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BACKGROUND China has a high prevalence of hepatitis B virus (HBV), but most chronic hepatitis B (CHB) patients do not receive standardized antiviral therapy. There are few relevant reports addressing the outcomes of the large number of CHB patients who do not receive antiviral therapy. AIM To observe the outcomes of long-term follow-up of patients with CHB without antiviral treatment. METHODS This study included 362 patients with CHB and 96 with hepatitis B cirrhosis without antiviral treatment and with only liver protection and anti-inflammatory treatment from 1993 to 1998. The median follow-up times were 10 and 7 years, respectively. A total of 203 CHB and 129 hepatitis B cirrhosis patients receiving antiviral therapy were selected as the control groups. The median follow-up times were 8 and 7 years, respectively. Kaplan-Meier curves were used to analyze the cumulative incidence of hepatocellular carcinoma (HCC), and the Cox regression model was used to analyze the risk factors for HCC. RESULTS Among the patients in the non-antiviral group, 16.9% had spontaneous decreases in HBV DNA to undetectable levels, and 32.8% showed hepatitis B e antigen (HBeAg) seroconversion. In the antiviral group, 87.2% of patients had undetectable HBV DNA, and 52% showed HBeAg seroconversion. Among CHB and hepatitis B cirrhosis patients, the cumulative incidence rates of HCC were 14.9% and 53.1%, respectively, in the non-antiviral group and were 10.7% and 31.9%, respectively, in the antiviral group. There was no difference between the two groups regarding the CHB patients (P = 0.842), but there was a difference between the groups regarding the hepatitis B cirrhosis patients (P = 0.026). The cumulative incidence rates of HCC were 1.6% and 22.3% (P = 0.022) in the groups with and without spontaneous HBeAg seroconversion, respectively. The incidence rates of HCC among patients with and without spontaneous declines in HBV DNA to undetectable levels were 1.6% and 19.1%, respectively (P = 0.051). There was no difference in the cumulative incidence of HCC between the two groups regarding the patients with drug-resistant CHB (P = 0.119), but there was a significant difference between the two groups regarding the patients with cirrhosis (P = 0.004). The Cox regression model was used for regression of the corrected REACH-B score, which showed that alanine aminotransferase > 400 U/L, history of diabetes, and family history of liver cancer were risk factors for HCC among men aged > 40 years (P < 0.05). Multifactorial analysis showed that a family history of HCC among men was a risk factor for HCC. CONCLUSION Antiviral therapy and non-antiviral therapy with liver protection and anti-inflammatory therapy can reduce the risk of HCC. Antiviral therapy may mask the spontaneous serological response of some patients during CHB. Therefore, the effect of early antiviral therapy on reducing the incidence of HCC cannot be overestimated.

Summary Coronavirus disease 2019 (COVID-19) occurs in the influenza season and has become a global pandemic. The present study aimed to examine severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) co-infection with influenza A virus (IAV) in an attempt to provide clues for the antiviral interventions of co-infected patients. We described two patients who were co-infected with SARS-CoV-2 and IAV treated at Wuhan Union Hospital, China. In addition, we performed a review in PubMed, Web of Science and CNKI (from January 1 up to November 1, 2020) with combinations of the following key words: “COVID-19, SARS-COV-2, influenza A and co-infection”. A total of 28 co-infected patients were enrolled in the analysis. Of the 28 patients, the median age was 54.5 years (IQR, 34.25–67.5) and 14 cases (50.0%) were classified as severe types. The most common symptoms were fever (85.71%), cough (82.14%) and dyspnea (60.71%). Sixteen patients had lymphocytopenia on admission and 23 patients exhibited abnormal radiological changes. The median time from symptom onset to hospital admission was 4 days (IQR, 3–6), and the median time of hospital stay was 14 days (IQR, 8.5–16.75). In conclusion, patients with SARS-COV-2 and IAV co-infection were similar to those infected with SARS-COV-2 alone in symptoms and radiological images. SARS-COV-2 co-infection with IAV could lead to more severe clinical condition but did not experience longer hospital stay compared with patients infected with SARS-COV-2 alone.

Background: Transport proteins, soluble LRP1 (sLRP1) and soluble RAGE (sRAGE), play a pivotal role in the peripheral clearance of plasma amyloid-β (Aβ). However, their relationship is seldom discussed, especially in Alzheimer’s disease (AD). Objective: To explore whether their relationship in patients with AD varied from those in cognitively normal (CN) controls. Methods: We initially recruited 70 patients with AD and 725 CN controls, then applied propensity score matching (PSM) analysis to balance the differences between two groups. Plasma levels of sLRP1, sRAGE, and Aβ were measured using commercial ELISA kits and log transformed when skewed distributed. The relationship between sLRP1/sRAGE and plasma Aβ were analyzed using Pearson’s correlation analysis followed by multiple linear regression separately in the original population and matched participants. Results: After PSM, 70 patients with AD and 140 matched controls were included for further analysis. Log sLRP1 was positively correlated with plasma Aβ40 in matched CN controls (r = 0.222, p = 0.008) but not in patients with AD (r = 0.137, p = 0.260). After multivariable adjustment, Log sLRP1 remained significantly associated with plasma Aβ40 in the CN group (β= 7.347, p = 0.014) but not in the AD group (β= 10.409, p = 0.105). In contrast, Log sLRP1 was not correlated with plasma Aβ42 in patients with AD or CN controls, and Log sRAGE was consistently not associated with plasma Aβ40 or Aβ42 in either group. Conclusion: The significant correlation between sLRP1 and plasma Aβ40 present in CN controls was not found in patients with AD, suggesting that their relationship was different in AD. However, the specific mechanisms and its influence on cerebral amyloid burden require further validation.

Multidirectionally unstable supracondylar humeral fractures cause severe instability in both flexion and extension movements. The traditional closed reduction often fails to overcome this lack of stability. The aim of this study is to use a closed reduction technique with a transolecranon pin to achieve temporary stability. From 35 pediatric multidirectionally unstable supracondylar humeral fractures hospitalized between March 2012 and March 2018 at our hospital, 23 fractures (65.7%) were treated with closed reduction and percutaneous pinning (CRPP) (group 1) and the remaining twelve fractures (34.3%) were treated utilizing a transolecranon pin joystick technique of CRPP (group 2). Both groups were followed over 16 weeks. The outcomes of our analysis included surgical time, times of fluoroscopy, Baumann angle, postoperative range of motion and complications. The surgical time and times of fluoroscopy were significantly shorter for patients in group 2 when compared with group 1 (P < 0.05). All cases showed restoration of the normal anterior humeral line-capitellar relationship. However, the quality of reduction on the anteroposterior radiographic view was significantly better for patients in group 2 than that of group 1 (P < 0.05). No immediate postoperative complications were observed. The range of motion was similar in both groups during the last follow-up appointment. A transolecranon pin is a safe and effective method for closed reduction of multidirectionally unstable supracondylar humeral fractures in children. The joystick technique can shorten surgical time and improve quality of reduction with no increasing risk of complications. Level of evidence: level III.

Background No guideline recommends antiviral therapy for hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients with persistently normal alanine aminotransferase levels and a high hepatitis B virus (HBV) DNA viral load. Aim To evaluate the feasibility and safety of a Chinese herbal formula as a therapeutic option for chronic HBV infection. Methods In total, 395 patients (30-65 years old) with confirmed HBeAg-positive chronic hepatitis B infection and persistently normal alanine aminotransferase were randomized to receive either Chinese herbal formula or placebo for 96 wk. Endpoints to evaluate therapeutic efficacy included: (1) HBV DNA levels decreased to less than 4 log10 IU/mL at weeks 48 and 96; and (2) HBeAg clearance and seroconversion rates at weeks 48 and 96. Results HBV DNA levels ≤ 4 log10 IU/mL were 10.05% at week 48 and 18.59% at week 96 in the treatment group. The HBeAg clearance and conversion rates were 8.54% and 8.04% at week 48 and 16.08% and 14.57% at week 96, respectively. However, HBV DNA levels ≤ 4 log10 IU/mL were 2.55% and 2.55% at weeks 48 and 96, respectively, and the HBeAg clearance rates were 3.06% and 5.61% at weeks 48 and 96, respectively, in the control group. The quantitative hepatitis B surface antigen and HBeAg levels at baseline and changes during the treatment period as well as the alanine aminotransferase elevation at weeks 12 and 24 were strong predictors of HBeAg clearance. Conclusion High rates of HBV DNA reduction, HBeAg clearance and seroconversion could be achieved with Chinese herbal formula treatments, and the treatments were relatively safe for HBeAg-positive chronic hepatitis B-infected patients with persistently normal alanine aminotransferase. The ability of the compound to modulate host immune function probably contributed to this effect.

