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Objective To evaluate the adjuvant treatment of acute stage symptoms and quality of life of patients with bullous pemphigoid (BP) with ozone. Methods We included 74 patients with moderate and severe BP hospitalized from July 2018 to December 2020. The participants were randomly divided into the control group and the ozone group, with 37 patients in each group (n = 37). The control group used tap water to wash the whole body, and mupirocin ointment was used for the erosions. The ozone group used ozone water to wash the whole body, and the erosion place was coated with ozone oil. The bullous pemphigoid disease area index (BPDAI) score of BP disease was used to observe the clinical symptoms and skin lesions of the two groups before and on day 3, 7, and 14 after treatment. Pruritus and sleep were observed before and on day 3, 7, and 14 after treatment. The Dermatology Life Quality Index (DLQI) was used to observe the quality of life before and after treatment and the adverse reactions were recorded. Results The total BPDAI score and erythema score in the ozone group were significantly different from those in the control group on day 3, 7, and 14 after treatment (P < 0.050). The scab drying time and erosion drying time of ozone group were shorter than that of control group (P < 0.001). There were statistically significant differences between the ozone group and the control group in pruritus score and sleep score on day 3, 7, and 14 after treatment (P < 0.001). There was statistically significant difference in skin disease quality of life between the two groups 14 days after treatment (P < 0.001). No significant adverse reactions and complications were observed in both groups. Conclusions Ozone external use can rapidly improve the acute stage of edema erythema, erosion, and itching of BP, improve the quality of life of patients, is an effective treatment method, and worthy of clinical promotion.

Long noncoding RNAs (lncRNAs) play roles in the development and progression of many cancers; however, the contributions of lncRNAs to human gallbladder cancer (GBC) remain largely unknown. In this study, we identify a group of differentially expressed lncRNAs in human GBC tissues, including prognosis‐associated gallbladder cancer lncRNA (lncRNA‐PAGBC), which we find to be an independent prognostic marker in GBC. Functional analysis indicates that lncRNA‐PAGBC promotes tumour growth and metastasis of GBC cells. More importantly, as a competitive endogenous RNA (ceRNA), lncRNA‐PAGBC competitively binds to the tumour suppressive microRNAs miR‐133b and miR‐511. This competitive role of lncRNA‐PAGBC is required for its ability to promote tumour growth and metastasis and to activate the AKT/mTOR pathway. Moreover, lncRNA‐PAGBC interacts with polyadenylate binding protein cytoplasmic 1 (PABPC1) and is stabilized by this interaction. This work provides novel insight on the molecular pathogenesis of GBC.

Wen-Guang Zhang,1 Jia-Wei Liu,2 Su-Yun Yang,3 Qiao-Qian Wang,4 Chen-Xing Liu,2 Yao Li2 1Department of Nursing, The First Hospital of Shanxi Medical University, Taiyuan, 030000, People’s Republic of China; 2School of Nursing, Shanxi Medical University, Taiyuan, 030000, People’s Republic of China; 3Department of Nuclear Medicine, The First Hospital of Shanxi Medical University, Taiyuan, 030000, People’s Republic of China; 4Department of Hypertension, The First Hospital of Shanxi Medical University, Taiyuan, 030000, People’s Republic of ChinaCorrespondence: Su-Yun YangDepartment of Nuclear Medicine, The First Hospital of Shanxi Medical University, Room 601, Unit 8, Building 1, No. 8 Wenyuan Lane, Yingze District, Taiyuan, 030000, People’s Republic of ChinaTel +8613603512029Email syy_dr09sun@163.comObjective: This study aimed to evaluate the effect of closed-loop management on nursing disruption risk.Methods: Using a quasi-experimental research method, convenient sampling was used to extract 20 nurses working at our hospital as the research objects. The control group members were selected from January to March 2018 via the traditional method, and the experimental group members were selected from April to June 2018 via the closed-loop management method. At three months before and after the implementation of the management model, a self-designed quantitative test form and satisfaction questionnaire were used to analyze the frequency of nursing disruption events, the accuracy rate of doctors’ advice, the average drug delivery time of the static distribution center, the implementation rate of personal digital assistant (PDA) code scanning, and the report rate of risk-outcome nursing disruption events.Results: After the implementation of the management model, the frequency of nursing disruptions and average drug delivery time of the static distribution center were significantly lower than before, and the differences were statistically significant (p < 0.05). Moreover, the accuracy rate of doctors’ advice, the implementation rate of PDA code scanning, and the reporting rate of risk-outcome nursing disruption events were significantly higher than before, and these differences were statistically significant as well (p < 0.05).Conclusion: The application of a closed-loop management model could significantly reduce the occurrence and optimize the outcomes of nursing disruption events and improve the work processes of medical care.Keywords: closed-loop management, nursing interruption, risk control, personal digital assistant, PDA, management mode

Facial nerve palsy (FNP) is extremely rare in Kawasaki disease (KD) and the incidence is just 0.9-1.3%. Our objective was to study the clinical features and prognosis of KD accompanied with FNP and to determine whether FNP indicated an increased risk of coronary artery lesions (CALs) in KD. An observational study was performed on 9 patients diagnosed as KD accompanied with FNP in Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China between September 2012 and December 2019. Patients were followed up from September 2012 till September 2020. Clinical features, laboratory and echocardiography findings, treatments, and prognosis were analyzed retrospectively. And the clinical data of patients with FNP (group A, n = 9) were compared to matched KD patients without FNP (group B, n = 27) in order to determine whether FNP indicated an increased risk of CALs in KD. The matching factors included sex, age, days of illness at the intravenous immunoglobulin use, and classic/incomplete KD forms. Clinical data of 9 patients were analyzed in this study. Patients tended to be younger than 24 months of age (88.9%) and 55.6% were under 12 months. Median onset of FNP was day 10 of illness. Eight patients (88.9%) showed unilateral FNP. The levels of laboratory inflammatory markers (White blood cells count, neutrophil percentage, C-reactive protein, erythrocyte sedimentation rate, etc.) were significantly increased in most cases. CALs were noted in 8 of 9 patients (88.9%). Coronary artery aneurysms occurred in 4 cases (44.4%) and the remaining 4 patients showed coronary artery dilation. All patients were given intravenous immunoglobulin therapy (2 g/kg), aspirin (30-50 mg/kg/day), and short-term dexamethasone. During follow-up, both FNP and CALs were completely recovered in all patients. The duration time of FNP ranged from 10 to 130 days. And the time for CALs to normal ranged from 12 to 282 days. The occurrence of CALs was significantly higher in patients with FNP than those without FNP (88.9% vs. 25.9%, P

