TFPI is a colonic crypt receptor for TcdB from hypervirulent clade 2 C. difficile.

The emergence of hypervirulent clade 2 Clostridioides difficile is associated with severe symptoms and accounts for >20% of global infections. TcdB is a dominant virulence factor of C. difficile, and clade 2 strains exclusively express two TcdB variants (TcdB2 and TcdB4) that use unknown receptors distinct from the classic TcdB. Here, we performed CRISPR/Cas9 screens for TcdB4 and identified tissue factor pathway inhibitor (TFPI) as its receptor. Using cryo-EM, we determined a complex structure of the full-length TcdB4 with TFPI, defining a common receptor-binding region for TcdB. Residue variations within this region divide major TcdB variants into 2 classes: one recognizes Frizzled (FZD), and the other recognizes TFPI. TFPI is highly expressed in the intestinal glands, and recombinant TFPI protects the colonic epithelium from TcdB2/4. These findings establish TFPI as a colonic crypt receptor for TcdB from clade 2 C. difficile and reveal new mechanisms for CDI pathogenesis.

Greater strength of selection and higher proportion of beneficial amino acid changing mutations in humans compared with mice and Drosophila melanogaster.

Quantifying and comparing the amount of adaptive evolution among different species is key to understanding how evolution works. Previous studies have shown differences in adaptive evolution across species; however, their specific causes remain elusive. Here, we use improved modeling of weakly deleterious mutations and the demographic history of the outgroup species and ancestral population and estimate that at least 20% of nonsynonymous substitutions between humans and an outgroup species were fixed by positive selection. This estimate is much higher than previous estimates, which did not correct for the sizes of the outgroup species and ancestral population. Next, we jointly estimate the proportion and selection coefficient (p + and s +, respectively) of newly arising beneficial nonsynonymous mutations in humans, mice, and Drosophila melanogaster by examining patterns of polymorphism and divergence. We develop a novel composite likelihood framework to test whether these parameters differ across species. Overall, we reject a model with the same p + and s + of beneficial mutations across species and estimate that humans have a higher p+s + compared with that of D. melanogaster and mice. We show that this result cannot be caused by biased gene conversion or hypermutable CpG sites. We discuss possible biological explanations that could generate the observed differences in the amount of adaptive evolution across species.

Evidence for ecotone speciation across an African rainforest-savanna gradient.

Accelerating climate change and habitat loss make it imperative that plans to conserve biodiversity consider species' ability to adapt to changing environments. However, in biomes where biodiversity is highest, the evolutionary mechanisms responsible for generating adaptative variation and, ultimately, new species are frequently poorly understood. African rainforests represent one such biome, as decadal debates continue concerning the mechanisms generating African rainforest biodiversity. These debates hinge on the relative importance of geographic isolation versus divergent natural selection across environmental gradients. Hindering progress is a lack of robust tests of these competing hypotheses. Because African rainforests are severely at-risk due to climate change and other anthropogenic activities, addressing this long-standing debate is critical for making informed conservation decisions. We use demographic inference and allele frequency-environment relationships to investigate mechanisms of diversification in an African rainforest skink, Trachylepis affinis, a species inhabiting the gradient between rainforest and rainforest-savanna mosaic (ecotone). We provide compelling evidence of ecotone speciation, in which gene flow has all but ceased between rainforest and ecotone populations, at a level consistent with infrequent hybridization between sister species. Parallel patterns of genomic, morphological, and physiological divergence across this environmental gradient and pronounced allele frequency-environment correlation indicate speciation is mostly probably driven by ecological divergence, supporting a central role for divergent natural selection. Our results provide strong evidence for the importance of ecological gradients in African rainforest speciation and inform conservation strategies that preserve the processes that produce and maintain biodiversity.

[Research status of insect infestation of Chinese medicinal materials during storage].

