Bombinin-BO1 induces hepatocellular carcinoma cell-cycle arrest and apoptosis via the HSP90A-Cdc37-CDK1 axis.

Bombinin-BO1 (BO1), a bombinin peptide derived from the skin secretion of Bombina orientalis, exhibits broad-spectrum antimicrobial activity. To date, the anticancer effect of BO1 remains unclear. This study confirmed cytotoxicity of BO1 on hepatocellular carcinoma cells by inducing S-phase cycle block and apoptosis. In addition, BO1 was found to be localized in cytoplasm through endocytosis. The combined results of pull down, mass spectrometry, and co-immunoprecipitation suggested that BO1 induced misfolding of CDK1 and degradation by competitively binding HSP90A with Cdc37. It was verified that overexpression of HSP90A in BO1-treated cells significantly inhibited degradation of CDK1. In vivo, BO1 inhibited tumor without being toxic to individuals. This study reveals the anti-tumor mechanism of BO1 in inducing cell-cycle arrest and apoptosis by interfering with HSP90A-Cdc37-CDK1 system. This is the first study to analyze the mechanism of BO1 regulation of tumor cells, providing theoretical basis for BO1 treatment of hepatocellular carcinoma.

Assessing causal relationships between gut microbiota and abortion: evidence from two sample Mendelian randomization analysis.

Background: While some studies have suggested a link between gut microbiota (GM) and abortion, the causal relationship remains unclear. Methods: To explore the causal relationship between GM and abortion, including spontaneous abortion (SA) and habitual abortion (HA), we performed a two-sample Mendelian randomization (MR) analysis. We used summary statistics data from MiBioGen and FinnGen for genome-wide association studies (GWAS), with GM data as the exposure variable and abortion data as the outcome variable. Results: In the absence of heterogeneity and horizontal pleiotropy, the inverse-variance weighted (IVW) method identified five genetically predicted GM genera linked to the risk of abortions. Lactococcus was negatively correlated with the risk of SA, whereas the Eubacterium fissicatena group was positively correlated with the risk of SA. Genetic predictions of Coprococcus3 and Odoribacter were linked to a reduced risk of HA, while the Eubacterium ruminantium group was associated with an increased risk of HA. Conclusion: Our study suggests a genetic causal relationship between specific GM and two types of abortions, improving our understanding of the pathological relationship between GM and abortion.

Silencing of tropomodulin 1 inhibits acute myeloid leukemia cell proliferation and tumor growth by elevating karyopherin alpha 2-mediated autophagy.

Evidence shows that tropomodulin 1 (TMOD1) is a powerful diagnostic marker in the progression of several cancer types. However, the regulatory mechanism of TMOD1 in tumor progression is still unclear. Here, we showed that TMOD1 was highly expressed in acute myeloid leukemia (AML) specimens, and TMOD1-silencing inhibited cell proliferation by inducing autophagy in AML THP-1 and MOLM-13 cells. Mechanistically, the C-terminal region of TMOD1 directly bound to KPNA2, and TMOD1-overexpression promoted KPNA2 ubiquitylation and reduced KPNA2 levels. In contrast, TMOD1-silencing increased KPNA2 levels and facilitated the nuclear transfer of KPNA2, then subsequently induced autophagy and inhibited cell proliferation by increasing the nucleocytoplasmic transport of p53 and AMPK activation. KPNA2/p53 inhibitors attenuated autophagy induced by silencing TMOD1 in AML cells. Silencing TMOD1 also inhibited tumor growth by elevating KPNA2-mediated autophagy in nude mice bearing MOLM-13 xenografts. Collectively, our data demonstrated that TMOD1 could be a novel therapeutic target for AML treatment.

Heterogeneous effects of hospital competition on inpatient quality: an analysis of five common diseases in China.