Objectives To investigate the cup survivorship, patient satisfaction level, clinical function, and radiographic outcomes of patients who underwent total hip arthroplasty (THA) using electron beam melting (EBM)‐produced porous coated titanium cups at mid‐term follow up. Methods A total of 32 patients (32 hips) from five hospitals in China who underwent primary THA using EBM‐produced trabecular titanium cups between May and December 2012 were retrospectively reviewed. The inclusion criteria were: (i) patients who underwent THA with the use of EBM‐produced cups with possible 7‐year follow up; and (ii) patients with follow‐up information, including the cup survivorship, patient satisfaction level, and clinical outcomes such as Harris hip score. The exclusion criteria were: (i) patients with neuropathic diseases; and (ii) patients who underwent THA due to neoplastic disease. Five (15.6%) patients were lost to follow up before the 7‐year follow‐up and, thus, were excluded; none of these patients died due to disease associated with the THA or had undergone removal of their cups as of our last evaluation. The mean age and body mass index of the patients were 59.37 (range: 38.00–69.00) years and 24.51 (range: 16.50–34.10) kg/m2, respectively. Thirteen (48.1%) of the patients were female. Results The average duration of follow‐up was 93.48 (range: 89.00–99.00) months. The median Harris hip score improved from 42.00 (interquartile range: 37.00–49.00) to 97.00 (interquartile range: 92.00–97.00) at the latest follow up (P, Electron beam melting (EBM) technology is an important branch of 3D printing technology and has been used in manufacturing trabecular titanium acetabular cups with high porosity (65%), diffuse pore interconnections, a low modulus of elasticity, high frictional resistance, and large holes (700 μm). The mid‐term follow up of patients who underwent primary THA using EBM‐produced porous coated titanium cups demonstrated favorable patient satisfaction, good clinical function, excellent survivorship, and adequate biological fixation.

In this paper, a three-dimensional quantitative structure-activity relationship (3D-QSAR) namely CoMFA and CoMSIA has been carried out on a series (43 compounds) of capsid assembly inhibitors on N-...

The HBV capsid protein (CP) plays a vital role in the multiple life cycles of HBV and represents a novel anti-HBV target. Recently, a novel series of heteroaryldihydropyrimidine (HAP) derivatives were reported as potent inhibitors of HBV capsid assembly, and they also exhibit antiviral activities. In this study, the structure and activity relationship of 36 heteroaryldihydropyrimidine-based compounds was explored by conducting structure–activity relationship (3D-QSAR) studies using CoMFA and CoMSIA models. The results showed that CoMFA (q2 = 0.610, r2 = 0.998, and rpred2 = 0.837) and CoMSIA (q2 = 0.586, r2 = 0.998, and rpred2 = 0.698) have excellent estimation stability and prediction capability. The contour maps of the steric field, electrostaticfield, and hydrogen bond acceptor field revealed the modified regions of these compounds. Subsequently, molecular docking was carried out to investigate the docking mode of the template molecule and receptors, thereby further verifying the results of the 3D-QSAR model. Molecular dynamics (MD) simulations were performed to validate the accuracy of the docking results. Based on these results, we designed 4 new heteroaryldihydropyrimidine-based compounds and predicted their activity. These results may provide important reference for the design and development of potent and new HBV capsid assembly inhibitors.

”Focusing on treating the spirit (神)” is an important principle in acupuncture and moxibustion. It is a unique psychosomatic therapy involving the doctor and the patient, which includes regulating the spirit and the body. Traditional Chinese medicine attaches great importance to it. Focusing on treating the spirit is also a component of the standards of medical ethics. Only when doctors have noble medical ethics can they achieve clinical treatment of the mind and give full play to their skills to cure diseases. Focusing on treating the spirit runs through the entire clinical process of acupuncture and moxibustion. Before the treatment, it is necessary to focus on the spirit to distinguish the spirit and qi. During the treatment, attention should be paid to the mind to regulate the spirit and qi. It is the premise of clinical diagnosis and treatment of acupuncture and moxibustion and the key to the curative effect. Focusing on treating the spirit is also in the realm of doctor-patient double treatment, which requires doctor-patient communication before treatment and the preservation of the body and spirit after treatment. Therefore, concentration of the mind is the key to acupuncture and moxibustion treatment.

