Risk factors for anastomotic leak and postoperative morbidity after right hemicolectomy for colon cancer: results from a prospective, multi-centre, snapshot study in China.

BACKGROUND: Right hemicolectomy is the standard treatment for right-sided colon cancer. There is variation in the technical aspects of performing right hemicolectomy as well as in short-term outcomes. It is therefore necessary to explore best clinical practice following right hemicolectomy in expert centres. METHODS: This snapshot study of right hemicolectomy for colon cancer in China was a prospective, multicentre cohort study in which 52 tertiary hospitals participated. Eligible patients with stage I-III right-sided colon cancer who underwent elective right hemicolectomy were consecutively enrolled in all centres over 10 months. The primary endpoint was the incidence of postoperative 30-day anastomotic leak. RESULTS: Of the 1854 patients, 89.9 per cent underwent laparoscopic surgery and 52.3 per cent underwent D3 lymph node dissection. The overall 30-day morbidity and mortality were 11.7 and 0.2 per cent, respectively. The 30-day anastomotic leak rate was 1.4 per cent. In multivariate analysis, ASA grade > II (P < 0.001), intraoperative blood loss > 50 ml (P = 0.044) and D3 lymph node dissection (P = 0.008) were identified as independent risk factors for postoperative morbidity. Extracorporeal side-to-side anastomosis (P = 0.031), intraoperative blood loss > 50 ml (P = 0.004) and neoadjuvant chemotherapy (P = 0.004) were identified as independent risk factors for anastomotic leak. CONCLUSION: In high-volume expert centres in China, laparoscopic resection with D3 lymph node dissection was performed in most patients with right-sided colon cancer, and overall postoperative morbidity and mortality was low. Further studies are needed to explore the optimal technique for right hemicolectomy in order to improve outcomes further.

Effects of two fillers and process conditions on the water treatment efficiency of a continuous packed bed biofilm reactor.

This study evaluated the treatment efficiency of two selected fillers and their combination for improving the water quality of aquaculture wastewater using a packed bed biofilm reactor (PBBR) under various process conditions. The fillers used were nanosheet (NS), activated carbon (AC), and a combination of both. The results indicated that the use of combined fillers and the hydraulic retention time (HRT) of 4 h significantly enhanced water quality in the PBBR. The removal rates of chemical oxygen demand, NO2-─N, total suspended solids（TSS）, and chlorophyll a were 63.55%, 74.25%, 62.75%, and 92.85%, respectively. The microbiota analysis revealed that the presence of NS increased the abundance of microbial phyla associated with nitrogen removal, such as Nitrospirae and Proteobacteria. The difference between the M1 and M2 communities was minimal. Additionally, the microbiota in different PBBR samples displayed similar preferences for carbon sources, and carbohydrates and amino acids were the most commonly utilized carbon sources by microbiota. These results indicated that the combination of NS and AC fillers in a PBBR effectively enhanced the treatment efficiency of aquaculture wastewater when operated at an HRT of 4 h. The findings provide valuable insights into optimizing the design of aquaculture wastewater treatment systems.

Fibrinogen to pre-albumin ratio is an independent prognostic index for patients with pancreatic ductal adenocarcinoma after radical resection.

BACKGROUND: This study aims to elucidate the significance of the preoperative fibrinogen to pre-albumin ratio (FPR) in predicting the prognosis of pancreatic ductal adenocarcinoma (PDAC), a correlation not extensively explored previously. METHODS: A cohort of 563 patients diagnosed with PDAC and subjected to radical surgical resection was examined. We meticulously documented a range of inflammatory markers, clinical-pathological features, and oncological outcomes. The prognostic value of preoperative FPR was assessed using Kaplan-Meier survival analysis and Cox proportional hazards regression modeling. Furthermore, the predictive accuracy of FPR was evaluated through time-dependent receiver operating characteristic (ROC) curves and decision curve analyses (DCA). RESULTS: The determined optimal threshold for FPR was 14.77, which facilitated the stratification of patients into groups with low and high FPR levels. Notably, patients in the high FPR cohort exhibited significantly reduced recurrence-free survival (RFS) and overall survival (OS) rates compared to their low FPR counterparts. Multivariate Cox regression analysis underscored FPR as an independent prognostic indicator for both RFS and OS. In comparison to the neutrophil-to-lymphocyte ratio (NLR), FPR demonstrated superior prognostic accuracy and clinical utility. CONCLUSION: The preoperative fibrinogen to pre-albumin ratio serves as an independent prognostic marker for RFS and OS among PDAC patients undergoing radical resection. Our findings suggest that FPR could be a valuable addition to the current prognostic models, potentially guiding therapeutic decision-making and patient management strategies in PDAC.

Effect of WeChat-Based Medication Guidance on Symptoms and Serological Parameters in Children with Mycoplasma Pneumoniae.