Background The coronavirus disease 2019 (COVID-19), caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been rapidly spreading nationwide and abroad. A serologic test to identify antibody dynamics and response to SARS-CoV-2 was developed. Methods The antibodies against SARS-CoV-2 were detected by an enzyme-linked immunosorbent assay based on the recombinant nucleocapsid protein of SARS-CoV-2 in patients with confirmed or suspected COVID-19 at 3–40 days after symptom onset. The gold standard for COVID-19 diagnosis was nucleic acid testing for SARS-CoV-2 by real-time reverse-transcription polymerase chain reaction (rRT-PCR). The serodiagnostic power of the specific immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies against SARS-CoV-2 was investigated in terms of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and consistency rate. Results The seroconversion of specific IgM and IgG antibodies were observed as early as the fourth day after symptom onset. In the patients with confirmed COVID-19, sensitivity, specificity, PPV, NPV, and consistency rate of IgM were 77.3% (51/66), 100%, 100%, 80.0%, and 88.1%, respectively, and those of IgG were 83.3% (55/66), 95.0%, 94.8%, 83.8%, and 88.9%. In patients with suspected COVID-19, sensitivity, specificity, PPV, NPV, and consistency rate of IgM were 87.5% (21/24), 100%, 100%, 95.2%, and 96.4%, respectively, and those of IgG were 70.8% (17/24), 96.6%, 85.0%, 89.1%, and 88.1%. Both antibodies performed well in serodiagnosis for COVID-19 and rely on great specificity. Conclusions The antibodies against SARS-CoV-2 can be detected in the middle and later stages of the illness. Antibody detection may play an important role in the diagnosis of COVID-19 as a complementary approach to viral nucleic acid assays.

Objective The effects of the Apolipoprotein E (ApoE) genotype on peripheral amyloid beta (Aβ) and Aβ transporter levels are still unclear. Soluble low-density lipoprotein receptor-related protein-1 (sLRP1) and soluble receptor of advanced glycation end products (sRAGE) are the major transporter for Aβ, which can prevent plasma Aβ from flowing into brain. The aim of this study was to investigate the relationships between the ApoE genotype and plasma Aβ, sLRP1, sRAGE levels. Design Cross-sectional study. Setting The committee office of the village. Participants Residents lived in the village for more than 3 years, aged 40–85 years (n = 1,119, 63.5% women). Measurements Plasma biomarkers include ApoE genotype, Aβ, sLRP1, sRAGE, fasting blood-glucose, and blood lipids. General information, medical history, living habits, and cognitive status (cognitive impairment or not) were also collected. Results After controlling for all possible covariates, multiple linear regression analysis showed that the plasma level of Aβ42 was higher and log-transformed sLRP1 was lower in ApoE e4 carriers than that in noncarriers (βAβ42 = 1.214, 95% confidence interval: 0.105–2.316, pAβ42 = 0.031; βsLRP1 = −0.075, 95% confidence interval: −0.129 to −0.021, psLRP1 = 0.006, respectively). Partial correlation analysis showed that plasma Aβ40 was positively correlated with log-transformed sLRP1 and log-transformed sRAGE (rsLRP1 = 0.116, psLRP1 Conclusion ApoE e4 carriers had higher plasma Aβ42 levels and lower sLRP1 levels. These data indicated that the ApoE e4 allele may also contribute to the pathogenesis of Alzheimer's disease through its effects on peripheral Aβ42 and sLRP1 levels, but it needs to be further elucidated.

Background and Aims: The relationships between blood lipid levels and obesity and cognitive impairment have not been fully determined. Considering that the lipid accumulation product (LAP) is a composite index of blood lipid levels and obesity, we investigated the relationships between LAP levels at baseline and cognitive decline over 4 years.Methods: A total of 983 subjects (≥40 years) from a longitudinal cohort in a village of Xi’an, China, who completed the baseline survey were followed-up for 4 years. All participants underwent face-to-face interviews and cognitive assessments at baseline and at the 4-year follow-up. The Mini-Mental State Examination (MMSE) was used to assess cognitive function, and an MMSE score dropping ≥ 2 points from baseline was defined as cognitive decline. The relationships between LAP and cognitive decline were analyzed by linear regression models.Results: During the 4-year follow-up, 172 patients exhibited cognitive decline (17.5%). Univariate analysis showed that the rate of change in MMSE score was significantly different between the low-LAP group and the high-LAP group (t = −2.26, p = 0.024). Multiple linear regression indicated that a high LAP was positively associated with cognitive decline (β = 0.564, p = 0.012). Stratified multivariate analysis showed that LAP was positively associated with cognitive decline in the normal blood pressure female subgroup (β = 1.29, p = 0.002) but not in the high blood pressure group or the male group.Conclusions: High LAP is associated with cognitive decline in females with normal blood pressure but not in those with high blood pressure or males. This indicates that the relationships between blood lipid levels and obesity and cognitive impairment may be affected by blood pressure and sex.

The role of autophagy in lung cancer is context-dependent and complex. Recent studies have reported the important role of autophagy in tumor immune escape. However, the association between autophagy and tumor-infiltrating lymphocytes (TILs) in early-stage lung adenocarcinoma (LUAD) remains unclear. In this study, we aimed to develop and validate the autophagy-related gene pair index (ATGPI) and autophagy clinical prognostic index (ACPI) in multiple LUAD cohorts, including The Cancer Genome Atlas (TCGA) cohort, Gene Expression Omnibus cohorts, and one cohort from Union Hospital, Wuhan (UH cohort), using a Cox proportional hazards regression model with the least absolute shrinkage and selection operator. Multivariate Cox regression analysis demonstrated that there was a significant difference in overall survival (OS) between patients with high and low ATGPI in the testing [hazard ratio (HR) = 1.97; P < 0.001] and TCGA validation (HR = 2.25; P < 0.001) cohorts. Time-dependent receiver operating characteristic curve analysis was also performed. We found that high ATGPI could accurately identify patients with early-stage LUAD with shorter OS, with the areas under the curve of 0.703 and 0.676 in the testing and TCGA validation cohorts, respectively. Concordance index (C-index) was used to evaluate the efficiency of ATGPI and ACPI. The C-index of ACPI was higher than that of ATGPI in the testing (0.71 vs. 0.66; P < 0.001), TCGA validation (0.69 vs. 0.65; P = 0.028), and UH (0.80 vs. 0.70; P = 0.015) cohorts. TIL analysis demonstrated that the proportions of tumor-infiltrating CD4+ T cells were lower in the high-ATGPI group than in the low-ATGPI group in both the TCGA validation and UH cohorts. These results indicate the potential clinical use of ATG signatures which are associated with TILs, in identifying patients with early-stage LUAD with different OS.

Objectives: Amyloid-β (Aβ) deposition in the brain is the hallmark of Alzheimer’s disease (AD) pathology. Hypertension is a risk factor for AD, but the effects of hypertension on Aβ deposition are not fully determined. Considering peripheral Aβ closely relates to Aβ deposition in the brain, we investigated the relationships between blood pressure (BP) level and plasma Aβ concentrations.Methods: One-thousand and sixty-nine participants (age above 45) from a village in the suburbs of Xi’an, China were enrolled. Questionnaires and validated Chinese versions of the Mini-Mental State Examination (MMSE) were used to collect information about vascular risk factors and assess cognition function. The apolipoprotein E (ApoE) genotype was detected using PCR and sequencing. Plasma Aβ levels were measured using ELISA. The associations between BP and plasma Aβ levels were analyzed by using multivariate linear regression.Results: Plasma Aβ1–40 level was higher in high BP group than that in normal BP group (53.34 ± 8.50 pg/ml vs. 51.98 ± 8.96 pg/ml, P = 0.013), in high SBP group than that in normal SBP group (53.68 ± 8.69 pg/ml vs. 51.88 ± 8.80 pg/ml, P = 0.001) and in high MABP group than that in normal MABP group (54.05 ± 8.78 pg/ml vs. 52.04 ± 8.75 pg/ml, P = 0.001). After controlling for the confounding factors, SBP (b = 0.078, P < 0.001), DBP (b = 0.090, P = 0.008) and MABP (b = 0.104, P < 0.001) correlated with plasma Aβ1–40 level positively in ApoE ε4 non-carriers, but not ApoE ε4 carriers.Conclusions: Elevated BP levels were associated with increased plasma Aβ1–40 levels in middle-aged and elderly ApoE ε4 non-carriers.