BACKGROUND: Many countries has introduced pro-competition policies in the delivery of healthcare to improve medical quality, including China. With the increasing intensity of competition in China's healthcare market, there are rising concerns among policymakers about the impact of hospital competition on quality. This study investigated heterogeneous effects of hospital competition on inpatient quality. METHODS: We analyzed the inpatient discharge dataset and selected chronic obstructive pulmonary disease (COPD), ischemic stroke, pneumonia, hemorrhagic stroke, and acute myocardial infarction (AMI) as representative diseases. A total of 561,429 patients in Sichuan Province in 2017 and 2019 were included. The outcomes of interest were in-hospital mortality and 30-day unplanned readmissions. The Herfindahl-Hirschman Index was calculated using predicted patient flows to measure hospital competition. To address the spatial correlations of hospitals and the structure of the dataset, the multiple membership multiple classification model was employed for analysis. RESULTS: Amid intensifying competition in the hospital market, our study discerned no marked statistical variance in the risk of inpatient quality across most diseases examined. Amplified competition exhibited a positive correlation with heightened in-hospital mortality for both COPD and pneumonia patients. Elevated competition escalated the risk of 30-day unplanned readmissions for COPD patients, while inversely affecting the risk for AMI patients. CONCLUSIONS: There is the heterogeneous impact of hospital competition on quality across various diseases in China. Policymakers who intend to leverage hospital competition as a tool to enhance healthcare quality must be cognizant of the possible influences of it.

Trade-offs between economic benefits and environmental impacts in non-grain expansion: a case study in the eastern plain of China.

China has experienced a boom expansion of non-grain production in recent years. While the non-grain production can increase the economic benefits of farmers, its expansion has significant impacts on the ecological environment and agricultural sustainability. This study attempted to assess the trade-offs between the economic benefits and environmental costs of non-grain production and to provide reference for future land use management. Focusing on the non-grain expansion in Tongxiang City, eastern China, empirical models and field surveys were used to evaluate its environmental impacts and monetary analysis was used to assess the trade-offs between the economic benefits and environmental costs. The results showed that the area of non-grain production increased by 2464.74 ha from 2005 to 2020, and pond fish farming accounted for the largest proportion. The economic benefits and environmental costs of non-grain production increased continuously during 2005-2020, and the net economic-environmental benefits gradually expanded after 2010. Trade-off analysis indicates that the economic benefits of duck rearing did not compensate for the environmental costs, while the other non-grain productions did. Nevertheless, the potential impact of non-grain conversion on the local environment is still underestimated. Some suggestions are proposed to achieve a win-win situation between cultivated land utilization and ecological protection.

Colitis cystica profunda: A report of two cases.

Colitis cystica profunda (CCP) is a rare benign disease characterized by mucus-filled cysts in the submucosa. Endoscopic, radiological and histological examinations are not highly specific, which can lead to misdiagnosis, resulting in unnecessary radical surgical resection. This report presents two cases of CCP with their clinical and imaging features.

Identification of a Putative CFSH Receptor Inhibiting IAG Expression in Crabs.

The crustacean female sex hormone (CFSH) is a neurohormone peculiar to crustaceans that plays a vital role in sexual differentiation. This includes the preservation and establishment of secondary female sexual traits, as well as the inhibition of insulin-like androgenic gland factor (IAG) expression in the androgenic gland (AG). There have been no reports of CFSH receptors in crustaceans up to this point. In this study, we identified a candidate CFSH receptor from the mud crab Scylla paramamosain (named Sp-SEFIR) via protein interaction experiments and biological function experiments. Results of GST pull-down assays indicated that Sp-SEFIR could combine with Sp-CFSH. Findings of in vitro and in vivo interference investigations exhibited that knockdown of Sp-SEFIR could significantly induce Sp-IAG and Sp-STAT expression in the AG. In brief, Sp-SEFIR is a potential CFSH receptor in S. paramamosain, and Sp-CFSH controls Sp-IAG production through the CFSH-SEFIR-STAT-IAG axis.

Silicone gel sheeting for treating keloid scars.