Objective: The aim of this study was to assess the effect of microsoft-based medication guidance on the level of symptoms and serological indicators in children receiving budesonide nebulisation combined with terbutaline for the treatment of Mycoplasma pneumoniae pneumoniae (MPP). Methods: A total of 109 children with MPP treated in The First Affiliated Hospital of Ningbo University of China between October 2022 and April 2023 were divided into the conventional group (n=54, with medication guidance by telephone follow-up) and the WeChat group (n=55, with medication guidance based on the WeChat platform) using a randomized number table. The time to resolution of symptoms, serological index levels, incidence of adverse drug events, medication adherence scores and satisfaction rate of family guidance were compared between the two groups. Results: The disappearance time of symptoms such as wheezing and cough in the WeChat group was shorter than that in the conventional group (P < .05). After treatment, the C-reactive protein (CRP), interleukin-6 (IL-6) and calcitoninogen (PCT) levels and the incidence of adverse drug events were lower in the WeChat group than in the conventional group (P < .05). After treatment, the levels of forceful spirometry (FVC), 1st-second expiratory volume (FEV1), peak expiratory flow rate (PEF), medication compliance score and family guidance satisfaction rate were higher in the WeChat group than in the conventional group (P < .05). Conclusion: WeChat-based medication guidance can optimize the therapeutic effect of MPP, improve children's medication compliance and satisfaction rate of family guidance, and reduce the occurrence of adverse drug events.

Remission of copper-induced liver injury through the PXR/NF-kB signaling pathway: The effects of dietary curcumin supplementation in largemouth bass (Micropterus salmoides).

The pregnane X receptor (PXR)/nuclear factor-kB (NF-kB) signaling pathway plays a critical role in regulating toxin-induced inflammation and apoptosis in mammals. Whether dietary curcumin (CUR) can prevent copper (Cu)-induced liver injury via this signaling pathway remains to be established in aquatic animals. Juvenile largemouth bass (Micropterus salmoides) were exposed to dietary Cu and CUR treatments for 8 weeks. The results showed that chronic Cu exposure induced oxidative stress, causing liver function damage and liver injury. Cu exposure stimulated inflammation by regulating nf-kb and pro-inflammatory genes such as tnfα and il-1ß and promoted apoptotic signals in the liver by modulating bcl2 and casp3 mRNA levels. In addition, Pearson correlation analysis verified that inflammatory and apoptotic responses were important indicators of Cu-induced liver injury. CUR attenuated stress responses by enhancing the antioxidant system. Importantly, CUR significantly stimulated PXR mRNA and protein levels in the Cu + CUR group and suppressed NF-κB activation to inhibit the inflammatory and apoptotic signaling cascade. These results suggest that CUR may be an effective activator of PXR in teleost fishes, exerting cytoprotective effects on Cu-induced liver injury via a PXR-mediated NF-κB repression mechanism. In conclusion, this study is the first to demonstrate that CUR may act as a potent PXR ligand that exerts hepatoprotective effects against Cu-induced liver injury. The findings shed light on the specific regulatory role of the PXR/NF-κB signaling pathway in liver pathogenesis and its potential as a therapeutic target in teleost fishes.

Mechanisms of resistance to trastuzumab in HER2-positive gastric cancer.

Gastric cancer is one of the most prevalent cancers worldwide, and human epidermal growth factor receptor 2 (HER2)-positive cases account for approximately 20% of the total cases. Currently, trastuzumab + chemotherapy is the recommended first-line treatment for patients with HER2-positive advanced gastric cancer, and the combination has exhibited definite efficacy in HER2-targeted therapy. However, the emergence of drug resistance during treatment considerably reduces its effectiveness; thus, it is imperative to investigate the potential mechanisms underlying resistance. In the present review article, we comprehensively introduce multiple mechanisms underlying resistance to trastuzumab in HER2-positive gastric cancer cases, aiming to provide insights for rectifying issues associated with resistance to trastuzumab and devising subsequent treatment strategies.

SLC35B2 Acts in a Dual Role in the Host Sulfation Required for EV71 Infection.

