Search

OBJECTIVE: To investigate whether Mianyi granules (+mianyi+) are effective and safe in reversing immune nonresponse following antiretroviral therapy (ART) in individuals with human immunodeficiency virus (HIV) infection. METHODS: Randomized, double-blind, multi-center, placebo-controlled trial (factorial design) of daily oral Mianyi granules versus placebo for 72 weeks. A total of 361 HIV-positive individuals receiving ART at five Class III Grade I hospitals in China between September 2013 and January 2016 completed the study. The primary endpoints were frequencies of CD3+, CD4+, CD8+, and CD45RA+ cells at seven timepoints over the 72 weeks. Secondary endpoints included viral loads, clinical symptoms, and quality of life at 72 weeks. RESULTS: A total of 400 participants were enrolled in the study and randomized, of whom 361 completed the study: 189 individuals (140 men and 49 women) in the Mianyi granule group and 172 individuals (135 men and 37 women) in the placebo group. In the intent-to-treat population, CD4+ T cell counts increased from (193 ± 71) cells/mm(3) at baseline to (288 ± 131) cells/mm(3) post-treatment in the Mianyi granule group and from (200 ± 75) cells/mm(3) at baseline to (264 ± 124) cells/mm(3) post-treatment in the placebo group. Patients treated with Mianyi granule had higher increases in CD4+ T cell counts than those treated with placebo (P = 0.045). Reversal of immune nonresponse was defined as a CD4+ T cell increase of more than 100 cells/mm3. After treatment for 72 weeks, Mianyi granule was effective in reversing immune nonresponse in a higher proportion of individuals (20.2%) compared with placebo (9.7%). CD45RA+ cell counts increased from (34 ± 32) cell/mm(3) at baseline to (51 ± 61) cells/mm(3) post-treatment in the Mianyi granule group and from (37 ± 33) cells/mm(3) at baseline to (48 ± 37) cells/mm(3) post-treatment in the placebo group. Mianyi granules were more effective than placebo in increasing CD45RA+ cell counts. CONCLUSIONS: In ART-treated HIV-positive adults with immune nonresponse, treatment with Mianyi granules for 72 weeks was safe and significantly increased CD4+ and CD45RA+ cell counts, thereby promoting immune reconstitution.

Background Solute carrier family 35 (SLC35) is one of a large number of membrane transporter protein families. Member D3 of this family is thought to be involved in adipose deposition and metabolic control. Results We obtained 2238 bp cDNA of porcine SLC35D3, it contains a 1272 bp ORF, encoding a 423 amino acid polypeptide, and a 966 bp 3′ UTR. BLAST results revealed that the amino acid sequence of porcine SLC35D3 had the closest phylogenetic relationship with members of the genus Ovis aries. Further bioinformatics analysis showed that the SLC35D3 protein contains 8 transmembrane domains, and that there is no signal peptide structure. The secondary structure of the protein mainly contains 37.12% α-helixes, 7.8% in β-folds, and 33.57% random coils. mRNA expression analysis showed that SLC35D3 is expressed in lung, liver, heart, spleen, kidney, longissimus dorsi muscle (LDM), leaf fat (LF), and subcutaneous adipose tissue (SAT). To examine the effects of SLC35D3 expression on fat synthesis and catabolism, SLC35D3-siRNA was transfected into cultured intramuscular adipocytes. SLC35D3 silenced cells showed increased expression of genes related to fat synthesis, and increased deposition of intramuscular fat (IMF), abundance of lipid droplets, and the level of free fatty acid (FFA) in the culture medium. In contrast, the siRNA decreased the expression genes involved in fat catabolism. Conclusions Our results demonstrate that silenced SLC35D3 results in increased adipogenic processes in pig intramuscular adipocytes. These data represent the first exploration of SLC35D3 expression in swine, and provide valuable insights into the functions of SLC35D3 in adipocyte differentiation.

Objective To determine the association of carotid plaque features with collateral circulation status in elderly patients with moderate to severe carotid stenosis. Methods Elderly patients (> 60 years) with moderate to severe carotid stenosis were recruited and categorized into good and poor collateral circulation groups, and underwent magnetic resonance imaging and computed tomography imaging. The carotid plaque features including lipid-rich necrotic core, intraplaque hemorrhage, calcification, and fibrous cap rupture (FCR) were evaluated, and maximum wall thickness, normalized wall index (NWI), and luminal stenosis were measured. The association between these variables and collateral circulation status was analyzed. Results Of the 97 patients (78 males, mean age: 69.0 ± 6.1 years), 19 (19.6%) had poor collaterals. The poor collateral group had a significantly higher NWI (93.7% ± 5.0% vs. 89.0% ± 7.9%, P = 0.011), a greater extent of stenosis (80.0% ± 11.4% vs. 75.3% ± 9.4%, P = 0.036) and FCR (84.2% vs. 55.1%, P = 0.020) compared with good collateral group. Carotid NWI (OR = 3.83, 95% CI: 1.36–10.82, P = 0.011) and more FCR (OR = 6.77, 95% CI: 1.35–33.85, P = 0.020) were associated with poor collateral circulation after adjustment for the confounding factors. The combination of NWI, FCR, systolic blood pressure, and triglycerides had the highest area-under-the-curve (AUC = 0.85) for detection of poor collaterals. Conclusions Carotid plaque features, specifically NWI and FCR, are independently associated with poor collateral circulation, and the combination of carotid plaque features and traditional risk factors has a stronger predictive value for poor collateral circulation than plaque features alone.

