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Background Herpes zoster presents as clustered blisters on one side of the body, accompanied by nerve pain. This is caused by reactivation of the varicella zoster virus, and it occurs primarily in people with weakened immunity. Tumor and chemotherapy drugs can impair the patient's immune function, induce herpes zoster and prolong the course of disease.In these patients, skin changes can last for months and blisters can recur and cause serious complications such as postherpetic neuralgia.Acupuncture is a common alternative therapy for herpes zoster in East Asia. Case presentation We report a case of an elderly male patient with widespread herpes zoster in the trunk after non-Hodgkin's lymphoma chemotherapy. The patient had received conventional treatment with valaciclovir and mecobalamin within 24 hours of symptom onset. Because neither the clustered blisters nor the nerve pain were improved a week later, acupuncture and related techniques were applied. These included electro-acupuncture, surrounding acupuncture, fire acupuncture, and cupping. The patient recovered 20 days after the herpes zoster attack, and there were no adverse reactions during the treatment process. Conclusions This case suggests that acupuncture and related techniques are effective interventions for this condition.This case report is innovative because it shows that acupuncture as an adjuvant treatment can improve the skin lesions in patients with HZ after tumour chemotherapy, relieve pain, and shorten the course of HZ.

The objective of this study was to investigate the clinical manifestations and pathologic appearances of the submandibular gland (SMG) in Stevens-Johnson syndrome (SJS).Patients with autologous transplantation of SMG for treatment of severe dry eye between March 1998 and May 2018 were divided into the SJS group (70 cases) and non-SJS group (50 cases) according to the history of SJS. The SMG weight and computed tomography volume and salivary flow rate were measured. The concentration index and secretion index were estimated using scintigraphy with technetium-99m-pertechnetate. Histopathology studies of SMG tissues were conducted, and the acini parameters were measured using a digital image analyzer.A decreased computed tomography volume and weight was observed in 48.57% the SJS group and 2% in the non-SJS group (P.01). The rest whole, acid-stimulated whole, and SMG rest salivary flow rates decreased in the SJS group (P.05). The normal SMG concentration index (37.5% vs 96.67%, P.001) and secretion index (35% vs 96.67%, P.001) rates were lower in the SJS group than in the non-SJS group. The glandular parenchyma was reduced, the acinar space was widened, and the fat content was increased in the SJS group.SMG atrophic and degenerative changes occurred in the SJS group, with a decrease in salivary secretion function in more than half of the patients.

Background: Coronavirus disease 2019 (COVID-19) pandemic continues to escalate intensively worldwide. Massive studies on general populations with SARS-CoV-2 infection have revealed that pre-existing comorbidities were a major risk factor for the poor prognosis of COVID-19. Notably, 49–75% of COVID-19 patients had no comorbidities, but this cohort would also progress to severe COVID-19 or even death. However, risk factors contributing to disease progression and death in patients without chronic comorbidities are largely unknown; thus, specific clinical interventions for those patients are challenging. Methods: A multicenter, retrospective study based on 4806 COVID-19 patients without chronic comorbidities was performed to identify potential risk factors contributing to COVID-19 progression and death using LASSO and a stepwise logistic regression model. Results: Among 4806 patients without pre-existing comorbidities, the proportions with severe progression and mortality were 34.29% and 2.10%, respectively. The median age was 47.00 years [interquartile range, 36.00–56.00], and 2162 (44.99%) were men. Among 51 clinical parameters on admission, age ≥ 47, oxygen saturation < 95%, increased lactate dehydrogenase, neutrophil count, direct bilirubin, creatine phosphokinase, blood urea nitrogen levels, dyspnea, increased blood glucose and prothrombin time levels were associated with COVID-19 mortality in the entire cohort. Of the 3647 patients diagnosed with non-severe COVID-19 on admission, 489(13.41%) progressed to severe disease. The risk factors associated with COVID-19 progression from non-severe to severe illness were increased procalcitonin levels, SpO2 < 95%, age ≥ 47, increased LDH, activated partial thromboplastin time levels, decreased high-density lipoprotein cholesterol levels, dyspnea and increased D-dimer levels. Conclusions: COVID-19 patients without pre-existing chronic comorbidities have specific traits and disease patterns. COVID-19 accompanied by severe bacterial infections, as indicated by increased procalcitonin levels, was highly associated with disease progression from non-severe to severe. Aging, impaired respiratory function, coagulation dysfunction, tissue injury, and lipid metabolism dysregulation were also associated with disease progression. Once factors for multi-organ damage were elevated and glucose increased at admission, these findings indicated a higher risk for mortality. This study provides information that helps to predict COVID-19 prognosis specifically in patients without chronic comorbidities.

Glucose and lipid homeostasis is altered by the CD cycles in a light-intensity-dependent manner. Lower-intensity light reverses the negative metabolic effects of the CD cycles, especially under HFD feeding. The interaction of light intensity and light cycle on metabolism is independent of energy intake and eating pattern. Glucose metabolic disorders caused by rotating light cycles occur along with compensatory β-cell mass expansion.

Celiac disease (CD) is an autoimmune intestinal disease caused by the intake of gluten-containing cereals and their products by individuals with genetic susceptibility genes. Vitiligo is a commonly acquired depigmentation of the skin; its clinical manifestation are skin patches caused by localized or generalized melanin deficiency. Both diseases have similar global incidence rates (approximately 1%) and are associated to similar diseases, including autoimmune bullous disease, inflammatory bowel disease, autoimmune thyroiditis, autoimmune gastritis, and type 1 diabetes. The relationship between CD and vitiligo has been reported in several studies, but their conclusions are inconsistent. Further, it has also been reported that a gluten-free diet (GFD) can improve the symptoms of immune-related skin diseases such as vitiligo. In this mini-review, we summarize and review the literature on the relationship between CD and vitiligo, assess the therapeutic significance of GFD for patients with vitiligo, and explore their possible physiopathology. We are hopeful that the information summarized here will assist physicians who treat patients with CD or vitiligo, thereby improving the prognosis.

BACKGROUND Pegylated liposomal doxorubicin (PLD) uses the hydrophilic layer of liposomes to reach the sweat on the skin surface or accumulate in the sweat glands, producing toxic free radicals and oxidative damage, resulting in hand-foot syndrome (HFS). Regional cooling can induce vasoconstriction to reduce the release of drugs in the limbs and reduce the accumulation of drugs in sweat glands; thus, decreasing the incidence and severity of HFS. AIM To study the efficacy of cooling patches to prevent HFS caused by PLD in the short-term. METHODS This is a retrospective cohort study. Female breast cancer patients (n = 101) who were treated with PLD in two breast wards at our department from February 2020 to February 2021 were enrolled in the study and were randomly divided into the cooling group (51 patients) and the control group (50 patients). Patients in the control group only received routine care, while the patients in the cooling group applied cooling patches, based on routine care, to the palm and back of the hands 15 min before chemotherapy infusion for 10 h. All patients took a corresponding dose of dexamethasone orally one day before chemotherapy, on the day of chemotherapy, and one day after chemotherapy. SPSS23.0 version was used to analyze the data in this study. The occurrence and severity of HFS was analyzed by the Mann-Whitney U test, and scores were analyzed by the Student’s t test or Wilcoxon rank-sum test. A P value < 0.05 was regarded as statistically significant. RESULTS In this study, neither group of patients developed Grade 3 HFS. In the control group, the incidence of Grade 1 HFS and Grade 2 HFS was 38% and 2%, respectively. However, in the cooling group, only one person developed Grade 1 HFS (2%), and none of the patients developed Grade 2 HFS. These findings showed that cooling patches can effectively reduce the frequency and severity of HFS (P < 0.0001) in the short-term. Before the fourth chemotherapy cycle, although general self-efficacy scale scores in the cooling group were low, they were still significantly higher than those in the control group (17.22 ± 5.16 vs 19.63 ± 6.42, P = 0.041). Compared with the control group, the mean Hand-Foot Skin Reaction and Quality of Life Questionnaire score in the cooling group was significantly lower (18.08 ± 7.01 vs 14.20 ± 7.39, P = 0.008). CONCLUSION Cooling patches can effectively reduce the frequency and severity of HFS caused by PLD in the short-term. In addition, it may help delay the decline in patients’ self-efficacy.