As an important neurotropic enterovirus, enterovirus 71 (EV71) is occasionally associated with severe neurological diseases and high mortality rates in infants and young children. Understanding the interaction between host factors and EV71 will play a vital role in developing antivirals and optimizing vaccines. Here, we performed a genome-wide CRISPR-Cas9 knockout screen and revealed that scavenger receptor class B member 2 (SCARB2), solute carrier family 35 member B2 (SLC35B2), and beta-1,3-glucuronyltransferase 3 (B3GAT3) are essential in facilitating EV71 replication. Subsequently, the exploration of molecular mechanisms suggested that the knockout of SLC35B2 or B3GAT3, not SCARB2, led to a remarkable decrease in the binding of EV71 to cells and internalization into cells. Furthermore, we found that the infection efficiency for EV71 was positively correlated with the level of host cell sulfation, not simply with the amount of heparan sulfate, suggesting that an unidentified sulfated protein(s) must contribute to EV71 infection. In support of this idea, we screened possible sulfated proteins among the proteinous receptors for EV71 and confirmed that SCARB2 could uniquely interact with both tyrosyl protein sulfotransferases in humans. We then performed mass spectrometric analysis of SCARB2, identifying five sites with tyrosine sulfation. The function verification test indicated that there were more than five tyrosine-sulfated sites on SCARB2. Finally, we constructed a model for EV71 entry in which both heparan sulfate and SCARB2 are regulated by SLC35B2 and act cooperatively to support viral binding, internalization, and uncoating. Taken together, this is the first time that we performed the pooled CRISPR-Cas9 genetic screening to investigate the interplay of host cells and EV71. Furthermore, we found that a novel host factor, SLC35B2, played a dual role in regulating the overall sulfation comprising heparan sulfate sulfation and protein tyrosine sulfation, which are critical for EV71 entry. IMPORTANCE As the most important nonpolio neurotropic enterovirus lacking specific treatments, EV71 can transmit to the central nervous system, leading to severe and fatal neurological complications in infants and young children. The identification of new factors that facilitate or inhibit EV71 replication is crucial to uncover the mechanisms of viral infection and pathogenesis. To date, only a few host factors involved in EV71 infection have been characterized. Herein, we conducted a genome-wide CRISPR-Cas9 functional knockout (GeCKO) screen for the first time to study EV71 in HeLa cells. The screening results are presented as a ranked list of candidates, including 518 hits in the positive selection that facilitate EV71 replication and 1,044 hits in the negative selection that may be essential for cell growth and survival or for suppressing EV71 infection. We subsequently concentrated on the top three hits in the positive selection: SCARB2, SLC35B2, and B3GAT3. The knockout of any of these three genes confers strong resistance against EV71 infection. We confirmed that EV71 infection is codependent on two receptors, heparan sulfate and SCARB2. We also identified a host entry factor, SLC35B2, indirectly facilitating EV71 infection through regulation of the host cell sulfation, and determined a novel posttranslational modification, protein tyrosine sulfation existing in SCARB2. This study revealed that EV71 infectivity exhibits a significant positive correlation with the level of cellular sulfation regulated by SLC35B2. Due to the sulfation pathway being required for many distinct viruses, including but not limited to EV71 and respiratory syncytial virus (RSV), which were tested in this study, SLC35B2 represents a target of broad-spectrum antiviral therapy.

High mobility group A3 enhances transcription of the DNA demethylase gene SlDML2 to promote tomato fruit ripening.

DNA methylation plays an important role in regulating tomato (Solanum lycopersicum) fruit ripening. Although SlDML2, a DNA demethylase (DML) gene, is critically involved in tomato fruit ripening, little is known about genes that regulate its expression. Using yeast one-hybrid screening, we identified a High Mobility Group A protein, named SlHMGA3, and demonstrated its binding activity to the AT-rich region of the SlDML2 promoter. We produced slhmga3 tomato mutants using CRISPR/Cas9 and observed that slhmga3 fruit reached the breaker stage much later than fruit from the wild-type. We further demonstrated that at the initiation stage of fruit ripening, the increased expression of SlDML2 and ethylene biosynthetic and signaling genes was significantly delayed in slhmga3 fruit, along with delays in ethylene production and demethylation and activation of ripening-associated transcription factor genes. Our results demonstrate that SlHMGA3 plays a role in enhancing SlDML2 expression, and its effects on tomato fruit ripening are largely through DNA demethylation of ripening-associated transcription factor genes.

Complete genome analysis of Pseudomonas furukawaii ZS1 isolated from grass carp (Ctenopharyngodon idellus) culture water.

Pseudomonas furukawaii ZS1, isolated from grass carp (Ctenopharyngodon idellus) culture water, exhibits efficient aerobic nitrate reduction without nitrite accumulation; however, the molecular pathway underlying this aerobic nitrate reduction remains unclear. In this study, we constructed a complete genome map of P. furukawaii ZS1 and performed a comparative genomic analysis with a reference strain. The results showed that P. furukawaii ZS1 genome was 6 026 050 bp in size and contained 5427 predicted protein-coding sequences. The genome contained all the necessary genes for the dissimilatory nitrate reduction to ammonia pathway but lacked those for the assimilatory nitrate reduction pathway; additionally, genes that convert ammonia to organic nitrogen were also identified. The presence of putative genes associated with the nitrogen and oxidative phosphorylation pathways implied that ZS1 can perform respiration and nitrate reduction simultaneously under aerobic conditions, so that nitrite is rapidly consumed for detoxication by denitrification. The aim of this study is to indicate the great potential of strain ZS1 for future full-scale applications in aquaculture. This work provided insights at the molecular level on the nitrogen metabolic pathways in Pseudomonas species. The understanding of nitrogen metabolic pathways also provides significant molecular information for further Pseudomonas species modification and development.