BACKGROUND: Keloid scarring is one of the most common types of pathological scarring. Keloid scars that fail to heal can affect a person's physical and psychological function by causing pain, pruritus, contractures, and cosmetic disfigurement. Silicone gel sheeting (SGS) is made from medical-grade silicone reinforced with a silicone membrane backing and is one of the most commonly used treatments for keloid scars. However, there is no up-to-date systematic review assessing the effectiveness of SGS for keloid scars. A clear and rigorous review of current evidence is required to guide clinicians, healthcare managers and people with keloid scarring. OBJECTIVES: To assess the effectiveness of silicone gel sheeting for the treatment of keloid scars compared with standard care or other therapies. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was December 2021. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that recruited people with any keloid scars and assessed the effectiveness of SGS. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, risk of bias assessment, data extraction and GRADE assessment of the certainty of evidence. We resolved initial disagreements by discussion, or by consulting a third review author when necessary. MAIN RESULTS: Two studies met the inclusion criteria. Study sample sizes were 16 and 20 participants. The trials were clinically heterogeneous with differences in causes for scarring (e.g. surgery, infected wounds, and trauma), site (e.g. chest and back), and ages of scars. The duration of follow-up was three and four and a half months. The included studies reported three comparisons; SGS compared with no treatment, SGS compared with non-silicone gel sheeting (a dressing similar to SGS but which does not contain silicone), and SGS compared with intralesional injections of triamcinolone acetonide. One trial had a split-body design and one trial had an unclear design (resulting in a mix of paired and clustered data). The included studies reported limited outcome data for the primary review outcome of scar severity measured by health professionals and no data were reported for severity of scar measured by patients or adverse events. For secondary outcomes some data on pain were reported, but health-related quality of life and cost-effectiveness were not reported. Both trials had suboptimal outcome reporting, thus many domains in the risk of bias were assessed as unclear. All evidence was rated as being very low-certainty, mainly due to risk of bias, indirectness, and imprecision.  SGS compared with no treatment Two studies with 33 participants (76 scars) reported the severity of scar assessed by health professionals, and we are uncertain about the effect of SGS on scar severity compared with no treatment (very low-certainty evidence, downgraded once for risk of bias, once for inconsistency, once for indirectness, and once for imprecision). We are uncertain about the effect of SGS on pain compared with no treatment (21 participants with 40 scars; very low-certainty evidence, downgraded once for risk of bias, once for inconsistency, once for indirectness, and once for imprecision). No data were reported for other outcomes including scar severity assessed by patients, adverse events, adherence to treatment, health-related quality of life and cost-effectiveness. SGS compared with non-SGS One study with 16 participants (25 scars) was included in this comparison. We are uncertain about the effect of SGS on scar severity assessed by health professionals compared with non-SGS (very low-certainty evidence, downgraded once for risk of bias, once for indirectness, and once for imprecision). We are also uncertain about the effect of SGS on pain compared with non-SGS (very low-certainty evidence, downgraded once for risk of bias, once for indirectness, and once for imprecision). No data were reported for other outcomes including scar severity assessed by patients, adverse events, adherence to treatment, health-related quality of life and cost-effectiveness. SGS compared with intralesional injections of triamcinolone acetonide One study with 17 participants (51 scars) reported scar severity assessed by health professionals, and we are uncertain about the effect of SGS on scar severity compared with intralesional injections of triamcinolone acetonide (very low-certainty evidence, downgraded once for risk of bias, once for indirectness, and once for imprecision). This study also reported pain assessed by health professionals among 5 participants (15 scars) and we are uncertain about the effect of SGS on pain compared with intralesional injections of triamcinolone acetonide (very low-certainty evidence, downgraded once for risk of bias, once for indirectness, and twice for imprecision). No data were reported for other outcomes including scar severity assessed by patients, adverse events, adherence to treatment, health-related quality of life and cost-effectiveness. AUTHORS' CONCLUSIONS: There is currently a lack of RCT evidence about the clinical effectiveness of SGS in the treatment of keloid scars. From the two studies identified, there is insufficient evidence to demonstrate whether the use of SGS compared with no treatment, non-SGS, or intralesional injections of triamcinolone acetonide makes any difference in the treatment of keloid scars. Evidence from the included studies is of very low certainty, mainly driven by the risk of bias, indirectness, and imprecision due to small sample size. Further well-designed studies that have good reporting methodologies and address important clinical, quality of life and economic outcomes are required to reduce uncertainty around decision-making in the use of SGS to treat keloid scars.

Low copy numbers for mitochondrial DNA moderates the strength of nuclear-cytoplasmic incompatibility in plants.