The emerging Porcine circovirus type 3 (PCV3) is associated with porcine dermatitis and nephropathy syndrome, reproductive failure and cardiac and multisystemic inflammation. To trace the prevalence and evolution of PCV3 in pigs with respiratory diseases or digestive diseases in China, 616 samples were collected from 21 provinces or municipalities of China from 2015 to 2017. All samples were analysed with PCR and a cap-gene-based phylogeny. The results indicated that the positive rate of PCV3 was 12.2% (75/616) at the sample level; 24.1% (42/174) at the farm level; 10.4% (50/480) in the digestive-disease-affected samples; 26.6% (25/94) in the respiratory-disease-affected samples; all 42 healthy samples were negative for PCV3. A statistical analysis showed that PCV3 infection was closely associated with both digestive diseases (p

Background. In traditional Chinese medicine (TCM), TCM syndrome is a key guideline, and Chinese materia medicas are widely used to treat hepatitis B virus- (HBV-) related hepatocellular carcinoma (HCC) according to different TCM syndromes. However, the prognostic value of TCM syndromes in HBV-related HCC patients has never been studied. Methods. A retrospective cohort of HBV-related HCC patients at Shenzhen Traditional Chinese Medicine Hospital from December 2005 to October 2017 was analyzed. The prognostic value of TCM syndromes in HBV-related HCC patients was assessed by Kaplan–Meier survival curves and Cox analysis, and the TCM syndrome with the best prognosis of HBV-related HCC patients was determined. To further study the relevant mechanisms, key Chinese materia medicas (KCMMs) for the TCM syndrome with the best prognosis were summarized, and network pharmacology was also performed. Results. A total of 207 HBV-related HCC patients were included in this research, and we found that HBV-related HCC patients with TCM excess syndrome had better OS. Then, a total of eight KCMMs for TCM excess syndrome were identified, whose crucial ingredients included quercetin, beta-sitosterol, kaempferol, luteolin, and XH-14, and KCMMs could play a therapeutic role through MAPK, JAK-STAT, Wnt, Hippo, and other pathways. Moreover, TP53, SRC, STAT3, MAPK3, PIK3R1, HRAS, VEGFA, HSP90AA1, EGFR, and JAK2 were determined as the key targets. Conclusion. We propose a new research method of “prognosis of TCM syndromes-KCMMs-network pharmacology” to reveal the prognostic value of TCM syndromes and the potential mechanism by which TCM syndromes affect prognosis.

Patella alta is an established risk factor for recurrent lateral patella dislocations. Medial patellofemoral ligament (MPFL) reconstruction has been shown to reduce patella height. Our hypothesis is that isolated MPFL reconstruction corrects patella alta, thereby reducing the risk of recurrent patella dislocation. A prospective cohort study of 33 knees which underwent MPFL reconstruction for recurrent patella dislocation. The pre-operative and post-operative patella height and Kujala knee outcome scores, as well as tibial tuberosity–trochlear groove (TT-TG) distance, and the grade of trochlear dysplasia were recorded. The mean age was 21.5 years (16–34 years). There was significant reduction in patella height in all patients (p

Background The current outbreak of coronavirus disease 2019 (COVID-19) caused by Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, Hubei, China, spreads across national and international borders. Methods We prospectively collected medical records of 14 health care workers (HCWs) who were infected with SARS-CoV-2, in neurosurgery department of Wuhan Union Hospital, China. Results Among the 14 HCWs, 12 were conformed cases, the other 2 were suspected cases. Most of them were either exposed to the two index patients or infected coworkers, without knowing they were COVID-19 patients. There were 4 male and 10 female infected HCWs in this cohort, whose mean age was 36 years (SD, 6 years). The main symptoms included myalgia or fatigue (100%), fever (86%) and dry cough (71%). On admission, 79% of infected HCWs showed leucopenia and 43% lymphopenia. Reduced complement C3 could be seen in 57% of the infected HCWs and IL-6 was significantly elevated in 86% of them. The proportion of lymphocytes subsets, concentrations of immunoglobulins, complement C4, IL-2, IL-4, IL-10, TNF-α and IFN-γ were within normal range in these 14 infected HCWs. The most frequent findings on pulmonary computed tomographic images were bilateral multifocal ground-glass opacifications (86%). Conclusions Human-to-human transmission of COVID-19 pneumonia has occurred among HCWs, and most of these infected HCWs with confirmed COVID-19 are mild cases. Our data suggest that in the epidemic area of COVID-19, stringent and urgent surveillance and infection-control measures should be implemented to protect doctors and nurses from COVID-19 infection.

Background The relationship between malnutrition-inflammation-atherosclerosis syndrome (MIAS) and self-management ability has not been previously revealed even though both play an important role in the management of peritoneal dialysis (PD) patients. Methods In total, 93 patients were enrolled in this study. A self-management questionnaire was used for the evaluation of self-management ability. The identification of MIAS was based on one or more of the following three conditions: C-reactive protein (CRP)≥10 mg/L, malnutrition–inflammation score (MIS)> 7, and the presence of atherosclerosis-related medical records. The possible association between different self-management abilities and MIAS was analyzed with a Spearman correlation analysis. Results There were 40 (43.0%) patients in the atherosclerosis group, and 38 (40.9%), 38 (40.9%), 10 (10.8%), and 7 (7.5%) patients in the MIAS0, MIAS1, MIAS2, and MIAS3 groups, respectively. The group with a score above the mean score of the Dialysis Effect Evaluation and Monitoring dimension had a fewer number of hospitalizations, higher albumin levels, lower MIS scores, a lower level of IL-6, and a lower number of MIAS factors. The Pearson and Spearman correlation analyses also revealed that this dimension was negatively correlated with the MIAS, MIS, IL-6, BNP, number of hospitalizations, and age and positively associated with albumin and prealbumin. Conclusion The Dialysis Effect Evaluation and Monitoring dimension of the self-management scale for PD patients is closely linked to the MIAS, and a better dialysis effect evaluation and monitoring capacity results in a decreased likelihood of exposure to malnutrition and inflammation. Trial registration Chinese Clinical Trial Registry: ChiCTR2000035525 (http://www.chictr.org.cn/showproj.aspx?proj=58110), registered August 13, 2020.

BackgroundThe global pandemic of COVID-19 cases caused by infection with SARS-CoV-2 is ongoing, with no approved antiviral intervention. We describe here the effects of treatment with interferon-α2b in a cohort of confirmed COVID-19 cases in Wuhan, China.MethodsIn this retrospective study, 77 adults hospitalized with confirmed COVID-19 were treated with either nebulized IFN-α2b (5mU b.i.d.), arbidol (200mg t.i.d.) or a combination of IFN-α2b plus arbidol. Serial SARS-CoV-2 testing along with hematological measurements, including cell counts and blood biochemistry, serum cytokine levels, temperature and blood oxygen saturation levels were recorded for each patient during their hospital stay.ResultsTreatment with IFN-α2b with or without arbidol significantly reduced the duration of detectable virus in the upper respiratory tract and in parallel reduced duration of elevated blood levels for the inflammatory markers IL-6 and CRP.ConclusionThese findings suggest that IFN-α2b should be further investigated as a therapy in COVID-19 cases.

Objective Numerous studies have demonstrated the close relationship between chronic stress and blood pressure (BP). Hypertensive subjects exhibit exaggerated reactions to stress, especially higher BP. The mechanisms by which stress affects pre-existing hypertension still need to be explored. Danzhi Xiaoyao Powder (DP), a historical traditional Chinese medicine formula, is a promising treatment for BP control in hypertensive patients under stress. The present study investigated the metabolomic disruption caused by chronic stress and the treatment effect and mechanism of DP. Methods Spontaneously hypertensive rats (SHRs) were subjected to chronic restraint stress (CRS) for 4 weeks. BP was measured via the tail-cuff method, and anxiety-like behavior was quantified using the elevated-plus-maze test. Meanwhile, DP was administered intragastrically, and its effects were observed. Global metabolomic analysis was performed using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry, followed by multivariate statistical analysis to detect differential metabolites and pathways. Results DP alleviated the CRS-induced increase in BP and anxiety-like behavior. Systematic metabolic differences were found among the three study groups. A total of 29 differential plasma metabolites were identified in both positive- and negative-ion modes. These metabolites were involved in triglyceride metabolism, amino acid (phenylalanine, tryptophan, and glycine) metabolism, and steroid hormone pathways. Conclusion These findings expose the metabolomic disturbances induced by chronic stress in SHRs and suggest an innovative treatment for this disorder.