During the storage process, Chinese medicinal materials are susceptible to insect infestation due to their own nature and external storage factors. Infestation by insects can have varying impacts on the materials. In mild cases, it affects the appearance and reduces consumer purchasing power, while in severe cases, it affects the quality, reduces medicinal value, and introduces impurities such as insect bodies, excrement, and secretions, resulting in significant contamination of the medicinal materials. This study reviewed the rele-vant factors influencing insect infestation in Chinese medicinal materials and the compositional changes that occur after infestation and summarized maintenance measures for preventing insect infestation. Additionally, it provided an overview of detection techniques applicable to identifying insect infestation during the storage of Chinese medicinal materials. During the storage process, insect infestation is the result of the combined effects of biological factors(source, species, and population density of insects), intrinsic factors(moisture, chemical composition, and metabolism), and environmental factors(temperature, relative humidity, and oxygen content). After infestation, there are significant changes in the content of constituents in the medicinal materials. By implementing strict pre-storage inspections, regular maintenance after storage, and appropriate storage and maintenance methods, the occurrence of insect infestation can be reduced, and the preservation rate of Chinese medicinal materials can be improved. The storage and maintenance of Chinese medicinal materials are critical for ensuring their quality. Through scientifically standardized storage and strict adherence to operational management standards, the risk of insect infestation can be minimized, thus guaranteeing the quality of Chinese medicinal materials.

First use of gene therapy to treat growth hormone resistant dwarfism in a mouse model.

The only treatment tested for growth hormone receptor (GHR) defective Laron Syndrome (LS) is injections of recombinant insulin-like-growth factor 1 (rhIGF1). The response is suboptimal and associated with progressive obesity. In this study, we treated 4-5-week-old Laron dwarf mice (GHR-/-) with an adeno-associated virus expressing murine GHR (AAV-GHR) injection at a dose of 4 × 1010 vector genome per mouse. Serum growth hormone (GH) levels decreased, and GH-responsive IGF1, IGF binding protein 3 (IGFBP3) and acid labile subunit (ALS) increased. There was a significant but limited increase in body weight and length, similar to the response to rhIGF1 treatment in LS patients. All the major organs increased in weight except the brain. Our study is the first to use gene therapy to treat GH-receptor deficiency. We propose that gene therapy with AAV-GHR may eventually be useful for the treatment of human LS.

Characterizing Emerging Canine H3 Influenza Viruses.

The continual emergence of novel influenza A strains from non-human hosts requires constant vigilance and the need for ongoing research to identify strains that may pose a human public health risk. Since 1999, canine H3 influenza A viruses (CIVs) have caused many thousands or millions of respiratory infections in dogs in the United States. While no human infections with CIVs have been reported to date, these viruses could pose a zoonotic risk. In these studies, the National Institutes of Allergy and Infectious Diseases (NIAID) Centers of Excellence for Influenza Research and Surveillance (CEIRS) network collaboratively demonstrated that CIVs replicated in some primary human cells and transmitted effectively in mammalian models. While people born after 1970 had little or no pre-existing humoral immunity against CIVs, the viruses were sensitive to existing antivirals and we identified a panel of H3 cross-reactive human monoclonal antibodies (hmAbs) that could have prophylactic and/or therapeutic value. Our data predict these CIVs posed a low risk to humans. Importantly, we showed that the CEIRS network could work together to provide basic research information important for characterizing emerging influenza viruses, although there were valuable lessons learned.

Initial respiratory support modality and outcome in preterm infants with less than 32 weeks of gestation in China: A multicentre retrospective cohort study.

