16:1 may function to “fine-tune” the pro-inflammatory effects of d18:1. Conclusion Taken together, our data suggest that plasma d16:1 S1P may be useful as a diagnostic marker for VCI, while the d18:1 to d16:1 S1P ratio is an index of dysregulated S1P-mediated immunomodulation leading to chronic inflammation-associated neurodegeneration and cerebrovascular damage.

Introduction We evaluated the risk factors associated with Type 1 retinopathy of prematurity (ROP) in very low birth weight (VLBW) infants and compared ophthalmologic outcomes between cases with Type 1 ROP who received treatment and gestational age-matched controls with mild or no ROP not requiring treatment. Methods This was a retrospective case-control study of VLBW infants born in National University Hospital, Singapore, from January 2001 to December 2013. 17 cases with Type 1 ROP were each matched for gestational age with controls who had either mild (below Stage 2) or no ROP. Antenatal, perinatal and postnatal variables, as well as childhood ophthalmologic outcomes, were collected from their clinical records and analysed. Results The number of packed cell transfusions and highest fraction of inspired oxygen given at weeks 7-10 were found to be statistically significant on multivariate analysis (p = 0.045 and p = 0.049, respectively). None of the infants had blindness or retinal detachment, and there were no significant differences in refractive errors between the groups at 1-4 years of age. Strabismus at four years of age was more common in the group with Type 1 ROP (p = 0.023). Conclusion Increased episodes of blood transfusions and chronic lung disease requiring high oxygen supplementation at 7-10 weeks of life are significant risk factors associated with Type 1 ROP in VLBW infants in our study. Strabismus at four years is more common in this group of patients. This study highlights the importance of long-term ophthalmologic surveillance for these high-risk children.

Background Heterotopic pancreas is a common lesion found in the gastrointestinal tract and is usually considered a benign disease. Reports of malignant change of heterotopic pancreas are scarce. Case summary A 44-year-old Chinese female underwent a gastroscopy to assess abdominal distension that had persisted for 2 months. A protruding lesion in the gastric antrum was revealed but no malignant tissue was found in the biopsy specimen. The patient's symptom persisted and progressed to repeated vomiting. Endoscopy after 4 months revealed obstruction of the gastric outlet caused by the protruding lesion. A distal gastrectomy was performed. Histopathological examination of the surgical specimen showed the malignant transformation of aberrant pancreas in the stomach. Chemotherapy consisting of folinic acid, fluorouracil, and oxaliplatin was administered for three cycles, and was changed to gemcitabine monotherapy because of adverse effects and increased serum tumor marker levels. The patient remained asymptomatic during a 12-month follow-up. Conclusion Pancreatic heterotopy should be considered as source of a potentially malignant lesion, and early treatment or close monitoring for aberrant pancreas is recommended.

Background Sphingosine-1-phosphate (S1P) is a bioactive metabolite of sphingolipids and produced by sphingosine kinases (SphK1 and SphK2). SphK1/S1P pathway is implicated in the progression of chronic kidney disease. However, the role of SphK1/S1P pathway in renal injury in hypertension has not been reported. This study tested the hypothesis that SphK1/S1P pathway mediates the kidney damage in DOCA-salt hypertensive mice. Methods Male wild type (WT) C57BL6 and SphK1 knockout (KO) mice were subjected to unilateral nephrectomy, subcutaneous implant containing 50 mg of deoxycorticosterone acetate (DOCA) and 1% NaCl drinking water for 7 weeks. At the end of experiments, blood pressure data, 24 h urine and kidney samples were collected. Renal mRNA levels of SphK1 were measured by real-time RT-PCR. Markers for fibrogenesis and immune cell infiltration in kidneys were detected using Western blot and immunohistochemistray analysis, respectively. The glomerular morphological changes were examined in kidney tissue slides stained with Periodic-Acid Schiff. Four groups were studied: wild type control (WT-C), WT-DOCA, KO-C and KO-DOCA. Results The renal SphK1 mRNA expression was significantly upregulated in WT-DOCA mice, whereas this upregulation of renal SphK1 mRNA was blocked in KO-DOCA mice. There was no difference in DOCA-salt-induced hypertension between WT and KO mice. The urinary albumin was increased in both DOCA-salt groups. However, the albuminuria was significantly lower in KO-DOCA than in WT-DOCA group. There were increases in glomerulosclerosis indices in both DOCA-salt groups, whereas the increases were also significantly lower in KO-DOCA than in WT-DOCA mice. Renal protein levels of α-smooth muscle actin were upregulated in both DOCA-salt groups, but the increase was significant lower in KO-DOCA than in WT-DOCA group. The increased staining areas of collagen detected by Sirius Red-staining in kidney tissue sections were also attenuated in KO-DOCA compared with WT-DOCA mice. In contrast, the increased infiltration of CD43+ (a T cell marker) or CD68+ (a macrophage marker) cells in DOCA-salt kidneys showed no significant difference between WT-DOCA and KO-DOCA mice. Conclusions SphK1/S1P signaling pathway mediates kidney damage in DOCA-salt hypertensive mice independent of blood pressure and immune modulation.

Background Breast cancer is the leading cause of death among women worldwide. Studies have identified breast density as a controversial risk factor of breast cancer. Moreover, studies found that breast density reduction through Tamoxifen could reduce risk of breast cancer significantly. To date, no study on the association between breast density and breast cancer has been carried out in Malaysia. If breast density is proven to be a risk factor of breast cancer, intervention could be carried out to reduce breast cancer risk through breast density reduction. Purpose To determine if density of breast is an independent risk factor which will contribute to development of breast cancer. Materials and Methods A prospective cohort study is carried out in two hospitals targeting adult female patients who presented to the Breast Clinic with symptoms suspicious of breast cancer. Participants recruited were investigated for breast cancer based on their symptoms. Breast density assessed from mammogram was correlated with tissue biopsy results and final diagnosis of benign or malignant breast disease. Results Participants with dense breasts showed 29% increased risk of breast cancer when compared to those with almost entirely fatty breasts (odds ratio [OR] 1.29, 95% CI 0.38‐4.44, P = .683). Among the postmenopausal women, those with dense breasts were 3.1 times more likely to develop breast cancer compared with those with fatty breasts (OR 3.125, 95% CI 0.72‐13.64, P = .13). Moreover, the chance of developing breast cancer increases with age (OR 1.046, 95% CI 1.003‐1.090, P, There are many established risk factors of breast cancer, and density of breast is a controversial risk factor which we wanted to evaluate. Our study shows that postmenopausal women with dense breasts are 3 times more likely to develop breast cancer compared to those with low breast density.