Age-related impairment of macroautophagy/autophagy and loss of cardiac tissue homeostasis contribute significantly to cardiovascular diseases later in life. MTOR (mechanistic target of rapamycin kinase) signaling is the most well-known regulator of autophagy, cellular homeostasis, and longevity. The MTOR signaling consists of two structurally and functionally distinct multiprotein complexes, MTORC1 and MTORC2. While MTORC1 is well characterized but the role of MTORC2 in aging and autophagy remains poorly understood. Here we identified TGFB-INHB/activin signaling as a novel upstream regulator of MTORC2 to control autophagy and cardiac health during aging. Using Drosophila heart as a model system, we show that cardiac-specific knockdown of TGFB-INHB/activin-like protein daw induces autophagy and alleviates age-related heart dysfunction, including cardiac arrhythmias and bradycardia. Interestingly, the downregulation of daw activates TORC2 signaling to regulate cardiac autophagy. Activation of TORC2 alone through overexpressing its subunit protein rictor promotes autophagic flux and preserves cardiac function with aging. In contrast, activation of TORC1 does not block autophagy induction in daw knockdown flies. Lastly, either daw knockdown or rictor overexpression in fly hearts prolongs lifespan, suggesting that manipulation of these pathways in the heart has systemic effects on longevity control. Thus, our studies discover the TGFB-INHB/activin-mediated inhibition of TORC2 as a novel mechanism for age-dependent decreases in autophagic activity and cardiac health. Abbreviations: AI: arrhythmia index; BafA1: bafilomycin A1; BMP: bone morphogenetic protein; CQ: chloroquine; CVD: cardiovascular diseases; DI: diastolic interval; ER: endoplasmic reticulum; HP: heart period; HR: heart rate; MTOR: mechanistic target of rapamycin kinase; NGS: normal goat serum; PBST: PBS with 0.1% Triton X-100; PDPK1: 3-phosphoinositide dependent protein kinase 1; RICTOR: RPTOR independent companion of MTOR complex 2; ROI: region of interest; ROUT: robust regression and outlier removal; ROS: reactive oxygen species; R-SMAD: receptor-activated SMAD; SI: systolic interval; SOHA: semi-automatic optical heartbeat analysis; TGFB: transformation growth factor beta; TSC1: TSC complex subunit 1

The archaeal tailed viruses (arTV), evolutionarily related to tailed double-stranded DNA (dsDNA) bacteriophages of the class Caudoviricetes, represent the most common isolates infecting halophilic archaea. Only a handful of these viruses have been genomically characterized, limiting our appreciation of their ecological impacts and evolution. Here, we present 37 new genomes of haloarchaeal tailed virus isolates, more than doubling the current number of sequenced arTVs. Analysis of all 63 available complete genomes of arTVs, which we propose to classify into 14 new families and 3 orders, suggests ancient divergence of archaeal and bacterial tailed viruses and points to an extensive sharing of genes involved in DNA metabolism and counterdefense mechanisms, illuminating common strategies of virus–host interactions with tailed bacteriophages. Coupling of the comparative genomics with the host range analysis on a broad panel of haloarchaeal species uncovered 4 distinct groups of viral tail fiber adhesins controlling the host range expansion. The survey of metagenomes using viral hallmark genes suggests that the global architecture of the arTV community is shaped through recurrent transfers between different biomes, including hypersaline, marine, and anoxic environments., Comparative genomics and host range analysis reveals the remarkable diversity and evolution of tailed archaeal viruses of the order Caudoviricetes, which together with their bacterial relatives arguably represent the most abundant and widespread virus group on our planet.

The pyrroline-5-carboxylate reductase 1 (PYCR1) plays important roles in cancers, but its contribution to adenocarcinoma of the kidney (AK) and the potential mechanism remain to be clarified. In this study, we aimed to demonstrate the relationship between PYCR1 mRNA and AK based on The Cancer Genome Atlas database. PYCR1 mRNA in AK and normal tissues was compared using Wilcoxon rank sum test. The relationship between PYCR1 mRNA and clinicopathological characters was evaluated using logistic regression. The association between PYCR1 mRNA and survival rate was evaluated using Kaplan-Meier test and Cox regression of univariate and multivariate analysis. Additionally, Gene Set Enrichment Analysis was conducted to annotate the biological function of PYCR1 mRNA. Increased PYCR1 mRNA was found in AK tissues. Increased PYCR1 mRNA was related to high histologic grade, clinical stage, and lymph node and distant metastasis. Kaplan-Meier survival analysis and univariate analysis showed that AK patients with increased PYCR1 mRNA had worse prognosis than those without. PYCR1 mRNA remained independently associated with overall survival (HR: 1.34; 95% CI: 1.07–1.66; P = .009) in multivariate analysis. The Gene Set Enrichment Analysis suggested that ribosome, proteasome, inhibition of p53 signaling pathway, extracellular matrix receptor interaction, and homologous recombination were differentially enriched in increased PYCR1 mRNA phenotype. Increased PYCR1 mRNA is a potential marker in patients with AK. More importantly, p53 pathway, ribosome, proteasome, extracellular matrix receptor interaction, and homologous are differentially enriched in AK patients with increased PYCR1 mRNA.

Background: Parkinson disease (PD) is a common neurodegenerative disease among middle-aged and elderly people. Clinically, it is a movement disorder characterized mainly by static tremors, kinesia, myotonia, and postural balance disorder. In recent years, an increasing number of clinical reports on moxibustion therapy for PD have been published. Despite this, no systematic review of moxibustion therapy for PD has been undertaken. Methods: Two reviewers will search the following 7 English and Chinese databases online: the Cochrane Library; PubMed; EMBASE; the China National Knowledge Infrastructure; the Wan Fang databases; the China Science and Technology Journal Database; and the Chinese Biomedical Literature Database. Reviewers will search each electronic database for studies published from journal inception to May 2021. Two reviewers will independently conduct clinical study inclusion, data extraction, and risk bias assessment. Any differences in the above process will be resolved through discussion with a third reviewer. If the data are sufficient, RevMan software 5.3 (Cochrane Community, London, UK) will be used for the meta-analysis of the extracted data. Results: In this systematic review, the effectiveness and safety of moxibustion therapy in PD treatment will be evaluated. Conclusion: This systematic review may provide further evidence to encourage clinicians to use moxibustion in the treatment of PD. INPLASY registration number: INPLASY202140097

Background: Latest clinical trials have proved the better overall survival (OS) for the use of immune checkpoint inhibitors verse chemotherapy in non-small cell lung cancer (NSCLC) patients. However, we still have no clear ideas of the factors which could affect the efficacy of immune checkpoint inhibitors. Cancer, essentially, is a disease related to genes mutation. Therefore, we conducted a systematic review and meta-analysis to compare efficacy of immune checkpoint inhibitors for NSCLC patients with different genes mutation. Methods: PubMed, EMBASE, Web of Science, and the Cochrane Library databases were searched for all clinical trials in NSCLC until December 16, 2019. The hazard ratio (HR) and 95% confidence intervals (CIs) of OS or progression-free survival (PFS) were used. Results: A total of 4453 patients from 7 randomized controlled trials (RCTs) were included. Immune checkpoint inhibitors significantly prolonged the OS (HR, 0.67; 95% CI, 0.60–0.67) in NSCLC patients having epidermal growth factor receptor (EGFR) wild-type versus chemotherapy. Meanwhile, they prolonged the OS (HR, 0.61; 95% CI, 0.39–0.94) in NSCLC patients with Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation. No matter PD-L1 tumor proportion scores were >1% or