Lijin Lin,1– 4,&ast; Ze Chen,4,5,&ast; Ting Ding,1,2,&ast; Hui Liu,4,6,&ast; Feng Zhou,4,7 Xuewei Huang,3,4 Xingyuan Zhang,4,8 Weifang Liu,4,8 Bing-Hong Zhang,9 Yufeng Yuan,10 Peng Zhang,4,8 Xiao-Jing Zhang,4,8 Zhi-Gang She,3,4 Jingjing Cai,4,11 Wenping Chen,1,2 Hongliang Li2– 4,7 1Department of Endocrinology, Huanggang Central Hospital, Huanggang, People’s Republic of China; 2Huanggang Institute of Translational Medicine, Huanggang, People’s Republic of China; 3Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China; 4Institute of Model Animal of Wuhan University, Wuhan, People’s Republic of China; 5Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 6Neonatology of Gastroenterology, Tongren Hospital of Wuhan University & Wuhan Third Hospital, Wuhan, People’s Republic of China; 7Medical Science Research Center, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 8Basic Medical School of Wuhan University, Wuhan, People’s Republic of China; 9Neonatology Department, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China; 10Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 11Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongliang Li; Wenping Chen Email lihl@whu.edu.cn; chenwenping@hgyy.org.cnPurpose: To analyze the impact of hyperglycemia on the clinical outcome of COVID-19 in patients with newly diagnosed diabetes (NDD).Patients and Methods: We performed a retrospective study of 3114 cases of COVID-19 without pre-existing diabetes, 351 of which had NDD, in Hubei Province, China. The Cox regression model was used to calculate the risk of adverse clinical outcomes comparing the NDD vs non-NDD group before and after propensity score-matched (PSM) analysis. Patients with NDD were further divided into a sustained hyperglycemia group, a fluctuating group, and a remitted group based on their blood glucose levels during hospitalization as well as into hypoglycemic agent users and nonusers.Results: Compared to the non-NDD individuals, individuals with NDD had a significantly increased risk of all-cause mortality (adjusted HR after PSM, 2.65; 95% CI, 1.49– 4.72; P = 0.001) and secondary outcomes involving organ damage during the 28-day follow-up period. Subgroup analyses indicated that among individuals with NDD, the individuals with remitted hyperglycemia had the lowest 28-day mortality, whereas those with sustained hyperglycemia had the highest (IRR 24.27; 95% CI, 3.21– 183.36; P < 0.001). Moreover, individuals treated with hypoglycemic agents had significantly lower all-cause mortality than those not treated with hypoglycemic agents (IRR 0.08; 95% CI, 0.01– 0.56; P < 0.001).Conclusion: Our study reinforces the clinical message that NDD is strongly associated with poor outcomes in COVID-19 patients. Furthermore, resolved hyperglycemia in the later phase of the disease and the use of hypoglycemic agents were associated with improved prognosis in patients with NDD.Keywords: COVID-19, newly diagnosed diabetes, hyperglycemia, prognosis, blood glucose

Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor originating in the nasopharynx and has a high incidence in Southeast Asia and North Africa. To develop these comprehensive guidelines for the diagnosis and management of NPC, the Chinese Society of Clinical Oncology (CSCO) arranged a multi‐disciplinary team comprising of experts from all sub‐specialties of NPC to write, discuss, and revise the guidelines. Based on the findings of evidence‐based medicine in China and abroad, domestic experts have iteratively developed these guidelines to provide proper management of NPC. Overall, the guidelines describe the screening, clinical and pathological diagnosis, staging and risk assessment, therapies, and follow‐up of NPC, which aim to improve the management of NPC.

Astaxanthin (AST) has a variety of biochemical effects, including anti-inflammatory, antioxidative, and antihypertensive functions. The aim of the present study was to determine whether AST ameliorates blood pressure in salt-induced prehypertensive rats by ROS/MAPK/NF-κB pathways in hypothalamic paraventricular nucleus. To explore the central effects of AST on the development of blood pressure, prehypertensive rats were induced by a high-salt diet (HS, 8% NaCl) and its control groups were treated with normal-salt diet (NS, 0.3% NaCl). The Dahl salt-sensitive (S) rats with HS diet for 6 weeks received AST or vehicle by gastric perfusion for 6 weeks. Compared to those with NS diet, rats with HS diet exhibited increased mean arterial pressure (MAP) and heart rate (HR). These increases were associated with higher plasma level of norepinephrine (NE), interleukin 1β (IL-1β), and interleukin 6 (IL-6); elevated PVN level of reactive oxygen species (ROS), NOX2, and NOX4, that of IL-1β, IL-6, monocyte chemotactic protein 1 (MCP-1), tyrosine hydroxylase (TH), phosphorylation extracellular-signal-regulated kinase (p-ERK1/2), phosphorylation Jun N-terminal kinases (p-JNK), nuclear factor-kappa B (NF-κB) activity; and lower levels of IL-10, superoxide dismutase (SOD), and catalase (CAT) in the PVN. In addition, our data demonstrated that chronic AST treatment ameliorated these changes in the HS but not NS diet rats. These data suggested that AST could alleviate prehypertensive response in HS-induced prehypertension through ROS/MAPK/NF-κB pathways in the PVN.

Paraneoplastic autoimmune and inflammatory disorders are often associated with myelodysplastic syndromes (MDS). The etiopathogenesis of MDS-associated autoimmune and inflammatory disorders is still unclear and treatment options are limited. Patients with MDS are at high risk of infections, which can be increased by the use of steroids. In the present study, we report on two patients with MDS-related autoimmune and inflammatory disorders who were in remission and reduced the steroid dose with 5-azacytidine treatment. The first case was a 67-year-old patient diagnosed with MDS and the whole-body erythroderma was the chief complaint. When the patient was treated with decitabine, steroid treatment was needed to control the erythroderma. When we changed decitabine to 5-azacytidine, both his erythroderma and his dependency on the steroid treatment were resolved. The second patient was a 68-year-old man with MDS who presented with Sweet's syndrome. Sweet's syndrome was completely treated after the first cycle of 5-azacytidine. In addition, Sweet's syndrome can occur as an adverse reaction of 5-azacitidine, so we illustrate that it is important to distinguish whether Sweet's syndrome is MDS-related skin disorders or 5-azacitidine-related skin side-effects.

Background Lung cancer is the most prevalent cancer, and the leading cause of cancer-related deaths in China. The aim of this study was to estimate the direct medical expenditure incurred for lung cancer care and analyze the trend therein for the period 2002–2011 using nationally representative data in China Methods This study was based on 10-year, multicenter retrospective expenditure data collected from hospital records, covering 15,437 lung cancer patients from 13 provinces diagnosed during the period 2002–2011. All expenditure data were adjusted to 2011 to eliminate the effects of inflation using China’s annual consumer price index. Results The direct medical expenditure for lung cancer care (in 2011) was 39,015 CNY (US$6,041) per case, with an annual growth rate of 7.55% from 2002 to 2011. Drug costs were the highest proportionally in the total medical expenditure (54.27%), followed by treatment expenditure (14.32%) and surgical expenditure (8.10%). Medical expenditures for the disease varied based on region, hospital level, type, and stage. Conclusion The medical expenditure for lung cancer care is substantial in China. Drug costs and laboratory test are the main factors increasing medical costs.

Epithelial cysts run a high risk of recurrence and conversion to sheet-like ingrowth after surgical intervention. In this retrospective study, we introduced a modified iridectomy for treatment of secondary epithelial iris cysts (EICs) in the anterior chamber. Twenty-nine patients (29 eyes) aged 2–61 years received “open iridectomy” for EICs between April 1995 and July 2019. After viscodissection, most of the cyst wall was cut using a 20-gauge aspiration cutter via a 2.5-mm clear corneal incision. The residue closely adhering to the iris stroma was remained to avoid photophobia and diplopia. At 3 months, best corrected visual acuity was ≥ 20/100 in 55.5% (15/27, except two pediatric patients with poor cooperation) of patients. Among the eight patients suffering partial corneal edema preoperatively, six patients received surgery treatment at 3–6.5 months, and the cornea in the other two patients became transparent after medication. In a mean follow-up of 47.4 months, recurrence occurred in 3 patients at 7, 37, and 118 months, respectively. The percentage of treatment success was 96%, 87%, and 65% at 1, 5, and 10 years, respectively. “Open iridectomy” was effective for EICs, with a minimal invasion, less damage to the corneal endothelium, and a low recurrence rate.