Background Curative medical treatment for patients with discogenic sciatica is limited. Acupuncture is an important non-pharmacological therapy reported to have positive therapeutic effects on discogenic sciatica. According to traditional Chinese acupuncture theory, discogenic sciatica is a channel tendon disease which can be treated by a special "Fan-zhen Jie-ci (FZJC)" method. Our recent preliminary clinical evidence indicated that the FZJC method had a positive treatment effect on the disease. This study will further evaluate the efficacy and safety of FZJC on patients with discogenic sciatica. Methods A single-blind randomized controlled clinical trial will be conducted, assigning 76 participants with discogenic sciatica to a randomly assigned FZJC group or a control group. Acupuncture treatment combined with the FZJC method will be applied in the FZJC group while routine acupuncture treatment only will be applied in the control group. Treatments will be administered three times a week for a total of 3 consecutive weeks. The primary outcome of this trial is change in the visual analogue scale of leg pain (VASLP), and the secondary outcomes are changes in the visual analogue scale of back pain (VAS-BP), the Brief Pain Inventory (BPI), the Oswestry Disability Index (ODI), the 36-Item Short Form Health Survey (SF-36), and serum concentrations of mitochondrial DNA (mtDNA) and high sensitivity C reactive protein (hsCRP). Discussion The results of this study will provide insight into the efficacy and safety of FZJC acupuncture as a treatment for discogenic sciatica. Trial registration The trial has been registered at the Chinese Clinical Trial Registry (ChiCTR1900026272) and the Acupuncture-Moxibustion Clinical Trial Registry (AMCTR-IOR-19000275).

To observe the clinical effect of acupoint sticking therapy with Mian Tan Gao (facial paralysis paste) plus electroacupuncture (EA) for treating peripheral facial paralysis and its influence on patients’ facial nerve functions, facial disability index and clinical symptoms and signs. A total of 96 peripheral facial paralysis patients were allocated into an observation group, a medicine group and an EA group by simple randomization, with 32 cases in each group. Patients in the medicine group were treated with oral mecobalamine and prednisone acetate; patients in the EA group were treated with EA on the basis of the medicine treatment; while patients in the observation group were treated with acupoint sticking therapy with Mian Tan Gao (facial paralysis paste) plus EA. After 4-week treatment, the clinical efficacy, the adverse events, and the scores of House-Brackmann (H-B) facial nerve function grading scale, visual analog scale (VAS), clinical symptoms and signs, and facial disability index (FDI) were compared. After 4-week treatment, the total effective rate was 96.9% in the observation group, higher than 68.7% in the medicine group and 75.0% in the EA group (both P 0.05). The between-group comparison of the adverse event across the three groups showed no statistical significance (P>0.05). Acupoint sticking therapy with Mian Tan Gao (facial paralysis paste) plus EA can decrease H-B grade, reduce pain severity and improve clinical symptoms and signs as well as the facial disability condition in peripheral facial paralysis patients. This method produced more significant efficacy compared with oral medicine and medicine plus EA.

In December 2019, the corona virus disease 2019 (COVID-19) caused by novel coronavirus (SARS-CoV-2) emerged in Wuhan, China and rapidly spread worldwide. Few information on clinical features and immunological profile of COVID-19 in paediatrics. The clinical features and treatment outcomes of twelve paediatric patients confirmed as COVID-19 were analyzed. The immunological features of children patients was investigated and compared with twenty adult patients. The median age was 14.5-years (range from 0.64 to 17), and six of the patients were male. The average incubation period was 8 days. Clinically, cough (9/12, 75%) and fever (7/12, 58.3%) were the most common symptoms. Four patients (33.3%) had diarrhea during the disease. As to the immune profile, children had higher amount of total T cell, CD8+ T cell and B cell but lower CRP levels than adults (P

Long noncoding RNAs (lncRNAs) have drawn growing attention due to their regulatory roles in various diseases, including tumors. Recently, lncRNA FOXD3 antisense RNA 1 (FOXD3-AS1) was shown to be overexpressed in colon adenocarcinoma and glioma, exerting oncogenic functions. However, its expression and effects in cervical cancer (CC) remained unknown. In this research, our group first reported that the levels of FOXD3-AS1 were distinctly elevated in CC samples and cell lines. The distinct upregulation of FOXD3-AS1 was associated with lymphatic invasion, distant metastasis, and International Federation of Gynecology and Obstetrics stage, and also predicted poor clinical results of CC patients. Next, transcription factor SP1 was demonstrated to resulting in the upregulation of FOXD3-AS1 in CC. Functional assays indicated that knockdown of FOXD3-AS1 distinctly suppressed CC progression via affecting cell proliferation, cell apoptosis, and metastasis. Moreover, mechanistic studies suggested that FOXD3-AS1 acted as an endogenous sponge by directly binding miR-296-5p, resulting in the suppression of miR-296-5p. In addition, we also reported that high mobility group A, a direct target of miR-296-5p, could mediate the tumor-promotive effects that FOXD3-AS1 displayed. Overall, our present study might help to lead a better understanding of the pathogenesis of CC, provide a novel possible tumor biomarker, and probe the feasibility of lncRNA-directed treatments for CC.

New antibiotics are urgently required in clinical treatment and agriculture with the development of antimicrobial resistance. However, products discovered by repeating previous strategies are either not antibiotics or already known antibiotics. There is a growing demand for efficient strategies to discover new antibiotics. With the continuous improvement of gene sequencing technology and genomic data, some mining strategies have emerged. These strategies are expected to alleviate the current dilemma of antibiotics. In this review, we discuss the recent advances in discovery of bacterial antibiotics from the following aspects: activation of silent gene clusters, genome mining and metagenome mining. In the future, we envision the discovery of natural antibiotic will be accelerated by the combination of these strategies.

Highlights • T-cell responses in term of frequency and intensity are clearly distinct between mild illness and severe pneumonia patients. • High levels of IFNᵧ production observed with all CoV proteins support that SARS-CoV-2 elicit potent memory immune responses. • Recent history of COVID-19 did not hamper viral memory T-cell pool against common viruses., Adaptive Immune responses generated by SARS-CoV-2 virus in convalescent patients according to disease severity remain poorly characterized. To this end, we designed a prospective study (NCT04365322) that included 60 COVID-19 convalescent patients (1-month post infection) in two cohorts respectively entitled mild illness and severe pneumonia. The monitoring of peripheral immune responses was performed using IFNᵧ ELISpot assay. The serology index of each patient was investigated at the same time. Patients with severe pneumonia were older and had more comorbidities than patients with mild illness. T-cell responses in term of frequency and intensity were clearly distinct between mild illness and severe pneumonia patients. Furthermore, our results demonstrated that recent history of COVID-19 did not hamper viral memory T-cell pool against common viruses (Cytomegalovirus, Epstein-Barr-virus and Flu-virus). The presence of potent adaptive immunity even in patients who underwent severe pneumonia sustain the rationale for the development of protective therapeutics against SARS-CoV-2.