Background and aims The SPINK1 c.194 + 2T > C variant has been increasingly recognized as an important risk factor for chronic pancreatitis (CP). However, there is no clear agreement on its contribution to different ethnicities and CP etiologies. To address this issue, a meta-analysis of literature was performed. Methods Studies addressing the presence of the SPINK1 c.194 + 2T > C variant in CP patients and controls were retrieved from the PubMed, EMBASE and Cochrane databases. Initial analysis included all CP patients, followed by subgroup analyses for East Asian and non-East Asian patients, and for idiopathic CP (ICP) and non-ICP. Results A total of 13 studies were retrieved for analysis, comprising 2097 cases and 4019 controls. There were 126 cases (10.01%) carrying the SPINK1 c.194 + 2T > C variant in cases, while only two controls were carriers (0.05%). Overall, the variant was significantly associated with an increased risk of CP (OR = 25.73). In the subgroup, the variant was significantly associated with increased risk of CP in East Asians (OR = 73.16), and in non-East Asians (OR = 10.21). Further, the contribution of the variant in ICP (OR = 35.31) was found to be higher than in non-ICP (25.75). Conclusions The SPINK1 c.194 + 2T > C variant is a strong risk factor for CP, especially in East Asian patients with ICP.

Background Some studies suggest that people with haemophilia (PwH) who use prophylaxis value low frequency of clotting factor administration more than a lower risk of bleeding. However, more frequent infusions offer the potential of reducing joint disease and pain, which in turn may improve functioning and quality of life. Aims To explore the impact on health-related quality of life (HRQoL) aspects of haemophilia associated with adherence and annual infusion rate in the context of factors influencing treatment that are important to patients, including prophylaxis, chronic pain, concomitant conditions and hospital admission. Materials and methods HRQoL was assessed in participants with severe haemophilia in the ‘Cost of Haemophilia in Europe: a Socioeconomic Survey’ (CHESS) study who were using prophylaxis. Patients using on-demand treatment were excluded. This multivariate analysis examined the interaction between factors potentially influencing treatment and HRQoL, and minor and major bleeds. Results From the total CHESS population (n=1,285), 338 (26%) participants provided responses for major and minor bleeds and target joints, and 145 (11%) provided EQ-5D-3L responses. Major and minor bleeds were associated with pain. Patients with severe chronic pain reported a substantial negative impact on HRQoL; but this was significantly improved by increases in the annual infusion rate. This was not apparent in participants with mild or moderate pain. Conclusion Increasing the frequency of prophylaxis infusions is associated with improved quality of life in PwH who have severe chronic pain. However, increasing the number of infusions per week in those with mild or moderate chronic pain with the intention of improving prophylactic effect may not have the same effect.

Background: With reports of higher mortality and complications occurring in patients with perioperative 2019 novel coronarvirus disease (COVID-19), most elective surgeries have been postponed. However, evidence regarding emergency surgeries in patients with COVID-19 remains scarce. We report the case of a patient with asymptomatic perioperative COVID-19, presenting with an acute abdomen requiring surgery. Case: A 25-year-old male, with a prior nasopharyngeal swab that was negative for SARS-CoV-2, presented with classical signs and symptoms of acute appendicitis. Clinical examination and investigations were not suggestive of COVID-19 infection. He underwent laparoscopic appendicectomy with infection control precautions. Post-operatively, he was found to be positive for SARS-CoV-2 but remained asymptomatic and had an uneventful recovery. Conclusion: In asymptomatic individuals with higher risks, negative test results should be viewed cautiously. The benefits of urgent surgical interventions must be weighed against the risks of complications due to perioperative COVID-19 in these patients.

Since the end of 2019, a new type of coronavirus pneumonia (COVID-19) caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has been spreading rapidly throughout the world. Previously, there were two outbreaks of severe coronavirus caused by different coronaviruses worldwide, namely Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). This article introduced the origin, virological characteristics and epidemiological overview of SARS-CoV-2, reviewed the currently known drugs that may prevent and treat coronavirus, explained the characteristics of the new coronavirus and provided novel information for the prevention and treatment of COVID-19.

Introduction: This meta-analysis aimed to explore the preventive effects of combined statin and antihypertensive therapy on major cardiovascular outcomes in patients with hypertension. Methods: PubMed, Embase, and the Cochrane Library databases and reference lists of published studies were systematically searched throughout October 9, 2019. Studies designed as randomized controlled trials and investigating the effects of combined statin and antihypertensive therapy versus antihypertensive therapy alone were included. Data abstraction and quality of included studies were assessed by 2 independent authors. The summary results were calculated using relative risks (RRs) with 95% CIs employing a random-effects model. Results: A total of 8 randomized controlled trials including 38,618 patients were finally enrolled. The summary RRs indicated that the combined therapy significantly reduced the risk of major adverse cardiovascular events compared with antihypertensive therapy alone (RR 0.79; 95% CI 0.71–0.88; p < 0.001). Furthermore, the patients in the combined therapy group also experienced less myocardial infarction (RR 0.67; 95% CI 0.53–0.84; p = 0.001) and stroke risks (RR 0.82; 95% CI 0.72–0.94; p = 0.005), while no significant difference was observed between combined therapy and antihypertensive therapy alone regarding cardiac death (RR 0.96; 95% CI 0.84–1.08; p = 0.465) and all-cause mortality (RR 0.95; 95% CI 0.86–1.04; p = 0.277). Conclusion: These findings suggested that combined statin and antihypertensive therapy was associated with more cardiovascular benefits compared with antihypertensive therapy alone.