Rationale: Histone LSD1 (lysine-specific demethylase 1) is an important epigenetic antitumor drug target, whose inhibitors are currently in phase I/II clinical trials. However, the potential side effects of LSD1 inhibition in the progress of cardiac remodeling to heart failure remain to be investigated. Objective: To evaluate the roles of myofibroblast- or cardiomyocyte-specific LSD1 deficiency in pressure overload-induced cardiac remodeling. Methods and Results: Adult mouse cardiac fibroblasts, neonatal rat cardiac myocytes, and fibroblasts were isolated, respectively. The myofibroblast-specific and cardiomyocyte-specific LSD1 inducible knockout mice were then generated. We found that LSD1 was increased not only in human dilated cardiomyopathy hearts but also in wild-type mouse heart homogenates and isolated cardiac fibroblasts, following 20 weeks of transverse aortic constriction. The upregulation of LSD1 was also observed in Ang II-treated neonatal rat cardiac fibroblasts, which was reversed by LSD1 silence or its activity inhibition by ORY-1001. These findings suggested a potential involvement of LSD1 in cardiac remodeling. Importantly, myofibroblast-specific LSD1 inducible knockout in vivo significantly alleviated systolic dysfunction, cardiac hypertrophy, and fibrosis, following 6 and 20 weeks of transverse aortic constriction. Mechanistically, through RNA-sequencing and the following Western blot analysis, we found that loss of LSD1 in Ang II-induced myofibroblasts not only inhibited the intracellular upregulation of TGFβ1 (transforming growth factor β1), its downstream effectors Smad2/3 phosphorylation, as well as the phosphorylation of p38, ERK1/2 and JNK, but also reduced the supernatant TGFβ1 secretion, which then decreased myocyte hypertrophy in the indirect coculture model. On the other hand, cardiomyocyte-specific LSD1-inducible knockout in vivo triggered the reprogramming of fetal genes, mild cardiac hypertrophy, and dysfunction under both basal and stressed conditions. Conclusions: Our findings, for the first time, implicate that myofibroblast-specific LSD1 deletion attenuates transverse aortic constriction-induced cardiac remodeling and improves heart function, suggesting that LSD1 is a potential therapeutic target for late-stage heart failure.

Background The calcification sign assessed by computed tomography appears to be a potential marker for benignities among patients diagnosed with pulmonary nodules (PNs). The following meta-analysis has been purposefully designed to figure-out the diagnostic value of the calcification signature as a way of identifying benignities from PNs. Methods Cochrane Library, Embase and PubMed were considered as a reference to obtain the required data from January 2000 until October 2020. Stata v12.0 was used as a standard tool for statistical assessment. Results Eleven retrospective studies were assessed via this meta-analysis, which included 6136 PNs (1827 benign and 4309 malignant). The pooled diagnostic odd ratios, positive likelihood ratio (PLR), negative likelihood ratio (NLR), sensitivity and specificity were 6.79, 6.06, 0.89, 13% and 98%, respectively. The value obtained for the area under the curve was 0.65, showing moderate overall diagnostic accuracy. A significant heterogeneity was found while calculating the pooled sensitivity (I2 = 85.5%), specificity (I2 = 75.0%), PLR (I2 = 59.0%), NLR (I2 = 79.5%) and DOR (I2 = 100.0%) in the current analysis. Sub-group analyses presented better PLR and specificity values for the study with a sample size ≥ 400. Deeks' funnel plot asymmetry test detected no potential evidence of significant publication bias (p = 0.091). Conclusions Calcification signs have been identified as moderate regulators corresponding to overall diagnostic performance (via marking a distinct differentiation between malignant and benign) for PNs. However, the manifestation of the calcification sign had a good directive property for benign PNs.

Background Microwave ablation (MWA) and radiofrequency ablation (RFA) have recently attracted interest as minimally invasive treatment modalities for papillary thyroid carcinoma (PTC). However, the ablation outcomes of T1N0M0 PTC are not well characterized. Purpose To evaluate the efficacy and safety of thermal ablation (MWA or RFA) of solitary T1N0M0 PTC in patients who were ineligible for (due to presence of comorbid cardiovascular disease, renal failure, other malignancy, etc) or who refused surgery. Materials and Methods This was a retrospective multicenter study of 847 patients (660 women) who underwent thermal ablation for PTC (673 T1a, 174 T1b) between March 2015 and March 2020; of these patients, 645 underwent MWA and 202 underwent RFA. The mean age of patients was 46 years ± 11 (standard deviation) (age range, 18-81 years); the mean follow-up time was 22 months ± 13 (range, 6-60 months). Changes in tumor size and volume and the rates of technical success, tumor disappearance, disease progression, and complications were assessed. Results The technical success rate was 100%. Relative to preablation measurements, the maximum diameter and volume of the ablation zone increased during the 1st month after ablation (P < .001), whereas there was no difference by the 3rd month; subsequently, the tumors showed reduction in size at 6, 9, and 12 months (all P < .001). Complete disappearance of tumors occurred in 68% of patients (577 of 847; 69% [466 of 673] in the T1a group vs 64% [111 of 174] in the T1b group; P < .001). The postablation disease progression rate was 1.1% (nine of 847 patients; 0.9% [six of 673 patients] in the T1a group vs 1.7% [three of 174 patients] in the T1b group; P = .54). The overall complication rate was 3.4% (29 of 847 patients; 2.7% [18 of 673 patients] in the T1a group vs 6.3% [11 of 174 patients] in the T1b group; P = .02). Conclusion This multicenter study provided evidence that thermal ablation is an effective and safe treatment option in selected -patients with solitary T1N0M0 papillary thyroid carcinoma. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Baek and Cho in this issue.

A recent paper published in Nature Medicine by Calle et al. reported anti-nonalcoholic steatohepatitis (NASH) efficiencies by acetyl-CoA carboxylase (ACC) 1/2 inhibitors alone or by co-administration with a ACC1/2 inhibitor and a diacylglycerol acyltransferase 2 (DGAT2) inhibitor. Whereas the monotherapy achieved remarkable reductions in liver steatosis but induced hyperlipidemia, DGAT2 inhibitor co-administration mitigated the increase in serum triglycerides (TGs).

Background We aimed to assess the efficacy of different initial intravenous immunoglobulin (IVIG) regimens in Kawasaki disease (KD) patients to find more cost‐effective therapy options. Methods A multicenter, open‐label, blind‐endpoint randomized controlled trial was conducted from January 2014 to December 2015. Patients with KD, within 10 days of illness, were randomly assigned to receive different IVIG regimens (Group A, 2 g/kg once; Group B, 1 g/kg for 2 consecutive days; Group C, 1 g/kg once) and aspirin 30mg/kg/d. Primary outcomes included hours to defervescence and development of coronary artery lesions during the study period. Major secondary outcomes included total fever days, total dose of IVIG, changes of laboratory data, length of stay, and hospitalization expenses. (ClinicalTrials.gov: NCT02439996). Results A total of 404 patients underwent randomization. No difference was found in the outcomes of defervescence among three groups at 6, 12, 24, and 36 hours after completion of initial IVIG infusion. There were no differences in the incidence of coronary artery lesions during the study period (at week 2, month 1, month 3, and month 6 of illness), changes of laboratory data, total fever days, and length of stay. Group C patients had the lowest total dose of IVIG (mean: 1.2 vs 2.2 vs 2.1 g/kg; P < 0.001) and hospitalization expenses (mean: 8443.8 vs 10798.4 vs 11011.4 Chinese Yuan; P < 0.001) than other two groups. Conclusions A single dose of 1g/kg IVIG is a low‐cost treatment with the same efficacy as 2 g/kg IVIG and can be an option for the initial therapy of KD patients.

Acne inversa/hidradenitis suppurativa is a chronic, recurrent, inflammatory skin disease that affects the pilosebaceous units, causinfollicular occlusion. The etiology and pathogenesis of acne inversa/hidradenitis suppurativa involves internal and external factors such as genetic susceptibility, inflammation and immunity, microorganisms, obesity, and smoking. acne inversa/hidradenitis suppurativa is difficult to treat, and the current aim of treatment is to control the frequency and duration of disease flares and improve the quality of life. Treatment protocols for acne inversa/hidradenitis suppurativa should be selected based on the disease severity grade. Medical treatments include antibiotics, retinoids, biologics, immunosuppressive agents, and antiandrogen agents. Adjuvant treatments include surgery and laser/light therapies. This consensus aims to further standardize the diagnosis and treatment procedures of acne inversa/hidradenitis suppurativa in China to facilitate its diagnosis and treatment.