We report acute antibody responses to SARS-CoV-2 in 285 patients with COVID-19. Within 19 days after symptom onset, 100% of patients tested positive for antiviral immunoglobulin-G (IgG). Seroconversion for IgG and IgM occurred simultaneously or sequentially. Both IgG and IgM titers plateaued within 6 days after seroconversion. Serological testing may be helpful for the diagnosis of suspected patients with negative RT-PCR results and for the identification of asymptomatic infections.

Acetaminophen (APAP) is one of the safest and most effective over-the-counter (OTC) analgesics and antipyretics, but excessive doses of APAP will induce hepatotoxicity with high morbidity and mortality worldwide. Kaempferol (KA), a flavonoid compound derived from the medicinal and edible plant of Penthorum chinense Pursh, has been reported to exert a profound anti-inflammatory and antioxidant activity. In this study, we explored the protective effect and novel mechanism of KA against APAP-induced hepatotoxicity. The results revealed that KA pretreatment significantly reduced the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), relieved hepatocellular damage and apoptosis, attenuated the exhaustion of glutathione (GSH) and accumulation of malondialdehyde (MDA), increased the expression of antioxidative enzymes (e.g., heme oxygenase 1 (HO-1) and NADPH quinone oxidoreductase 1 (NQO1)), and thus restrained APAP-induced oxidative damage in the liver. KA suppressed the expression of NLRP3 and reduced the levels of pro-inflammatory factors, including interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6). Moreover, KA remarkably inhibited high-mobility group box 1 (HMGB1) and toll-like receptor 4 (TLR4) expression as well as nuclear factor kappa-B (NF-κB) activation for liver protection against APAP-induced inflammatory responses and apoptosis. Taken together, our findings suggested that KA could effectively protect hepatocytes from APAP hepatotoxicity through the up-regulation of HO-1 and NQO1 expression, the down-regulation of NLRP3 expression, and the inhibition of the HMGB1/TLR4/NF-κB signaling pathway.

Objective To determine the safety and effectiveness of a cross-linked sodium hyaluronate (CHA) scaffold in cartilage repair. Methods Physicochemical properties of the scaffold were determined. The safety and effectiveness of the scaffold for cartilage repair were evaluated in a minipig model of a full-thickness cartilage defect with microfracture surgery. Postoperative observation and hematological examination were used to evaluate the safety of the CHA scaffold implantation. Pathological examination as well as biomechanical testing, including Young's modulus, stress relaxation time, and creep time, were conducted at 6 and 12 months postsurgery to assess the effectiveness of the scaffold for cartilage repair. Furthermore, type II collagen and glycosaminoglycan content were determined to confirm the influence of the scaffold in the damaged cartilage tissue. Results The results showed that the routine hematological indexes of the experimental animals were within the normal physiological ranges, which confirmed the safety of CHA scaffold implantation. Based on macroscopic observation, it was evident that repair of the defective cartilage in the animal knee joint began during the 6 months postoperation and was gradually enhanced from the central to the surrounding region. The repair smoothness and color of the 12-month cartilage samples from the operation area were better than those of the 6-month samples, and the results for the CHA scaffold implantation group were better than the control group. Greater cell degeneration and degeneration of the adjacent cartilage was found in the implantation group compared with the control group at both 6 and 12 months postoperation, evaluated by O'Driscoll Articular Cartilage Histology Scoring. Implantation with the CHA scaffold matrix promoted cartilage repair and improved its compression capacity. The type II collagen level in the CHA scaffold implantation group tended to be higher than that in the control group at 6 months (2.33 ± 1.50 vs 1.68 ± 0.56) and 12 months postsurgery (3.37 ± 1.70 vs 2.06 ± 0.63). The GAG content in the cartilage of the control group was significantly lower than that of the experimental group (2.17 ± 0.43 vs 3.64 ± 1.17, P = 0.002 at 6 months and 2.27 ± 0.38 vs 4.12 ± 1.02, P = 0.002 at 12 months). Type II collagen and glycosaminoglycan content also demonstrated that CHA was beneficial for the accumulation of both these vital substances in the cartilage tissue. Conclusions The CHA scaffold displayed the ability to promote cartilage repair when applied in microfracture surgery, which makes it a promising material for application in the area of cartilage tissue engineering.

Epithelioid sarcoma (ES) was first described by Enzinger in 1970. It is a rare variant of soft tissue sarcoma with a 5-year overall survival (OS) rate of 50%. Here, we reported a case of epithelioid sarcoma in the parapharyngeal space of an adult, resulting in a favorable prognosis after chemotherapy and radiation therapy. A 34-year-old female who complained of pharynx pain and discomfort was suspected of having a tumor in the right parapharyngeal space by CT scan. Excision biopsy suggested epithelioid sarcoma. Clinical and radiological studies did not reveal tumor distant metastasis in the patient. After excisional biopsy, the patient underwent chemotherapy and external beam radiation treatment. She has remained alive for 2 years and 7 months without recurrence since her last treatment. In this paper, we also provide a detailed review of the role of radiotherapy in the treatment of epithelioid sarcoma in previously reported cases.