Plant cells contain only small amounts of mitochondrial DNA (mtDNA), with the genomic information shared among multiple mitochondria. The biological relevance and molecular mechanism underlying this hallmark of plant cells has been unclear. Here, we report that Arabidopsis thaliana plants exhibited significantly reduced growth and mitochondrial dysfunction when the mtDNA copy number was increased to the degree that each mitochondrion possessed DNA. The amounts of mitochondrion-encoded transcripts increased several fold in the presence of elevated mtDNA levels. However, the efficiency of RNA editing decreased with this excess of mitochondrion-encoded transcripts, resulting in impaired assembly of mitochondrial complexes containing mtDNA-encoded subunits, such as respiratory complexes I and IV. These observations indicate the occurrence of nuclear-mitochondrial incompatibility in the cells with increased amounts of mtDNA and provide an initial answer to the fundamental question of why plant cells have much lower mtDNA levels than animal cells. We propose that keeping mtDNA levels low moderates nuclear-mitochondrial incompatibility and that this may be a crucial factor driving plant cells to restrict the copy numbers of mtDNA.

Circ_0002099 is a novel molecular therapeutic target for bladder cancer.

Bladder cancer (BLCA) acts as one of the most common malignant tumors in the urinary system without ideal therapy. We performed the present study to explore the role and mechanism of Circ_0002099 in BLCA progression. RNase R treatment assay and actinomycin D treatment assay were used to confirm the circular structure of Circ_0002099. Nuclear-cytoplasmic fractionation assay and fluorescence in situ hybridization (FISH) were used to indicate the subcellular localization of Circ_0002099. The CCK-8 assay, colony formation assay, wound-healing assay, Transwell assay, and animal experiment were used to reveal the facilitative effect of Circ_0002099 on BLCA both in vitro and in vivo. Furthermore, bioinformatic analysis, western blot analysis, FISH, and dual-luciferase reporter assay were conducted to demonstrate the role of Circ_0002099 in BLCA progression. The results indicated that Circ_0002099 was significantly upregulated in BLCA and could enhance the progression of BLCA in vivo and in vitro. Furthermore, dual-luciferase reporter assay and FISH assay revealed that Circ_0002099 could regulate miR-217-5p/miR-103a-3p/Kirsten RAS (KRAS) axis in BLCA. In addition, rescue experiments confirmed that miR-217-5p/miR-103a-3p could rescue the facilitative effect of Circ_0002099 on BLCA progression. Moreover, FUS (FUSed in sarcoma) was identified to regulate the Circ_0002099-miR-217-5p/miR-103a-3p/KRAS axis in BLCA progression. The present study suggested that FUS-medicated Circ_0002099 could promote the epithelial-mesenchymal transition process in BLCA progression via miR-217-5p/miR-103a-3p/KRAS axis-WNT/ß-catenin axis. It could be a promising prognostic biomarker and therapeutic target for BLCA.

Hernandezine Regulates Proliferation and Autophagy-Induced Apoptosis in Melanoma Cells.

Hernandezine is isolated from an herbal medicine that selectively inhibits multidrug resistance and improves the efficacy of drugs for cancer treatment. To date, no studies on hernandezine in melanoma have been conducted. In this study, hernandezine was found to inhibit proliferation and induce apoptosis in melanoma A375 cells and B16 cells. In hernandezine-treated melanoma cells, G0/G1 cycle arrest occurred accompanied by significantly downregulated levels of phosphorylated JAK2 and STAT3. In addition, the cycle arrest could be enhanced by AG490 (JAK2 inhibitor), suggesting that the JAK2/STAT3 pathway is involved in cell cycle regulation in hernandezine-treated melanoma cells. Hernandezine-treated melanoma cells exhibited autophagy-specific structures, autophagy markers (LC3II/LC3-I), and autophagic flow over time. Moreover, 3-MA (autophagy inhibitor) significantly inhibited apoptosis, indicating that hernandezine promotes apoptosis by inducing autophagy. Combined with differential expression of P-AMPK, P-ACC (downstream targets of adenine monophosphate activated protein kinase, AMPK), and P-p70S6K (downstream targets of mammalian target of rapamycin, mTOR) and significant inhibition of apoptosis by AMPK inhibitor complex C (CC) in hernandezine-treated melanoma cells suggested that hernandezine could induce autophagy via the AMPK-mTOR pathway, thereby inducing apoptosis. This study first analyzed the effect of melanoma cells by hernandezine and provided a theory for hernandezine in the treatment of melanoma.

A noncoding regulatory RNA Gm31932 induces cell cycle arrest and differentiation in melanoma via the miR-344d-3-5p/Prc1 (and Nuf2) axis.