Quorum-quenching potential of recombinant PvdQ-engineered bacteria for biofilm formation.

Quorum sensing (QS) is a core mechanism for bacteria to regulate biofilm formation, and therefore, QS inhibition or quorum quenching (QQ) is used as an effective and economically feasible strategy against biofilms. In this study, the PvdQ gene encoding AHL acylase was introduced into Escherichia coli (DE3), and a PvdQ-engineered bacterium with highly efficient QQ activity was obtained and used to inhibit biofilm formation. Gene sequencing and western blot analysis showed that the recombinant pET-PvdQ strain was successfully constructed. The color reaction of Agrobacterium tumefaciens A136 indicated that PvdQ engineering bacteria had shown strong AHL signal molecule quenching activity and significantly inhibited the adhesion (motility) of Pseudomonas aeruginosa and biofilm formation of activated sludge bacteria in Membrane Bio-Reactor (MBR; inhibition rate 51-85%, p < 0.05). In addition, qRT-PCR testing revealed that recombinant PvdQ acylase significantly reduced the transcription level of QS biofilm formation-related genes (cdrA, pqsA, and lasR; p < 0.05). In this study, QQ genetically engineered bacteria enhanced by genetic engineering could effectively inhibit the QS signal transduction mechanism and have the potential to control biofilm formation of pathogenic bacteria in the aquaculture environment, providing an environmentally friendly and alternative antibiotic strategy to suppress biofilm contamination.

Can Virtual Reality-Assisted Therapy Offer Additional Benefits to Patients With Vestibular Disorders Compared With Conventional Vestibular Physical Therapy? A Meta-analysis.

OBJECTIVE: To determine whether virtual reality-assisted therapy (VRAT) significantly improves the treatment of peripheral or central vestibular disorders when compared with conventional vestibular physical therapy (CVPT) alone. Indicators of vestibular symptoms are used to determine this. DATA SOURCES: Two reviewers independently searched PubMed, EMBASE, ClinicalTrials.gov, Web of Science, and the Cochrane Collaboration database from January 2010 to January 2022 for studies reporting on VRAT in vestibular disorders. STUDY SELECTION: Randomized controlled trials (RCTs) were included that mainly focused on the following measures: the Dizziness Handicap Inventory (DHI), Simulator Sickness Questionnaire, visual analog scale, and balance measures such as the Activities-specific Balance Confidence Scale (ABC), timed Up and Go test, sensory organization test, and center of pressure. The primary outcome was assessment of symptomatic changes before and after VRAT. DATA EXTRACTION: Two authors independently conducted the literature search and selection. After screening, meta-analysis was performed on the RCTs using RevMan 5.3 software. DATA SYNTHESIS: The results showed that VRAT produced significantly greater improvement than CVPT alone in scores of DHI-Total (standardized mean difference [SMD]: -7.09, 95% confidence interval [CI]: [-12.17, -2.00], P=.006), DHI-Functional (SMD=-3.66, 95% CI: [-6.34, -0.98], P=.007), DHI-Physical (SMD=-3.14, 95% CI: [-5.46, -0.83], P=.008), and DHI-Emotional (SMD=-3.10, 95% CI: [-5.13, -1.08], P=.003). ABC scores did not show improvement (SMD: 0.58, 95% CI: [-3.69, 4.85], P=.79). Subgroup analysis showed that DHI-Total between-group differences were insignificant for central vestibular disorders (SMD=-1.47, 95% CI: [-8.71, -5.78], P=.69), although peripheral disorders showed significant improvements (SMD=-9.58, 95% CI: [-13.92, -5.25], P<.0001). However, the included studies showed high heterogeneity (I2>75%). CONCLUSIONS: VRAT may offer additional benefits for rehabilitation from vestibular diseases, especially peripheral disorders, when compared with CVPT alone. However, because of high heterogeneity and limited data, additional studies with a larger sample size and more sensitive and specific measurements are required to conclusively determine the evidence-based utility of virtual reality.

Fatty infiltration of the cervical multifidus musculature and its clinical correlation to cervical spondylosis.