Cardiac arrhythmias and the resulting sudden cardiac death are significant cardiovascular complications that continue to impose a heavy burden on patients and society. An emerging body of evidence indicates that nonalcoholic fatty liver disease (NAFLD) is closely associated with the risk of cardiac arrhythmias, independent of other conventional cardiometabolic comorbidities. Although most studies focus on the relationship between NAFLD and atrial fibrillation, associations with ventricular arrhythmias and cardiac conduction defects have also been reported. Mechanistic investigations suggest that a number of NAFLD-related pathophysiological alterations may potentially elicit structural, electrical, and autonomic remodeling in the heart, contributing to arrhythmogenic substrates in the heart. NAFLD is now the most common liver and metabolic disease in the world. However, the upsurge in the prevalence of NAFLD as an emerging risk factor for cardiac arrhythmias has received little attention. In this review, we summarize the clinical evidence and putative pathophysiological mechanisms for the emerging roles of NAFLD in cardiac arrhythmias, with the purpose of highlighting the notion that NAFLD may serve as an independent risk factor and a potential driving force in the development and progression of cardiac arrhythmias.

To investigate the prognostic value of pre-procedure neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) and construct a nomogram to predict disease-free survival (DFS) in patients receiving radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) within Milan criteria. The data of 515 patients of HCC within Milan criteria receiving RFA were retrospectively collected. The patients were divided into two groups: the training group (n = 382) and the validation group (n = 133). Several preprocedural variables were analyzed in the two groups to determine the prognostic factors. The median DFS time of the training and validation group was 28.4 months and 24.5 months, respectively. Multivariate analyses showed that number of lesions, alpha-feto protein levels, NLR and PLR were independent risk factors of DFS. According to the time-dependent receiver operating characteristic curve (t-ROC), the optimal cutoff value of the NLR and PLR was 1.55 and 75.30, respectively, with sensitivity of 0.737 and 0.648 and specificity of 0.541 and 0.508, respectively. The area under curve (AUC) of the t-ROC curves for the NLR was 0.662 and PLR was 0.597. The DFS was significantly higher in the NLR ≤ 1.55 group compared to NLR > 1.55 group and the PLR ≤ 75.30 group compared to PLR > 75.30 group in both training and validation datasets. Nomogram was developed based on the prognostic factors indicated by the Cox regression to predict 1-, 2-, 3- and 5-year DFS probabilities. The cutoff value of the NLR and PLR was 1.55 and 75.30. This new nomogram based on NLR and PLR may provide good and individualized prediction of recurrence for HCC patients within Milan criteria after RFA.

Purpose: The current stratification system for acute promyelocytic leukemia (APL) is based on the white blood cell (WBC) and the platelet counts (i.e., Sanz score) over the past two decades. However, the borderlines among different risk groups are sometimes ambiguous, and for some patients, early death and relapse remained challenges. Besides, with the evolving of the treatment strategy from all-trans-retinoic acid (ATRA) and chemotherapy to ATRA–arsenic trioxide-based synergistic targeted therapy, the precise risk stratification with molecular markers is needed. Experimental Design: This study performed a systematic analysis of APL genomics and transcriptomics to identify genetic abnormalities in 348 patients mainly from the APL2012 trial (NCT01987297) to illustrate the potential molecular background of Sanz score and further optimize it. The least absolute shrinkage and selection operator algorithm was used to analyze the gene expression in 323 cases to establish a scoring system (i.e., APL9 score). Results: Through combining NRAS mutations, APL9 score, and WBC, 321 cases can be stratified into two groups with significantly different outcomes. The estimated 5-year overall (P = 0.00031), event-free (P < 0.0001), and disease-free (P = 0.001) survival rates in the revised standard-risk group (95.6%, 93.8%, and 98.1%, respectively) were significantly better than those in the revised high-risk group (82.9%, 77.4%, and 88.4%, respectively), which could be validated using The Cancer Genome Atlas dataset. Conclusions: We have proposed a two-category system for improving prognosis in patients with APL. Molecular markers identified in this study may also provide genomic insights into the disease mechanism for improved therapy.

Objective: The aim of this study is to compare the short- and long-term reproducibility of verbal and nonverbal facial expressions of normal people using dynamic 3-dimensional (3-D) imaging. Design: Prospective, cross-sectional, controlled study. Setting: Peking University School and Hospital of Stomatology, Beijing, China. Patients and Participants: Twenty-seven participants, 12 males and 15 females, were recruited for this study. Methods: A 3-D dynamic system was applied to capture the process of 4 nonverbal facial expressions (smile lips closed, smile lips open, lip purse, cheek puff) and 2 verbal facial expressions (/i:/, /u:/) at an initial time point, 15 minutes later, and 1 week later. Key frames were selected from each expression recording sequence. Main Outcome Measures: The root mean square (RMS) between each key frame and its corresponding frame at rest was calculated. ΔRMS reflected the difference of the same key frames between the different sessions of the same expression of the same participant. The reproducibility of different facial expressions at different time intervals were analyzed. Results: There was no significant difference in verbal and nonverbal expression repeatability during a 15-minute interval, except for cheek puff motion. Following a 1-week interval, verbal expression repeatability was superior to that of nonverbal expressions ( P < .01). Compared with nonverbal expressions, the repeatability of verbal expressions did not obviously decrease with the increase in recording interval. Conclusions: Dynamic 3-D imaging is a useful technique for facial expression analysis. Verbal expressions showed greater reproducibility than nonverbal expressions.

BACKGROUND N-Methyl-d-aspartate receptor (NMDAR) in the hypothalamic paraventricular nucleus (PVN) plays critical roles in regulating sympathetic outflow. Studies showed that acute application of the antagonists of NMDAR or its subunits would reduce sympathetic nerve discharges. However, little is known about the effect of long-term management of NMDAR in hypertensive animals. METHODS PEAQX, the specific antagonist of NMDAR subunit 2A (GluN2A) was injected into both sides of the PVN of two-kidney, one-clip (2K1C) renal hypertensive rats and control (normotensive rats) for 3 weeks. RESULTS Three weeks of PEAQX infusion significantly reduced the blood pressure of the 2K1C rats. It managed to resume the balance between excitatory and inhibitory neural transmitters, reduce the level of proinflammatory cytokines and reactive oxygen species in the PVN, and reduce the level of norepinephrine in plasma of the 2K1C rats. PEAQX administration also largely reduced the transcription and translation levels of GluN2A and changed the expression levels of NMDAR subunits 1 and 2B (GluN1 and GluN2B). In addition, NMDAR was known to function through activating the extracellular regulated protein kinases (ERK) or phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathways. In our study, we found that in the PVN of 2K1C rats treated with PEAQX, the phosphorylation levels of mitogen-activated protein kinase kinase (MEK), ERK1/2, and cAMP-response element-binding protein (CREB) significantly reduced, while the phosphorylation level of PI3K did not change significantly. CONCLUSIONS Chronic blockade of GluN2A alleviates hypertension through suppression of MEK/ERK/CREB pathway.

Context Ultrasound (US)-guided thermal ablation has generated recent interest as minimally invasive treatments of primary hyperparathyroidism (pHPT). But definitive evidence for the efficacy of thermal ablation in treating pHPT is not well characterized. Objective This work aims to evaluate the effectiveness and safety of thermal ablation for pHPT. Methods From January 2015 to March 2020, data pertaining to patients who received thermal ablation for pHPT at 4 centers were retrospectively analyzed. The median follow-up duration was 18.1 months (interquartile range, 6.5-42.2 months). A cure referred to the reestablishment of normal values of serum calcium and intact parathyroid hormone throughout the entire follow-up period, at least more than 6 months. The technical success, effectiveness, and safety of treatment were analyzed. Results A total of 119 patients (mean age, 57.2 ± 16.3 years; 81 female) with 134 parathyroid nodules were enrolled. The mean maximum diameter of the parathyroid glands was 1.6 ± 0.9 cm. Ninety-six patients underwent microwave ablation (MWA), and 23 patients underwent radiofrequency ablation (RFA). The technical success rate was 98.3% and the cure rate was 89.9%. Significant differences were found in the maximum diameter between the cured patients and the patients who did not undergo ablation of the target lesions. Except for cases with pHPT nodules less than 0.6 cm in diameter, the cure rate was 95%. There were no difference in cure rates at 6 months between the MWA and RFA groups (MWA vs RFA, 90.6% vs 87.0%; χ 2 = 0.275, P = .699). The volume reduction rate of the ablation zone was 94.6% at 12 months. The complication rate was 6.7% (8/119). With the exception of one patient with persistent voice impairment, other symptoms spontaneously resolved within 6 months. Conclusion Thermal ablation is effective and safe for pHPT.