Objectives: Till now, the effect of serum lipid levels on cognitive function is still controversial. The apolipoprotein E (APOE) e4 allele is the most critical genetic risk factor for Alzheimer's disease (AD) and cognitive impairment. Additionally, APOE e4 allele has a major impact on lipid metabolism. The aim of this study was to investigate the APOE genotype-dependent relationship between peripheral serum lipid levels and cognitive impairment. Methods: A total of 1,273 subjects aged 40-86 years participated in this cross-sectional study. Serum lipid levels and the APOE genotype were detected. Mini-Mental State Examination was used to diagnose the cognitive impairment or not. Univariate and multivariate analyses were used to analyze the relationships between APOE genotype, serum lipid levels, and cognition function. Results: After controlling for all possible covariates, a significant interaction between low serum high-density lipoprotein and the APOE e4 allele on cognitive impairment (Wald's χ2 = 4.269, df = 1, OR = 20.094, p = 0.039) was found in the total participants. In APOE e4 carriers, low serum high-density lipoprotein was positively associated with cognitive impairment (Wald's χ2 = 8.200, df = 1, OR = 60.335, p = 0.004) and serum high-density lipoprotein levels were positively correlated with Mini-Mental State Examination score (r = 0.217, df = 176, p = 0.004). There was no significant correlation between serum total cholesterol (TC), low-density lipoprotein, triglycerides (TG) levels, and cognitive impairment in either the total participants or APOE e4 carriers/non-carriers. Conclusions: APOE e4 carriers, but not non-carriers, with lower serum high-density lipoprotein had a higher prevalence of cognitive impairment and a lower Mini-Mental State Examination score. These results suggest that the APOE e4 allele may affect the relationship between serum lipid levels and cognitive impairment. However, the specific mechanism needs to be further elucidated.

To safely re-open economies and prevent future outbreaks, rapid, frequent, point-of-need, SARS-CoV-2 diagnostic testing is necessary. However, existing field-deployable COVID-19 testing methods require the use of uncomfortable swabs and trained providers in PPE, while saliva-based methods must be transported to high complexity laboratories for testing. Here, we report the development and clinical validation of High-Performance Loop-mediated isothermal Amplification (HP-LAMP), a rapid, saliva-based, SARS-CoV-2 test with a limit of detection of 1.4 copies of virus per µl of saliva and a sensitivity and specificity with clinical samples of > 96%, on par with traditional RT-PCR based methods using swabs, but can deliver results using only a single fluid transfer step and simple heat block. Testing of 120 patient samples in 40 pools comprised of 5 patient samples each with either all negative or a single positive patient sample was 100% accurate. Thus, HP-LAMP may enable rapid and accurate results in the field using saliva, without need of a high-complexity laboratory.

Objective: Growing evidence suggests that sleep disturbance is a risk factor for Alzheimer's disease (AD). Amyloid-β (Aβ) deposition in the brain is a main pathophysiology of AD. Considering that peripheral Aβ level is associated with brain Aβ deposition, the present study investigated the relationship between sleep disturbance and plasma Aβ levels.Methods: This is a population-based cross-sectional study. A total of 1,459 participants from a village in the suburbs of Xi'an, China, were enrolled from January 3, 2017 to March 26, 2017. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI), and a PSQI score of 10 points as poor sleep quality. Cognitive function was assessed with the Mini-Mental State Examination (MMSE). Fasting venous blood was taken in the morning, and the plasma Aβ levels were measured using ELISA. The relationships between plasma Aβ levels and sleep quality were analyzed using multiple linear regression.Results: Among the participants, 231 had poor sleep quality (15.83%). The log-transformed Aβ40 level had significant differences among the different sleep groups (F = 3.216, p = 0.040). The log-transformed Aβ40 level was higher in the poor sleep quality group than that in the general sleep quality group [87.17 (73.42, 107.34) vs. 89.69 (74.81, 125.79) pg/ml, p = 0.016]. In bivariate analysis, sleep quality was negatively associated with the log-transformed plasma Aβ40 level (β = −0.025, p = 0.011).Conclusion: In the community population, poorer sleep quality is associated with a higher plasma Aβ40 level. This indicated that sleep disturbance might also involve in dysfunction of peripheral Aβ clearance.

Since the past decade, aspirin, a popular anti-inflammatory drug, has been increasingly studied for its potential antimicrobial and antibiofilm activity with promising results, but studies were limited to in vitro and in vivo investigations. Moreover, evidence concerning the beneficial effects of aspirin on the treatment of biofilm-related infections in real-world population is limited. Thus, this study aimed to investigate whether aspirin could promote infection control for patients with periprosthetic joint infections (PJIs). A single-center database was searched. Regular aspirin exposure was defined as a prescription of aspirin for > 6 months before diagnosis of PJIs and consecutive use during the PJI treatment course at a dose ≧ 100 mg/day. General data, treatment modalities, and recurrence status were collected from medical records by an independent orthopedic surgeon. From January 01, 2010, to February 17, 2019, 88 patients who met the PJI criteria were identified and included in this study. Of these patients, 12 were taking aspirin regularly during the infectious events. In the Cox proportional hazards model, multivariate analysis revealed that the aspirin group demonstrated significant benefit via superior resolution of PJIs (HR 2.200; 95% CI 1.018–4.757; p = 0.045). In this study, aspirin is beneficial for infection resolution when combined with the current standard of PJI treatment and conventional antibiotics in the management of PJIs.

Osteomyelitis from a retained foreign body should be included in the differential diagnosis of any osteolytic lesion of the foot. We report here a case of a 59-year-old man who presented with swelling over the dorsolateral aspect of the right foot. Plain x-ray showed an osteolytic lesion that mimicked a pseudotumor. Magnetic resonance imaging (MRI) showed multilocular fluid collection over the right cuboid with a hypointense lesion over the plantar fascia. The patient underwent surgery and a rubber fragment (1 cm × 0.8 cm) was removed from his foot that had been present for two years following a stabbing injury. The patient fully recovered without complication or disability.

Diffuse pigmented villonodular synovitis (PVNS) of knee is a rare benign disease that has a destructive clinical course. Synovectomy and adjuvant radiotherapy (RT) have been reported as treatment options but literatures reporting functional outcomes were sparse. This study aimed to evaluate the long-term functional outcomes and disease control among treatment modalities through the 22 years of experience.A single-center database was searched for patients who received synovectomy of knee with the pathologic diagnosis of PVNS. General data, treatment modalities, and recurrent status were retrospectively collected from medical records. Functional outcomes were evaluated by Western Ontario and McMaster Universities Osteoarthritis Index through phone interviews by an independent orthopedist.From January 1995 to December 2017, 24 patients with diffuse PVNS of knee were identified, including 19 receiving open synovectomy (OP) and 5 undergoing arthroscopic surgery. Adjuvant RT was performed on 14 patients with a median dose of 35 Gy (range 20-40 Gy). After median follow up of 6 years, recurrences were recorded in 10 cases. The recurrence rate was significantly lower in the OP + RT group than the OP group (8.3% vs 57.1%, P = .038). Among those with preserved knee joints, there was no significant difference in the Western Ontario and McMaster Universities Osteoarthritis Index score and stiffness score between patients in the OP + RT and OP groups.For patients with diffuse PVNS of knee, the addition of moderate-dose adjuvant RT following OP provided excellent local control while maintaining good joint function with limited treatment-related morbidity. Our study emphasized the importance of moderate dose RT in diffuse PVNS of knee joint.

In this study, we aimed to identify the cultivatable oral anaerobic bacterial distribution in oral cavity by MALDI-TOF Biotyper. The bacterial distribution of three groups, including subjects with/without periodontal disease, two clusters of age (60 years as the cutoff), and before/after treatment, were investigated in this study. There were 38 participants recruited in this study, involving 18 subjects with moderate to severe periodontal-infected patients and 20 healthy controls. Total number of 126 bacterial species were identified by MALDI-TOF MS. The relative abundance of Streptococcus gordonii and Streptococcus intermedius in periodontal patients is higher than healthy controls indicating potential biomarkers for periodontal disease. Participants with periodontal disease were subdivided in to two clusters of age (60 years as the cutoff), 11 and 7 participants were age60 years and60 years, respectively. Meanwhile, the incidence of Streptococcus pneumoniae and Streptococcus oralis infection were higher in the subjects above 60 years old than below. Moreover, the bacterial distribution between pre-treatment and post-treatment was similar indicating that basic treatment without the ability to redistribute the microbiota. In summary, the cultivable oral anaerobic bacteria were identified by MALDI-TOF MS and the bacterial distribution shifting was shown to be associated with the progress of periodontal disease to aging and basic treatment. This study provided information for diagnosis and treatment guidelines for oral healthcare.