PURPOSE: Fat infiltration (FI) of the deep neck extensor muscles has been shown to be associated with poor outcomes in cervical injury, mechanical neck pain, and axial symptoms after cervical spine surgery. However, information is scarce on the severity of FI in cervical extensors associated with different clinical syndromes in patients with cervical spondylosis. OBJECTIVE: To investigate the relationship between the severity of FI in the cervical multifidus musculature and its clinical correlates in the syndromes and sagittal alignment of patients with cervical spondylosis. METHODS: This study was conducted as a retrospective study of twenty-eight healthy volunteers (HV) together with sixty-six patients who underwent cervical radiculopathy (CR), degenerative myelopathy (DM), and axial joint pain (AJP) from January 2020 to March 2022. MRI was used to measure the fat cross-sectional area (FCSA), functional muscle cross-sectional area (FMCSA), total muscle cross-sectional area (TMCSA), FI ratio of the cervical multifidus musculature at each cervical level from the C3 to C6 segments and the cervical lordosis angle in the included subjects. RESULTS: The difference in the FCSA and FI ratio in patient groups with cervical spondylosis was significantly greater than that of the HV group (P < 0.05), and the Cobb angle of the DM group, AJP group and HV group was significantly greater than that of the CR group (P < 0.05). The FI ratio comparison showed no significant difference by sex, and the comparison of FCSA, FMCSA, TMCSA and FI ratio showed no significant difference by age range from 35 to 69 in the included subjects. The FCSA and TMCSA in patients with cervical spondylosis were positively related to the Cobb angle (rs= 0.336, P = 0.006, rs =0.319, P = 0.009, respectively), and the FI ratio was inversely correlated with the Cobb angle (rs= -0.285, P = 0.020) and positively correlated with age (rs =0.261, P = 0.034). In the HV group, FMCSA was inversely correlated with age (rs= -0.400, P = 0.035), while the FI ratio had a positive correlation with age (rs= -0.423, P = 0.025). CONCLUSION: Compared with healthy subjects, a more severe degree of FI in the multifidus musculature and sagittal imbalance were found in patients with cervical spondylosis. These two imaging features are considered to be important concomitant phenomena of cervical spondylosis, and the more severe FI is, the worse the sagittal imbalance. However, each syndrome had no obvious difference in FI in the multifidus musculature.

Integrated Nursing and Targeted Functional Training for Cerebral Hemorrhage Recovery.

Objective: This study aimed to investigate the impact of integrating medical nursing with targeted functional training interventions on neurological and limb motor function and self-care ability in patients diagnosed with cerebral hemorrhage. Methods: A retrospective cohort study was conducted, including 100 patients diagnosed with cerebral hemorrhage who received interventions at our hospital between January 2020 and June 2022. The patients were divided into two groups: the research group (50 cases) and the reference group (50 cases), based on different intervention methods. The reference group received targeted functional training intervention, while the research group implemented the integration of medical nursing in addition to the reference group intervention. Differences in the National Institutes of Health Stroke Scale (NIHSS) score, Barthel index, Modified Barthel Index (MBI) score, Glasgow Coma Scale (GCS) score, Edinburgh Speech Scale (ESS) score, Fugl-Meyer score, Ability of Daily Living (ADL) score, and efficacy evaluation were observed and compared between the two groups of patients. Results: After nursing, the Fugl-Meyer score and Barthel index score were significantly higher in both groups compared to before nursing, with the research group showing higher scores than the reference group (P < 0.05). There was no significant difference in limb motor function scores between the two groups before nursing (P > 0.05). After the integrated nursing intervention, the NIHSS and ADL scores of both groups were significantly higher than before nursing, with the research group demonstrating higher scores than the reference group (P < 0.05). Conclusions: Integrating medical nursing with targeted functional training interventions has the potential to significantly improve cognitive function, neurological function, and daily activity engagement in patients with cerebral hemorrhage, thereby enhancing their overall quality of life.

Hif1α/Dhrs3a Pathway Participates in Lipid Droplet Accumulation via Retinol and Ppar-γ in Fish Hepatocytes.

Excessive hepatic lipid accumulation is a common phenomenon in cultured fish; however, its underlying mechanisms are poorly understood. Lipid droplet (LD)-related proteins play vital roles in LD accumulation. Herein, using a zebrafish liver cell line (ZFL), we show that LD accumulation is accompanied by differential expression of seven LD-annotated genes, among which the expression of dehydrogenase/reductase (SDR family) member 3 a/b (dhrs3a/b) increased synchronously. RNAi-mediated knockdown of dhrs3a delayed LD accumulation and downregulated the mRNA expression of peroxisome proliferator-activated receptor gamma (pparg) in cells incubated with fatty acids. Notably, Dhrs3 catalyzed retinene to retinol, the content of which increased in LD-enriched cells. The addition of exogenous retinyl acetate maintained LD accumulation only in cells incubated in a lipid-rich medium. Correspondingly, exogenous retinyl acetate significantly increased pparg mRNA expression levels and altered the lipidome of the cells by increasing the phosphatidylcholine and triacylglycerol contents and decreasing the cardiolipin, phosphatidylinositol, and phosphatidylserine contents. Administration of LW6, an hypoxia-inducible factor 1α (HIF1α) inhibitor, reduced the size and number of LDs in ZFL cells and attenuated hif1αa, hif1αb, dhrs3a, and pparg mRNA expression levels. We propose that the Hif-1α/Dhrs3a pathway participates in LD accumulation in hepatocytes, which induces retinol formation and the Ppar-γ pathway.