Asprosin, coiled-coil domain-containing 80(CCDC80) and angiopoietin-like 4(ANGPTL4) are newly discovered adipocytokine that affects glucose tolerance, insulin resistance and cardiovascular diseases. The goal of this study was to investigate if a relationship exists among asprosin, CCDC80 and ANGPTL4 and inflammatory bowel disease (IBD). Fifty subjects with newly diagnosed IBD and fifty healthy individuals were enrolled. Patients were treated with standard therapies for 3 months. Plasma asprosin, CCDC80 and ANGPTL4 levels were measured with enzyme-linked immunosorbent assay. High resolution ultrasound was used to measure brachial artery diameter at rest, after reactive hyperemia (flow-mediated dilation, FMD) and after sublingual glyceryltrinitrate. Compare with healthy individuals, plasma CCDC80, erythrocyte sedi¬mentation rate (ESR), C-reactive protein (CRP) levels and homeostasis model assessment of insulin resistance (HOMA-IR) were significantly higher (p < 0.05, respectively), whereas plasma asprosin, ANGPTL4 levels and FMD were significantly lower in both UC and CD patients (p < 0.05). Plasma CCDC80 levels were significantly higher in patients with CD (p < 0.05), while plasma asprosin and ANGPTL4 levels were lower (pP < 0.05) as compared with those in patients with UC. Standard therapies increased plasma asprosin, ANGPTL4 levels and FMD in both UC and CD (p < 0.05), UC and CD patientswhile decreased plasma CCDC80, ESR, CRP levels and HOMA-IR (p < 0.05). The changes in HOMA-IR and FMD were correlated with the changes in plasma asprosin, CCDC80 and ANGPTL4 levels over the study period (p < 0.05). Plasma asprosin, CCDC80 and ANGPTL4 levels may be applied as a significant marker for early stage of insulin resistance and atherosclerosis in IBD, especially of CD.

The therapeutic strategies of stage II/III colorectal cancer (CRC) patients after curative surgery remain controversial. In the clinical decision-making process, oncologists need to answer questions such as whether adjuvant chemotherapy is necessary or which therapeutic regimen should be given to each patient. At present, whether adjuvant chemotherapy should be applied is primarily based on histopathological features and clinical risk factors. However, only a fraction of patients can benefit from it. More rigorous stratifying biomarkers are urgently needed to help further distinguishing these populations of patients. Recent progress in next-generation sequencing and high-throughput technologies has greatly promoted biomarker discovery as well as our understanding of the underlying mechanisms in CRC. Novel genetic and epigenetic biomarkers that are associated with prognosis or therapeutic responses have emerged. In this review, we discuss the strategies of biomarker discovery and summarize the status and assess the utility of previously published biomarkers in CRC.

Oxidative stress, the renin-angiotensin system (RAS), and inflammation are some of the mechanisms involved in the pathogenesis of hypertension. The aim of this study is to examine the protective effect of the chronic administration of astaxanthin, which is extracted from the shell of crabs and shrimps, into hypothalamic paraventricular nucleus (PVN) in spontaneously hypertensive rats. Animals were randomly assigned to 2 groups and treated with bilateral PVN infusion of astaxanthin or vehicle (artificial cerebrospinal fluid) through osmotic minipumps (Alzet Osmotic Pumps, Model 2004, 0.25 μL/h) for 4 weeks. Spontaneously hypertensive rats had higher mean arterial pressure and plasma level of norepinephrine and proinflammatory cytokine; higher PVN levels of reactive oxygen species, NOX2, NOX4, IL-1β, IL-6, ACE, and AT1-R; and lower PVN levels of IL-10 and Cu/Zn SOD, Mn SOD, ACE2, and Mas receptors than Wistar-Kyoto rats. Our data showed that chronic administration of astaxanthin into PVN attenuated the overexpression of reactive oxygen species, NOX2, NOX4, inflammatory cytokines, and components of RAS within the PVN and suppressed hypertension. The present results revealed that astaxanthin played a role in the brain. Our findings demonstrated that astaxanthin had protective effect on hypertension by improving the balance between inflammatory cytokines and components of RAS.

Insertion or deletion of single copy of octapeptide repeat (OR) in human PrP protein are considered as polymorphism, while of insertions of more numbers of OR and deletion of two copies of OR are associated with genetic prion diseases. Here, we reported a 58-year-old female patient who displayed clinical manifestations of Parkinson’s disease (PD) but contained deletion mutation of single copy of OR in one PRNP allele. The patient complained involuntary tremor of left upper limb for 18 months and her symptoms aggravation for 6 months at the time referring to Chinese National CJD surveillance system. The tremor was pronounced at rest, exacerbated by stress and disappear during sleep. Her symptoms were partially relieved after receiving medicament for PD. Neurological examination recorded involuntary movement of left hand and gear-like muscle tension of left upper limb. Coordination movement reported positive of Romberg sign and unstable in heel-keen test. EEG recorded a mild abnormality, but without periodic sharp wave complexes (PSWC). MRI showed a mild write matter demyelination. CSF protein 14-3-3 was negative. PRNP sequencing revealed heterozygosity of single copy deletion on ORs (R1-2-3-4/R1-2-2-3-4). No family history of neurodegenerative disease was recorded. Such case with a single copy of OR deletion in PRNP displaying the feature of PD is rarely reported in Chinese mainland.

Objective To compare the clinical outcomes of microwave ablation (MWA) and radiofrequency ablation (RFA) in the treatment of primary hyperparathyroidism (pHPT). Method This retrospective study included 104 pHPT patients treated by MWA or RFA between January 2015 and March 2020 in four centers. The clinical outcomes including effectiveness and complications were compared between the two groups. Ablation cure was defined as the reestablishment of normal values of serum calcium and intact parathyroid hormone (iPTH) at least more than 6 months. Clinical cure was defined as the reestablishment of normal values of serum calcium and iPTH throughout the entire follow-up period. Results A total of 77 patients underwent MWA (mean age, 55.5 ± 16.4 years) and 27 underwent RFA (mean age, 58.9 ± 15.6 years). During the follow-up (median, 18.7 months in the MWA group; 12 months in the RFA group), no difference was observed between ablation cure rates (88.3% vs. 88.9%, p = 1.000), clinical cure rates (87.0% vs. 82.3%, p = .880), recurrent pHPT (5.2% vs. 3.7%, p = .447), persistent pHPT (11.7% vs. 11.1%, p = 1.000) and complication rate (9.1% vs. 3.7%, p = .677). A maximum diameter less than 0.7 cm was an independent prognostic factor of uncured pHPT in ablation (hazard ratio, 0.1; 95% confidence interval: 0.02, 0.54; p = .007). Major complication – voice change encountered in five patients (6.5%) in the MWA group and in one patient (3.7%) in the RFA group. Conclusion Both RFA and MWA are safe and effective techniques for patients with pHPT, with comparable clinical outcomes.

Exercise (Ex) has long been recognized to produce beneficial effects on hypertension (HTN). This coupled with evidence of gut dysbiosis and an impaired gut-brain axis led us to hypothesize that reshaping of gut microbiota and improvement in impaired gut-brain axis would, in part, be associated with beneficial influence of exercise. Male spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats were randomized into sedentary, trained, and detrained groups. Trained rats underwent moderate-intensity exercise for 12 weeks, whereas, detrained groups underwent 8 weeks of moderate-intensity exercise followed by 4 weeks of detraining. Fecal microbiota, gut pathology, intestinal inflammation, and permeability, brain microglia and neuroinflammation were analyzed. We observed that exercise training resulted in a persistent decrease in systolic blood pressure in the SHR. This was associated with increase in microbial α diversity, altered β diversity, and enrichment of beneficial bacterial genera. Furthermore, decrease in the number of activated microglia, neuroinflammation in the hypothalamic paraventricular nucleus, improved gut pathology, inflammation, and permeability were also observed in the SHR following exercise. Interestingly, short-term detraining did not abolish these exercise-mediated improvements. Finally, fecal microbiota transplantation from exercised SHR into sedentary SHR resulted in attenuated SBP and an improved gut-brain axis. These observations support our concept that an impaired gut-brain axis is linked to HTN and exercise ameliorates this impairment to induce antihypertensive effects.