BACKGROUND: For initial respiratory management, continuous positive airway pressure (CPAP) is increasingly used for preterm infants, especially for gestational age less than 32 weeks. However, neonatologists are concerned about the potential risks of CPAP support failure. OBJECTIVES: To examine the association between different initial respiratory support modalities and the outcomes of preterm infants at <32 weeks of gestation across multiple neonatal intensive care units (NICU) in China. METHODS: This study was carried out over a period of 12 months in 2018. Unadjusted relative risks (RR) for demographic and clinical characteristics were calculated for CPAP failure and CPAP success in the total cohort using log-linear model based on generalised estimating equations for clustered observations. RESULTS: Among 1560 preterm infants delivered at <32 weeks, the incidence of CPAP failure was 10.3%. After adjustment for demographic and clinical factors, the relative risk of mortality (RR 7.54, 95% CI 5.56, 10.44), pneumothorax (RR 9.85, 95% CI 2.89, 61.53), pulmonary haemorrhage (RR 7.78, 95% CI 4.51, 14.64) and BPD (RR 3.65, 95% CI 3.65, 4.51) were considerably higher for infants in the CPAP failure group than those in the CPAP-S group. However, the risk of poor outcomes in CPAP failure infants was similar to that of those in the initial mechanical ventilation (MV) group. CONCLUSIONS: Continuous positive airway pressure failure was associated with an increased risk of mortality and major morbidities, including BPD, pulmonary haemorrhage and pneumothorax, and was comparable to the risk associated with initial MV.

Can CD147 work as a therapeutic target for tumors through COVID-19 infection?

In this review, we discussed an interesting case infected with "COVID-19" (Corona Virus Disease 2019). The patients with Hodgkin's lymphoma recovered after infection with COVID-19. It may be that COVID-19 activates the patient's immune system, or it may be a coincidence. COVID-19 spike protein can interact with CD147 and use it as an entry to invade host cells. CD147 is a partner of SLC3A2, which is the chaperone subunit of cystine/glutamate reverse transporter (system XC). The catalytic subunit of system XC is SLC7A11. SLC7A11 mediated cysteine uptake plays a key role in ferroptosis. Through literature review and data analysis, we suggest that CD147, as a new potential COVID-19 infection entry, may also lead to ferroptosis of host cells. Our hypothesis is that spike protein of COVID-19 induced ferroptosis in host cells via CD147/SLC3A2/SLC7A11 complex. This is another explanation for the cancer patient recovered after COVID-19 infection.

[Aflatoxins and fungal community distribution during harvesting and processing of Platycladi Semen].

This study aimed to analyze aflatoxins content and fungal community distribution in the harvesting and processing of Platycladi Semen, and explore the key link that affects aflatoxins contamination. The related Platycladi Semen samples of different maturity periods(cone non-rupture period, early rupture, and complete rupture period) and different processing periods(before drying, during 2-d drying, during 7-d drying, before and after seed scale removal, before and after peeling, 1 d after color sorting, and 7 d after color sorting) were collected for identifying the fungal community composition on sample surface by ITS amplicon sequencing. Then the content of aflatoxins B_1, B_2, G_1 and G_2 was determined by HPLC-MS/MS. The results showed that during the harvesting of Platycladi Semen from cone non-rupture to complete rupture, aflatoxins were only detected in the seed scale and seed coat, with aflatoxin G_2 in the seed scale and aflatoxin B_1 in the seed coat. During the drying, with the prolongation of drying time, aflatoxins B_1 and G_2 were detected simultaneously in the seed scale, aflatoxin B_1 in the seed coat, and low-content aflatoxin B_1 in the seed kernel. During subsequent processing, the aflatoxin content in seed kernel during subsequent processing was slighted increased. As demonstrated by fungal detection, Aspergillus flavus was not present during the harvesting of Platycladi Semen, but present during the drying and processing. Its content in the seed coat during the drying process was relatively higher. In short, Platycladi Semen should be harvested as soon as possible after it becomes fully mature. Drying process is the key link of preventing aflatoxin contamination. It is advised to build a sunlight room or adopt similar settings, standardize the operations in other processes, and keep the surrounding environment clean to minimize aflatoxin contamination.

MicroRNA-506 modulates insulin resistance in human adipocytes by targeting S6K1 and altering the IRS1/PI3K/AKT insulin signaling pathway.