Objective The prevalence of inflammatory bowel disease (IBD) has been increasing worldwide, and the risk of infection has increased due to the use of immunosuppressive and biologic medications. Some of these infections can be prevented with vaccinations. The aim of this study was to evaluate the vaccination practices of Chinese gastroenterologists for patients with IBD. Methods Questionnaires based on quick response codes were sent using email and the WeChat platform to gastroenterologists at 20 hospitals in China. The vaccination practices of the gastroenterologists, including vaccinating for hepatitis B, hepatitis A, and varicella, were assessed. Results Of the 468 gastroenterologists who received the questionnaire, 307 (65.6%) completed it. Of the gastroenterologists who were most concerned about hepatitis B; 83.4% always or frequently asked about an infection history, 53.7% took an immunization history, and 73.6% tested patients for hepatitis B infection. However, few gastroenterologists did so for hepatitis A or varicella. The proportion of patients who were asked about an infection and immunization history and tested for varicella infection was 16.0%, 15.0%, and 9.4%, respectively. Only a few gastroenterologists recommended vaccination for patients without an infection before IBD medical treatment (26.7% for hepatitis A, 45.6% for hepatitis B, and 28% for varicella vaccination). Conclusion Vaccination practices for patients with IBD used by Chinese gastroenterologists vary greatly, suggesting that education about immunization is needed.

Inflammation is usually a tightly regulated process whose termination by mediators including Annexin A1 (AnxA1) results in the resolution of inflammatory responses. In neurodegenerative dementias, chronic neuroinflammation, along with accumulation of aggregated β-amyloid (Aβ) peptides and apoptosis, has long been recognized to be a pathological hallmark; but it is unclear whether a failure of inflammation resolution contributes to this pathophysiological process. In this study, we measured AnxA1 immunoreactivities in postmortem neocortex (Brodmann areas BA9 and BA40) of well characterized Alzheimer's disease (AD), Parkinson disease dementia (PDD) and dementia with Lewy bodies (DLB) patients as well as aged controls. Inactive cleaved AnxA1 was found to be elevated in AD and DLB in BA40. Levels of cleaved AnxA1 also positively correlated with amyloidogenic brain Aβ, anti-inflammatory markers such as IL10 and IL13, as well as with the pro-apoptotic marker cleaved caspase-3 in BA40. Our findings suggest that elevated cleaved AnxA1 in neurodegenerative dementias may reflect a failure of inflammation resolution in certain regions of the diseased brain, and also support a mechanistic link between AnxA1 and amyloid pathology, neuroinflammation and apoptosis.

Hydrogen sulfide (H2S), as one of the three known gaseous signal transduction molecules in organisms, has attracted a surging amount of attention. H2S is involved in a variety of physiological and pathological processes in the body, such as dilating blood vessels (regulating blood pressure), protecting tissue from ischemia-reperfusion injury, anti-inflammation, carcinogenesis, or inhibition of cancer, as well as acting on the hypothalamus and pancreas to regulate hormonal metabolism. The change of H2S concentration is related to a variety of endocrine disorders, and the change of hormone concentration also affects the synthesis of H2S. Understanding the effect of biosynthesis and the concentration of H2S on the endocrine system is useful to develop drugs for the treatment of hypertension, diabetes, and other diseases.

Respiratory diseases are leading causes of death and disability around the globe, with a diverse range of health problems. Treatment of respiratory diseases and infections has been verified to be thought-provoking because of the increasing incidence and mortality rate. Hydrogen sulfide (H2S) is one of the recognized gaseous transmitters involved in an extensive range of cellular functions, and physiological and pathological processes in a variety of diseases, including respiratory diseases. Recently, the therapeutic potential of H2S for respiratory diseases has been widely investigated. H2S plays a vital therapeutic role in obstructive respiratory disease, pulmonary fibrosis, emphysema, pancreatic inflammatory/respiratory lung injury, pulmonary inflammation, bronchial asthma and bronchiectasis. Although the therapeutic role of H2S has been extensively studied in various respiratory diseases, a concrete literature review will have an extraordinary impact on future therapeutics. This review provides a comprehensive overview of the effective role of H2S in respiratory diseases. Besides, we also summarized H2S production in the lung and its metabolism processes in respiratory diseases.

Background/AimsTo compensate the retinal nerve fibre layer (RNFL) thickness assessed by spectral-domain optical coherence tomography (SD-OCT) for anatomical confounders.MethodsThe Singapore Epidemiology of Eye Diseases is a population-based study, where 2698 eyes (1076 Chinese, 704 Malays and 918 Indians) with high-quality SD-OCT images from individuals without eye diseases were identified. Optic disc and macular cube scans were registered to determine the distance between fovea and optic disc centres (fovea distance) and their respective angle (fovea angle). Retinal vessels were segmented in the projection images and used to calculate the circumpapillary retinal vessel density profile. Compensated RNFL thickness was generated based on optic disc (ratio, orientation and area), fovea (distance and angle), retinal vessel density, refractive error and age. Linear regression models were used to investigate the effects of clinical factors on RNFL thickness.ResultsRetinal vessel density reduced significantly with increasing age (1487±214 µm in 40–49, 1458±208 µm in 50–59, 1429±223 µm in 60–69 and 1415±233 µm in ≥70). Compensation reduced the variability of RNFL thickness, where the effect was greatest for Chinese (10.9%; pConclusionsRNFL thickness compensated for anatomical parameters reduced the variability of measurements and may improve glaucoma detection, which needs to be confirmed in future studies.