Jiqi Wang,1 Youming Zhao,1 Bingjie Jiang,1 Xiaojing Huang2 1Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, People’s Republic of China; 2Department of Orthopaedics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, People’s Republic of ChinaCorrespondence: Xiaojing HuangDepartment of Orthopaedics, The First Affiliated Hospital of Wenzhou Medical University, Shangcai Village Ouhai District, Wenzhou 325000, Zhejiang, People’s Republic of ChinaEmail wzhuangxiaojing@hotmail.comPurpose: The aim of our study was to explore the risk factors related to blood transfusion after intramedullary nail fixation of elderly femoral intertrochanteric fracture (FTF) and establish a nomogram prediction model.Patients and Methods: We conducted a retrospective study including elderly FTF patients treated by intramedullary nail between January 2017 and December 2019. Perioperative information was obtained retrospectively, uni- and multivariate regression analyses were performed to determine risk factors for blood transfusion. A nomogram model was established to predict the risk of blood transfusion, and consistency coefficient (C-index) and correction curve were used to evaluate the prediction performance and consistency of the model.Results: Of 148 patients, 119 were finally enrolled in the study and and 46 patients (38.7%) received a blood transfusion after the operation. Logistic regression analysis the female, lower preoperative Hb, ASA score > 2, general anesthesia, and higher intraoperative blood loss were independently associated with the blood transfusion. The accuracy of the contour map for predicting transfusion risk was 0.910.Conclusion: These risk factors are shown on the nomogram and verified. Through the assessment of the risk of blood transfusion and the intervention of modifiable risk factors, we may be able to reduce the blood transfusion rate to a certain extent, so as to further guarantee the safety of the elderly patients during the perioperative period.Keywords: blood transfusion, femoral intertrochanteric fracture (FTF), elderly, nomograms, risk factors, intramedullary nail fixation

BACKGROUND A modified Valsalva maneuver (VM) has been suggested to be superior to the standard VM for conversion of paroxysmal supraventricular tachycardia (PSVT). AIM To evaluate the efficacy and economic benefits of a modified VM in Chinese patients. METHODS Patients with PSVT admitted to our center between October 2017 and September 2019 were randomly assigned to the modified and standard VM groups. Conversion via VM was performed up to three times. The primary outcome of the study was the success rate of PSVT conversion to sinus rhythm. The secondary outcomes included the incidence of adverse events, economic cost during the visit, and the degree of patient acceptance of the treatment. RESULTS Overall, 361 patients were enrolled, with 180 allocated to the modified VM group and 181 to the standard VM group. Baseline characteristics were well matched in the groups. Overall, the modified VM group had higher success rates of PSVT conversion after single (47.78% vs 15.38%, P < 0.001) and multiple (62.22% vs 19.78%, P < 0.001) VM sessions. No significant differences in the incidences of adverse events and rates of patient acceptance were detected between the two groups (both P > 0.05). Moreover, the economic cost of the clinic visit was significantly lower for the modified VM group than for the standard VM group (P < 0.05). CONCLUSION The modified VM may confer both therapeutic and economic benefits as compared with the standard VM for conversion of PSVT.

Sheng-Yan Huang,* Yang Chen,* Xi-Rong Tan, Sha Gong, Xiao-Jing Yang, Qing-Mei He, Shi-Wei He, Na Liu, Ying-Qing Li Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou 510060, People’s Republic of China*These authors contributed equally to this workCorrespondence: Na Liu; Ying-Qing LiSun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, 651 Dongfeng Road East, Guangzhou 510060, People’s Republic of ChinaTel/Fax +86-20-87342370; +86-20-87343255 Email liun1@sysucc.org.cn; liyingq1@sysucc.org.cnPurpose: The prognostic value of serum calcium levels in nasopharyngeal carcinoma (NPC) remains unknown. This study aimed to evaluate the prognostic value of serum calcium levels in patients with NPC.Patients and Methods: A total of 2094 patients diagnosed with NPC between April 2009 and September 2012 were enrolled in this retrospective analysis. The median follow-up time was 96.3 months (range: 4.1– 120.0 months). Univariate and multivariable Cox proportional hazards models were used to identify significant and independent prognostic predictors of overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and relapse-free survival (RFS).Results: Overall, low serum calcium levels were detected in 1109/2094 (53.00%) patients and tended to be more frequently detected in older (P< 0.001) and female (P=0.001) patients. Patients with low serum calcium levels had poorer OS (P=0.011), DFS (P=0.012) and DMFS (P=0.004) than those with high serum calcium levels, but serum calcium levels had no significant effect on RFS (P=0.376). In univariate and multivariable analyses, low serum calcium levels were a statistically significant and independent prognostic factor for OS, DFS, and DMFS but had no prognostic value for RFS.Conclusion: Serum calcium levels can serve as a prognostic predictor and guide more individualized treatment for NPC patients.Keywords: nasopharyngeal carcinoma, serum calcium level, prognosis, survival

Background and Aim Liraglutide, a long‐acting GLP‐1 analog, is approved for the treatment of obesity with improvements in fasting blood glucose, hemoglobin A1c, and cardiovascular health. Our aim was to measure the impact of liraglutide dose for obesity on hepatic steatosis measured by ultrasound. Methods A single‐center, randomized, double‐blind, placebo‐controlled pilot trial was undertaken in nondiabetic obese, otherwise healthy patients aged 18–65 years. Participants were randomly assigned to receive subcutaneous liraglutide (3.0 mg) or placebo over 16 weeks with dose escalation following US Food and Drug Administration guidelines. Both groups received standardized nutritional and behavioral counseling during the 16 weeks. Hepatic fat content was measured by ultrasound at baseline, 8 weeks, and 16 weeks as an attenuation coefficient (ACE). Effects of treatment were assessed using t‐test for the entire groups and for patient subgroup with baseline ACE >0.66 (indicating significant steatosis). Results Among 30 patients (93% female) enrolled, 16 were randomized to placebo and 14 to liraglutide. Baseline body mass indices (BMIs) and average age were similar in the two groups. After 16 weeks, the liraglutide group had a significant improvement in steatosis ACE scores (−0.068 ± 0.02 vs −0.0077 ± 0.02 placebo, P = 0.05). Change in steatosis was positively correlated with change in BMI (R2 = 0.402, P = 0.0007). Within the liraglutide group, patients with baseline ACE >0.66 had improvement in ACE (−0.134 ± 0.03) compared to those without significant steatosis (−0.041 ± 0.02, P = 0.05). Conclusions In this pilot trial, liraglutide, 3.0 mg over 16 weeks, reduced hepatic steatosis; a reduction in hepatic steatosis is correlated with BMI reduction, and effects are particularly evident in those with a significant degree of steatosis by ultrasound imaging., Liraglutide, a long‐acting GLP‐1 analog, is approved for the treatment of obesity with improvements in fasting blood glucose, hemoglobin A1c, and cardiovascular health. Liraglutide, 3.0 mg over 16 weeks, reduced hepatic steatosis; a reduction in hepatic steatosis is correlated with body mass index reduction, and effects are particularly evident in those with a significant degree of steatosis by ultrasound imaging.