Background: As nursing resources is directly related to patient outcomes in the intensive care unit setting, identifying factors related to nursing resources at various levels could contribute to improving those outcomes. This study aims to determine the association of nursing resources with outcomes of intensive care unit patients. Method: This study adheres to the Preferred Reporting Items for Systematic Reviews and Meta-analysis for Protocols. Chinese electronic Database (Chinese Biomedical Literature Database, Wanfang, and China National Knowledge Infrastructure) and international electronic databases (PubMed, Embase, Cochrane Library, and Web of Science) will be searched for all relevant published articles, with no restrictions on the year of publication or language. Study selection, data collection and assessment of study bias will be conducted independently by a pair of independent reviewers. The Newcastle–Ottawa Scale tool will be used for the risk of bias assessment. The Grading of Recommendations Assessment Development and Evaluation system will be used to assess the quality of evidence. The statistical analysis of this meta-analysis will be calculated by Review manager version 5.3. Results: The results of this study will be published in a peer-reviewed journal. Conclusion: The findings of this systematic review will provide a high-quality synthesis of latest evidence and provide a basis for assessing the association of nursing resources on patients’ outcomes in intensive care units. Trial registration number: 10.17605/OSF.IO/9FNEX

The coronavirus disease 19 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become the worst public health crisis in a century. However, knowledge about the dynamics of antibody responses in patients with COVID-19 is still poorly understood. In this study, we performed a serological study with serum specimens collected at the acute and the convalescent phases from 104 patients with severe COVID-19 who were part of the first wave of COVID-19 cases in Wuhan, China. Our findings revealed that neutralizing antibodies to SARS-CoV-2 are persistent for at least 6 months in patients with severe COVID-19, despite that IgG levels against the receptor binding domain (RBD) and nucleocapsid protein (N) IgG declined from the acute to the convalescent phase. Moreover, we demonstrate that the level of RBD-IgG is capable of correlating with SARS-CoV-2-neutralizing activities in COVID-19 serum. In summary, our findings identify the magnitude, functionality, and longevity of antibody responses in patients with COVID-19, which sheds light on the humoral immune response to COVID-19 and would be beneficial for developing vaccines.

Background: The objective of this study is to systematically evaluate the efficacy and safety of the calcitonin gene-related peptide (CGRP) receptor antagonist ubrogepant for the treatment of acute migraine. Methods: Randomized controlled trials (RCTs) of ubrogepant for treatment of acute migraine were identified in PubMed, MEDLINE, EMBASE, and the Cochrane Library from database establishment to June 2020; we also searched ClinicalTrials.gov manually during the same period. Then, RevMan 5.3 software was used to perform a meta-analysis on each outcome measure. Results: A total of 5 RCTs involving 4903 patients were included; there were 3358 cases in the ubrogepant group and 1545 cases in the placebo group. The meta-analysis showed the following results: at 2 hours postdose, the percentages of participants reporting pain relief and the absence of photophobia, nausea, and phonophobia were significantly higher in the ubrogepant group than in the placebo group (odds ratio [OR] = 1.71, 95%CI: 1.48–1.97, P .05). Conclusion: Ubrogepant is effective and safe for the treatment of acute migraine. Registration number: PROSPERO CRD42019145286.

Background: This study will assess the efficacy and safety of arthroscopic capsular release (ACR) for the treatment of post-stroke frozen shoulder (PSFS). Methods: We will carry out a systematic study of randomized controlled trials that assess the efficacy and safety of ACR for PSFS. We will search all potential records for any eligible trials from selected electronic databases (MEDLINE, EMBASE, Cochrane Library, Web of Science, Chinese Biomedical Literature Database, WANGFANG, and China National Knowledge Infrastructure) and grey literature sources from inception to the present. Two authors will independently perform study selection, data extraction, and study quality assessment. Any disagreement will be solved by a third author via consultation. Statistical analysis will be carried out by RevMan 5.3 software. Results: This study will comprehensively summarize current eligible studies to systematically assess the efficacy and safety of ACR for PSFS. Conclusion: This study will provide evidence to determine whether ACR is an effective management for patients with PSFS.

Background: To investigate the efficacy and safety of compound glycyrrhizin (CG) combined with antihistamines in the treatment of chronic urticaria (CU). Methods: We will use computers to search all databases including Medline, Embase, Pubmed, Web of Science and Cochrane Central Register of Controlled Trials and China's 4 databases: China National Knowledge Infrastructure Database, China Biomedical Literature Database, China Science Journal Database, and Wanfang Database. Find data from creation date to July 2020. In addition, we will manually search the list of medical journals as a supplement. The scope of the search included randomized controlled clinical studies related to CG combined with antihistamines for CU. The primary outcome is the disease activity control. Secondary outcomes include response rate, adverse events, and recurrence rates. The Cochrane RevMan V5.3 Deviation Assessment Tool will be used to assess bias assessment risk, data integration risk, meta-analysis risk, and subgroup analysis risk (if conditions are met). The average difference, standard mean difference, and binary data will be used to represent continuous results. Results: This study will comprehensively review the existing evidence on CG combined with antihistamines for CU. Conclusion: This systematic review will provide a basis for judging the effectiveness and safety of CG combined with antihistamines in the treatment of CU. Systematic review registration: PROSPERO, CRD42020156153