IntroductionCoronavirus disease-2019 (COVID-19) spreads worldwide. The study Aimed to understand the clinical characteristics of young COVID-19 patients.Material and methods90 patients with severe COVID-19 infection in western Chongqing were collected from 21 January to 14 March 2020. They were divided into 4 groups based on age: youth ( 60 years). The clinical symptoms, laboratory findings, imaging findings, and treatment effects were compared among the groups.ResultsThere were 22, 27, 19, and 22 cases in the youth, middle-aged, middle-elderly, and elderly groups, respectively. There were no significant differences with respect to gender or smoking status among the four groups. The clinical indicators of severe disease in the youth group were significantly different from the other three groups, and included the lymphocyte count (P = 0.00), C-reactive protein level (P = 0.03), interleukin-6 level (P = 0.01), chest computed tomography (CT) findings (P = 0.00), number of mild cases (P = 0.02), the education level (P = 0.00), and the CD4 + T lymphocyte level (P = 0.02) at the time of admission, and the pneumonia severity index (PSI) at the time of discharge (P = 0.00). The complications (P = 0.00) among the youth group were also significantly different from the other groups.ConclusionsYoung patients have milder clinical manifestations, which may be related to higher education level, higher awareness and higher acceptance of the prevention and control of the COVID-19 epidemic, as well as their good immune function.

Alcoholic liver disease (ALD), a type of chronic liver disease that is prevalent worldwide, is still identified to have a poor prognosis despite many medical treatment protocols. Thus, it is urgent to develop and test new treatment protocols for ALD. Lactobacillus reuteri (L. reuteri) has been widely used in the clinical treatment of digestive system diseases, but studies on the protective effect of L. reuteri on ALD are considered to be rare. Therefore, in the present study, we examined the effect of L. reuteri on ALD and provide data that are significant in the development of new treatment protocols for ALD. An ALD model has been established in C57BL/6J mice treated according to the Gao-binge modeling method. Mice in the treatment group were administered with L. reuteri. Hematoxylin and eosin (H&E) staining, oil red O staining, immunohistochemistry, and biochemical analyses were performed to detect the phenotypic changes in the liver among mice in the different treatment groups. L. reuteri treatment reversed inflammatory cell infiltration and lipid accumulation. Moreover, AST, ALT, TG, and TCH levels were also reduced in the probiotics-treatment group. Five candidate biomarkers were found in the liver metabolites of different treatment groups by UPLC/QTOF-MS and a multivariate analysis. Several fatty acid metabolic pathways such as linoleic acid metabolism and glycerolipid metabolism were involved. All these findings suggested that L. reuteri treatment reversed the phenotype of ethanol-induced hepatitis and metabolic disorders. These findings provide evidence that L. reuteri might serve as a new therapeutic strategy for ALD.

Emerging evidence indicates that A1 reactive astrocytes play crucial roles in the pathogenesis of Parkinson’s disease (PD). Thus, development of agents that could inhibit the formation of A1 reactive astrocytes could be used to treat PD. Simvastatin has been touted as a potential neuroprotective agent for neurologic disorders such as PD, but the specific underlying mechanism remains unclear. The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD and primary astrocytes/neurons were prepared to investigate the effects of simvastatin on PD and its underlying mechanisms in vitro and in vivo. We show that simvastatin protects against the loss of dopamine neurons and behavioral deficits in the MPTP mouse model of PD. We also found that simvastatin suppressed the expression of A1 astrocytic specific markers in vivo and in vitro. In addition, simvastatin alleviated neuron death induced by A1 astrocytes. Our findings reveal that simvastatin is neuroprotective via the prevention of conversion of astrocytes to an A1 neurotoxic phenotype. In light of simvastatin favorable properties, it should be evaluated in the treatment of PD and related neurologic disorders characterized by A1 reactive astrocytes.

Objective MicroRNA-122 (miR-122) has been identified as a biomarker of liver diseases. However, the miR-122 detection accuracy in patients with hepatocellular carcinoma (HCC) associated with hepatitis C virus (HCV) is inconclusive. Methods We conducted a systematic literature search of Web of Science, Cochrane Library, PubMed, and Embase to identify studies related to the diagnostic value of miR-122 in HCV-related HCC. We analyzed the results and validated them using data from the Cancer Genome Atlas (TCGA). Results Six articles were included in this meta-analysis, comprising 354 cases and 420 controls. The pooled specificity, sensitivity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the curve were 0.87, 0.83, 5.1, 0.16, 32, and 0.92, respectively. Additional sub-group analyses showed that results for plasma were more sensitive than those for serum. In addition, miR-122 was better at distinguishing between HCV-associated HCC and healthy people or those with HCV than between those with HCV-associated HCC and HCV-related cirrhosis. Small samples (≤100) had better diagnostic odds ratios than larger samples (>100). Analysis of data from TCGA confirmed that miRNA-122 had a high diagnostic value. Conclusion This meta-analysis demonstrates that miR-122 may be a useful diagnostic biomarker for HCV-associated HCC.

Emerging evidence indicates that NLRP3 inflammasome-induced inflammation plays a crucial role in the pathogenesis of depression. Thus, inhibition of NLRP3 inflammasome activation may offer a therapeutic benefit in the treatment of depression. Metformin has been shown to have potential anti-inflammatory activity, but the underlying mechanisms remain obscure. We used a chronic mild stress model of depression and cultured primary macrophage to investigate the effects of metformin on depression and its underlying mechanisms. We demonstrated that metformin alleviated depressive-like behaviors in the chronic mild stress-induced anhedonia model of depression. We further found that metformin significantly suppressed NLRP3 inflammasome activation, subsequent caspase-1 cleavage, and interleukin-1β secretion in both peripheral macrophages and central hippocampus. Our findings reveal that metformin confers an antidepressant effect partly through inhibition of peripheral and central NLRP3 inflammasome activation. In light of metformin favorable properties, it should be evaluated in the treatment of depression and related neurologic disorders characterized by NLRP3 inflammasome activation.