[Meta-analysis and trial sequential analysis of Chaihuang Granules in treatment of upper respiratory tract infection in children].

This study aimed to evaluate the efficacy and safety of Chaihuang Granules in the treatment of upper respiratory tract infection in children. The databases such as CNKI, Wanfang, VIP, SinoMed, Cochrane Library, PubMed, EMbase, Web of Science, Chinese Clinical Trial Registry, and ClinicalTrials.gov were searched for randomized controlled trial(RCT) of Chaihuang Granules for the treatment of upper respiratory tract infection in children, and supplemented by manual searching of gray literature. Two investigators independently screened the literature, extracted data, and assessed the methodological quality. Meta-analysis was performed using RevMan 5.4 software, trial sequential analysis was conducted using TSA 0.9.5.10 Beta software, and evidence quality evaluation was carried out using GRADE profiler 3.6.1 software. Eighteen RCTs involving 2 459 patients(1 262 in the treatment group and 1 197 in the control group) were included. Meta-analysis showed that compared with conventional therapy alone, Chaihuang Granules significantly improved the total effective rate(RR=1.18, 95%CI[1.15, 1.22], P<0.000 01), reduced the disappearance time of symptoms/signs(MD=-1.39, 95%CI[-1.66,-1.12], P<0.000 01), improved cytokine levels(MD=-2.40, 95%CI[-3.80,-1.00], P=0.000 8), improved humoral immune levels(MD=0.75, 95%CI[0.60, 0.90], P<0.000 01), and reduced the recurrence rate(MD=-2.11, 95%CI[-2.98,-1.25], P<0.000 01). However, the incidence of adverse reactions was not increased(RR=0.94, 95%CI[0.59, 1.49], P=0.78). Subgroup analysis showed that:(1) both Chaihuang Granules used alone(RR=1.19, 95%CI[1.11, 1.27], P<0.000 01) and in combination with other therapies(RR=1.18, 95%CI[1.14, 1.22], P<0.000 01) effectively improved the total effective rate.(2) In terms of symptoms/signs disappearance time, Chaihuang Granules effectively reduced the duration of fever(MD=-1.18, 95%CI[-1.78,-0.58], P=0.000 1), cough with sputum(MD=-1.82, 95%CI[-2.38,-1.25], P<0.000 01), cough(MD=-1.31, 95%CI[-1.89,-0.74], P<0.000 01), sore throat(MD=-1.57, 95%CI[-2.25,-0.89], P<0.000 01), and lung rales(MD=-1.49, 95%CI[-2.06,-0.92], P<0.000 01).(3) Regarding cytokine levels, Chaihuang Gra-nules effectively improved the levels of interleukin(IL)-2(MD=-0.94, 95%CI[-1.16,-0.72], P<0.000 01), IL-6(MD=-4.71, 95%CI[-6.39,-3.03], P<0.000 01), and tumor necrosis factor-α(TNF-α)(MD=-2.07, 95%CI[-2.43,-1.71], P<0.000 01).(4) In terms of cellular immune levels, Chaihuang Granules effectively improved the levels of CD3~+(MD=4.11, 95%CI[1.53, 6.69], P=0.002), CD4~+(MD=4.21, 95%CI[1.69, 6.73], P=0.001), CD8~+(MD=-2.65, 95%CI[-3.93,-1.37], P<0.000 1), and CD4~+/CD8~+(MD=0.25, 95%CI[0.14, 0.37], P<0.000 1).(5) In terms of humoral immune levels, Chaihuang Granules effectively improved the levels of IgA(MD=0.44, 95%CI[0.23, 0.64], P<0.000 1), IgM(MD=0.31, 95%CI[0.15, 0.46], P=0.000 1), and IgG(MD=2.02, 95%CI[1.60, 2.43], P<0.000 01). Trial sequential analysis showed that the cumulative Z-curve of the total effective rate crossed the boundary value, further confirming its clinical efficacy. The GRADE evidence quality evaluation showed that the evidence quality of the above outcome indicators was low or very low, and the recommendation strength was weak. Compared to conventional therapy alone, Chaihuang Granules can effectively improve the total effective rate of treatment, alle-viate symptoms and signs of upper respiratory tract infection in children, improve inflammatory conditions, enhance immune function, and reduce the recurrence rate. Due to the limited quality of the included studies, high-quality RCT is still needed to provide evidence support for the above conclusions.