Background: In China, traditional Chinese medicine (TCM) is an increasingly important part of the treatment of non-small cell lung cancer (NSCLC), which usually includes a combination of prescription and syndrome differentiation. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have been proven to be the first-line drugs for the treatment of advanced EGFR mutation-positive NSCLC. In China, EGFR-TKIs are used in combination with traditional Chinese medicines to reduce side effects and/or enhance effectiveness. Nevertheless, the relationship between TCMs and EGFR-TKIs remain unclear. This meta-review aimed to explore the clinical evidence of TCMs combined with EGFR-TKIs in the treatment of NSCLC. Methods: Related studies were found by searching the databases of EMBASE, PubMed, Web of Science, MEDLINE, Cochrane library database, China Academic Journals (CNKI), Wanfang and Weipu. This study included 57 randomized controlled trials, all of these were processed by Stata software (version 12.0). In the study, all the materials are published articles, patient anonymity and informed consent and ethics Approval/Institutional review board are not necessary. Results: This study demonstrated that the objective response rate was higher in the group of TCMs plus EGFR-TKIs than in the group of EGFR-TKIs alone (risk ratios 1.39, 95% confidence intervals [1.29, 1.50]). Further research of specific herbal medicines showed that Huangqi, Baishu, Fuling, Gancao, Maidong, Baihuashecao, Shashen, Dangshen and Renshen, had significant higher contributions to results. Conclusion: TCMs may improve the efficacy of EGFR-TKIs in the treatment of NSCLC.

Introduction: Pancreatic pseudocyst is one of the most common cystic lesions. It always occurs following pancreatitis and is rarely found in combination with pancreatic adenocarcinoma. The coexistence of exocrine and neuroendocrine tumors of the pancreas is also infrequent. We herein report a case of simultaneous occurrence of a pancreatic ductal adenocarcinoma (PDAC), pseudocyst, and neuroendocrine tumor (NET), showing a “side-by-side pattern.” Patient concern: A 74-year-old man was hospitalized for epigastric pain and poor appetite. He had no history of pancreatitis, alcohol consumption, or smoking. Diagnosis and intervention: Abdominal enhanced computed tomography and magnetic resonance imaging revealed a 15 × 8 cm cystic lesion with poor enhancement located in the tail of the pancreas. The distal aspect of the main pancreatic duct was dilated. The pancreatic parenchyma adjacent to the cystic lesion showed slightly heterogeneous enhancement on computed tomography and magnetic resonance imaging. Laboratory examination showed an elevated carbohydrate antigen 19–9 serum level. The patient was preoperatively diagnosed with intraductal papillary mucinous neoplasm and subsequently underwent laparotomy. During the operation, a hard white tumor measuring about 4 × 3 cm was palpated adjacent to the cystic lesion on the duodenal side, and a 0.6-cm nodule was simultaneously found in the pancreatic tail. Therefore, total pancreatectomy and splenectomy were performed. Histopathological examination showed that the tumor was PDAC with an adjacent pseudocyst, and the small nodule was suggestive of a NET. Outcomes: The patient survived without recurrence or metastasis in the follow-up visit 10 months after the operation and adjuvant chemotherapy. Conclusions: The concomitant occurrence of a PDAC, pseudocyst, and NET has not been previously reported. We suggest that if a pancreatic cyst is found, the coincidental occurrence of a malignant tumor should be considered, especially if the carbohydrate antigen 19–9 level is increased. Additionally, dilation of the pancreatic duct may be a diagnostic clue. Furthermore, the simultaneous occurrence of pancreatic endocrine and exocrine tumors is very uncommon. Preoperative diagnosis becomes difficult because of the lack of specific symptoms and radiological features.

Introduction: Transitional drainage, which is followed by cholecystectomy plays a key role in the management of acute cholecystitis, especially in high-risk surgical patients. Endoscopic naso-gallbladder drainage (ENGBD) is an alternative to percutaneous transhepatic gallbladder drainage (PTGBD) for patients who need temporary drainage. There is a lack of prospective comparison on the relevant outcomes of the two drainage methods during the period of drainage, especially the subsequent cholecystectomy. Methods: This is a randomized controlled two-arm non-blind single center trial. Patients with acute cholecystitis undergo emergent or early cholecystectomy and need drainage will be randomly assigned to group PTGBD or ENGBD. Pain score is defined as the primary endpoint, whereas several secondary endpoints, such as the rates of technical success, clinical remission, open conversion of cholecystectomy will be determined to elucidate more detailed differences between two groups. The general feasibility, safety, and quality checks required for high-quality evidence will be adhered to. Discussion: This study would provide the first type A evidence concerning the comparison of ENGBD versus PTGBD in surgically high-risk patients with acute cholecystitis, it will be the first trial designed to determine the impact of two drainage methods on not only peri-drainage but also peri-LC. Trial registration: NCT03701464. Registered on October 10, 2018.

Cumulus cells secreting steroid hormones have important functions in oocyte development. Several members of the short‐chain dehydrogenase/reductase (SDR) family are critical to the biosynthesis of steroid hormones. NADPH‐dependent retinol dehydrogenase/reductase ( NRDR), a member of the SDR superfamily, is overexpressed in pig breeds that also show high levels of androstenone. However, the potential functions and regulatory mechanisms of NRDR in pig ovaries have not been reported to date. The present study demonstrated that NRDR is highly expressed in pig ovaries and is specifically located in cumulus granulosa cells. Functional studies showed that NRDR inhibition increased estradiol synthesis. Both pregnant mare serum gonadotropin and human chorionic gonadotropin downregulated the expression of NRDR in pig cumulus granulosa cells. When the relationship between reproductive traits and single‐nucleotide polymorphisms (SNPs) of the NRDR gene was examined, we found that two SNPs affected reproductive traits. SNP rs701332503 was significantly associated with a decrease in the total number of piglets born during multiparity, and rs326982309 was significantly associated with an increase in the average birth weight during primiparity. Thus, NRDR has an important role in steroid hormone biosynthesis in cumulus granulosa cells, and NRDR SNPs are associated with changes in porcine reproduction traits.