Background Corona Virus Disease-2019 (COVID-19) is an acute respiratory infectious disease. Despite being clinically cured, some patients still find it difficult to return to their normal life and work due to the varying degree of dysfunctions that they have, as part of the disease's aftereffect. Through this study, we aim to learn more about the dysfunctions and rehabilitation needs of COVID-19 patients. Methods In this survey, the basic information, dysfunctions, and rehabilitation needs of the hospitalized COVID-19 patients, who were selected by convenience sampling in Hubei Provincial Hospital of Integrated Traditional Chinese and Western Medicine, were obtained using a self-designed questionnaire. The research was conducted from February 29, 2020 to March 2, 2020. Results A total of 280 patients were finally included, who were mainly over 51 years of age (64.2%). The main physical dysfunctions that the patients had were sleep disorders (63.6%), decreased activity endurance (61.4%), and respiratory dysfunction (57.9%), while the main psychological dysfunctions included anxiety (62.1%) and fear (50.0%). Rehabilitation that mainly requested by the patients included exercise guidance, dietary instruction, traditional Chinese medicine therapy, physical therapy, and Chinese traditional health exercises. Conclusions The demand for rehabilitation is high among COVID-19 patients, which requires the quick establishment of a comprehensive and individualized rehabilitation program, to be fulfilled.

Background Since December 2019, over 80,000 patients with coronavirus disease 2019 (COVID-19) have been confirmed in China. With the increasing number of recovered patients, more attention should be paid to the follow-up of these patients. Methods In the study, 576 patients with COVID-19 discharged from hospital in Chongqing, China from January 24, 2020, to March 10, 2020 were evaluated by viral nucleic acid tests for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) to determine if they could be released from quarantine. Among the 576 patients, 61 patients (10.6%) had positive RT-PCR test results of SARS-CoV-2. We aimed to analyze the demographics, clinical characteristics and treatment of 61 patients. Results These positive patients were characterized by older age, chronic medical illness and mild conditions. 38 (62.3%) patients who were asymptomatic without abnormalities on chest radiographs were found in the positive with COVID-19. Also, they showed positive results of stool or sputum specimens with negative results of nasal and pharyngeal swab specimens. The median duration of positive result of SARS-CoV-2 was varied from 3 days to 35 days in the patients discharged from hospital with no family member infection. Conclusions Multi-site screening of SARS-CoV-2 including nasal and pharyngeal swabs, stool and sputum specimens could be considered to improve the diagnosis, treatment and infection control in patients with COVID-19. Our findings provide the important information and clinical evidence for the improved management of patients recovered from COVID-19.

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel β-coronavirus, causes severe pneumonia and has spread throughout the globe rapidly. The disease associated with SARS-CoV-2 infection is named coronavirus disease 2019 (COVID-19). To date, real-time reverse-transcription polymerase chain reaction (RT-PCR) is the only test able to confirm this infection. However, the accuracy of RT-PCR depends on several factors; variations in these factors might significantly lower the sensitivity of detection. Methods In this study, we developed a peptide-based luminescent immunoassay that detected immunoglobulin (Ig)G and IgM. The assay cutoff value was determined by evaluating the sera from healthy and infected patients for pathogens other than SARS-CoV-2. Results To evaluate assay performance, we detected IgG and IgM in the sera from confirmed patients. The positive rate of IgG and IgM was 71.4% and 57.2%, respectively. Conclusions Therefore, combining our immunoassay with real-time RT-PCR might enhance the diagnostic accuracy of COVID-19.

BackgroundTo clarify the characteristic and the duration of positive nucleic acid in children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including asymptomatic children.MethodsA total of 32 children confirmed with SARS-CoV-2 infection between January 24 and February 12, 2020 from four provinces in Western China were enrolled in this study and followed up until discharge and quarantine 14 days later.ResultsEleven children (34%) were asymptomatic, among whom six children had normal computed tomographic (CT) scan images. Age and gender were not associated with clinical symptoms or the results of CT scan in children infected with SARS-CoV-2. The concentrations of white blood cells and neutrophils were higher in children with asymptomatic infection than in children with clinical symptoms or CT abnormalities. Patients who presented with CT abnormalities had lower D-dimer or lower total bilirubin than those who had normal CT scan but clinical symptoms. All children recovered and no one died or was admitted to the pediatric intensive care unit (PICU). The mean duration of positive SARS-CoV-2 nucleic acid was 15.4 (SD=7.2) days and similar for both asymptomatic children and children with symptoms or CT abnormalities. We found a significant negative correlation between the lymphocyte count and the duration of positive nucleic acid test.ConclusionsChildren with asymptomatic infection should be quarantined for the same duration as symptomatic patients infected with SARS-CoV-2. The clinical significance and mechanism behind the negative correlation between the number of lymphocytes and the duration of positive SARS-CoV-2 needs further study.