Emerging evidence has shown that long non-coding RNAs (lncRNAs) play an important role in inhibiting tumor cell proliferation and inducing differentiation. In this study, integrative analysis of whole transcriptome sequencing data demonstrated that lncRNA-Gm31932 is significantly decreased in all-trans retinoic acid (ATRA)-induced and sodium 4-phenylbutanoate (PB-4)-induced mouse melanoma B16 cells. Silencing lncRNA-Gm31932 could inhibit B16 cell proliferation, with cell cycle arrest at the G0/G1 phase and obvious differentiation characteristics, e.g., increased cell volume, melanin content and tyrosinase (Tyr) activity. Furthermore, a series of experiments (luciferase reporter assay, RNA pull-down assay, and western blotting) showed that lncRNA-Gm3932 down-regulated Prc1 and Nuf2 by competitively sponging miR-344d-3-5p, which subsequently reduced the expression of cell cycle-related proteins CDK2, CDC2, and Cyclin B1, and increased the expression of P21 and P27. Moreover, silencing lncRNA-Gm31932 could significantly inhibit tumor growth in B16 melanoma-bearing mice. Taken together, these results indicate that as a possible signaling pathway for ATRA and PB-4, lncRNA-Gm31932 can induce cell cycle arrest and differentiation via miR-344d-3-5p/Prc1 (and Nuf2) axis.

Effect of bevacizumab plus paclitaxel and carboplatin regimen on prognostic survival of ovarian cancer patients.

OBJECTIVE: To investigate the efficacy of bevacizumab, paclitaxel and carboplatin in the treatment of ovarian cancer (OC) and the impact on patients' prognosis. METHODS: A total of 90 patients with OC treated at our institution were enrolled in this retrospective analysis. Among them, 30 patients treated with bevacizumab plus paclitaxel and carboplatin regimen were classified as an observation group (OG), and 60 other patients who received paclitaxel and carboplatin were assigned as a control group (CG). The changes of carbohydrate antigen 199 (CA199), carcinoembryonic antigen (CEA) and carcinoembryonic antigen 242 (CA242) were observed before and after treatment in both groups. The clinical efficacy was observed, and the patients were followed up for 3 years to observe their survival and the adverse effects. Independent factors affecting patient's prognosis were evaluated by Cox regression analysis. RESULTS: After treatment, the objective remission rate and disease control rate were markedly higher in the OG than those in the CG (P<0.05). The serum CA199, CEA and CA242 levels of patients in the OG were dramatically lower than those in the CG after chemotherapy (P<0.05). There was no statistically significant difference in the incidence of leukopenia, hemoglobin reduction, neutropenia, gastrointestinal reactions, abnormal renal function and abnormal liver function between the two groups (P>0.05). Cox regression analysis identified that the degree of differentiation, International Federation of Gynecology and Obstetrics stage, CA199 and treatment regimen were independent factors affecting the prognosis of patients (P<0.05). CONCLUSION: Combined treatment of bevacizumab plus paclitaxel and carboplatin improved the treatment outcome and reduced the levels of CA199, CEA and CA242 in OC without increasing the incidence of adverse events.

Silicone gel sheeting for treating hypertrophic scars.