[Meta-analysis and trial sequential analysis of Compound Qinlan Oral Liquid in treatment of acute upper respiratory tract infection].

This study aims to evaluate the efficacy and safety of Compound Qinlan Oral Liquid in the treatment of acute upper respiratory tract infection. Computer-based online searching of CNKI, VIP, SinoMed, Wanfang, ChiCTR, ClinicalTrials.gov, Cochrane Library, PubMed, EMbase, and Web of Science was performed to retrieve the randomized controlled trial(RCT) regarding Compound Qinlan Oral Liquid in the treatment of acute upper respiratory tract infection. In addition, manual searching of gray literature was conducted. After two evaluators independently selected articles, extracted data, and evaluated the quality of methodology included in the studies, Meta-analysis was carried out in RevMan 5.4 and trial sequential analysis(TSA) in TSA 0.9.5.10 Beta. GRADE profiler 3.6.1 was employed to evaluate the evidence quality. A total of 21 RCTs were included in this study, involving 2 651 patients(1 330 patients in the observation group and 1 321 patients in the control group). Meta-analysis showed that compared with conventional western medicine alone, Compound Qinlan Oral liquid improved the total response rate(RR=1.15, 95%CI[1.12, 1.19], P<0.000 01) without increasing the incidence of adverse reactions(RR=0.77, 95%CI[0.47, 1.25], P=0.16). The results of subgroup analysis are described as follows:(1) Compared with conventional western medicine alone, Compound Qinlan Oral Liquid improved the total response rate(RR=1.10, 95%CI[1.05, 1.14], P<0.000 01) and shortened the time to symptom relief(SMD=-0.76, 95%CI[-1.02,-0.51], P<0.000 01). There was no significant difference in the incidence of adverse reactions between the two groups(RR=1.16, 95%CI[0.54, 2.47], P=0.71).(2) Compared with conventional western medicine alone, Compound Qinlan Oral Liquid + conventional western medicine improved the total response rate(RR=1.20, 95%CI[1.15, 1.25], P<0.000 01), decreased traditional Chinese medicine(TCM) syndrome scores(MD=-0.58, 95%CI[-0.75,-0.41], P<0.000 01), shortened the time to symptom relief(SMD=-2.44, 95%CI[-3.09,-1.80], P<0.000 01) and physical sign improvement(MD=-2.57, 95%CI[-4.11,-1.04], P=0.001), lowered the serum levels of inflammatory cytokines(SMD=-2.16, 95%CI[-2.61,-1.70], P<0.000 01), improved respiratory function indicators(SMD=1.48, 95%CI[1.00, 1.96], P<0.000 01), and enhanced the humoral immunity(MD=0.94, 95%CI[0.69, 1.18], P<0.000 01). There was no significant difference in the incidence of adverse reactions between the two groups(RR=0.57, 95%CI[0.29, 1.09], P=0.09). TSA showed that the cumulative Z curve of total response rate crossed the traditional threshold and TSA threshold, further confirming the clinical efficacy of Compound Qinlan Oral Liquid. The GRADE graded the evidence of the above outcome indicators as low or extremely low, and yielded weak recommendation. Compared with conventional western medicine alone, Compound Qinlan Oral Liquid can improve the total effective rate and reduce the time to symptom relief. The combination of Compound Qinlan Oral Liquid and conventional western medicine can improve the total response rate, mitigate the symptoms and improve the physical signs, reduce inflammation, and improve respiratory function and immunity of the patients with acute upper respiratory tract infection. In view of the limited number and quality of the included studies, the above conclusions still require high-quality RCT to provide evidence support.

Impact of microecological agents on water environment restoration and microbial community structures of trench system in a Baiyangdian wetland ecosystem.

AIMS: To evaluate the effects of periodic application of effective microorganism (EM) bacteria and calcium peroxide on water environment restoration of a trench wetland ecosystem and its impact on microbiota in water and sediment. METHODS AND RESULTS: The EM bacteria and calcium peroxide were alternately sprayed into the trench water, and changes in the physicochemical indices of water and sediment, and in microbiota structure were subsequently investigated. Alternately spraying of calcium peroxide and EM bacteria improved the water quality, especially in terms of the dissolved oxygen and transparency of water body, and could further reduce the levels of total nitrogen, total phosphorus and ammonia nitrogen. At the same time, the microbiota structure of the water body was significantly changed by spraying with calcium peroxide and EM bacteria, and the relative abundances of Pseudanabaena, Legionellaceae, Planktothrix, Planctomyces, Phenylobacterium, Rhodobacter, Rhodoferax and Aquirestis were significantly increased. However, there was no significant effect on the physicochemical indexes and microbiota composition of the sediment. CONCLUSIONS: The water quality of the Baiyangdian trench could be significantly restored by regular sprinkling of calcium peroxide and EM bacteria. SIGNIFICANCE AND IMPACT OF STUDY: The results provide an effective technical method for the restoration of trench wetland water.