Exposure to repeated stress is associated with the occurrence and development of many prevalent diseases. Here, we evaluated the impact of a repeated restraint stress (RRS) paradigm on male Wistar rats and compared global plasma metabolites in stressed and unstressed rats using an ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC/Q-TOF-MS) approach and multivariate statistical analysis. The data showed that ten days of RRS induced weight loss and anxiety-like behavior, possibly through elevating plasma corticosterone levels in rats. Different metabolic characteristics were found between the two groups. Seventeen differential metabolites were identified and considered as potential biomarkers in the stress process, including histidine metabolism, neurotransmitter synthesis, and bile acid metabolism. Furthermore, l-carnosine, an identified metabolite, was examined in the same model and found to attenuate weight loss and anxiety-like behavior in RRS rats. Hence, these findings describe the metabolomic profiling of repeated stress and provide new insights into the pathophysiological mechanism of stress-induced deflections and potential pharmacological interventions.

Background Diffuse pigmented villonodular synovitis (PVNS) of the knee is a rare benign disease that has a destructive clinical course. Reported treatment options include arthroscopic or open synovectomy with or without adjuvant radiotherapy of various doses. This study compared the long-term functional outcomes and disease control among treatment modalities and discussed 22 years of experience with radiotherapy (RT) as an adjuvant treatment for PVNS of knee.Methods A single-center database was searched for patients who received synovectomy of knee with the pathologic diagnosis of PVNS. General data, treatment modalities, and recurrent status were retrospectively collected from medical records. Functional outcomes were evaluated by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) through phone interviews by an independent orthopedist.Results From January 1995 to December 2017, 24 patients with diffuse PVNS of knee were identified, including 19 receiving open synovectomy (OP) and 5 undergoing arthroscopic surgery (AS). Adjuvant RT was performed on 14 patients with a median dose of 34.25 Gy (range 20-40 Gy). After median follow up of 6 years, clinically or radiographically confirmed recurrences were recorded in 10 cases. The local recurrence rate was significantly lower in the OP+RT group than the OP group (8.3% vs. 57.1%, p =0.038). Among those with preserved knee joints, there was no significant difference in the WOMAC score and stiffness score between patients in the OP+RT and OP groups.Conclusions In conclusion, for patients with diffuse PVNS of knee, the addition of moderate-dose adjuvant RT to open synovectomy provided excellent local control while maintaining good joint function with limited treatment-related morbidity. Our study emphasized the importance of moderate dose of RT in diffuse PVNS of knee joint.

Objectives: Till now, the effect of serum lipid levels on cognitive function is still controversial. The apolipoprotein E (APOE) ε4 allele is the most critical genetic risk factor for Alzheimer’s disease (AD) and cognitive impairment. Additionally, APOE ε4 allele has a major impact on lipid metabolism. The aim of this study was to investigate the APOE genotype-dependent relationship between peripheral serum lipid levels and cognitive impairment. Methods: A total of 1,273 subjects aged 40–86 years participated in this cross-sectional study. Serum lipid levels and the APOE genotype were detected. Mini-Mental State Examination was used to diagnose the cognitive impairment or not. Univariate and multivariate analyses were used to analyze the relationships between APOE genotype, serum lipid levels, and cognition function. Results: After controlling for all possible covariates, a significant interaction between low serum high-density lipoprotein and the APOE ε4 allele on cognitive impairment (Wald’s χ2 = 4.269, df = 1, OR = 20.094, p = 0.039) was found in the total participants. In APOE ε4 carriers, low serum high-density lipoprotein was positively associated with cognitive impairment (Wald’s χ2 = 8.200, df = 1, OR = 60.335, p = 0.004) and serum high-density lipoprotein levels were positively correlated with Mini-Mental State Examination score (r = 0.217, df = 176, p = 0.004). There was no significant correlation between serum total cholesterol (TC), low-density lipoprotein, triglycerides (TG) levels, and cognitive impairment in either the total participants or APOE ε4 carriers/non-carriers. Conclusions: APOE ε4 carriers, but not non-carriers, with lower serum high-density lipoprotein had a higher prevalence of cognitive impairment and a lower Mini-Mental State Examination score. These results suggest that the APOE ε4 allele may affect the relationship between serum lipid levels and cognitive impairment. However, the specific mechanism needs to be further elucidated.

Obesity is associated with metabolic disorders. Thus, obesity prevention and treatment are essential for health. Antrodia cinnamomea (AC) is a multifunctional medicinal fungus used for the treatment of various diseases and for preventing diet-induced obesity. Leptin deficiency causes over-eating and spontaneous obesity. The concomitant metabolic symptoms are more severe than diet-induced obesity. Here, we used leptin-deficient (ob/ob) mice as an animal model for over-feeding to study the effect of AC on obesity. We fed C57BL/6 mice (WT, ob+/+) and ob/ob mice with AC for four weeks before performing qRT-PCR and immunoblot analysis to elaborate AC-modulated mechanisms. Further, we used Caco-2 cells as a human intestinal epithelial barrier model to examine the effect of AC on intestinal permeability. Our results suggested that AC reduces lipid deposits of the liver and epididymal white adipose tissue (EWAT) by promoting lipid metabolism and inhibiting lipogenesis-associated genes and proteins in ob/ob mice. Moreover, AC effectively repaired intestinal-barrier injury caused by leptin deficiency and enhanced intestinal barrier integrity in Caco-2 cells. Interestingly, AC significantly reduced body weight and EWAT with no compromise on food intake in ob/ob mice. Thus, AC effectively reduced obesity caused by leptin-deficiency and can potentially be used as a nutraceutical for treating obesity.

Background It is believed that deposition of amyloid beta (Aβ) in the brain is the central pathological changes of Alzheimer’s disease (AD), which triggers a series of pathological processes. However, the relationship between dyslipidemia and AD is uncertain. Considering the peripheral Aβ levels are related to brain Aβ deposition, we explore the relationships between blood lipids and plasma Aβ. Methods Participants who lived in the selected village of Xi’an for more than 3 years were enrolled, aged 40–85 years (n = 1282, 37.9% male). Fasting blood lipid, plasma Aβ levels, basic information and living habits were measured. Multiple linear regressions were used. Results In total population, blood lipids were not associated with plasma Aβ. After stratified by blood pressure, serum total cholesterol (TC) and low-density lipoprotein (LDL-c) were positively associated with plasma Aβ42 levels (βTC = 0.666, PTC = 0.024; βLDL-c = 0.743, PLDL-c = 0.011, respectively) in normal blood pressure. LDL-c was negatively associated with plasma Aβ40 levels (β = − 0.986, P = 0.037) in high blood pressure. Conclusion Elevated plasma Aβ42 levels are associated with higher TC and LDL-c in normal blood pressure. Elevated plasma Aβ40 levels are associated with lower LDL-c in high blood pressure. This indicated that the relationships between blood lipids and plasma Aβ were confounded by blood pressure.

BACKGROUND: Progressive familial intrahepatic cholestasis (PFIC) encompasses a group of autosomal recessive disorders with high morbidity and mortality. Variants in the gene encoding tight junction protein-2 (TJP2) have been linked to PFIC type 4 (PFIC4), which predominantly presents in childhood. However, there are only limited data from adults with TJP2-related PFIC4. We report a family with an autosomal recessive disorder with a novel variant in the TJP2 gene in adults with very variable expression of PFIC4. CASE SUMMARY: The index patient presented at 19 years old with liver cirrhosis and variceal bleeding and was treated with endoscopic banding and beta-blockers. In 2018, he developed primary liver cancer that was treated with radiofrequency ablation followed by liver transplantation in 2019. Genetic testing revealed a novel homozygous TJP2 variant causing PFIC4 (TJP2([NM_004817.3]:c.[3334C>T]; [3334C>T])). The consanguineous family consists of the father and mother (both heterozygous) and their 12 children, of which five carry the variant in a homozygous state; however, these five siblings have highly variable expression of PFIC4. Two homozygous brothers had cirrhosis and portal hypertension at diagnosis at the ages of 19 and 36. Two other homozygous brothers, age 23 and 19, and the homozygous sister, age 21, have elevated liver enzymes but presently no cirrhosis, which may suggest an age-dependent penetrance. In addition, five sisters had severe and mild intrahepatic cholestasis of pregnancy and carry the TJP2 variant in a homozygous and heterozygous state, respectively. CONCLUSION: This novel TJP2 variant is associated with PFIC4 causing severe liver disease with cirrhosis and primary liver cancer in adolescents/adults.