Background & aims Milk fat globule-EGF factor 8 (MFGE8) has been shown to be a critical extracellular molecule that mediates apoptotic signaling in the pathological process of nonalcoholic fatty liver disease (NAFLD). MFGE8 is abundantly expressed in hepatocyte, but its function in the pathogenesis of NAFLD has not been characterized. Approach & results In our current study, hepatic MFGE8 showed a protective role in the pathogenesis of NAFLD. Hepatic MFGE8 deletion largely exacerbated lipid accumulation and inflammatory responses in the liver in response to overnutrition. Mechanistically, intercellular MFGE8 was shown to directly bind to apoptosis signal-regulating kinase 1 (ASK1) and inhibits its dimerization and phosphorylation under a normal diet. However, under metabolic challenges, decreased cytoplasmic MFGE8 facilitated the dimerization and phosphorylation of ASK1 and subsequent MAPK signaling in hepatocytes. Conclusion Hepatic MFGE8 is an endogenous inhibitor that halts the progression of hepatic steatosis and inflammation. Metabolic challenge-induced loss of intracellular MFGE8 facilitates ASK1 dimerization and phosphorylation. Therefore, maintaining hepatic MFGE8 level may serve as an alternative strategy for the treatment of NAFLD.

Background Cystic adenomyosis is a particular type of adenomyosis, High intensity focused ultrasound (HIFU), as a non-invasive method, has also been used to treat adenomyosis. The purpose of this study was to investigate the efficacy, safety, and feasibility of HIFU for the treatment of cystic adenomyosis. Methods Diagnosis of cystic adenomyosis was obtained through trans-vaginal ultrasound and magnetic resonance imaging (MRI). Ultrasound-guided HIFU ablation was performed under conscious sedation. The patients were evaluated by the comparison of pre-HIFU and post-HIFU imaging, as well as the Uterine Fibroid Symptom and Quality of Life (UFS-QOL) questionnaire subscales, consisting of Symptom Severity Score (SSS) and Heath Related Quality of Life (HRQL). Results HIFU was effective in treating cystic adenomyosis. No complications were observed in the four patients who were successfully treated with HIFU. Compared to preoperative symptoms and patient satisfaction, symptoms at the first follow-up observed significant improvements, with no dysmenorrhea and high health-related quality of life. During the outpatient follow-up of one month, three months, and six months postoperation, the four patients were still without dysmenorrhea and were highly satisfied with the HIFU ablation. Conclusions HIFU, as a non-invasive treatment, supplies a safe and effective possibility for the treatment of cystic adenomyosis.

Background:. Sleep disorders are common but under-researched symptoms in patients with multiple system atrophy (MSA). We investigated the frequency and factors associated with sleep-related symptoms in patients with MSA and the impact of sleep disturbances on disease severity. Methods:. This cross-sectional study involved 165 patients with MSA. Three sleep-related symptoms, namely Parkinson's disease (PD)-related sleep problems (PD-SP), excessive daytime sleepiness (EDS), and rapid eye movement sleep behavior disorder (RBD), were evaluated using the PD Sleep Scale-2 (PDSS-2), Epworth Sleepiness Scale (ESS), and RBD Screening Questionnaire (RBDSQ), respectively. Disease severity was evaluated using the Unified MSA Rating Scale (UMSARS). Results:. The frequency of PD-SP (PDSS-2 score of ≥18), EDS (ESS score of ≥10), and RBD (RBDSQ score of ≥5) in patients with MSA was 18.8%, 27.3%, and 49.7%, respectively. The frequency of coexistence of all three sleep-related symptoms was 7.3%. Compared with the cerebellar subtype of MSA (MSA-C), the parkinsonism subtype of MSA (MSA-P) was associated with a higher frequency of PD-SP and EDS, but not of RBD. Binary logistic regression revealed that the MSA-P subtype, a higher total UMSARS score, and anxiety were associated with PD-SP; that male sex, a higher total UMSARS score, the MSA-P subtype, and fatigue were associated with EDS; and that male sex, a higher total UMSARS score, and autonomic onset were associated with RBD in patients with MSA. Stepwise linear regression showed that the number of sleep-related symptoms (PD-SP, EDS, and RBD), disease duration, depression, fatigue, and total Montreal Cognitive Assessment score were predictors of disease severity in patients with MSA. Conclusions:. Sleep-related disorders were associated with both MSA subtypes and the severity of disease in patients with MSA, indicating that sleep disorders may reflect the distribution and degree of dopaminergic/non-dopaminergic neuron degeneration in MSA.

Objectives. To investigate the metabolic profile in patients with aortic stenosis (AS) after transcatheter aortic valve replacement (TAVR) and explore the potential biomarkers to predict prognosis after TAVR based on metabolomics. Methods and Results. Fifty-nine consecutive AS patients were prospectively recruited. Blood samples from the ascending aorta, coronary sinus, and peripheral vein at before and after TAVR were collected, respectively. Liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry were performed to analyze the metabolic profile before and after TAVR. Influential metabolites were identified by integrating the univariate test, multivariate analysis, and weighted gene coexpression network analysis (WGCNA) algorithm. PLS-DA analysis revealed a significant extremely early (within 30 minutes after TAVR) alterations of metabolites in the ascending aorta, coronary sinus, and peripheral vein. The early (within 7 days after TAVR) changed metabolites in the peripheral vein were involved in purine metabolism, primary bile acid biosynthesis, glycerolipid metabolism, amino sugar and nucleotide sugar metabolism, one carbon pool by folate and alanine, and the aspartate and glutamate metabolism pathway. We used volcano plots to find that the cardiac-specific changed metabolites were enriched to the sphingolipid metabolism pathway after TAVR. Besides, WGCNA algorithm was performed to reveal that arginine and proline metabolites could reflect left ventricle regression to some extent. Conclusion. This is the first study to reveal systemic and cardiac metabolites changed significantly in patients with AS after TAVR. Some altered metabolites involved in the arginine and proline metabolism pathway in the peripheral vein could predict left ventricle regression, which merited further study.

Background Ultrasound-guided thermal ablation plays an important role in the management of thyroid disease. The objective of this study was to evaluate the feasibility, efficacy, and safety of thermal ablation for patients with solitary T1bN0M0 papillary thyroid carcinoma (PTC) who are ineligible for or unwilling to undergo surgery. Materials and Methods Data pertaining to 172 patients (38 males and 134 females) who received thermal ablation therapy at 12 hospitals between April 2015 and March 2020 were retrospectively analyzed. The mean duration of follow-up was 24.9 ± 14.1 months (range, 12–60). The technical feasibility, technical success, efficacy, and safety of treatment were analyzed. Postablation tumor size at various time points was compared with preablation measurement. Results All patients selected for thermal ablation received enlarged ablation, according to contrast-enhanced ultrasound postablation. The maximum diameter and volume of ablation zone at 6, 12, 18, 24, 36, and 48 months postablation were significantly smaller than those recorded preablation (P Conclusion Thermal ablation may be a feasible, effective, and safe treatment option for patients with solitary T1bN0M0 PTC who are ineligible for or unwilling to undergo surgery. It may provide a novel treatment option for selected patients.

BACKGROUND Gastro-thoracic fistula is a serious complication after radical surgery for esophageal cancer, and a conservative approach or endoscopic intervention is commonly applied to treat most cases. CASE SUMMARY Here we describe the case of a patient with a gastro-thoracic fistula which could not be closed during gastroscopy after receiving postoperative radiotherapy, together with severe multiple drug-resistant bacterial infection and chest wall fistula. The abscess was drained and local irrigation applied with ozonated water, together with oral ozonated water, which achieved a good effect and highlighted a new way to cure fistula in such patients. CONCLUSION Patients with gastro-thoracic fistula that cannot be closed and severe infection can be treated by drainage and flushing with ozonated water.

Pathological cardiac hypertrophy is one of the major predictors and inducers of heart failure, the end stage of various cardiovascular diseases. However, the molecular mechanisms underlying pathogenesis of pathological cardiac hypertrophy remain largely unknown. Here, we provided the first evidence that STEAP3 (Six-Transmembrane Epithelial Antigen of Prostate 3) is a key negative regulator of this disease. We found that the expression of STEAP3 was reduced in pressure overload-induced hypertrophic hearts and phenylephrine-induced hypertrophic cardiomyocytes. In a transverse aortic constriction-triggered mouse cardiac hypertrophy model, STEAP3 deficiency remarkably deteriorated cardiac hypertrophy and fibrosis, whereas the opposite phenotype was observed in the cardiomyocyte-specific STEAP3 overexpressing mice. Accordingly, STEAP3 significantly mitigated phenylephrine-induced cell enlargement in primary neonatal rat cardiomyocytes. Mechanistically, via RNA-seq and immunoprecipitation-mass screening, we demonstrated that STEAP3 directly bond to Rho family small GTPase 1 and suppressed the activation of downstream mitogen-activated protein kinase-extracellular signal-regulated kinase signaling cascade. Remarkably, the antihypertrophic effect of STEAP3 was largely blocked by overexpression of constitutively active mutant Rac1 (G12V). Our study indicates that STEAP3 serves as a novel negative regulator of pathological cardiac hypertrophy by blocking the activation of the Rac1-dependent signaling cascade and may contribute to exploring effective therapeutic strategies of pathological cardiac hypertrophy treatment.