Introduction: The purpose of this paper is to evaluate the efficacy and safety of moxibustion in infertility females/women undergoing in vitro fertilization and embryo transfer (IVF-ET). Methods and analysis: We will electronically search PubMed, Medline, Embase, Web of Science, the Cochrane Central Register of Controlled Trial, China National Knowledge Infrastructure, China Biomedical Literature Database, China Science Journal Database, and Wan-fang Database from their inception. Also, we will manually retrieve other resources, including reference lists of identified publications, conference articles, and grey literature. The clinical randomized controlled trials or quasi-randomized controlled trials related to moxibustion in female infertility patients undergoing IVF-ET will be included in the study. The language is limited to Chinese and English. Research selection, data extraction, and research quality assessment will be independently completed by 2 researchers. Data were synthesized by using a fixed effect model or random effect model depend on the heterogeneity test. The clinical total effective rate and the clinical pregnancy rate will be the primary outcomes. Ovulation rate, endometrial thickness, hormone level, traditional Chinese medicine (TCM) Syndrome Integral Scale and the adverse event will also be assessed as secondary outcomes. RevMan V.5.3 statistical software will be used for meta-analysis, and the level of evidence will be assessed by Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Continuous data will be expressed in the form of weighted mean difference or standardized mean difference with 95% confidence intervals (CIs), while dichotomous data will be expressed in the form of relative risk with 95% CIs. Results: This study will provide a high-quality comprehensive evaluation of the efficacy and safety of moxibustion in the treatment of female infertility patients undergoing IVF-ET. Conclusion: This review will provide evidence to judge for judging whether moxibustion is effective in treating female infertility patients undergoing IVF-ET. Systematic review registration: PROSPERO, CRD42019135593

Background To evaluate the early growth (weight and length) of HIV-exposed uninfected (HEU) children from the prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV) program in Guangdong Province, China. Methods A total of 731 HEU children were longitudinally followed up at 7 time points, with anthropometric measurement conducted of weight and length (supine) in the first 18 months. Z scores were calculated, with and without adjustment for gestational age. Results A total of 708 HEU children were included in the final follow-up cohort, and 105 (14.83%) children completed all 7 follow-up visits. The mean of adjusted weight-for-age Z scores in these children was above zero and showed a decreasing trend in 18 months. The mean of adjusted length-for-age Z scores showed a decreasing trend and was above zero in the first 12 months; this declined to under zero at age 18 months. The proportion of underweight was 0.28–2.19% and that of stunting was 0.71–4.63% at each follow-up month-age. Slower growth in HEU children was associated with no sustained food subside after 6 month, mothers’ hemoglobin content less than 100 g/L during pregnancy, preterm birth, and low birth weight (p Conclusions HEU children could catch up to WHO growth standards in first 18 months in Guangdong; however, growth declined after 12 months, and these children need sustained nutritional support.

Many compounds of ginsenosides show anti-inflammatory properties. However, their anti-inflammatory effects in intervertebral chondrocytes in the presence of inflammatory factors have never been shown. Increased levels of pro-inflammatory cytokines are generally associated with the degradation and death of chondrocytes; therefore, finding an effective and nontoxic substance that attenuates the inflammation is worthwhile. In this study, chondrocytes were isolated from the nucleus pulposus tissues, and the cells were treated with ginsenoside compounds and IL-1β, alone and in combination. Cell viability and death rate were assessed by CCK-8 and flow cytometry methods, respectively. PCR, western blot, and immunoprecipitation assays were performed to determine the mRNA and protein expression, and the interactions between proteins, respectively. Monomeric component of ginsenoside Rd had no toxicity at the tested range of concentrations. Furthermore, Rd suppressed the inflammatory response of chondrocytes to interleukin (IL)-1β by suppressing the increase in IL-1β, tumor necrosis factor (TNF)-α, IL-6, COX-2, and inducible nitric oxide synthase (iNOS) expression, and retarding IL-1β-induced degradation of chondrocytes by improving cell proliferation characteristics and expression of aggrecan and COL2A1. These protective effects of Rd were associated with ubiquitination of IL-1 receptor accessory protein (IL1RAP), blocking the stimulation of IL-1β to NF-κB. Bioinformatics analysis showed that NEDD4, CBL, CBLB, CBLC, and ITCH most likely target IL1RAP. Rd increased intracellular ITCH level and the amount of ITCH attaching to IL1RAP. Thus, IL1RAP ubiquitination promoted by Rd is likely to occur by up-regulation of ITCH. In summary, Rd inhibited IL-1β-induced inflammation and degradation of intervertebral disc chondrocytes by increasing IL1RAP ubiquitination.

Background: The purpose of this paper is to evaluate the effectiveness and safety of acupoint catgut embedding in the treatment of chronic urticaria (CU). Methods: We will electronically search PubMed, Medline, Embase, Web of Science, the Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chinese Scientific Journal Database, and Wan-Fang Database from their inception to March 2019. In addition, we will manually retrieve other resources including the reference lists of identified publications, conference articles, and gray literature. The clinical randomized controlled trials or quasi-randomized controlled trials related to acupoint catgut embedding for the treatment of CU will be included in the study. The language is limited to Chinese and English. Research selection, data extraction, and research quality assessment will be independently completed by 2 researchers. Data were synthesized by using a fixed effect model or random effect model depend on the heterogeneity test. The total effective rate was the primary outcomes. Skin disease quality of life index scores, adverse events, and recurrence rates will also be assessed as secondary outcomes. RevMan V.5.3 statistical software will be used for meta-analysis. If it is not appropriate for a meta-analysis, then a descriptive analysis will be conducted. Data synthesis will use the risk ratio and the standardized or weighted average difference of continuous data to represent the results. Results: This study will provide a high-quality synthesis to assess the effectiveness and safety of acupoint catgut embedding for patients with CU. Conclusion: This systematic review will provide evidence to judge whether acupoint catgut embedding is an effective intervention for patients with CU. Systematic review registration: PROSPERO, CRD42019129459.

Background: Chronic urticaria (CU) is a common and easily recurring skin disease in the world. Many trials have shown that autologous whole-blood or autologous serum acupoint injection therapy is effective in treating CU. There is currently no systematic review of this therapy. The program aims to evaluate the effectiveness and safety of this therapy in patients with CU. Methods: Literature search will be conducted at Medline, PubMed, Excerpt Medica Database, Springer, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Chinese Scientific Journal Database, and other databases. The search date is until May 2019. We will search for popular terms including CU and this therapy. Import the literature electronically. Duplicate documents will be deleted. The primary outcome is the urticaria activity score or other validated scales. Secondary outcomes included response rate, quality of life scale, recurrence rate, and adverse events. A systematic review and search for a randomized controlled trial of this therapy for CU. Implement the Cochrane RevMan V5.3 bias assessment tool to assess bias assessment risk, data integration risk, meta-analysis risk, and subgroup analysis risk (if conditions are met). The mean difference, standard MD, and binary data will be used to represent continuous results. Results: This study will provide a comprehensive review of the available evidence for the treatment of CU with this therapy. Conclusion: This study will provide new evidence for assessing the effectiveness and side effects of this therapy for CU. Since the data is not individualized, there is no need for formal ethical approval. PROSPERO registration number: CRD42019128364.

