Prognostic value of the Naples prognostic score in patients with intrahepatic cholangiocarcinoma after hepatectomy.

BACKGROUND: The Naples Prognostic Score (NPS), integrating inflammatory and nutritional biomarkers, has been reported to be associated with the prognosis of various malignancies, but there is no report on intrahepatic cholangiocarcinoma (ICC). This study aimed to explore the prognostic value of NPS in patients with ICC. METHODS: Patients with ICC after hepatectomy were collected, and divided into three groups. The prognosis factors were determined by Cox regression analysis. Predictive efficacy was evaluated by the time-dependent receiver operating characteristic (ROC) curves. RESULTS: A total of 174 patients were included (Group 1: 33 (19.0%) patients; Group 2: 83 (47.7%) patients; and Group 3: 58 (33.3%) patients). The baseline characteristics showed the higher the NPS, the higher the proportion of patients with cirrhosis and Child-Pugh B, and more advanced tumors. The Kaplan-Meier curves reflect higher NPS were associated with poor survival. Multivariable analysis showed NPS was an independent risk factor of overall survival (NPS group 2 vs. 1: HR = 1.671, 95% CI: 1.022-3.027, p = 0.009; NPS group 3 vs. 1: HR = 2.208, 95% CI: 1.259-4.780, p = 0.007) and recurrence-free survival (NPS group 2 vs. 1: HR = 1.506, 95% CI: 1.184-3.498, p = 0.010; NPS group 3 vs. 1: HR = 2.141, 95% CI: 2.519-4.087, P = 0.001). The time ROC indicated NPS was superior to other models in predicting prognosis. CONCLUSIONS: NPS is a simple and effective tool for predicting the long-term survival of patients with ICC after hepatectomy. Patients with high NPS require close follow-up, and improving NPS may prolong the survival time.

The Reduced Gray Matter Volume and Functional Connectivity of the Cerebellum in Type 2 Diabetes Mellitus with High Insulin Resistance.

INTRODUCTION: Insulin resistance is widely thought to be a critical feature in type 2 diabetes mellitus (T2DM), and there is significant evidence indicating a higher abundance of insulin receptors in the human cerebellum than cerebrum. However, the specific structural or functional changes in the cerebellum related to T2DM remain unclear, and the association between cerebellar alterations, insulin resistance, cognition, and emotion is yet to be determined. METHODS: We investigated neuropsychological performance, and structural and functional changes in specific cerebellar subregions in 43 T2DM patients with high insulin resistance (T2DM-highIR), 72 T2DM patients with low insulin resistance (T2DM-lowIR), and 50 controls. Furthermore, the correlation and stepwise multiple linear regression analysis were performed. RESULTS: Compared to the controls, T2DM exhibited lower cognitive scores and higher depressive/anxious scores. Furthermore, T2DM-highIR patients showed reduced gray matter volume (GMV) in the right cerebellar lobules VIIb, Crus I/II, and T2DM showed reduced GMV in left lobules I-IV compared to controls. Additionally, functional connectivity decrease was observed between the right lobules I-V and orbital part of the superior frontal gyrus in T2DM-highIR compared to both T2DM-lowIR and controls. Notably, there were negative correlations between the GMV of the lobules VIIb, Crus I/II, and updated homeostatic model assessment of insulin resistance, and positive correlation with executive/visuospatial performance in T2DM patients. CONCLUSIONS: These results suggest that the cerebellar lobules VIIb, Crus I/II, represent vulnerable brain regions in the context of insulin resistance. Overall, this study offers new insights into the neuropathophysiological mechanisms of brain impairment in patients with T2DM.

Multicenter propensity score-matched analysis to compare perioperative morbidity after laparoscopic or robotic complex hepatectomy for solitary hepatocellular carcinoma.

BACKGROUND: Postoperative complications are vital factors affecting the prognosis of patients with hepatocellular carcinoma (HCC), especially for complex hepatectomy. The present study aimed to compare perioperative complications between laparoscopic and robotic complex hepatectomy (LCH vs. RCH). METHODS: Patients with solitary HCC after complex hepatectomy were collected from a multicenter database. Propensity score-matched (PSM) analysis was adopted to control confounding bias. Multivariable analysis was performed to determine the prognostic factors. RESULTS: 436 patients were included. After PSM, 43 patients were included in both the LCH and RCH groups. The results showed that compared to LCH, RCH had lower rates of blood loss and transfusion, and lower postoperative 30-day and major morbidity, and post-hepatectomy liver failure (PHLF) (all P < 0.05). Additionally, the length of hospital stay was shorter in the RCH group (P = 0.026). Multivariable analysis showed RCH is an independent protective factor for reducing the 30-day morbidity, major morbidity and PHLF. CONCLUSION: RCH has advantages over LCH in the minimally invasive treatment of complex HCC, as it can reduce the incidence of postoperative morbidity. Therefore, RCH should be considered for patients with HCC who require complex hepatectomy.

Advancing treatment strategies for posterior malleolar malunion: The ankle dislocation method.