BACKGROUND: Each year, in high-income countries alone, approximately 100 million people develop scars. Excessive scarring can cause pruritus, pain, contractures, and cosmetic disfigurement, and can dramatically affect people's quality of life, both physically and psychologically. Hypertrophic scars are visible and elevated scars that do not spread into surrounding tissues and that often regress spontaneously. Silicone gel sheeting (SGS) is made from medical-grade silicone reinforced with a silicone membrane backing and is one of the most commonly used treatments for hypertrophic scars. OBJECTIVES: To assess the effects of silicone gel sheeting for the treatment of hypertrophic scars in any care setting. SEARCH METHODS: In April 2021 we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE (including In-Process & Other Non-Indexed Citations); Ovid Embase and EBSCO CINAHL Plus. We also searched clinical trials registries for ongoing and unpublished studies, and scanned reference lists of relevant included studies as well as reviews, meta-analyses and health technology reports to identify additional studies. There were no restrictions with respect to language, date of publication or study setting. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that enrolled people with any hypertrophic scars and assessed the use of SGS. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, 'Risk of bias' assessment, data extraction and GRADE assessment of the certainty of evidence. We resolved initial disagreements by discussion, or by consulting a third review author when necessary. MAIN RESULTS: Thirteen studies met the inclusion criteria. Study sample sizes ranged from 10 to 60 participants. The trials were clinically heterogeneous with differences in duration of follow-up, and scar site. We report 10 comparisons, SGS compared with no SGS treatment and SGS compared with the following treatments: pressure garments; silicone gel; topical onion extract; polyurethane; propylene glycol and hydroxyethyl cellulose sheeting; Kenalog injection; flashlamp-pumped pulsed-dye laser; intense pulsed light  and Gecko Nanoplast (a silicone gel bandage). Six trials had a split-site design and three trials had an unclear design (resulting in a mix of paired and clustered data). Included studies reported limited outcome data for the primary review outcomes of severity of scarring measured by health professionals and adverse events (limited data reported by some included studies, but further analyses of these data was not possible) and no data were reported for severity of scarring reported by patients. For secondary outcomes some pain data were reported, but health-related quality of life and cost effectiveness were not reported. Many trials had poorly-reported methodology, meaning the risk of bias was unclear. We rated all evidence as being either of low or very low certainty, often because of imprecision resulting from few participants, low event rates, or both, all in single studies. SGS compared with no SGS Seven studies with 177 participants compared SGS with no SGS for hypertrophic scars. Two studies with 31 participants (32 scars) reported severity of scarring assessed by health professionals, and it is uncertain whether there is a difference in severity of scarring between the two groups (mean difference (MD) -1.83, 95% confidence interval (CI) -3.77 to 0.12; very low-certainty evidence, downgraded once for risk of bias, and twice for serious imprecision). One study with 34 participants suggests SGS may result in a slight reduction in pain level compared with no SGS treatment (MD -1.26, 95% CI -2.26 to -0.26; low-certainty evidence, downgraded once for risk of bias and once for imprecision). SGS compared with pressure garments One study with 54 participants was included in this comparison. The study reported that SGS may reduce pain levels compared with pressure garments (MD -1.90, 95% CI -2.99 to -0.81;  low-certainty evidence, downgraded once for risk of bias and once for imprecision). SGS compared with silicone gel One study with 32 participants was included in this comparison. It is unclear if SGS impacts on severity of scarring assessed by health professionals compared with silicone gel (MD 0.40, 95% CI -0.88 to 1.68; very low-certainty evidence, downgraded once for risk of bias, twice for imprecision). SGS compared with topical onion extract One trial (32 participants) was included in this comparison. SGS may slightly reduce severity of scarring compared with topical onion extract (MD -1.30, 95% CI -2.58 to -0.02; low-certainty evidence, downgraded once for risk of bias, and once for imprecision). SGS compared with polyurethane One study with 60 participants was included in this comparison. It is unclear if SGS impacts on the severity of scarring assessed by health professionals compared with polyurethane (MD 0.50, 95% CI -2.96 to 3.96; very low-certainty evidence, downgraded once for risk of bias, and twice for imprecision). SGS compared with self-adhesive propylene glycol and hydroxyethyl cellulose sheeting One study with 38 participants was included in this comparison. It is uncertain if SGS reduces pain compared with self-adhesive propylene glycol and hydroxyethyl cellulose sheeting (MD -0.12, 95% CI -0.18 to -0.06). This is very low-certainty evidence, downgraded once for risk of bias, once for imprecision and once for indirectness. SGS compared with Gecko Nanoplast One study with 60 participants was included in this comparison. It is unclear if SGS impacts on pain compared with Gecko Nanoplast (MD 0.70, 95% CI  -0.28 to 1.68; very low-certainty evidence, downgraded once for risk of bias and twice for imprecision. There was a lack of reportable data from the other three comparisons of SGS with Kenalog injection, flashlamp-pumped pulsed-dye laser or intense pulsed light. AUTHORS' CONCLUSIONS: There is currently limited rigorous RCT evidence available about the clinical effectiveness of SGS in the treatment of hypertrophic scars. None of the included studies provided evidence on severity of scarring validated by participants, health-related quality of life, or cost effectiveness. Reporting was poor, to the extent that we are not confident that most trials are free from risk of bias. The limitations in current RCT evidence suggest that further trials are required to reduce uncertainty around decision-making in the use of SGS to treat hypertrophic scars.