Ischemic stroke is one of the leading causes of death worldwide. In the post-stroke stage, cardiac dysfunction is common and is known as the brain–heart interaction. Diabetes mellitus worsens the post-stroke outcome. Stroke-induced systemic inflammation is the major causative factor for the sequential complications, but the mechanism underlying the brain–heart interaction in diabetes has not been clarified. The NLRP3 (NLR pyrin domain-containing 3) inflammasome, an important component of the inflammation after stroke, is mainly activated in M1-polarized macrophages. In this study, we found that the cardiac dysfunction induced by ischemic stroke is more severe in a mouse model of type 2 diabetes. Meanwhile, M1-polarized macrophage infiltration and NLRP3 inflammasome activation increased in the cardiac ventricle after diabetic stroke. Importantly, the NLRP3 inflammasome inhibitor CY-09 restored cardiac function, indicating that the M1-polarized macrophage–NLRP3 inflammasome activation is a pathway underlying the brain–heart interaction after diabetic stroke. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12264-020-00544-0) contains supplementary material, which is available to authorized users.

Objectives Fingertip amputation is often encountered in emergency departments, especially in hospitals located near industrial areas. Replantation of the fingertip can be considered when the normal architecture is preserved in cases of sharp amputation. The goal of replantation is to preserve cosmesis and function, especially for the thumb because of its involvement in grasping and the key pinch. Even when microsurgical vascular anastomosis is applied, the absence of venous anastomosis along with the high rate of failure of arterial anastomosis in zone 1A fingertip amputation may lead to replantation failure. Methods We herein present a case report of thumb tip amputation salvaged via a modified cross-finger technique. The recipient site was on the ipsilateral radial side of the intermediate phalanx of the middle finger. Results The thumb tip was successfully replanted with no vascular anastomosis, and this new technique prevented stiffness in the metacarpophalangeal and interphalangeal joints of the thumb and middle finger. Conclusions This procedure can be performed in local clinics and emergency departments without the need for arterial and venous anastomoses.

Medical thoracoscopy (MT) refers to a minimally invasive procedure to inspect and perform a biopsy of the pleural space, as well as to perform therapeutic interventions, in a nonintubated patient under local anesthesia. This procedure provides the physician a window into the pleural space. Over the past two decades, MT has been developed very rapidly in China. We performed a review of the published data on MT in China, and estimated the present status, the challenges, and future perspectives of MT. From the data we conduct that MT is widely used well in China, not only in the diagnosis of exudative pleural effusions, but also in the management of pleural diseases, such as tuberculous pleural effusion, malignant pleural effusion and spontaneous pneumothorax. Meanwhile, it is noteworthy that few prospective clinical trials, lack of routine follow-up of MT are current domestic problems for diagnosis and management in pleural effusion. Consequently, more prospective, randomized clinical trials are needed to assess the diagnostic value and treatment superiorities of MT compared with traditional methods or other subjects in China in the future.

Background It has long been known that carbon monoxide poisoning is associated with cognitive dysfunction but whether carbon monoxide poisoning is a risk factor for incident dementia is still inconclusive. Our objective was to assess whether carbon monoxide poisoning increases the incidence of dementia. Methods We conducted a systematic review and meta analysis of cohort studies examining the risk of dementia in people with carbon monoxide poisoning. We searched the Cochrane Library, PubMed, and EMBASE from inception to 31 March 2019. Two authors independently selected studies, assessed the quality of included studies, and extracted data. Any disagreement was resolved by discussion with a third author. Only cohort study with an enough follow-up period was included, which reported the association between carbon monoxide poisoning and incidence of dementia in adults. Exposure was carbon monoxide poisoning; primary outcomes were incident all-cause dementia, Alzheimer’s disease and cognitive disorder. Summary estimates were obtained using random effects meta-analysis. Results Thirty-three full texts were initially searched, but only three studies met our inclusion criteria, and they were comprised of 134,563 participants who were initially free of dementia. The follow-up period ranged from 9 to 12 years. We found that CO poisoning increased the risk of dementia incidence [adjusted hazard ratio 2.61, 95% confidence interval (CI) 1.56 to 4.36, P = 0.0003]. Subgroup analysis showed that the increased dementia risk was significant in males but not in females, and the highest risk was in young age group, followed by in middle age group, but not in the old one (P > 0.05). Conclusions This meta-analysis suggests that overall the evidence from prospective cohort studies supported a link between carbon monoxide exposure and an increased dementia risk, although all the included studies were limited to Taiwanese population. Further studies that provide data for different ethnic groups are needed to clarify whether a subgroup of patients with carbon monoxide exposure has an elevated risk of dementia.

Solitary calcified nodule-related carpal tunnel syndrome (CTS) is rare and easy to be misdiagnosed owing to the high incidence of primary CTS. Release of the transverse carpal ligament without removal of the mass leads to persistence of the symptoms and subsequent complications like wasting of the thenar muscles. Here, we report two cases of solitary calcified nodule-related CTS and discuss the role of ultrasound in preventing misdiagnosis. Both patients reported persistent numbness over the lateral side of their palm and weakness of the right wrist with thenar muscle atrophy. One patient had undergone transverse carpal ligament release 2 years previously, and the other had received a local injection of lidocaine at the clinic. Neither patient experienced symptom relief. X-ray revealed a similar finding of nodule lesions in front of the capitate–hamate region. Solitary calcified nodule-related CTS was diagnosed, and the patients underwent nodule removal with/without transverse ligament release. The first patient was a typical case of misdiagnosed solitary calcified nodule-related CTS. The second patient had a definitive clinical sonographic diagnosis before surgery. The accurate diagnosis of secondary CTS is paramount for performing effective surgery. Thus, ultrasonography is an easy, convenient, safe, and effective method in screening for secondary CTS.

Non-alcoholic fatty liver disease (NAFLD) is increasingly recognized as a significant liver disease, and it covers the disease spectrum from simple steatosis with a risk of development of non-alcoholic steatohepatitis (NASH) to fibrosis, subsequent cirrhosis, end-stage liver failure, and liver cancer with a potential need for liver transplantation. NAFLD and NASH are closely related to obesity, metabolic syndrome, and type 2 diabetes (T2D). The role of gut hormones, especially glucagon-like peptide 1 (GLP-1), is important in NAFLD. Bariatric surgery has the potential for inducing great weight loss and may improve the symptoms of metabolic syndrome and T2D. Recent data demonstrated significant effects of bariatric surgery on GLP-1 and other gut hormones and important lipid metabolic and inflammatory abnormalities in the pathophysiology of NAFLD. Therefore, bariatric surgery may reverse the pathological liver changes in NAFLD and NASH patients. In the present review, we describe NAFLD and NASH pathophysiology and the primary effects of bariatric surgery on metabolic pathways. We performed a systematic review of the beneficial and harmful effects and focused on changes in liver disease severity in NAFLD and NASH patients. The specific focus was liver histopathology as assessed by the invasive liver biopsy. Additionally, we reviewed several non-invasive methods used for the assessment of liver disease severity following bariatric surgery.

Background: Understanding the medical decision-making and information disclosure preferences is important for care quality. Objectives: To examine the feasibility of using the questionnaires and to identify modifications needed in the following study. Design: Thirty-three pairs of patients with advanced cancers and their caregivers were asked to complete the questionnaires. Results: More than 60% of patients and caregivers had an educational level of middle school and below. The active, passive, or shared decision-making preferences for patients were 33.3%, 39.4%, and 27.3%, respectively. Twenty of 33 patients and 24 of 33 caregivers misunderstood the questions. Conclusions: Low educational levels may be the reason for poor understanding imprecision. It is necessary to use the modification version of the questionnaires in developing countries.