Rationale: Ameloblastoma is generally characterized as a benign tumor originating in odontogenic epithelium. However, few cases of metastatic malignant ameloblastoma have also been reported. Due to the low incidence of malignant ameloblastoma, there is no established treatment regimen. To explore effective treatment for malignant ameloblastoma, we reported this case study. Patients concerns: This report described a case of a 28-year-old malignant ameloblastoma female patient with multiple metastasis (brain and lung). Diagnoses: The patient presented ameloblastoma of the left mandible in 2012. Three years later, local recurrence and brain metastasis was observed during a follow-up examination. Five years later, malignant ameloblastoma was detected by imaging and immunohistochemistry in the bilateral multiple pulmonary nodules and mediastinal lymph nodes. Interventions: The patient was initially treated with tumor resection. Three years later after local recurrence and brain metastasis, she was accepted the extensive mandibulectomy supplemented with brain stereotactic body radiotherapy (SBRT). When diagnosed with pulmonary metastasis, the patient received combined chemotherapy regimen of MAID (mesna, adriamycin, ifosfamide and dacarbazine) for 6 cycles. Outcomes: The efficacy evaluation was partial remission (PR) after the 6 cycles of MAID. The last patient follow-up was July 24th 2018, and no evidence of progression was observed. The progression-free survival (PFS) of the patient was more than 9 months. Lessons: Surgical resection is the optimal treatment for locally recurrent ameloblastoma. SBRT may be an effective treatment for unresectable oligometastasis of malignant ameloblastoma. Finally, combined chemotherapy of MAID showed encouraging effects in the management of metastatic malignant ameloblastoma.

Vitamin D deficiency is associated with numerous public health issues. Limited data are available for children in southern China, a region that receives abundant sunlight. We aimed to estimate the 25-hydroxyvitamin D (25(OH)D) levels in children in that area, and to determine seasonal variations in serum 25(OH)D levels. A total of 16,755 children aged 0 to 6 years, who visited the Guangdong Women and Children's Hospital for health examination between January 2016 and May 2017, were included in the present study. The serum 25(OH)D levels ranged from 10.5 to 307.4 nmol/L (mean ± standard deviation: 78.5 ± 26.3 nmol/L). The prevalence of vitamin D deficiency and insufficiency were 10.8% and 39.0%, respectively. The mean serum 25(OH)D level in spring (71.8 ± 24.9 nmol/L) was lower than that in other seasons. From January to April, we found a relatively high prevalence of vitamin D deficiency or insufficiency, both of which were also found to increase with age. Logistic regression analysis revealed that vitamin D deficiency and insufficiency were significantly associated with age and season. Deficiency and insufficiency of vitamin D are common among children in southern China, despite the area receiving sufficient sunlight.

Aim: To investigate the benefits of axillary dissection in patients with micrometastases. Methods: A review of data from the Surveillance, Epidemiology, and End Results database was performed from 2004 to 2013. Kaplan–Meier curves, Cox regression models, and propensity score matching were utilized to comprehensively evaluate the cohort. Results: Multivariate analysis after propensity score matching showed that patients with one to two micrometastases did not substantially benefit from axillary lymph node dissection in breast cancer-specific survival (p = 0.725). However, a subgroup analysis indicated that axillary dissection may benefit estrogen receptor-negative patients. Moreover, patients who carried three micrometastases had a significantly lower crude hazard ratio in breast cancer-specific survival. Conclusion: Axillary lymph node dissection may have advantages in high-risk micrometastatic patients. Patients with three micrometastases should be treated with caution., Lay abstract The current study demonstrated that among patients undergoing breast-conserving surgery following radiation with T1–T2 invasive breast cancer and one to two nodal micrometastases, there was no difference in the breast cancer-specific survival for patients with and without axillary lymph node dissection. Although negative results of the Z0011 and International Breast Cancer Study Group 23–01 trials have been reported, high-risk micrometastatic patients (e.g., estrogen receptor negative, young age) may be candidates for radical axillary treatment according to the unclear radiation field and higher recurrence rate. The preliminary assessment of three micrometastatic patients showed a lower breast cancer-specific survival than patients with one to two micrometastases. This study provides a novel perspective to the American Joint Committee on Cancer with respect to micrometastases.

This study was aimed to evaluate the image quality and lacunar lesion detection of thin-slice brain computed tomography (CT) images with different reconstruction algorithms, including filtered back projection (FBP), hybrid iterative reconstruction (HIR), and iterative model reconstruction (IMR) by comparison of routine slice images with FBP reconstruction. Sixty-one patients underwent noncontrast brain CT and images were reconstructed with a routine slice of 5.0 mm by FBP and thin slice of 1.0 mm by IMR, HIR, and FBP algorithms, respectively. Objective analyses included CT attenuation, noise, artifacts index of posterior cranial fossa, and contrast-to-noise ratio (CNR). Subjective analyses were performed according to overall image quality using a 5-point scale [1 (unacceptable) to 5 (excellent)]. In addition, lacunar lesion detection was compared in images with different reconstruction settings among 26 patients with lacunar lesions, with magnetic resonance imaging (MRI) as reference. Thin-slice IMR images enabled the lowest noise, artifacts index, and the best CNR. Both IMR and HIR thin-slice images enabled better scores in subjective image quality than routine slice FBP images. Moreover, both thin-slice IMR and HIR images enabled higher sensitivity and positive predictive value (PPV) in lesion detection of 35-mm lacunar lesions compared with routine slice FBP images. Thin-slice IMR images improve image quality, meanwhile yield better detection of small lacunar lesions in brain CT compared with routine slice FBP images.