The incidence of obesity has increased rapidly, becoming a worldwide public health issue that involves insulin resistance. A growing number of recent studies have demonstrated that microRNAs play a significant role in controlling the insulin signaling network. For example, miR-506-3p expression has been demonstrated to correlate with insulin sensitivity; however, the underlying mechanism remains unknown. In this study, we found that miR-506-3p enhanced glucose uptake by 2-deoxy-D-glucose uptake assays and regulated the protein expression of key genes involved in the PI3K/AKT insulin signaling pathway including IRS1, PI3K, AKT, and GlUT4. We next predicted ribosomal protein S6 kinase B1 (S6K1) to be a candidate target of miR-506-3p by bioinformatics analysis and confirmed using dual-luciferase assays that miR-506-3p regulated S6K1 expression by binding to its 3'-UTR. Moreover, modulating S6K1 expression counteracted the effects of miR-506-3p on glucose uptake and PI3K/AKT pathway activation. In conclusion, miR-506-3p altered IR in adipocytes by regulating S6K1-mediated PI3K/AKT pathway activation. Taken together, these findings provide novel insights and potential targets for IR therapy.

Postoperative adjuvant transcatheter arterial chemoembolization improves the prognosis of patients with huge hepatocellular carcinoma.

BACKGROUND: Surgical resection of huge hepatocellular carcinoma (HCC, ≥ 10 cm) is potentially curative. More adjuvant treatments are needed to reduce relapses in these patients. We evaluated the influence of postoperative adjuvant transcatheter arterial chemoembolization (PA-TACE) on the prognosis of huge HCC. METHODS: Data from consecutive patients who underwent curative resection for huge HCC in our center were retrospectively collected. Recurrence-free survival (RFS) and overall survival (OS) were compared between patients who did and did not undergo PA-TACE. Propensity score matching (PSM) was used. RESULTS: Among the 255 enrolled patients, 93 underwent PA-TACE. The clinical outcomes were significantly better in the PA-TACE group than those in the non PA-TACE group (5-year RFS rate: 33.5% vs. 18.0%; 5-year OS rate: 47.0% vs. 28.0%, all P < 0.001). After PSM, similar results were obtained (5-year RFS rate: 28.8% vs. 17.6%, P < 0.001; 5-year OS rate: 42.5% vs. 25.0%, P = 0.004). PA-TACE decreased the possibility of early recurrence (< 2 years, crude cohort: P < 0.001, PSM cohort: P < 0.001) but not late recurrence (≥ 2 years, crude cohort: P = 0.692, PSM cohort: P = 0.325). Multivariable Cox regression analysis suggested that PA-TACE was an independent protective factor prolonging early RFS, RFS and OS. CONCLUSIONS: PA-TACE is a safe intervention for huge HCC patients after liver resection and improves outcomes.

[Investigation and research on fungal diversity of Platycladi Semen on Chinese market].

In the process of harvesting, production and processing, storage, and transportation, the traditional Chinese medicine Platycladi Semen is prone to mildew due to its own and environmental factors, which can nourish the production of toxic or pathogenic fungi, and even produce mycotoxins, which affects the safety of clinical medication. The 2020 edition of Chinese Pharmacopoeia limits the highest standard of aflatoxin content in Platycladi Semen. However, there are few studies on the fungal contamination of Platycladi Semen, and it is difficult to prevent and control it in a targeted manner. Therefore, based on the Illumina NovaSeq6000 platform, this article uses ITS sequence amplicon technology to analyze the distribution and diversity of fungi in 27 batches of commercially available Platycladi Semen in the Chinese market. A total of 10 phyla, 35 classes, 93 orders, 193 families, 336 genera, and 372 species of fungi were identified in China. Among them, Aspergillus, Alternaria spp. were dominant, 20 batches of samples were detected for A. flavus, 10 batches of samples were detected for A. nidulans, and all samples were detected for potential pathogenic fungi such as A. fumigatus and A. niger. According to diversity analysis, the diversity of the fungal communities in the samples from Gansu province was high, the samples in Shandong province contain the largest number of fungal species, and the samples in Guangxi province had the lo-west diversity and the least number of species. In most samples, pathogenic fungi such as A. fumigatus, A. niger, A. flavus, A. parasiticus were detected in varying degrees. This study systematically investigated the fungal contamination of Platycladi Semen from the markets in the last link of the its industrial chain, and clarified the distribution of Platycladi Semen fungi, especially toxin-producing fungi, and provided theoretical basis for the targeted prevention and control of fungal contamination in Platycladi Semen.