To trace evolution of CBoV in Northeast China, 201 fecal samples from rectal swabs of diarrheic dogs collected from May 2014 to April 2015 were investigated using PCR targeting partial NS1 gene (440 bp). Furthermore, phylogenetic analysis of the identified CBoV strains was conducted using nucleotide sequences of the partial NS1 gene. The results indicated that 15 of 201 fecal samples (7.5%) were positive for CBoV; the partial NS1 genes of the 15 CBoV strains exhibited 83.1%–100% nucleotide identity, and 75.8%–100% amino acid identity; the entire VP2 gene of five selected CBoV strains exhibited 82.9%–96.8% nucleotide identity, and 90.4%–99.1% amino acid identity. The 15 CBoV strains exhibited high co-infection rates with CPV-2 (40%), CCoV (20%), and CaKV (26.67%). Phylogenetic analysis of the partial NS1 gene revealed that the 15 CBoV strains were divided into different subgroups of CBoV-2 when compared with CBoV-2 strains from South Korea, USA, Germany, and Hong Kong in China. Moreover, phylogenetic analysis of the VP2 gene indicated that five selected CBoV strains were divided into three different genetic groups of CBoV-2, involving in CBoV-2HK group, CBoV-2C group, and CBoV-2B group. The recombination analysis using the entire VP2 gene revealed three potential recombination events that occurred among five selected strains in our study. These data demonstrated that the CBoV strains circulating in Heilongjiang province, Northeast China showed genetic diversities, potential recombination events, and high co-infection rate. Further studies will be required to address the potential pathogenic role of these diverse CBoV strains., Highlights • Canine bocavirus (CBoV) exhibits high prevalence in Northeast China from 2.8% to 20%. • We revealed high co-infection of CBoV with canine parvovirus-2, canine coronavirus, and canine kobuvirus. • The CBoV strains circulating in Northeast China show multiple genetic groups. • Potential recombination events occur among the CBoV strains circulating in Northeast China.

// Shun-Hong Huang 1 , Ching-Hsuan Law 1 , Ping-Hsueh Kuo 2 , Ren-Yu Hu 1 , Ching-Chieh Yang 3, 4 , Ting-Wen Chung 1 , Ji-Min Li 1 , Li-Hsun Lin 1 , Yi-Chung Liu 1, 12 , En-Chi Liao 1 , Yi-Ting Tsai 1 , Yu-Shan Wei 1 , Chi-Chen Lin 5, 6, 7, 8 , Chien-Wen Chang 9 , Hsiu-Chuan Chou 10 , Wen-Ching Wang 2 , Margaret Dah-Tsyr Chang 2 , Lu-Hai Wang 11 , Hsing-Jien Kung 11 , Hong-Lin Chan 1, 2 , Ping-Chiang Lyu 1, 2 1 Department of Medical Sciences and Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan 2 Department of Medical Sciences and Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu, Taiwan 3 Department of Radiation Oncology, Chi-Mei Medical Center, Tainan, Taiwan 4 Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan 5 Institute of Biomedical Science, National Chung Hsing University, Taichung, Taiwan 6 Institute of Biomedical Science and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan 7 Department of Medical Research and Education, Taichung Veterans General Hospital, Taichung, Taiwan 8 Division of Chest Medicine. Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan 9 Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Taiwan 10 Department of Applied Science, National Hsinchu University of Education, Hsinchu, Taiwan 11 Institute of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli County, Taiwan 12 Institute of Population Sciences, National Health Research Institutes, Miaoli County, Taiwan Correspondence to: Hong-Lin Chan, e-mail: hlchan@life.nthu.edu.tw Ping-Chiang Lyu, e-mail: pclyu@mx.nthu.edu.tw Keywords: ECM, EMT, IF, MMP-13, OSCC Received: November 23, 2015 Accepted: February 09, 2016 Published: March 06, 2016 ABSTRACT The oral cancer cell line OC3-I5 with a highly invasive ability was selected and derived from an established OSCC line OC3. In this study, we demonstrated that matrix metalloproteinases protein MMP-13 was up-regulated in OC3-I5 than in OC3 cells. We also observed that expression of epithelial–mesenchymal transition (EMT) markers including Twist, p-Src, Snail1, SIP1, JAM-A, and vinculin were increased in OC3-I5 compared to OC3 cells, whereas E-cadherin expression was decreased in the OC3-I5 cells. Using siMMP-13 knockdown techniques, we showed that siMMP-13 not only reduced the invasion and migration, but also the adhesion abilities of oral cancer cells. In support of the role of MMP-13 in metastasis, we used MMP-13 expressing plasmid-transfected 293T cells to enhance MMP-13 expression in the OC3 cells, transplanting the MMP-13 over expressing OC3 cells into nude mice led to enhanced lung metastasis. In summary, our findings show that MMP-13 promotes invasion and metastasis in oral cancer cells, suggesting altered expression of MMP-13 may be utilized to impede the process of metastasis.

Canine kobuviruses (CaKVs) are newly recognized picornaviruses that have been recently detected in dogs in the U.S.A., Italy, U.K., the Republic of Korea and Tanzania. To trace the evolution of CaKV strains, a total of 201 fecal samples from rectal swabs of diarrheic dogs, which were obtained from May 2014 to April 2015 in northeast China, were detected by reverse transcription-PCR targeting a partial (504 bp) fragment of the 3D gene. Furthermore, a phylogenetic analysis of the CaKV strains identified in northeast China was conducted based on the partial 3D gene sequence. The results indicated that 36 fecal samples (17.91%, 36/201) were positive for CaKV, in which the co-infection rates of canine coronavirus, canine parvovirus-2 and canine bocavirus were 58.33%, 41.67%, and 11.11%, respectively. Sequence comparison of the partial 3D gene revealed nucleotide homologies of 94.4-100%, 95.6-98.6%, 94.3-97.6%, 94.4-96.3% and 93.3-95.1% within the 36 Chinese CaKV strains, and between the 36 Chinese CaKV strains and four CaKV reference strains from South Korea, Italy, U.S.A. and Tanzania, respectively. A phylogenetic tree revealed that the 36 Chinese CaKV strains formed one specific CaKV lineage with CaKVs that have recently been identified in other countries. The 36 Chinese CaKV strains were closely related to CaKV reference strains from Asia and Europe, but differed genetically from CaKV reference strains from North America and Africa. This study provides evidence that CaKVs circulate in diarrhoetic dogs in China and that they exhibit substantial genetic diversity and high co-infection rates with other enteric viruses.

Porcine epidemic diarrhea (PED) is an intestinal infectious disease caused by porcine epidemic diarrhea virus (PEDV); manifestations of the disease are diarrhea, vomiting and dehydration. Starting from the end of 2010, a PED outbreak occurred in several pig-producing provinces in southern China. Subsequently, the disease spread throughout the country and caused enormous economic losses to the pork industry. Accumulating studies demonstrated that new PEDV variants that appeared in China were responsible for the PED outbreak. In the current mini-review, we summarize PEDV epidemiology and vaccination in China.

Adipose-derived stem cells have been shown to promote peripheral nerve regeneration through the paracrine secretion of neurotrophic factors. However, it is unclear whether these cells can promote myogenic differentiation in muscular dystrophy. Adipose-derived stem cells (6 × 10 6 ) were injected into the gastrocnemius muscle of mdx mice at various sites. Dystrophin expression was found in the muscle fibers. Phosphorylation levels of Akt, mammalian target of rapamycin (mTOR), eIF-4E binding protein 1 and S6 kinase 1 were increased, and the Akt/mTOR pathway was activated. Simultaneously, myogenin levels were increased, whereas cleaved caspase 3 and vimentin levels were decreased. Necrosis and fibrosis were reduced in the muscle fibers. These findings suggest that adipose-derived stem cells promote the regeneration and survival of muscle cells by inhibiting apoptosis and fibrosis, thereby alleviating muscle damage in muscular dystrophy.