Susan Kearney,1,* Leslie J Raffini,2 Tan P Pham,3 Xin Ying Lee,4 Sylvia von Mackensen,5,* Andrea Landorph,6 Hideyuki Takedani,7 Johannes Oldenburg8 1Center for Bleeding and Clotting Disorders, Children’s Hospital Minnesota, Minneapolis, MN, USA; 2Division of Hematology, The Children’s Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; 3Mapi (an Icon plc company), Boston, MA, USA; 4Global Biopharm Patient Access, Biopharm Operations, Novo Nordisk A/S, Copenhagen, Denmark; 5Department of Medical Psychology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany; 6Medical & Science, Biopharm Operations, Novo Nordisk A/S, Copenhagen, Denmark; 7Department of Joint Surgery, Research Hospital of the Institute of Medical Science, The University of Tokyo, Tokyo, Japan; 8Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Bonn, Germany *These authors contributed equally to this work Background: Prophylactic treatment regimens lead to improvements in health-related quality-of-life (HRQoL) among individuals with hemophilia. Turoctocog alfa pegol (N8-GP) provides the benefit of extending the duration of protection from bleeding and reducing the number of injections, which is expected to impact HRQoL and treatment satisfaction (TS). Aim: To investigate the HRQoL and TS of patients with severe hemophilia A from two phase III trials evaluating the safety and efficacy of N8-GP. Methods: HRQoL was assessed using the Haemo-QoL (reported by children and their parents) and Haem-A-QoL (reported by adults). TS was assessed using Hemo-Sat. Domain and total scores for all questionnaires ranged from 0 to 100, with lower scores indicating a better HRQoL or TS. A negative change in score indicates an improvement in HRQoL/TS. Results: Mean changes in HRQoL scores were reported for 14 children aged 4–7 years, 21 children aged 8–11years, 10 adolescents aged 13–16years, and 163 adults (17years and above). Mean changes in children/adolescents-reported Haemo-QoL total score were -14.0 for ages 4–7years, -3.6 for ages 8–11years, and -0.1 for ages 13–16years. Mean changes in parent-reported Haemo-QoL total scores were -11.5 for 4–7years, -8.6 for ages 8–11years, and -4.0 for 13–16years. Adults’ mean change in Haem-A-QoL total score was -3.1 for those receiving on-demand treatment and -2.3 for those receiving prophylaxis treatment. High levels of TS with N8-GP were reported by parents of children/adolescents and the adults at the end of the trial. Conclusion: While most patients reported a relatively good baseline HRQoL when entering the respective trials, the HRQoL of patients was either maintained or further improved when treated with N8-GP. Adults and parents of children and adolescents reported a high level of treatment satisfaction with N8-GP. Keywords: hemophilia A, turoctocog alfa pegol, health-related quality-of-life, children, adults, treatment satisfaction

Background This study aims to understand suicidal ideation and suicide attempts among transgender individuals through an in-depth analysis of a nation-wide population general survey in China. Methods Transgender Men (TM) and Women (TW) were investigated through a cross-sectional survey. A structured questionnaire was used to investigate participants' demographic information, perceived sexuality conflicts, childhood adversity and mental health conditions. Logistic regression models were utilized to investigate risk factors associated with suicidal ideation and suicide attempts in these groups. We also conducted a quasi-meta-analysis in order to compare the prevalence of suicidal ideation and attempted suicide between general and transgender populations in China. Results A total of 1309 participants across 32 provinces and municipalities in China took part in this survey, out of 2060 valid questionnaires. In this transgender population, the lifetime prevalence of suicidal ideation and an attempt at suicide were 56.4% and 16.1%, respectively. This estimated prevalence rate is far greater than in Chinese community samples. For all transgender people, disliking birth-assigned sex, seeking sex reassignment surgery, having intense conflicts with parents, lifetime history of suffering from major depressive disorder, a recent episode of depression, self-harm, and seeking mental health services were significantly associated with increased risk of suicidal ideation. An education level of high school or equivalent, being married and/or separated/divorced, having intense conflicts with parents, or self-harm and seeking mental health services were all significantly associated with increased risk of suicide attempt. Although most risk factors for TM and TW were equivalent across groups, differences were observed in both suicidal ideation and suicide attempt models. Limitations The cross-sectional study design and lack of follow-up data are limitations of this study. Conclusions This is the first study to examine suicide within a Chinese transgender population. The clinical implications of these findings for Chinese mental health professionals are discussed. Also, the evidence from this study can be used to inform the practices of suicide prevention workers, and policy makers working with the transgender population.

Memory clinics play an important role in enabling early dementia diagnosis and intervention. Few studies have investigated the changing patient profiles at memory clinics over time. We studied the trend of patient characteristics in a geriatric medicine-led memory clinic over 12 years to improve services and care to meet their needs. Data from 2340 first-visit patients seen at a memory clinic from 2005–2017 were extracted from a registered database and analysed. ANOVA, Pearson chi-square and non-parametric tests were used to describe and compare between patients with dementia (PWD) and patients with no dementia (PND). Data included diagnoses of dementia and mild cognitive impairment, age, education, MMSE scores and comorbidities. Patients averaged 77.2 ± 8.3 years of age with mean MMSE score of 16.2 ± 6.7. Those diagnosed with dementia were older (78.3 ± 7.9 years) and almost half (48.4%) had moderate or moderately severe dementia (FAST 5-6). Over time, there was a growing proportion of patients with mild cognitive impairment (MCI) and mild Alzheimer’s dementia. Many PWD had co-morbidities of hypertension (65.9%), hyperlipidemia (55.1%), diabetes (33.5%) and 28.4% were frail. The findings call for services to better diagnose and manage patients at the earlier stages of cognitive impairment and provide holistic interventions for those with frailty and other co-morbidities. The continued rise in number of patients presenting to memory clinics provides impetus to expedite integration of tertiary-based memory clinics with primary and community care providers to better support PWD and their families.