Precipitation and vegetation shape patterns of genomic and craniometric variation in the central African rodent Praomys misonnei.

Predicting species' capacity to respond to climate change is an essential first step in developing effective conservation strategies. However, conservation prioritization schemes rarely take evolutionary potential into account. Ecotones provide important opportunities for diversifying selection and may thus constitute reservoirs of standing variation, increasing the capacity for future adaptation. Here, we map patterns of environmentally associated genomic and craniometric variation in the central African rodent Praomys misonnei to identify areas with the greatest turnover in genomic composition. We also project patterns of environmentally associated genomic variation under future climate change scenarios to determine where populations may be under the greatest pressure to adapt. While precipitation gradients influence both genomic and craniometric variation, vegetation structure is also an important determinant of craniometric variation. Areas of elevated environmentally associated genomic and craniometric variation overlap with zones of rapid ecological transition underlining their importance as reservoirs of evolutionary potential. We also find that populations in the Sanaga river basin, central Cameroon and coastal Gabon are likely to be under the greatest pressure from climate change. Lastly, we make specific conservation recommendations on how to protect zones of high evolutionary potential and identify areas where populations may be the most susceptible to climate change.

The role and possible mechanism of long noncoding RNA PVT1 in modulating 3T3-L1 preadipocyte proliferation and differentiation.

Obesity is considered as a high-risk susceptibility state for most metabolic disorders and is directly related to preadipocyte differentiation or adipogenesis. Long noncoding RNAs (lncRNAs) are the key factors which have regulatory functions on various critical physiological and biological processes. PVT1 was identified as an oncogenic lncRNA which could promote angiogenesis in gastric cancer. However, the functions and molecular pathways related to PVT1 in adipogenesis had not been clarified yet. In the current study, the purpose was to identify the effects of lncRNA PVT1 on adipogenesis and the relevant molecular processes. Quantitative real-time polymerase chain reaction (RT-qPCR) was used to quantify PVT1 expression. The mechanism for PVT1 to participate in 3T3-L1 adipogenesis was identified by lentivirus-mediated gain- and loss-of-function tests. The potential association of PVT1 with cell viability was checked by CCK-8 assay and EdU staining. The gene expression for cytokines was determined by quantitative PCR (qPCR) and western blotting. PVT1 expression level was strongly upregulated after 3T3-L1 preadipocytes differentiated. In mice, PVT1 was abundantly expressed in adipose tissue, and the obese mice had higher PVT1 expression in adipose tissue than that of nonobese mice. Predominantly, PVT1 was found inside the nuclei. Overexpressed PVT1 could promote 3T3-L1 adipocyte differentiation as proved, which was the cause for the ability to accelerate lipid accumulation, by upregulating the expression of peroxisome proliferator activated receptor gamma, CCAAT/enhancer-binding protein α, and adipocyte protein 2, while knockdown of PVT1 caused opposite effects. The RNA immunoprecipitation demonstrated the binding relationship between PVT1 and STAT3 suggesting the potential role of STAT3 in 3T3-L1 preadipocyte differentiation. Furthermore, PVT1 could promote fatty acid synthesis but inhibit fatty acid oxidation. PVT1 was positively associated with 3T3-L1 preadipocyte differentiation, which highlighted the potential of PVT1 as a therapeutic target for obesity treatment.