Hydroxyl safflower yellow B combined with doxorubicin inhibits the proliferation of human breast cancer MCF-7 cells.

Doxorubicin (DOX) is currently the preferred chemotherapeutic agent for breast cancer, and hydroxyl safflower yellow B (HSYB) has a tumor growth-inhibiting activity. The present study aimed to investigate the effects of HSYB combined with DOX on the proliferation of human breast cancer MCF-7 cells and explore the underlying mechanism. MTT and cell colony formation assays revealed that the proliferation rate of MCF-7 cells was signifiscantly decreased after HSYB and DOX treatment. Combined HSYB and DOX treatment significantly decreased the expression levels of BCL-2 in MCF-7 cells, while the expression levels of apoptosis-associated proteins, including cleaved caspase-9, BAX and cleaved caspase-3, were markedly increased. Furthermore, flow cytometry and western blot analysis demonstrated that combined HSYB and DOX treatment stimulated an increase in intracellular reactive oxygen species and promoted the release of cytochrome c, leading to apoptosis. The current data suggested that the combination of HSYB and DOX may have marked antitumor activity.

Opposing functions of ß-arrestin 1 and 2 in Parkinson's disease via microglia inflammation and Nprl3.

Although ß-arrestins (ARRBs) regulate diverse physiological and pathophysiological processes, their functions and regulation in Parkinson's disease (PD) remain poorly defined. In this study, we show that the expression of ß-arrestin 1 (ARRB1) and ß-arrestin 2 (ARRB2) is reciprocally regulated in PD mouse models, particularly in microglia. ARRB1 ablation ameliorates, whereas ARRB2 knockout aggravates, the pathological features of PD, including dopaminergic neuron loss, neuroinflammation and microglia activation in vivo, and microglia-mediated neuron damage in vitro. We also demonstrate that ARRB1 and ARRB2 produce adverse effects on inflammation and activation of the inflammatory STAT1 and NF-κB pathways in primary cultures of microglia and macrophages and that two ARRBs competitively interact with the activated form of p65, a component of the NF-κB pathway. We further find that ARRB1 and ARRB2 differentially regulate the expression of nitrogen permease regulator-like 3 (Nprl3), a functionally poorly characterized protein, as revealed by RNA sequencing, and that in the gain- and loss-of-function studies, Nprl3 mediates the functions of both ARRBs in microglia inflammatory responses. Collectively, these data demonstrate that two closely related ARRBs exert opposite functions in microglia-mediated inflammation and the pathogenesis of PD which are mediated at least in part through Nprl3 and provide novel insights into the understanding of the functional divergence of ARRBs in PD.

Hospital Competition and Unplanned Readmission: Evidence from a Systematic Review.

Competition has been widely introduced among hospitals in the hope of improving health-care quality. However, whether competition leads to higher-quality health care is a topic of considerable debate. We conducted a systematic review to assess the impact of hospital-market competition on unplanned readmission. We searched six electronic databases (PubMed, EmBase, Wiley Online Library, Web of Science, Scopus, and JSTOR) and reference lists of screened articles for relevant studies, and strictly followed methods proposed by the Cochrane Collaboration. Finally, nine observational studies with 2,241,767 patients were included. For the primary outcome, pooled results of three studies showed that it was uncertain whether or not hospital competition reduces readmission (ß=0.02, P=0.06; very low certainty of evidence, as they were all observational studies with high heterogeneity). Inconsistent results were found in the remaining six studies, and they were assessed as very low-certainty evidence, downgraded for either inconsistency or indirectness or both. As for secondary outcomes, seven of the nine studies reported on the impact of competition on the risk of mortality, and two reported on length of stay (LOS). It was uncertain whether competition had an effect on mortality or LOS. The relevant studies were limited and of very low certainty, which means there is currently no reliable evidence showing that hospital competition reduces quality of health care in terms of readmission/mortality/LOS. There is a need for rigorous studies to assess the impact of hospital competition on the quality of health care.

Enhancement versus neutralization by SARS-CoV-2 antibodies from a convalescent donor associates with distinct epitopes on the RBD.