Background: Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid metabolite involved in various diseases. S1P also plays significant roles in the differentiation of fibroblasts into myofibroblasts, being implicated in fibrotic diseases. S1P is produced by the phosphorylation of sphingosine catalyzed by sphingosine kinases (SphK1 and SphK2). It remains unclear if the activation of endogenous SphK1 contributes to fibrogenesis in kidneys. The present study determined the effect of SphK1 gene knockout (KO) on fibrotic markers in kidneys. Methods: The renal fibrosis was produced using the unilateral ureteral obstruction (UUO) model in wild-type (WT) and SphK1 gene KO mice. Renal mRNA levels of SphK1 and S1P receptors (S1PR) were measured by real-time RT-PCR. Fibrotic and immune cell markers in kidneys were measured by Western blot analysis and immunostaining, respectively. Renal morphological damage was examined by Periodic-Acid Schiff staining. Results: The mRNA levels of SphK1 and S1PRs were dramatically increased in renal tissues of WT-UUO mice, whereas the increase in renal SphK1 mRNA was blocked in KO-UUO mice. Interestingly, the increased levels of fibrotic markers, collagen and α-smooth muscle actin, in kidneys were significantly attenuated in KO-UUO versus WT-UUO mice. Meanwhile, kidney damage indices were remarkably attenuated in KO-UUO mice compared with WT-UUO mice. However, increased numbers of CD43+ and CD48+ cells, markers for T cell and macrophage, respectively, showed no significant difference between ­WT-UUO and KO-UUO kidneys. Conclusion: The activation of the SphK1-S1P pathway may contribute to tubulointerstitial fibrosis in UUO kidneys by affecting fibrotic signaling within renal cells independent of immune modulation.

Highlights • Adenoma, carcinoma and hyperplasia cause parathyroid gland enlargement. • Mimics include thyroid nodules and cystic structures in the head and neck. • Enlarged parathyroid glands can enhance variably following contrast administration. • Hyperparathyroidism can present acutely with respiratory compromise. • Syndromic associations., Primary hyperparathyroidism is associated with significant morbidity and mortality. It is in this day and age, an eminently treatable condition which relies heavily on preoperative imaging to localise enlarged parathyroid glands. The imaging appearances of parathyroid gland enlargement are varied; this paper seeks to address some of its more unusual manifestations with an emphasis on its atypical enhancement patterns, mimics and associations. An enlarged glands may also present as an ‘incidentaloma’ in head and neck imaging performed for entirely different indications, or as part of sporadic or familial syndrome. Radiologists are in a good position to expedite the relevant investigations and curative treatment, and knowledge of the spectrum of imaging appearances is crucial.

Securing a definitive airway in patients who require surgical fixation of complex maxillofacial fractures is an integral part of their perioperative management. For the ease of surgical access, an orotracheal tube is usually not preferred by surgeons. The presence of a base of skull or nasal bone fractures would also contraindicate nasotracheal intubation. Therefore, a tracheostomy may be the only option left to secure the airway in these patients who require surgical fixation. Submental intubation has been used as a safe and effective alternative method in patients who require intubation for maxillofacial reconstruction since it was first reported by Hernandez Altemir F in 1986. Many modifications to the original technique have been documented over the years, but there has been no consensus to support the use of a single method or device. In this case report, we described our experience with submental intubation using an LMAFastrachTM endotracheal tube (ETT) to facilitate the surgical fixation of bilateral Le Fort II fractures. We conclude that the LMAFastrachTM ETT is a suitable device for submental intubation. This technique should be included in airway workshops and courses for anaesthesia residents as it is a simple yet secure alternative to tracheostomy in the intraoperative airway management of maxillofacial trauma.

This study was designed to establish a modified prediction score system to improve the safety and success rate of vaginal birth after cesarean delivery (VBAC). We recruited 406 patients (between January 2012 and December 2016) and generated a modified score system in predicting the success rate of VBAC. All patients were required to sign informed consent forms. There were 87.2% of patients who had successful VBAC deliveries and 12.8% patients who had repeated cesarean sections. We conducted multivariable logistic regression and found seven variables that were associated with VBAC success, including previous primary indication of cesarean delivery (odds ratio (OR), 2.1; 95% confidence interval (CI), 1.4–3.0), previous vaginal birth history (OR, 2.5; 95% CI, 1.8–3.8)

Nazeer Hussain Khan,1,2 Shao-Feng Duan,3 Dong-Dong Wu,1,4 Xin-Ying Ji1,4,5 1Henan International Joint Laboratory for Nuclear Protein Regulation, Henan University, Kaifeng, Henan, 475004, People’s Republic of China; 2School of Life Sciences, Henan University, Kaifeng, Henan, 475004, People’s Republic of China; 3Institute for Innovative Drug Design and Evaluation, School of Pharmacy, Henan University, Kaifeng, Henan, 475004, People’s Republic of China; 4School of Basic Medical Sciences, Henan University College of Medicine, Kaifeng, Henan, 475004, People’s Republic of China; 5Kaifeng Key Laboratory of Infection and Biological Safety, Henan University College of Medicine, Kaifeng, Henan, 475004, People’s Republic of ChinaCorrespondence: Dong-Dong Wu; Xin-Ying Ji Email ddwubiomed2010@163.com; 10190096@vip.henu.edu.cnAbstract: Breast cancer is the most commonly diagnosed cancer and the leading cause of cancer deaths in women globally. In 2018, 2.1 million new cases were reported, with 627,000 deaths. Pakistan has the highest incidence rate of breast cancer among Asian countries: one in every nine women has a lifetime risk of being diagnosed with breast cancer. By reason of many misconceptions about the etiology of the disease and socioeconomic factors, Pakistani women have very low rates of early detection and diagnose breast cancer at advance stages with fewer chances of survival. The key to cure the breast cancer is early diagnosis. The aim of current review is to highlight the factors leading to the delays in early presentation of breast cancer in Pakistani women and to summarize possible recommendations for educating women about early diagnosis along with palliative care facilities for patients suffering from breast cancer. Furthermore, this study appeals to both the general public and government in the belief that better reporting and awareness campaigns may bring more women to clinics for early diagnosis.Keywords: breast cancer, health budget, Pakistani women, better reporting; awareness campaigns