Association between admission hypothermia and outcomes in very low birth weight infants in China: a multicentre prospective study.

BACKGROUND: The objective of this prospective, multicentre, observational cohort study was to evaluate the association between admission hypothermia and neonatal outcomes in very low-birth weight (VLBW) infants in multiple neonatal intensive care units (NICUs) in China. METHODS: Since January 1, 2018, a neonatal homogeneous cooperative research platform-Shandong Neonatal Network (SNN) has been established. The platform collects clinical data in a prospective manner on preterm infants with birth weights (BWs) < 1500 g and gestational ages (GAs) < 34 weeks born in 28 NICUs in Shandong Province. These infants were divided into normothermia, mild or moderate/severe hypothermia groups according to the World Health Organization (WHO) classifications of hypothermia. Associations between outcomes and hypothermia were tested in a bivariate analysis, followed by a logistic regression analysis. RESULTS: A total of 1247 VLBW infants were included in this analysis, of which 1100 infants (88.2%) were included in the hypothermia group, 554 infants (44.4%) in the mild hypothermia group and 546 infants (43.8%) in the moderate/severe hypothermia group. Small for gestational age (SGA), caesarean section, a low Apgar score at 5 min and intubation in the delivery room (DR) were related to admission hypothermia (AH). Mortality was the lowest when their admission temperature was 36.5 ~ 37.5 °C, and after adjustment for maternal and infant characteristics, mortality was significantly associated with AH. Compared with infants with normothermia (36.5 ~ 37.5 °C), the adjusted ORs of all deaths increased to 4.148 (95% CI 1.505-11.437) and 1.806 (95% CI 0.651-5.009) for infants with moderate/severe hypothermia and mild hypothermia, respectively. AH was also associated with a high likelihood of respiratory distress syndrome (RDS), intraventricular haemorrhage (IVH), and late-onset neonatal sepsis (LOS). CONCLUSIONS: AH is still very high in VLBW infants in NICUs in China. SGA, caesarean section, a low Apgar score at 5 min and intubation in the DR were associated with increased odds of hypothermia. Moderate/severe hypothermia was associated with mortality and poor outcomes, such as RDS, IVH, LOS.

Application of Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common malignant tumor of the liver, and its morbidity and mortality have been increasing in recent years. The early diagnosis and prompt treatment of small HCC are crucial to improve the prognosis and quality of life of patients. In China, hepatitis B virus infection is the main cause. HCC with a single tumor nodule of ≤ 3 cm in diameter, or HCC with a number of nodules, in which each nodule is ≤ 2 cm in diameter, with a total diameter of ≤ 3 cm, is considered as small HCC. The MRI liver-specific contrast agent can detect small HCC at the early stage. This has important clinical implications for improving the survival rate of patients. MAIN BODY: Gd-EOB-DTPA-enhanced MRI can significantly improve the sensitivity and specificity of the detection of HBV-related small hepatocellular carcinoma, providing an important basis for the clinical selection of appropriate personalized treatment. Gd-EOB-DTPA-enhanced MRI can reflect the degree of HCC differentiation, and the evaluation of HCC on Gd-EOB-DTPA-enhanced MRI would be helpful for the selection of the treatment and prognosis of HCC patients. The present study reviews the progress of the application of Gd-EOB-DTPA in the early diagnosis of small HCC, its clinical treatment, the prediction of the degree of differentiation, and the assessment of recurrence and prognosis of HCC, including the pharmacoeconomics and application limitations of Gd-EOB-DTPA. The value of the application of HCC with the Gd-EOB-DTPA was summarized to provide information for improving the quality of life and prolonging the survival of patients. CONCLUSION: Gd-EOB-DTPA-enhanced MRI has the diagnostic capability for small HCC with a diameter of ≤ 2 cm. This will have a broader application prospect in the early diagnosis of small liver cancer with a diameter of ≤ 1 cm in the future. The relationship between GD-EOB-DTPA-MRI and the degree of HCC differentiation has a large research space, and Gd-EOB-DTPA is expected to become a potential tool for the preoperative prediction and postoperative evaluation of HCC, which would be beneficial for more appropriate treatments for HCC patients.