Chlororesistoflavins A and B, Chlorinated Benzopyrene Antibiotics Produced by the Marine-Derived Actinomycete Streptomyces sp. Strain EG32.

As part of a collaborative biomedical investigation of actinomycete bacteria isolated from sediments collected along the northern coast of Egypt (Mediterranean Sea), we explored the antibacterial metabolites from a bacterium identified as a Streptomyces sp., strain EG32. HPLC analysis and antibacterial testing against methicillin-resistant Staphylococcus aureus (MRSA) resulted in the identification of six compounds related to the resistoflavin and resistomycin class. Two of these metabolites were the chlorine-containing analogues chlororesistoflavins A (1) and B (2). The absolute configurations of the lone stereogenic center (C-11b) in these metabolites were assigned by analysis of their ECD spectra. Interestingly, the ECD spectrum of chlororesistoflavin A (1) shows a Cotton effect of the n-π* transition antipodal to that of the parent natural product, a consequence of 1,3-allylic strain induced by the adjacent bulky chlorine atom that distorts the coplanarity of the carbonyl group with the π-system. The chiroptical analysis thus resolves the paradox and uniformly aligns the configuration of all analogues as identical to that reported for natural resistoflavin. Chlororesistoflavins A (1) and B (2) exhibited antibacterial activity against MRSA with a minimum inhibitory concentration of 0.25 and 2.0 µg/mL, respectively.

Diverse roles of assembly factors revealed by structures of late nuclear pre-60S ribosomes.

Ribosome biogenesis is a highly complex process in eukaryotes, involving temporally and spatially regulated ribosomal protein (r-protein) binding and ribosomal RNA remodelling events in the nucleolus, nucleoplasm and cytoplasm. Hundreds of assembly factors, organized into sequential functional groups, facilitate and guide the maturation process into productive assembly branches in and across different cellular compartments. However, the precise mechanisms by which these assembly factors function are largely unknown. Here we use cryo-electron microscopy to characterize the structures of yeast nucleoplasmic pre-60S particles affinity-purified using the epitope-tagged assembly factor Nog2. Our data pinpoint the locations and determine the structures of over 20 assembly factors, which are enriched in two areas: an arc region extending from the central protuberance to the polypeptide tunnel exit, and the domain including the internal transcribed spacer 2 (ITS2) that separates 5.8S and 25S ribosomal RNAs. In particular, two regulatory GTPases, Nog2 and Nog1, act as hub proteins to interact with multiple, distant assembly factors and functional ribosomal RNA elements, manifesting their critical roles in structural remodelling checkpoints and nuclear export. Moreover, our snapshots of compositionally and structurally different pre-60S intermediates provide essential mechanistic details for three major remodelling events before nuclear export: rotation of the 5S ribonucleoprotein, construction of the active centre and ITS2 removal. The rich structural information in our structures provides a framework to dissect molecular roles of diverse assembly factors in eukaryotic ribosome assembly.

The strigolactone receptor SlDWARF14 plays a role in photosynthetic pigment accumulation and photosynthesis in tomato.

KEY MESSAGE: Tomato DWARF14 regulates the development of roots, shoot branches and leaves, and also plays a role in photosynthetic pigment accumulation and photosynthetic capacity. Strigolactones (SLs) are a novel class of plant hormones. DWARF14 (D14) is the only SL receptor identified to date, but it is not functionally analyzed in tomato (Solanum lycopersicum). In the present study, we identified the potential SL receptor in tomato by bioinformatic analysis, which was designated as SlD14. SlD14 was expressed in roots, stems, flowers and developing fruits, with the highest expression level in leaves. sld14 mutant plants produced by the CRISPR/Cas9 system displayed reduced plant height and root biomass, increased shoot branching and altered leaf shape comparing with WT plants. The cytokinin biosynthetic gene ISOPENTENYLTRANSFERASE 3 (SlIPT3), auxin biosynthetic genes FLOOZY (SlFZY) and TRYPTOPHAN AMINOTRANSFERASE RELATED 1 (SlTAR1) and several auxin transport genes SlPINs, which are involved in branch formation, showed higher expression levels in the sld14 plant stem. In addition, sld14 plants exhibited light-green leaves, reduced chlorophyll and carotenoid contents, abnormal chloroplast structure and reduced photosynthetic capacity. Transcriptomic analysis showed that the transcript levels of six chlorophyll biosynthetic genes, three carotenoid biosynthetic genes and numerous chlorophyll a/b-binding protein genes were decreased in sld14 plants. These results suggest that tomato SL receptor gene SlD14 not only regulates the development of roots, shoot branches and leaves, but also plays a role in regulating photosynthetic pigment accumulation and photosynthetic capacity.