Nerve demyelination or axonal lesions are characteristic of experimental autoimmune neuritis (EAN). Previous studies have demonstrated that microRNA-338 can regulate the differentiation and maturation of oligodendrocytes and Schwann cells and promote injured peripheral nerves in rats. In this study, we used microRNA-338 coded lentivirus vector (miR-338-LV) in a Lewis rat EAN model, in with the conjunction P0 peptide 180–199 which was injected into the footpads of animals to induce immunization. The clinical scores of miR-338-LV and intravenous immunoglobulin (IVIg) (positive drug) groups were significantly superior to those of untreated group at disease peak and disease plateau (p

NOX5 (NADPH oxidase 5) is a homolog of the gp91 phox subunit of the phagocyte NOX, which generates reactive oxygen species. NOX5 is involved in sperm motility and vascular contraction and has been implicated in diabetic nephropathy, atherosclerosis, and stroke. The function of NOX5 in the cardiac hypertrophy is unknown. Because NOX5 is a Ca 2+ -sensitive, procontractile NOX isoform, we questioned whether it plays a role in cardiac hypertrophy. Studies were performed in (1) cardiac tissue from patients undergoing heart transplant for cardiomyopathy and heart failure, (2) NOX5-expressing rat cardiomyocytes, and (3) mice expressing human NOX5 in a cardiomyocyte-specific manner. Cardiac hypertrophy was induced in mice by transverse aorta coarctation and Ang II (angiotensin II) infusion. NOX5 expression was increased in human failing hearts. Rat cardiomyocytes infected with adenoviral vector encoding human NOX5 cDNA exhibited elevated reactive oxygen species levels with significant enlargement and associated increased expression of ANP (atrial natriuretic peptides) and β-MHC (β-myosin heavy chain) and prohypertrophic genes ( Nppa , Nppb , and Myh7 ) under Ang II stimulation. These effects were reduced by N-acetylcysteine and diltiazem. Pressure overload and Ang II infusion induced left ventricular hypertrophy, interstitial fibrosis, and contractile dysfunction, responses that were exaggerated in cardiac-specific NOX5 trangenic mice. These phenomena were associated with increased reactive oxygen species levels and activation of redox-sensitive MAPK (mitogen-activated protein kinase). N-acetylcysteine treatment reduced cardiac oxidative stress and attenuated cardiac hypertrophy in NOX5 trangenic. Our study defines Ca 2+ -regulated NOX5 as an important NOX isoform involved in oxidative stress- and MAPK-mediated cardiac hypertrophy and contractile dysfunction.

Objectives Beginning in June 2017, numerous dengue virus (DENV) infections occurred in the Jining City of Shandong Province, formerly a dengue-free region in East China. We sought to describe the clinical and epidemiological features of this outbreak. Methods We reviewed the clinical records and epidemiological data regarding a case series of patients diagnosed with DENV in Jining City, from June 30 to September 14, 2017. Diagnosis was confirmed by molecular method, culture, or rapid diagnostic tests. Sequencing of the DENV envelope gene or the whole viral genome was performed for 11 patients. Additionally, neutralizing antibodies against DENV was measured among patients and residents from their same villages. Results Data from 150 patients were evaluated in this outbreak. None were diagnosed with dengue hemorrhagic fever or dengue shock syndrome. The patients’ ages ranged between 2–88 years (median 51 years, [IQR=37.5–64.3]), and 100 (66.7%) were female. Epidemiological analyses implicated a man who had visited Saudi Arabia as the likely source of the outbreak. Phylogenetic studies identified DENV serotype 1. Most of the patients demonstrated increases of neutralizing antibody titers one year after infection compared with titers three months after infection. The residents living in dengue-affected villages had a significant higher seroprevalence of 21.2% (95%CI 16.9-25.5) than residents (3.2%, 95%CI-0.36-6.7) living in a non-dengue-affected village. Conclusions This report documents the first dengue outbreak in Shandong Province, China, in more than 60 years. It underscores the need for medical providers to record patients’ travel histories and to consider dengue in their differential diagnoses.

Yi-Bo Chen, Zhao-Hui Wang, Gui-Ming Fu, Quan-Xin Wan, Xiao-Jing Li, Jin Chen Department of Head and Neck Oncology, Sichuan Cancer Hospital, Chengdu 610041, People’s Republic of ChinaCorrespondence: Zhao-Hui Wang Email wangzh912@163.comBackground: To evaluate the application of computer-aided design (CAD) and three-dimensional (3D) visualization techniques in the diagnosis and treatment of refractory thyroid tumors.Materials and Methods: The clinical data from 12 cases of refractory thyroid tumors treated with CAD and 3D visualization techniques from September 2016 to January 2018 were analyzed retrospectively. Ten cases were malignant, while two cases were benign. All tracheas in the 12 cases were invaded or oppressed by the thyroid tumors. Six of the cases experienced type III dyspnea, while the other six cases had type II dyspnea. All patients underwent contrast-enhanced computed tomography (CT) imaging.Results: CAD and 3D visualization technologies were used to guide the surgeries. Ten cases of malignant thyroid tumors underwent total thyroidectomy, cervical lymph node dissection, and invaded organ resection. Among the ten cases, five underwent sleeve resections and anastomosis reconstructions, one underwent a tracheal sleeve resection and total laryngectomy, two underwent tracheal window resections, one case underwent a sternotomy, and one case underwent a laryngopharyngectomy, invaded skin resection, and pectoralis major muscle flap reconstruction. The two cases of benign thyroid tumors underwent subtotal thyroidectomies. Using CAD and 3D visualization techniques, surgeons can visually observe the relationship of the tumor with the respiratory tract and essential blood vessels, which can lead to optimized surgical plans and improved surgical outcomes.Conclusion: CAD and 3D visualization technologies have an important role in the personalized surgical intervention of thyroid cancer, which will likely have important clinical implications.Keywords: refractory thyroid tumors, thyroid cancer, computer-aided design, CAD, 3D visualization, contrast-enhanced CT, thyroidectomy

Background With guidance from the American Joint Committee on Cancer (AJCC) Cancer Staging Manual, 8th edition, we explored the characteristics of central lymph node metastasis (CLNM) of papillary thyroid micro-carcinoma (PTMC) in elderly patients ≥55 years of age. Our goal was to provide references for establishing a lymph node dissection scheme in such patients. Methods We retrospectively analyzed the clinical data of thyroid cancer patients admitted to the Head and Neck Surgery Center of Sichuan Cancer Hospital, Chengdu, China, from January 2015 to September 2018. Then, we screened and analyzed eligible PTMC cases in strict accordance with our inclusion and exclusion criteria. Results The study included 107 patients, including 24 men and 83 women. Median age was 59.99 ± 4.58 years. The maximum diameter range of the cancer foci was 4-10 mm, and the median was 7.59 ± 1.78 mm. Unilateral lobectomy had been performed in 32 cases, total thyroidectomy in 75 cases and lateral cervical lymph node dissection in 21 cases. There were 60 cases of CLNM (56.07%) and 13 cases of lateral cervical lymph node metastasis (12.10%). The sensitivity of preoperative ultrasound in predicting CLNM was 100%, but its accuracy was only 50.47%. Multivariate logistic regression analysis showed that multiple cancer foci (area under the curve [AUC] = 0.632), extra-thyroidal expansion of cancer focus (AUC = 0.721), and irregular nodules (AUC = 0.603) were independent risk factors for CLNM of PTMC in elderly patients (P < 0.05). Overall predictability for PTMC-CLNM was 80.30%. Conclusion 1) Preoperative color Doppler ultrasound is not recommended as the basis for cervical lymph node dissection in PTMC patients. 2) For multiple cancer foci, irregular nodules, and elderly patients with PTMC extra-thyroidal expansion, we recommend a prophylactic central lymph node dissecting. 3) Nonsurgical observation of PTMC in elderly patients with low risk should be carefully selected.