Calcification is common in atherosclerotic plaque and can induce vulnerability, which further leads to myocardial infarction, plaque rupture and stroke. The mechanisms of atherosclerotic calcification are poorly characterized. Interleukin enhancer binding factor 3 (ILF3) has been identified as a novel factor affecting dyslipidemia and stroke subtypes. However, the precise role of ILF3 in atherosclerotic calcification remains unclear. In this study, we used smooth muscle-conditional ILF3 knockout (ILF3SM-KO) and transgenic mice (ILF3SM-Tg) and macrophage-conditional ILF3 knockout (ILF3M-KO) and transgenic (ILF3M-Tg) mice respectively. Here we showed that ILF3 expression is increased in calcified human aortic vascular smooth muscle cells (HAVSMCs) and calcified atherosclerotic plaque in humans and mice. We then found that hyperlipidemia increases ILF3 expression and exacerbates calcification of VSMCs and macrophages by regulating bone morphogenetic protein 2 (BMP2) and signal transducer and activator of transcription 1 (STAT1) transcription. We further explored the molecular mechanisms of ILF3 in atherosclerotic calcification and revealed that ILF3 acts on the promoter regions of BMP2 and STAT1 and mediates BMP2 upregulation and STAT1 downregulation, which promotes atherosclerotic calcification. Our results demonstrate the effect of ILF3 in atherosclerotic calcification. Inhibition of ILF3 may be a useful therapy for preventing and even reversing atherosclerotic calcification.

COVID-19 has spread rapidly worldwide since its outbreak and has now become a major public health problem. More and more evidence indicates that SARS-CoV-2 may not only affect the respiratory system but also cause great harm to the central nervous system. Therefore, it is extremely important to explore in-depth the impact of SARS-CoV-2 infection on the nervous system. In this paper, the possible mechanisms of SARS-CoV-2 invading the central nervous system during COVID-19, and the neurological complications caused by SARS-CoV-2 infection were reviewed.

Xin-ying Cai,1 Dong-qi Lin,2 Zhi-zhen Xiao,3 Dan-dan Zhang,3 Ying Lin,3 Han-yu Chen,4 Yan-xing Xu,3 Yu-hua Zhou3 1Clinical Medical Research Center, Shantou Central Hospital, Affiliated Shantou Hospital of Sun Yat-Sen University, Shantou, Guangdong, People’s Republic of China; 2Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, People’s Republic of China; 3Nursing Department, Shantou Central Hospital, Affiliated Shantou Hospital of Sun Yat-Sen University, Shantou, Guangdong, People’s Republic of China; 4Rehabilitation Department, Shantou Central Hospital, Affiliated Shantou Hospital of Sun Yat-Sen University, Shantou, Guangdong, People’s Republic of ChinaCorrespondence: Yu-hua ZhouNursing Department, Shantou Central Hospital, Wai-ma Road 114, Shantou City, Guangdong Province, People’s Republic of ChinaTel +86 0754-88903584Fax +86 0754-88548117Email zhouyuhua1023@163.comDong-qi LinDepartment of Cardiothoracic Surgery, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, People’s Republic of ChinaTel +86 0754-88915647Email doctorldq@163.comBackground: Postoperative functional training for fracture or osteoarthritis is mainly focused on functional self-exercise, which aims to recover the function of the lower limbs.Purpose: To compare the function and life quality recovery in patients with fracture or arthritis treated with novel muscle training device (NMT) or conventional rehabilitation training (CRT) following surgery.Patients and Methods: A total of 32 fracture patients were randomly divided into the NMT or the CRT groups. The evaluation was performed on the first and 7th day after surgery. The outcome measurements included the incidence of foot drop, Deep Vein Thrombosis and pressure ulcers, Hospital for Special Surgery knee score (HSS scores), pain scores for the Visual Analogue Scale (Pain scores for VAS), Zung self-rating anxiety scale (SAS), Pittsburgh sleep quality index (PSQI) and the Barthel Index score.Results: The comparison of the change scores between the two groups indicated significant differences on day 7 following surgery in the Barthel Index score (P< 0.01). The Pain scores for VAS between the two groups indicated a significant difference (P< 0.05, U=20.0). The HSS scores between the two groups indicated a significant difference (P< 0.05, U=19.0). The HSS scores exhibited a highly significant difference in the NMT group (P< 0.01). The Mann–Whitney test was used to analyze the various components of the HSS scores. The comparison of the change scores on the function between the two groups indicated a significant difference (P< 0.05). The Range of Motion difference between groups exhibited highly significant differences (P< 0.01).Conclusion: The novel muscle training device positively influenced the decrease in pain score, which resulted in a range increase of knee joint movement and a significant overall improvement in motion.Keywords: orthopedics, fracture, middle-aged and elderly, function exercise

The chemokine (C-C motif) ligand 2 (CCL2) and its receptor CCR2 are involved in gestational diabetes mellitus (GDM). The present study aims to explore the effects of CCL2 blocking on GDM. Serum CCL2, interleukin (IL)-6, and tumor necrosis factor (TNF)-α were determined in GDM patients and healthy volunteers. C57BL/KsJdb/+mouse was used as the GDM model and CCL2 antibody (αCCL2) was applied. Flow cytometry was applied to determine the frequency of macrophages. Quantitative reverse transcription PCR (RT-qPCR) and western blot were determined to detect the mRNA and protein expressions, respectively. Enzyme-linked immunosorbent assay (ELISA) was applied to determine the levels of inflammatory cytokines and serum insulin. Serum CCL2 was correlated with inflammatory cytokines (IL-6 and TNF-α) in the GDM patients. Besides, the results showed high expressions of CCL2 in the visceral adipose tissue (VAT) and placenta tissue in the GDM mice. Flow cytometry and immunohistochemistry (IHC) staining showed the accumulations of macrophages in these tissues. Treatment of αCCL2 attenuated the GDM symptoms and ameliorated the inflammation. Furthermore, the treatment of αCCL2 improved reproductive outcomes in the GDM mice. Blockade of CCL2 attenuated GDM symptoms and reduced inflammatory cytokines in a genetic mice model.