BackgroundNotwithstanding the clinical hallmarks of COVID-19 patients were reported, several critical issues still remain mysterious, i.e., prognostic factors for COVID-19 including extrinsic factors as viral load of SARS-CoV-2 and intrinsic factors as individual’s health conditions; myocarditis incidence rate and hallmarks.MethodsDemographic, epidemiologic, radiologic and laboratory data were collected by medical record reviews of adult hospitalized patients diagnosed as COVID-19. Cycle threshold (Ct) value data of real-time PCR (RT-PCR) were collected. The time duration was from 21 January to 2 March, 2020. Pulmonary inflammation index (PII) values were used for chest CT findings. Multivariate logistic regression analysis was used to identify independent severity risk factors.RESULTSIn total, 84 hospitalized adult patients diagnosed as COVID-19 were included, including 20 severe and 64 nonsevere cases. The viral load of the severe group was significantly higher than that of the non-severe group, regardless of the Ct values forNorORF1abgene of virus (all pInterpretationThree key-independent risk factors of COVID-19 were identified, including age, PII, and Ct value. The Ct value is closely correlated with the severity of COVID-19, and may act as a predictor of clinical severity of COVID-19 in the early stage. SARS-CoV-2 myocarditis should be highlighted despite a relatively low incidence rate (4.8%). The oxygen pressure and blood oxygen saturation should not be neglected as closely linked with the altitude of epidemic regions.Research in contextEvidence before this studyWe searched Pubmed on March 15, 2020 using the terms (“COVID-19” OR “novel coronavirus” OR “2019 novel coronavirus” OR “2019-nCoV” OR “pneumonia” OR “coronavirus”), AND “Myocarditis” OR “Cycle threshold (Ct)” OR “Altitude”. We found that one article analyzed the risk factors affecting the prognosis of adult patients with COVID-19 in terms of survivorship, without considering Ct values as extrinsic factors. Moreover, there are no reported studies on viral myocarditis caused by COVID-19 and the relationship between the altitude and COVID-19.Added value of this studyWe retrospectively analyzed the clinical data, Ct values, laboratory indicators and imaging findings of 84 adult patients with confirmed COVID-19. Three key-independent risk factors of COVID-19 were identified in our study, including age [OR 2.350; 95% CI (1.206 to 4.580); p=0.012], Ct value [OR 0.158; 95% CI (0.025 to 0.987); p=0.048] and PII [OR 1.912; 95% CI (1.187 to 3.079); p=0.008]. Amongst 84 patients, 13 patients (15.48%) were noted with abnormal electrocardiograms (ECGs) and serum myocardial enzyme levels; whereas 4 (4.8%) were clinically diagnosed as SARS-CoV-2 myocarditis. Moreover, altitude should be considered for COVID-19 severity classification, given that oxygen partial pressure and blood oxygen saturation of regional patients vary with altitudes.Implications of all the available evidenceThree key-independent risk factors of COVID-19 were identified, including age, PII, and Ct value. The Ct value is closely correlated with the severity of COVID-19, and may act as a predictor of clinical severity of COVID-19 in the early stage. SARS-CoV-2 myocarditis should be highlighted despite a relatively low incidence rate (4.8%). The oxygen pressure and blood oxygen saturation should not be neglected as closely linked with the altitude of epidemic regions.

BackgroundWe aim to investigate the profile of acute antibody response in COVID-19 patients, and provide proposals for the usage of antibody test in clinical practice.MethodsA multi-center cross-section study (285 patients) and a single-center follow-up study (63 patients) were performed to investigate the feature of acute antibody response to SARS-CoV-2. A cohort of 52 COVID-19 suspects and 64 close contacts were enrolled to evaluate the potentiality of the antibody test.ResultsThe positive rate for IgG reached 100% around 20 days after symptoms onset. The median day of seroconversion for both lgG and IgM was 13 days after symptoms onset. Seroconversion of IgM occurred at the same time, or earlier, or later than that of IgG. IgG levels in 100% patients (19/19) entered a platform within 6 days after seroconversion. The criteria of ‘IgG seroconversion’ and ‘> 4-fold increase in the IgG titers in sequential samples’ together diagnosed 82.9% (34/41) of the patients. Antibody test aided to confirm 4 patients with COVID-19 from 52 suspects who failed to be confirmed by RT-PCR and 7 patients from 148 close contacts with negative RT-PCR.ConclusionIgM and IgG should be detected simultaneously at the early phase of infection. The serological diagnosis criterion of seroconversion or the ‘>; 4-fold increase in the IgG titer’ is suitable for a majority of COVID-19 patients. Serologic test is helpful for the diagnosis of SARS-CoV-2 infection in suspects and close contacts.

A respiratory illness has been spreading rapidly in China, since its outbreak in Wuhan city, Hubei province in December 2019. The illness was caused by a novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clinical manifestations related to SARS-CoV-2 infection ranged from no symptom to fatal pneumonia. World Health Organization (WHO) named the diseases associated with SARS-CoV-2 infection as COVID-19. Real time RT-PCR is the only laboratory test available till now to confirm the infection. However, the accuracy of real time RT-PCR depends on many factors, including sampling location and of methods, quality of RNA extraction and training of operators etc.. Variations in these factors might significantly lower the sensitivity of the detection. We developed a peptide-based luminescent immunoassay to detect IgG and IgM. Cut-off value of this assay was determined by the detection of 200 healthy sera and 167 sera from patients infected with other pathogens than SARS-CoV-2. To evaluate the performance of this assay, we detected IgG and IgM in the 276 sera from confirmed patients. The positive rate of IgG and IgM were 71.4% (197/276) and 57.2% (158/276) respectively. By combining with real time RT-PCR detection, this assay might help to enhance the accuracy of diagnosis of SARS-CoV-2 infection.

Epileptic seizures might be provoked and/or exacerbated by fever or viral infection in children with epilepsy. However, this is not true for infantile spasms; in this study, we report three cases with infantile spasms became seizure free within 2–5 days following rotavirus gastroenteritis without an exchange or addition of antiepileptic drugs, and hypsarrhythmia evolved to diffuse slow waves or localized spikes on electroencephalography. We propose that the probability regarding the mechanism of spontaneous mitigation is the suppression of immunopathological processes caused by infection, while the possibility of ketogenic effects of diarrhea and intestinal flora recombination after rotavirus gastroenteritis is unlikely. Further study may provide important information concerning the mechanism of seizure control and the applicability to treatment for infantile spasms.