Lymph node yield, survival benefit, and safety of high and low ligation of the inferior mesenteric artery in colorectal cancer surgery: a systematic review and meta-analysis.

PURPOSE: The aim of this meta-analysis was to compare high inferior mesenteric artery (IMA) ligation (HL) with low IMA ligation (LL) for the treatment of colorectal cancer and to evaluate the lymph node yield, survival benefit, and safety of these surgeries. METHODS: PubMed, Embase, Cochrane Library, Web of Science, and China Biomedical Literature Database (CBM) were systematically searched for relevant articles that compared HL and LL for sigmoid or rectal cancer. We calculated the odds ratio (OR) with 95% confidence intervals (CIs) for dichotomous outcomes and the weighted mean difference (WMD) for continuous outcomes. RESULTS: In total, 30 studies were included in this analysis. There were significantly higher odds of anastomotic leakage and urethral dysfunction in patients treated with HL compared to those treated with LL (OR = 1.29; 95% CI = 1.08 to 1.55; OR = 2.45; 95% CI = 1.39 to 4.33, respectively). There were no significant differences between the groups in terms of the total number of harvested lymph nodes, the number of harvested lymph nodes around root of the IMA, local recurrence rate, and operation time. Further, no statistically significant group differences in 5-year overall survival rates and 5-year disease-free survival rates were detected among all patients nor among subgroups of stage II patients and stage III patients, respectively. CONCLUSIONS: LL can achieve equivalent lymph node yield to HL, and both procedures have similar survival benefits. However, LL is associated with a lower incidence of leakage and urethral dysfunction. Thus, LL is recommended for colorectal cancer surgery.

Efficacy and safety of radiofrequency ablation versus minimally invasive liver surgery for small hepatocellular carcinoma: a systematic review and meta-analysis.

BACKGROUND: The aim of this study was to compare radiofrequency ablation (RFA) with minimally invasive liver surgery (MIS) in the treatment of small hepatocellular carcinoma (SHCC) and to assess short-term and long-term clinical outcomes. METHODS: PubMed, Embase, Cochrane Library, Web of science, and CBM were systematically searched for articles from inception to July 2018, comparing RFA and MIS in SHCC treatment. We evaluated overall survival (OS), disease-free survival (DFS), local recurrence, and complication rates, as well as hospitalization duration and operation times. RESULTS: Six retrospective studies were analyzed, including a total of 597 patients, 313 treated with RFA and 284 treated with MIS. OS rates were significantly higher in patients treated with MIS at 3 years, when compared to RFA (OR 0.55; 95% CI 0.36 to 0.84). The 3-year DFS MIS rates were also superior to RFA (OR 0.63; 95% CI 0.41 to 0.98). In contrast, when compared to MIS, RFA demonstrated a significantly higher rate of local intrahepatic recurrences, (OR 2.24; 95% CI 1.47 to 3.42), and a lower incidence of postoperative complications (OR 0.34; 95% CI 0.22 to 0.53), as well as shorter operation times (OR - 145.31, 95% CI - 200.24 to - 90.38) and hospitalization duration (OR - 4.02,95% CI - 4.94 to - 3.10). CONCLUSIONS: We found that MIS led to higher OS, DFS, and lower local recurrences in SHCC patients. Meanwhile, RFA treatments led to significantly lower complication rates, shorter operation times, and hospitalization duration. Considering long-term outcomes, MIS was found to be superior to RFA. However, RFA may be an alternative treatment for patients presenting a single SHCC nodule (≤ 3 cm), given its minimally invasive nature and its comparable long-term efficacy with MIS. Nevertheless, our findings should be explained with caution due to the low level of evidence obtained.