INTRODUCTION: The majority of patients with COVID-19 infection do not progress to pneumonia. We report emergency department (ED)-specific variables and evaluate their predictive performance on diagnosis of pneumonia, intensive care unit (ICU) admission and death. METHODS: This was a retrospective, single-centre cohort study of confirmed COVID-19 patients admitted to a Singapore tertiary hospital. Primary outcome was diagnosis of COVID-19 pneumonia. Secondary outcomes were ICU admission and/or death. Multivariate logistic regression was used to analyse the predictive performance of ED-specific variables. Accuracy of continuous variables was measured by area under receiver operating characteristic (ROC) curve. RESULTS: 294 patients were included. Patients with pneumonia were older (52.0 years, p < 0.001) and had higher C-reactive protein (CRP; 33.8 mg/L, p < 0.001). Patients with indeterminate chest radiograph (CRX) findings were at risk of pneumonia vs. patients with normal CRX (37.5% vs. 4.3%, p < 0.001). Patients admitted to ICU were older (60.0 years, p < 0.001) and had higher CRP (40.0 mg/L, p < 0.001). Diagnosis of COVID-19 pneumonia was associated with ICU admission and death (30.0% vs 0.39%, p < 0.001). Multivariate logistic regression analysis showed that age (aOR 1.07, p = 0.049), CRP (aOR 1.05, p = 0.006) and CRX findings (aOR 50.00, p < 0.001) had increased odds of pneumonia. ROC curve analysis showed that CRP of 23.3 mg/L was the optimal cut-off for predicting pneumonia. CONCLUSION: Older age, higher CRP and CRX findings are associated with COVID-19 pneumonia, ICU admission and death. Prospective studies should be undertaken to validate these findings.

We aimed to analyze the effect of lymph node dissection (LND) and accurate lymph node (LN) status on the survival and prognosis of patients with thymic carcinomas (TCs) and thymic neuroendocrine tumors (TNETs) undergoing surgical treatment. The Surveillance, Epidemiology, and End Results database was queried for patients who underwent surgical resection for TCs and TNETs during 1998-2016. LN status were defined as no LND (LND-), pathologically negative with LND (N0), and LN metastasis positive (N+). We investigated outcomes of LN status together with other clinicopathological features for overall survival (OS). Subgroup analyses were performed between LND-, N0, and N+ cohorts using propensity score matching, to analyze the significance of LND in prognosis. A total of 812 patients were enrolled, including 623 with TCs and 189 with TNETs. The proportion of LN metastasis positive in TNETs was 58.8% which was significantly higher than that in TCs (30%) (P0.001). In multivariable Cox analysis of OS, patients with LND- had a significantly worse prognosis than those with N0 (P = 0.018); there was no difference between N+ and LND- (P = 0.560). After propensity score matching, patients with N0 still had better survival than those with LND- and N+ in subgroup univariable and multivariable analyses of OS; however, the survival of patients with LND- and N+ was not significantly different in multivariable analysis. It was demonstrated that LND in TCs and TNETs can clarify the status of LN metastasis, to more accurately evaluate patients' long-term prognosis.

Aim: The aim of this study was to develop a population pharmacokinetic (PPK) model in Chinese children for intravenous busulfan, and to develop a novel busulfan dosing regimen to support better area under the concentration-time curve (AUC) targeting. Methods: We collected busulfan concentration-time samples from 69 children who received intravenous busulfan prior to allogeneic hematopoietic stem cell transplantation (allo-HSCT). A population pharmacokinetic model for busulfan was developed by nonlinear mixed effect modelling and was validated by an external dataset (n=14). A novel busulfan dosing regimen was developed through simulation on 1000 patients. Limited Sampling Strategy (LSS) was established by the Bayesian forecasting. Absolute Prediction Error (APE), Mean Absolute Prediction Error (MAPE) and relative Root Mean Squared Error (rRMSE) were calculated to evaluate predictive accuracy. Results: A one-compartment model with first-order elimination best described the data. GSTA1 genotypes, BSA and AST were found to be significant covariates of Bu clearance, and BSA had remarkable impact of the volume. Moreover, recommended dose regimens for children with different GSTA1 genotypes and BSA were developed with a perfect AUC targeting. A two-point LSS, two hours and four hours after dosing, behaved well with acceptable prediction precision. Conclusion: This study developed a PPK model for busulfan that firstly incorporated GSTA1 genotypes in an Asian pediatric population. We recommend a BSA-based dosing for personalizing busulfan therapy in pediatric population. Additionally, an optimal LSS (C2h and C4h) provides convenience for therapeutic drug monitoring (TDM) in the future.

Endoscopic ultrasound-guided minimally invasive tissue acquisition can be performed by two approaches as follows: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB). These have been evolved into leading approaches and widely used for the histological diagnosis of tumors in the gastrointestinal tract and adjacent organs. However, the role of EUS-FNA and EUS-FNB in disease diagnosis and evaluation remains controversial. Although the incidence of surgery-associated complications remains low, the consequences of needle tract seeding can be serious or even life-threatening. Recently, increasing case reports of needle tract seeding are emerging, especially caused by EUS-FNA. This complication needs serious consideration. In the present work, we integrated these case reports and the related literature, and summarized the relevant cases and technical characteristics of needle tract seeding caused by EUS-FNA and EUS-FNB. Collectively, our findings provided valuable insights into the prevention and reduction of such serious complication.