Background The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), infected over 3300 healthcare workers in early 2020 in China. Little information is known about nosocomial infections of healthcare workers in the initial period. We analysed data from healthcare workers with nosocomial infections in Wuhan Union Hospital (Wuhan, China) and their family members. Methods We collected and analysed data on exposure history, illness timelines and epidemiological characteristics from 25 healthcare workers with laboratory-confirmed coronavirus disease 2019 (COVID-19) and two healthcare workers in whom COVID-19 was highly suspected, as well as 10 of their family members with COVID-19, between 5 January and 12 February 2020. The demographics and clinical features of the 35 laboratory-confirmed cases were investigated and viral RNA of 12 cases was sequenced and analysed. Results Nine clusters were found among the patients. All patients showed mild to moderate clinical manifestation and recovered without deterioration. The mean period of incubation was 4.5 days, the mean±sd clinical onset serial interval (COSI) was 5.2±3.2 days, and the median virus shedding time was 18.5 days. Complete genomic sequences of 12 different coronavirus strains demonstrated that the viral structure, with small irrelevant mutations, was stable in the transmission chains and showed remarkable traits of infectious traceability. Conclusions SARS-CoV-2 can be rapidly transmitted from person to person, regardless of whether they have symptoms, in both hospital settings and social activities, based on the short period of incubation and COSI. The public health service should take practical measures to curb the spread, including isolation of cases, tracing close contacts, and containment of severe epidemic areas. Besides this, healthcare workers should be alert during the epidemic and self-quarantine if self-suspected of infection., SARS-CoV-2 can be rapidly transmitted from person to person in nosocomial and social settings, despite patients having no symptoms https://bit.ly/34BHtB5

BACKGROUND Transport proteins, soluble low-density lipoprotein receptor-related protein-1 (sLRP1), and soluble receptor of advanced glycation end products (sRAGE), play an important role in the clearance of plasma amyloid-β (Aβ). However, their relationship is not clear. OBJECTIVE The aim was to explore the relationship between plasma levels of sLRP1, sRAGE, and Aβ in a cross-sectional study. METHODS A total of 1,185 cognitively normal participants (age above 40) from a village in the suburbs of Xi'an, China were enrolled from October 8, 2014 to March 30, 2015. Plasma Aβ40, Aβ42, sLRP1, and sRAGE were tested using a commercial ELISA. Apolipoprotein E (APOE) genotyping was conducted using PCR and sequencing. The relationship between plasma levels of sLRP1, sRAGE, and Aβ was analyzed using Pearson's correlation analysis and multiple linear regression. RESULTS In the total population, Log sLRP1 and Log sRAGE were positively correlated with plasma Aβ40 (r= 0.103, p

Rationale In the past decade, only a few studies have focused on simultaneous bilateral ulnar neuropathy. Patient concerns A 54-year-old Asian male who has suffered from paranoid schizophrenia for 2 years. He reported that flexion contracture occurring over his fourth and fifth fingers on both hands appeared since six months after he started taking the antipsychotic drug. The electromyogram revealed bilateral ulnar neuropathy with chronic axonal degeneration at the elbow level. McGowan classification was performed to evaluate the severity of the ulnar nerve injury, and the patient was diagnosed with a grade 3 injury on his left hand and a grade 2 injury on his right hand. Diagnosis Simultaneous bilateral ulnar neuropathy at the elbow, a complication caused by tardive dyskinesia in a patient under the high-dose, first-generation, antipsychotic drug. Interventions We consulted a psychiatrist to assist in adjusting the patient's kind of the antipsychotic drug and performed the anterior transposition of ulnar nerve to avoid nerve entrapment caused by tardive dyskinesia. Outcomes Numbness of the palms continued to regress over the following 6 months after the anterior transposition of the ulnar nerve. Regression of the involuntary movements, including repeated bending of the elbows, and shaking of both feet, was noted from the patient but was incomplete. Lessons Two literatures concluded that parkinsonian rigidity is the main cause of simultaneous bilateral ulnar neuropathy by Sampath et al and Kurlan et al. Unlike the cases of stereotyped posture-caused neural compression reported previously, we inferred that repeated involuntary motion caused by first-generation antipsychotic drug might have been one of the causes of the patient's nerve compression.

Background The aim of this study is to reveal the clinical and histopathological features of HBsAg-positive and HBeAg-positive chronic hepatitis B infected patients with high level of HBV DNA, from 17 hospitals and medical centres in China, with alanine aminotransferase levels within the lower region of normal range versus those with levels within the upper region of normal range and to investigate the clinical risk factors for the requirement of treatment through the examination of liver biopsy. Methods Liver biopsy was performed on high level of HBV DNA of 455 patients with HBsAg-positive and HBeAg-positive chronic hepatitis B infection and persistently normal alanine aminotransferase level. Liver necroinflammation and fibrosis were graded per the Knodell histological activity index and Ishak's fibrosis score, respectively. Univariate analysis of the clinical parameters versus necroinflammation and fibrosis was carried out. Results Of the subjects in this multicentre-based study, 5.49% and 10.11% had significant necroinflammation with Knodell histological activity index ≥ 9 and hepatic fibrosis stages with Ishak scores ≥ 3, respectively. The subjects were stratified into three age groups (30-39, 40-49 and ≥ 50 years), and our data clearly suggested that age, particularly in the age group over 50, was an independent predictor of liver necroinflammation and fibrosis. Lower HBV-DNA viral levels were found in patients with Knodell histological activity index ≥ 9 or advanced fibrosis (Ishak scores ≥ 3). Conclusion Our results showed that histological changes in liver tissues were observed in a significant proportion of patients with persistently normal alanine aminotransferase level. According to the data evaluation results, liver biopsy is advisable for HBeAg-positive chronic hepatitis B infected patients aged older than 40 and high HBV-DNA viral load in China.

Background Here, we compared the clinical and radiographic outcomes between coracoclavicular (CC) fixation with Mersilene tape and hook plate for acute unstable acromioclavicular (AC) joint dislocation treatment. Methods We enrolled 49 patients with unstable acute AC dislocation who, between January 2010 and January 2014, underwent surgery with single CC suture fixation with Mersilene tape (M group, 25 cases) or clavicle hook plate (H group, 24 cases). In M and H groups, the average age was 43.7 (range 18–72) and 42.0 (range 17–84) years, the male to female ratio of each group was 15:20 and 19:5, and the injured side left to right ratio was 12:13 and 11:13, respectively. All patients were right-handed. We retrospectively compared the operation time, complication rate, visual analog scale (VAS), University of California at Los Angeles (UCLA) shoulder rating scale, Oxford shoulder scores, and the radiographic outcomes based on reduction loss of CC distance on postoperative follow-up. Results No significant difference in patient demographics between the two groups in age (p = 0.709), gender (p = 0.217), time from injury to surgery (p = 0.863), and injured side (p = 1.000). The mean follow-up was 26.2 months (range 24–35 months). Nine cases of reduction loss (36%) and one of distal clavicle osteolysis (4%) were noted in the M group. CC distance improvement in the H group was significantly superior to that in the M group at 3 months (before hook plate removal, p

Background The wide-awake local anesthesia no tourniquet (WALANT) technique is applied during various hand surgeries. We investigated the perioperative variables and clinical outcomes of open reduction and internal fixation (ORIF) for distal radius fractures under WALANT. Methods From January 2015 to January 2017, 60 patients with distal radius fractures were treated, and 24 patients (40% of all) were treated with either a volar or a dorsal plate via WALANT procedure. Of these 24 patients, 21 radius fractures were fixed with a volar plate, and the other 3 were fixed with a dorsal plate. Radiographs; range of motions; visual analog scale (VAS); quick disabilities of the arm, shoulder, and hand (Quick DASH) questionnaire; and time to union were evaluated. Results One of the 24 patients could not tolerate the WALANT procedure and was reported as a failed attempt at WALANT. In the cohort, 23 patients successfully received distal radius ORIF under WALANT procedure. The average age is 60.9 (range, 20–88) years. The average operation time was 64.3 (range, 45–85) minutes, the average blood loss was 18.9 (range, 5–30) ml, and the average of duration of hospitalization is 1.8 (range, 1–6) days. The average postoperative day one VAS was 1.6 (range, 1–3). The average time of union was 20.7 (range, 15–32) weeks. The mean follow-up period was 15.1 (range, 12–24) months. Functional 1-year postoperative outcomes revealed an average Quick DASH score of 7.60 (range, 4.5–13.6) and an average wrist flexion and extension of 69.6° (range, 55–80°) and 57.4° (range, 45–70°). There was no wound infection, neurovascular injury, or other major complication noted. Conclusions WALANT for distal radius fracture ORIF is a method to control blood loss by the effects of local anesthesia mixed with hemostatic agents. Without a tourniquet, the procedure prevents discomfort caused by tourniquet pain. Without sedation, patients could perform the active range of motion of the injured wrist to check if there is impingement of implants. It eliminates the need of numerous preoperative examinations, postoperative anesthesia recovery room care, and side effects of the sedation. However, patients who are not amenable to the awake procedure are contraindications. Electronic supplementary material The online version of this article (10.1186/s13018-018-0903-1) contains supplementary material, which is available to authorized users.