[Clinical effect and safety of different maintenance doses of caffeine citrate in treatment of apnea in very low birth weight preterm infants: a prospective randomized controlled trial].

OBJECTIVE: To study the clinical effect and safety of different maintenance doses of caffeine citrate in the treatment of apnea in very low birth weight preterm infants. METHODS: A total of 78 very low birth weight preterm infants with primary apnea were enrolled who were admitted from January 2016 to January 2018. They were randomly divided into high-dose caffeine group with 38 children and low-dose caffeine group with 40 children. Both groups received a loading dose of 20 mg/kg caffeine citrate, and 24 hours later, the children in the high-dose caffeine group were given a maintenance dose of 10 mg/kg, and those in the low-dose caffeine group were given a maintenance dose of 5 mg/kg. The two groups were compared in terms of response rate and incidence rate of adverse events. RESULTS: The high-dose caffeine group had a significantly higher response rate than the low-dose caffeine group (71% vs 48%; P<0.05). Compared with the low-dose caffeine group, the high-dose caffeine group had significantly shorter duration of apnea and time of caffeine treatment (P<0.05). There were no significant differences between the two groups in length of hospital stay and incidence rates of tachycardia, feeding intolerance, bronchopulmonary dysplasia, necrotizing enterocolitis, and intracranial hemorrhage (P>0.05). There was no significant difference in the mortality rate between the two groups (P>0.05). CONCLUSIONS: Higher maintenance dose of caffeine citrate has a better clinical effect than lower maintenance dose of caffeine citrate in the treatment of apnea in very low birth weight preterm infants, without increasing the incidence rates of adverse drug reactions and serious complications in preterm infants.

Nuclear factor kappa B regulated monocyte chemoattractant protein-1/chemokine CC motif receptor-2 expressing in spinal cord contributes to the maintenance of cancer-induced bone pain in rats.

BACKGROUND: Chemokine, monocyte chemoattractant protein-1 (MCP-1), is a potential factor to cause cancer-induced bone pain (CIBP). NF-κB signaling is very important in mediating the expression of chemokines and may have a role in CIBP. However, the mechanism is still unclear. This study investigates the role of NF-κB in CIBP by regulating MCP-1/chemokine CC motif receptor-2 (CCR2) signaling pathway. METHODS: A rat CIBP model was established by injecting Walker-256 cells into the tibia medullary cavity. Nine days later, animals were intrathecally administrated with MCP-1 neutralizing antibody, CCR2 antagonist (RS504393), or NF-кB inhibitor (BAY11-7081). Mechanical paw withdrawal threshold was used to assess pain behavior and sciatic functional index, and radiographic images were adopted to evaluate the damage of nerve and bone. The spinal cords were harvested for Western blot and quantitative reverse transcription polymerase chain reaction. The distribution of MCP-1, CCR2, and NF-кB was detected by double immunofluorescent staining. RESULTS: CIBP caused remarkable bone destruction, injury of sciatic and femoral nerve, and persistent (>15 days) mechanical allodynia in rats. Tumor cell inoculation upregulate MCP-1 and NF-кB in activated neurons as well as CCR2 in neurons and microglia of the spinal cord. MCP-1 antibody, RS504393, and BAY11-7081 partially reversed CIBP-induced mechanical allodynia, and CIBP regulated the expression levels of pro-inflammatory cytokines, tumor necrosis factor-α and interferon-γ, and anti-inflammatory cytokine, interleukin 4, and BAY11-7081 lowered CIBP-induced MCP-1 and CCR2 expressions in a dose-dependent manner. CONCLUSION: In conclusion, NF-кB signaling pathway regulates the expressions of MCP-1/CCR2-induced inflammatory factors in the spinal cord of CIBP rats.