Background Guangdong province is dominated by three cultural regions: Canton, Hakka and Hoklo. However, little is known about the disease burden within these regions, particularly because different population,environmental and socioeconomic risk factors might cause different patterns of mortality, disability-adjusted life-years (DALY), life expectancy and healthy life expectancy (HALE). We aimed to compare the patterns of disease burden in Canton, Hakka and Hoklo regions between 2005 and 2015. Method We calculated the mortality, YLL, YLD for 116 diseases for different cultural regions between 2005 and 2015. We calculated the DALYs for 116 causes as the sum of YLLs and YLDs. We estimated the life expectancy and HALE by using sex-specific mortality rates and YLDs for the three cultural regions. Results With a respective reduction of 22.3, 15.8 and 17.8% in 2015 compared with 2005, the age-standardized DALY rates in 2015 was 19,988.0, 14,396.5 and 20,436.6 in Hakka, Canton and Hoklo region. Canton region had a significantly lower mortality and DALYs in most diseases, followed by Hoklo and Hakka regions. The life expectancy and HALE at birth were highest in Canton region in both 2005 and 2015, than in Hoklo and Hakka region. Conclusions Our findings call for improved public health care via the refinement of policy and effective measures for disease prevention. Understanding the environmental and culture-related risk factors of diseases in Hoklo and Hakka regions may help inform public health sectors to reduce the disease burden and the between-region inequality.

This study is to explore the neuroprotective effects and involved glial scar of saffron (Crocus sativus L.) on the late cerebral ischemia in rats. Focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) in Sprague Dawley rats that were randomly divided into sham group, MCAO group, edaravone group (as a positive control) and saffron groups (saffron extract 30, 100, 300 mg/kg). Saffron was administered orally at 2 h at the first day and once daily from day 2 to 42 after ischemia. Behavioral changes were detected from day 43 to 46 after ischemia to evaluate the effects of saffron. Infarct volume, survival neuron density, activated astrocyte, and the thickness of glial scar were also detected. GFAP, neurocan, phosphocan, neurofilament expressions and inflammatory cytokine contents were detected by Western-blotting and ELISA methods, respectively. Saffron improved the body weight loss, neurological deficit and spontaneous activity. It also ameliorated anxiety-like state and cognitive dysfunction, which were detected by elevated plus maze (EPM), marble burying test (MBT) and novel object recognition test (NORT). Toluidine blue staining found that saffron treatment decreased the infarct volume and increased the neuron density in cortex in the ischemic boundary zone. The activated astrocyte number and the thickness of glial scar in the penumbra zone reduced after saffron treatment. Additionally, saffron decreased the contents of IL-6 and IL-1β, increased the content of IL-10 in the ischemic boundary zone. GFAP, neurocan, and phosphocan expressions in ischemic boundary zone and ischemic core zone all decreased after saffron treatment. Saffron exerted neuroprotective effects on late cerebral ischemia, associating with attenuating astrogliosis and glial scar formation after ischemic injury.

Background Since December 2019, the 2019 coronavirus disease (COVID-19) has expanded to cause a worldwide outbreak that more than 600,000 people infected and tens of thousands died. To date, the clinical characteristics of COVID-19 patients in the non-Wuhan areas of Hubei Province in China have not been described. Methods We retrospectively analyzed the clinical characteristics and treatment progress of 91 patients diagnosed with COVID-19 in Jingzhou Central Hospital. Results Of the 91 patients diagnosed with COVID-19, 30 cases (33.0%) were severe and two patients (2.2%) died. The severe disease group tended to be older (50.5 vs. 42.0 years; p = 0.049) and have more chronic disease (40% vs. 14.8%; p = 0.009) relative to mild disease group. Only 73.6% of the patients were quantitative polymerase chain reaction (qPCR)-positive on their first tests, while typical chest computed tomography images were obtained for each patient. The most common complaints were cough (n = 75; 82.4%), fever (n = 59; 64.8%), fatigue (n = 35; 38.5%), and diarrhea (n = 14; 15.4%). Non-respiratory injury was identified by elevated levels of aspartate aminotransferase (n = 18; 19.8%), creatinine (n = 5; 5.5%), and creatine kinase (n = 14; 15.4%) in laboratory tests. Twenty-eight cases (30.8%) suffered non-respiratory injury, including 50% of the critically ill patients and 21.3% of the mild patients. Conclusions Overall, the mortality rate of patients in Jingzhou was lower than that of Wuhan. Importantly, we found liver, kidney, digestive tract, and heart injuries in COVID-19 cases besides respiratory problems. Combining chest computed tomography images with the qPCR analysis of throat swab samples can improve the accuracy of COVID-19 diagnosis.

The high incidence of osteopathy among patients with chronic pancreatitis (CP) has garnered increased attention over recent years. The aims of this study were to assess the prevalence and risk factors for osteopathy in Chinese patients with CP. This was a cross-sectional study of CP patients from a large center in China; patients were recruited between 31 January 2017 and 31 January 2018. Bone density and laboratory tests, including bone-related biochemical, inflammatory, and hormone parameters, were assessed prospectively. Differences between patients with and without osteopathy were analyzed. Logistic regression analysis was used to investigate associations between variables. In total, 104 CP patients were enrolled in this study (68.3% idiopathic and 31.7% alcoholic). According to the M-ANNHEIM classification, 87.5% of the patients were at an early stage (0–II). Osteopenia was diagnosed in 30.8% of patients and osteoporosis in 5.8%; thus, a total of 36.5% of patients presented with osteopathy. In multivariate analysis, the independent risk factors for osteopathy in CP patients were age (OR = 1.04; 95% CI = 1.00–1.08; P = 0.030), BMI (OR = 0.72; 95% CI = 0.58–0.89; P = 0.003), and PTH (OR = 0.96; 95% CI = 0.93–1.00; P = 0.022). This study is the first to report the prevalence of osteopathy in Chinese patients with CP. It found that age and low BMI are significant risk factors for osteopathy. Low PTH (but within the normal range) showed a weak association with osteopathy, which warrants further exploration.