Background and Aim. Upper gastrointestinal bleeding is a threat to patients with gastric varices (GVs). Previous studies have concluded that both transjugular intrahepatic portosystemic shunt (TIPS) and balloon-occluded retrograde transvenous obliteration (BRTO) are effective treatments for patients with GV. We aimed to compare the efficiency and outcomes of these two procedures in GV patients through meta-analysis. Methods. The PubMed, Cochrane Library, EMBASE, and Web of Science databases were searched using the keywords: GV, bleeding, TIPS, and BRTO to identify relevant randomized controlled trials and cohort studies. The overall survival (OS) rate, imminent haemostasis rate, rebleeding rate, technical success rate, procedure complication rate (hepatic encephalopathy and aggravated ascites), and Child-Pugh score were evaluated. Randomized clinical trials and cohort studies comparing TIPS and BRTO for GV due to portal hypertension were included in our meta-analysis. Two independent reviewers performed data extraction and assessed the study quality. A meta-analysis was performed to calculate risk ratios (RRs), mean differences (MDs), and 95% CIs using random effects models. Results. A total of nine studies fulfilled the inclusion criteria. There was a significant difference between TIPS and BRTO in the OS rate (RR, 0.81 (95% CI, 0.66 to 0.98); P=0.03) and rebleeding rate (RR, 2.61 (95% CI, 1.75 to 3.90); P<0.00001). TIPS had a higher incidence rate of hepatic encephalopathy (RR, 16.11 (95% CI, 7.13 to 36.37); P<0.00001). There was no significant difference between TIPS and BRTO in the immediate haemostasis rate (RR, 0.99 (95% CI, 0.89 to 1.10); P=0.84), technical success rate (RR, 1.06 (95% CI, 0.98 to 1.16); P=0.16), aggravated ascites rate (RR, 0.60 (95% CI, 0.33 to 1.09); P=0.10), or Child-Pugh change (MD, 0.22 (95% CI, −0.21 to 0.65); P=0.31). Conclusions. In this meta-analysis, BRTO brought more benefits to patients, with a higher OS rate and lower rebleeding rate. BRTO is a feasible method for GVB.

Rhodococcus strains not only have been widely used in industries but also have a potential ability of producing new structural natural products. Integration of heterologous genes into chromosomes of Rhodococcus strains for gene expression can facilitate the studies and applications of these strains. A conjugation system was optimized in order to transfer enhanced green fluorescent protein (EGFP) encoding gene as a reporter from Escherichia coli into Rhodococcus erythropolis D-1. The influence of three native ribosome binding sites (RBSs) and two designed RBSs on the target protein production in R. erythropolis D-1 was also characterized. An efficient conjugation system of R. erythropolis D-1 was established to integrate EGFP gene into its chromosome. Among of five RBSs, RBS3 showed the highest translational activity in R. erythropolis D-1.

The effect of acupuncture cooperated with low-frequency repetitive transcranial magnetic stimulation (rTMS) on chronic insomnia was explored. Seventy-eight patients with chronic insomnia were randomly allocated into two groups: treatment group and control group. In the treatment group, the patients received acupuncture combined with rTMS treatment, and those in the control group were given acupuncture cooperated with sham rTMS treatment, 3 days per week for 4 weeks. Before and after treatment, the primary outcomes including the scores on Insomnia Severity Index (ISI) and Pittsburgh Sleep Quality Index (PSQI) and the secondary outcomes including total sleep time (TST), sleep onset latency (SOL), wake after sleep onset (WASO), sleep efficiency (SE%) recorded by sleeping diary and actigraphy were observed in both groups. Seventy-five participants finished the study (38 in treatment group and 37 in control group respectively). After treatment, the scores in the two groups were improved significantly, more significantly in the treatment group than in the control group. It can be inferred that acupuncture cooperated with rTMS can effectively improve sleep quality, enhance the quality of life of patients and has less side effects.

It is generally known that the culture for mycoplasma is time-consuming and a variety of nutrients are needed in the culture medium. This brings a lot of difficulties to mycoplasma research and application, including Mycoplasma mycoides subsp. capri (Mmc). Furthermore, little research on the characteristics of Mmc metabolism has been reported. In this study, Mmc PG3 strain cultures were investigated for dynamic gene expression. Culture samples were harvested during logarithmic phase (PG3-1), stationary phase (PG3-2), decline phase (PG3-3) and late decline phase (PG3-4). Twelve RNA samples (three replicates for each of the four growth stages considered) from these cultures were collected and sequenced. Paired comparison between consecutive growth phases in the four growth stages showed 45 significant differentially expressed genes (P

The Angolan strain of Marburg virus (MARV/Ang) can cause lethal disease in humans with a case fatality rate of up to 90%, but infection of immunocompetent rodents do not result in any observable symptoms. Our previous work includes the development and characterization of a MARV/Ang variant that can cause lethal disease in mice (MARV/Ang-MA), with the aim of using this tool to screen for promising prophylactic and therapeutic candidates. An intermediate animal model is needed to confirm any findings from mice studies before testing in the gold-standard non-human primate (NHP) model. In this study, we serially passaged the clinical isolate of MARV/Ang in the livers and spleens of guinea pigs until a variant emerged that causes 100% lethality in guinea pigs (MARV/Ang-GA). Animals infected with MARV/Ang-GA showed signs of filovirus infection including lymphocytopenia, thrombocytopenia, and high viremia leading to spread to major organs, including the liver, spleen, lungs, and kidneys. The MARV/Ang-GA guinea pigs died between 7-9 days after infection, and the LD50 was calculated to be 1.1×10-1 TCID50 (median tissue culture infective dose). Mutations in MARV/Ang-GA were identified and compared to sequences of known rodent-adapted MARV/Ang variants, which may benefit future studies characterizing important host adaptation sites in the MARV/Ang viral genome.