Several potent neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus have been identified. However, antibody-dependent enhancement (ADE) has not been comprehensively studied for SARS-CoV-2, and the relationship between enhancing versus neutralizing activities and antibody epitopes remains unknown. Here, we select a convalescent individual with potent IgG neutralizing activity and characterize his antibody response. Monoclonal antibodies isolated from memory B cells target four groups of five non-overlapping receptor-binding domain (RBD) epitopes. Antibodies to one group of these RBD epitopes mediate ADE of entry in Raji cells via an Fcγ receptor-dependent mechanism. In contrast, antibodies targeting two other distinct epitope groups neutralize SARS-CoV-2 without ADE, while antibodies against the fourth epitope group are poorly neutralizing. One antibody, XG014, potently cross-neutralizes SARS-CoV-2 variants, as well as SARS-CoV-1, with respective IC50 (50% inhibitory concentration) values as low as 5.1 and 23.7 ng/mL, while not exhibiting ADE. Therefore, neutralization and ADE of human SARS-CoV-2 antibodies correlate with non-overlapping RBD epitopes.

Accuracy of Full-Guided and Half-Guided Surgical Templates in Anterior Immediate and Delayed Implantation: A Retrospective Study.

Computer-aided implantology has developed rapidly in recent years, this study aimed to compare the accuracy of guided-surgery between anterior immediate and delayed implantation, and simultaneously assess the effect of full-guided and half-guided templates on accuracy values. Seventy-six implants were inserted in 63 patients using full-guided or half-guided template in the anterior zone. Postoperative cone beam computed tomography (CBCT) was matched with preoperative planning to evaluate the deviation between actual and planned implants. No statistical difference was found in any deviation between immediate and delayed implantation (p > 0.05). In anterior immediate implantation, the global coronal, apical, depth and angular deviations of full-guided templates were all significantly lower than those of half-guided templates (0.66 ± 0.26 vs. 1.10 ± 0.76 mm, 0.96 ± 0.41 vs. 1.43 ± 0.70 mm, 0.46 ± 0.24 mm vs. 0.93 ± 0.79 mm and 1.69° ± 0.94° vs. 2.57° ± 1.57°). While in delayed implantation, full-guided templates only perform better with statistical significance on global apical and depth deviation (1.01 ± 0.42 vs. 1.51 ± 0.55 mm and 0.32 ± 0.26 vs. 0.71 ± 0.47 mm). After excluding the influence of depth deviation, the coronal and apical deviations between the two systems in immediate implantation and the apical deviations in delayed implantation had no statistical difference. Within the limit of this study, the results suggested the accuracy of guided-surgeries for anterior immediate and delayed implantations was comparable, and full-guided template was more accurate for immediate and delayed implantation.

Epidemiology and disease burden of complex wounds for inpatients in China: an observational study from Sichuan province.

OBJECTIVES: To investigate the period prevalence of complex wounds among the overall inpatients, and the impact of complex wounds on inpatient health expense and length of hospital stay (LOS). DESIGN: An observational study. SETTING: 6056 healthcare institutions across Sichuan province in China. PARTICIPANTS: This study included 4 033 763 people admitted to healthcare institutions during 1 September 2018 and 31 December 2018. RESULTS: The point prevalence of complex wounds was 4.07 per 1000 among inpatients in Sichuan. The most common complex wounds were pressure ulcers (1.47 per 1000 among inpatients). Older, male, Han ethnic groups and retired people were most likely to suffer from complex wounds. The median LOS was longer for those with complex wounds as their main condition of treatment compared with all-cause admissions in Sichuan (12 days compared with 7 days; p<0.001). The median cost of care for people with complex wounds was higher than for admission for any cause (¥6500.18 compared with ¥3337.16; p<0.001). People with pressure ulcers had the longest LOS, while people with ulcers related to diabetes incurred the highest costs. CONCLUSIONS: Complex wounds, especially pressure ulcers, are common in Sichuan province and their presence is associated with significantly longer lengths of hospital stay and higher medical costs. Additionally, this study only included admitted inpatients during the sampling time period, hence the prevalence of complex wounds may be underestimated. The high prevalence rate and heavy direct and indirect disease burden of complex wounds indicate that health policies for early detection and prevention of complex wounds in elders are urgently needed.