Rationale: Ectopic pancreas, which is a kind of rare congenital disease, forms during embryonic development. It can occur throughout the whole gastrointestinal tract, but has a low tendency to develop in the wall of the small intestine. It is easy for patients with ectopic pancreases to be misdiagnosed because the symptoms are untypical and can vary. Patient concerns: In the present study, we reported two rare cases of ectopic pancreatic tissue in the wall of the small intestine, which presented with obvious abdominal pain and distention. Diagnosis: The laboratory tests and computed tomography (CT) scans didn’t reveal any evidence of ectopic pancreas. Interventions: The two patients received small intestine masses resection and intestinal anastomosis. Outcomes: During surgery, an intestinal mass with a diameter of 4.0 cm was found in the first patient. An intestinal mass with a diameter of 0.8 cm, jejunum perforation, and diffuse peritonitis were found in the second patient. Histological analyses of the dissected intestinal masses confirmed them as ectopic pancreatic tissue. Interestingly, for the second patient, the intestinal perforation and diffuse peritonitis were not induced by the ectopic pancreas, but by a jujube pit that was found in the perforated site of the intestine. Lessons: Our study demonstrated that an ectopic pancreas should be considered in cases of untypical abdominal symptoms with intestinal masses.

The aim of this study was to investigate the effects of early enteral nutrition (EEN) on T helper lymphocytes and the subpopulations ratios of surgical septic patients. We performed a retrospective study including 107 eligible patients from February 2014 to December 2015. Patients were divided into EEN, delayed enteral nutrition (DEN), or total parenteral nutrition (TPN) group according to the duration before enteral feeding. Th1, Th2, Th17, and Treg lymphocyte percentages were collected on days 3, 7, and 14 after admission. The disease severity and clinical outcome variables were also recorded. The Th1, Th17 percentages, and Th1/Th2, Th17/Treg ratios of EEN group were significantly lower than those of DEN or TPN group on the 14th day after admission (P

To retrospectively analyze the safety and efficacy of 350–560 μm gelatin sponge particles combined with single-chemotherapy drug transcatheter arterial chemoembolization (Gs-TACE) for the treatment of elderly hepatocellular carcinoma without surgical resection. Thirty elderly hepatocellular carcinoma patients without surgical resection, who received Gs-TACE in our hospital, were selected. Slowly injected gelatin sponge particles (350–560 μm)+ 10 mg lobaplatin injection into the regional embolization tumor target vessel. The Response Evaluation Criteria for Solid Tumors could be used to evaluate the tumor response after intervention surgery. Eighty-nine times of intervention TACE were conducted on the 30 patients. The average size of tumor was 8.3 cm. The median survival time was 28 months, and the 1 and 2-year survival rates were 89% and 58%, respectively. The Response Evaluation Criteria for Solid Tumors was used to evaluate the tumor response, and found that the complete response, partial response, and OR were 30%, 56.67%, and 86.67%, respectively, at 1 month after intervention surgery. The patients were divided into groups: 60 to 65 years age group (A), >65 to 75 years age group (B), and >75 years age group (C); the median survival times were 16, 32, and 33 months, respectively, and there was statistical difference between A group, B group, and C group. The analysis of prognosis factors showed that there was statistical significance in age, Barcelona Clinic Liver Cancer stage, portal vein invasion, and alpha fetal protein (AFP), and age was the protective factor. Gelatin sponge particles (350–560 μm), combined with transcatheter arterial chemoembolization, provide an alternative method for the treatment of elderly hepatocellular carcinoma without surgical resection.

In most of the developing countries, lack of resources and little market accessibility are among the major factors that affect small farming household food security. This study aims to investigate the status of small farming households' food security, and its determinants including the role of market accessibility factors in enhancing food security at household level. In addition, this study also determines the households' perception about different kinds of livelihoods risks. This study is based on a household survey of 576 households conducted through face-to-face interviews using structured interviews in Punjab, Pakistan. Food security status is calculated using dietary intake method. The study findings show that one-fourth of the households are food insecure. The study findings reveal that farm households perceive increase in food prices, crop diseases, lack of irrigation water and increase in health expenses as major livelihood risks. Further, the results of logistic regression show that family size, monthly income, food prices, health expenses and debt are main factors influencing the food security status of rural households. Furthermore, the market accessibility factors (road distance and transportation cost) do significantly affect the small farming household food security. The results suggest that local food security can be enhanced by creating off-farm employment opportunities, improved transportation facilities and road infrastructure.

The complete mitochondrial genome of Protosalanx chinensis was determined to be 16,879 bp in length. It consists of 13 protein-coding genes, 22 tRNAs, 2 ribosomal RNAs, and a control region. The gene composition and the structural arrangement of the P. chinensis complete mtDNA were identical to most of the other vertebrates. The molecular data here we presented could play a useful role to study the evolutionary relationships and population genetics of Salangidae fish.

Background: Recently, several studies using transcranial sonography (TCS) have demonstrated reduced echogenicity of the mesencephalic midline in unipolar depression and patients with comorbid depression and Parkinson disease (PD). However, there is no consensus on the conclusion that raphe nuclei (RN) hypoechogenicity is associated with depression in PD. The methods used in previous studies lack quantitative and objective indicators to some extent; therefore, the present study used the level of platelet 5-hydroxytryptamine (5-HT) as an objective indicator of depression. Additionally, the reason for the reduced echogenicity of the brainstem raphe is still unclear. Objectives: The purpose of the present study was to assess the correlation between alterations in RN echogenicity and depressive symptoms in patients with PD using transcranial sonography (TCS). This information could provide a meaningful clinical reference for the antidiastole between depressive symptoms in PD and unipolar depression in patients with PD in whom depressive symptoms occur before motor symptoms. Methods: TCS was performed in patients with PD, patients with PD and depression, patients with depression and no PD, and healthy controls. Using the red nucleus as a reference, the RN was rated from grades 0 to 1 (grade 0: invisible, slightly echogenic, or interrupted RN; grade 1: hyperechogenicity in the RN observed as a continuous line). Results: The rate of abnormal RN (grade 0) was found to be 16.67% in patients with PD (5/30) and 14.29% in healthy controls (4/28). The presence of abnormal RN was significantly higher (χ2 = 15.983, P .05). There were no statistical differences in the concentration of platelet serotonin among the 4 groups (P > .05). Conclusions: TCS of the mesencephalic midline may be useful for detecting depression, which is an early symptom of PD. However, further neuropathological studies are needed to understand the principles underlying the use of platelet serotonin as a peripheral biomarker, as well as the connection between PD and depression.

Background: Cardiac tumors, especially malignant, are rare but aggressive tumors that mostly arise from the mesenchymal cells and represent a challenging diagnosis for clinicians. Recently, fluorine-18-fluorodiography positron emission tomography and computed tomography (18F-FDG PET/CT) is an increasingly popular new technique with diagnosis of tumor. Methods: We report a case of a right heart tumor showing intense uptake of 18F-fluorodeoxyglucose (18F-FDG) on position emission tomography/computed tomography (PET/CT) imaging. We discuss the clinical course and diagnostic evaluations. Results: The maximal standardized uptake values (SUVmax) for the cardiac and metastatic lesion were 17.2 and 12.9, respectively. Conclusion: 18F-FDG PET/CT imaging, which enables both morphological characterization and visualization of tumor metabolism, may be an effective and feasible noninvasive method for the diagnosis of malignant cardiac tumors.

Ticagrelor is a direct acting on the P2Y12 receptor blocker, which provides faster and greater platelet inhibition than clopidogrel. However, several studies suggested that in ST-segment elevation myocardial infarction patients undergoing percutaneous coronary intervention (PCI), ticagrelor exhibits initial delay in the onset of antiplatelet action. Unlike ST-segment elevation myocardial infarction, in non-ST-segment elevation acute coronary syndrome (NSTE-ACS), management pathways are highly variable, and some patients may require surgery. Effect of higher loading dose (LD) of ticagrelor in patients with NSTE-ACS in providing faster and stronger inhibition of platelet aggregation is unknown and needs to be explored further. The AntiPlatelet Effect of different Loading dOse of Ticagrelor trial is an interventional, randomized, open-label, multicenter, phase IV trial designed to evaluate whether a high LD (360 mg) of ticagrelor compared with the conventional LD (180 mg) will result in a higher inhibition of platelet aggregation without increasing bleeding events in NSTE-ACS participants undergoing PCI. A total of 250 NSTE-ACS participants will be randomized to receive a ticagrelor LD (360 or 180 mg), followed by a maintenance dose of 90 mg twice a day (bid) starting 12 hours after the LD. The primary endpoint is platelet reactivity index measured by vasodilator-stimulated phosphoprotein phosphorylation 2 hours after the LD, and the secondary endpoints include occurrence of periprocedural myocardial infarction and bleeding events. The AntiPlatelet Effect of different Loading dOse of Ticagrelor trial will provide important information on the risks and benefits of a high LD (360 mg) of ticagrelor in achieving a faster and stronger platelet inhibition compared with the conventional LD (180 mg) in NSTE-ACS patients undergoing PCI.

Gelatin sponge particles are commonly used in the conventional transarterial chemoembolization (c-TACE) as an adjuvant embolizing agent for hepatocellular carcinoma (HCC). However, there are few reports regarding the clinical applications of gelatin sponge microparticles (GSMs) as a main embolizing agent in the treatment of HCC. This retrospective study aim to evaluate the efficacy and safety of patients with Barcelona Clinic Liver Cancer (BCLC) stage B HCC treated with intra-arterial injection of 350 to 560 μm GSMs mixed with anticancer agents. Twenty-four patients with unresectable BCLC stage B HCC without any prior treatment underwent transarterial chemoembolization with gelatin sponge microparticles (GSMs-TACE) of diameter 350 to 560 μm mixed with lobaplatin. The mixture was injected into tumor-feeding arteries until the sluggish flow in selective artery. Safety was measured by assessing complication rate, and efficacy was reflected by assessing response to mRECIST therapy and overall survival. The survival rate was calculated using the Kaplan–Meier method. All 24 BCLC stage B HCC patients showed good tolerance to the procedure. The mean follow-up period was 27 months and mean number of TACE treatments per patient was 3.7 sessions (range 1–10) during the follow-up period. Postprocedure complications were mild and treated by symptomatic treatment. Six months and 1 year overall survival rates were 100% and 87.5%, respectively. Overall median survival time was 25 months (95%CI: 21.06–28.95 months). GSMs-TACE is a safe and effective method for BCLC stage B HCC patients.

Purpose To develop a new culture system to cultivate differentiated autologous cells in vitro for cell therapy and tissue engineering. Methods After incubation in murine embryonic stem cell (ESC) extract for 1 h, streptolysin-O (SLO) permeabilized cells were resealed with CaCl2 and continually cultured for weeks. The morphological study was analyzed by light microscopy. Isolated colonies were selected and expanded to establish cell lines. Octamer-4 (Oct-4), stage-specific embryonic antigen-1 (SSEA-1), transformation-related protein 63 (p63), ATP-binding cassette subfamily G, member 2 (ABCG2), and cytokeratin3 (K3) were detected by indirect immunofluorescent staining. Oct-4, K3, and p63 were also detected by RT–PCR analysis. To examine the stemness characteristics of the induced cells, both alkaline phosphatase (AKP) staining and tumorigenicity detection were performed, respectively. Results Reprogramming was induced in corneal epithelial cells. The reprogrammed cells showed characteristics similar to ESCs in the early weeks, including colony formation, positive AKP staining, and multi-potential differentiation in vivo. Oct-4 and SSEA1 protein expression was upregulated. However, these changes were not persistent or stable. With the passage of time, the colonies became flat. The ESC markers were downregulated, while epithelial cell related proteins gradually increased. Conclusions Less terminal differentiated rabbit corneal epithelial cells could be induced to a more pluripotent state with embryonic stem cell extract (ESC-E). These cells have the potential to return to the beginning of their own lineage and obtain the ability of long-term growth. Our findings indicate that this culture system can generate low-immunogenic autologous cells for use in regenerative medicine.

DNA methylation is an important part of epigenetics. In this study, we examined the methylation state of two CpG islands in the promoter of the p16 gene in radiation-induced thymic lymphoma samples. The mRNA and protein levels of P16 were significantly reduced in radiation-induced thymic lymphoma tissue samples. Twenty-three CpG sites of the CpG islands in the p16 promoter region were detected, and the methylation percentages of −71, −63, −239, −29, −38, −40, −23, 46 CpG sites were significantly higher in radiation-induced thymic lymphoma tissue samples than those in matched non-irradiated thymus tissue samples. This study provides new evidence for the methylation state of p16 in the radiation-induced thymic lymphoma samples, which suggests that the methylation of these CpG sites in the p16 promoter may reduce its expression in the thymic lymphoma after irradiation.