BACKGROUND: This study aimed to assess the radiological and clinical outcomes of treatment using the ankle dislocation method for posterior malleolar malunion. METHOD: Thirty-one patients with posterior malleolar malunion who underwent treatment using the ankle dislocation method from May 2015 to October 2021 were retrospectively analyzed. Key outcome measures were radiographic parameters (articular step-off, tibiofibular clear space, fibular length, tibial lateral surface angle, and ankle osteoarthritis), clinical scores (American Orthopaedic Foot and Ankle Society ankle-hindfoot scale and Visual Analogue Scale), and patient satisfaction rate. RESULT: Preoperative computed tomography revealed that Bartoní cek types 3 and 4 accounted for 64.5 % (n = 20) of total cases. Most posterior malleolar malunions were accompanied by depressed intercalary fragments (61.2 % [n = 19]). At the final follow-up, radiographic parameters and clinical scores showed significant improvements postoperatively (P < 0.05), with a high patient satisfaction rate of 77.4 %. Subgroup analysis revealed that the posterior malleolar fracture morphology significantly affected postoperative pain, particularly in more complex fractures (P < 0.001). CONCLUSION: The ankle dislocation method effectively exposes the distal tibial articular surface and facilitates the anatomical restoration of joint congruity under direct vision. This approach substantially improves the clinical and imaging outcomes in patients with complex posterior malleolar malunion. LEVELS OF EVIDENCE: Level IV, retrospective case series.

Wnt/ß-catenin signalling pathway in breast cancer cells and its effect on reversing tumour drug resistance by alkaloids extracted from traditional Chinese medicine.

Breast cancer is a high-risk disease with a high mortality rate among women. Chemotherapy plays an important role in the treatment of breast cancer. However, chemotherapy eventually results in tumours that are resistant to drugs. In recent years, many studies have revealed that the activation of Wnt/ß-catenin signalling is crucial for the emergence and growth of breast tumours as well as the development of drug resistance. Additionally, drugs that target this pathway can reverse drug resistance in breast cancer therapy. Traditional Chinese medicine has the properties of multi-target and tenderness. Therefore, integrating traditional Chinese medicine and modern medicine into chemotherapy provides a new strategy for reversing the drug resistance of breast tumours. This paper mainly reviews the possible mechanism of Wnt/ß-catenin in promoting the process of breast tumour drug resistance, and the progress of alkaloids extracted from traditional Chinese medicine in the targeting of this pathway in order to reverse the drug resistance of breast cancer.

High SNHG expression may predict a poor lung cancer prognosis based on a meta-analysis.

BACKGROUND: An increasing number of small nucleolar RNA host genes (SNHGs) have been revealed to be dysregulated in lung cancer tissues, and abnormal expression of SNHGs is significantly correlated with the prognosis of lung cancer. The purpose of this study was to conduct a meta-analysis to explore the correlation between the expression level of SNHGs and the prognosis of lung cancer. METHODS: A comprehensive search of six related databases was conducted to obtain relevant literature. Relevant information, such as overall survival (OS), progression-free survival (PFS), TNM stage, lymph node metastasis (LNM), and tumor size, was extracted. Hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled to evaluate the relationship between SNHG expression and the survival outcome of lung cancers. Sensitivity and publication bias analyses were performed to explore the stability and reliability of the overall results. RESULTS: Forty publications involving 2205 lung cancer patients were included in this meta-analysis. The pooled HR and 95% CI values indicated a significant positive association between high SNHG expression and poor OS (HR: 1.890, 95% CI: 1.595-2.185), disease-free survival (DFS) (HR: 2.31, 95% CI: 1.57-3.39) and progression-free survival (PFS) (HR: 2.01, 95% CI: 0.66-6.07). The pooled odds ratio (OR) and 95% CI values indicated that increased SNHG expression may be correlated with advanced TNM stage (OR: 1.509, 95% CI: 1.267-1.799), increase risk of distant lymph node metastasis (OR: 1.540, 95% CI: 1.298-1.828), and large tumor size (OR: 1.509, 95% CI: 1.245-1.829). Sensitivity analysis and publication bias results showed that each result had strong reliability and robustness, and there was no significant publication bias or other bias. CONCLUSION: Most SNHGs are upregulated in lung cancer tissues, and high expression of SNHGs predicts poor survival outcomes in lung cancer. SNHGs may be potential prognostic markers and promising therapeutic targets.

Prognostic value of platelet distribution width to lymphocyte ratio in patients with hepatocellular carcinoma following hepatectomy.

BACKGROUND: Platelet distribution width (PDW), but not platelet count, was found to more comprehensively reflect platelet activity. The present study, thus, aimed to evaluate the prognostic value of PDW to lymphocyte ratio (PDWLR) in patients with hepatocellular carcinoma (HCC) following hepatectomy. METHODS: Patients following hepatectomy were analyzed retrospectively. The Kaplan-Meier survival curves and Cox regression model were used to determine the prognostic value of PDWLR. RESULTS: 241 patients were analyzed eventually, and stratified into low and high PDWLR groups (≤ 9.66 vs. > 9.66). Results of comparing the baseline characteristics showed that high PDWLR was significantly associated with cirrhosis, and intraoperative blood loss (all P < 0.05). In multivariate COX regression analysis, PDWLR was demonstrated as an independent risk factor for OS (HR: 1.549, P = 0.041) and RFS (HR: 1.655, P = 0.005). Moreover, PDWLR demonstrated a superior capacity for predicting prognosis compared to other indicators. CONCLUSION: Preoperative PDWLR has a potential value in predicting the prognosis of HCC patients following hepatectomy, which may help in clinical decision-making for individual treatment.

Immune functions of the Dscam extracellular variable region in Chinese mitten crab.

In arthropods, there is only a single copy of Down Syndrome Cell Adhesion Molecule (Dscam) in the genome, but it can exist as numerous splice variants. There are three hypervariable exons in the extracellular domain and one hypervariable exon in the transmembrane domain. In Chinese mitten crab (Eriocheir sinensis), exons 4, 6 and 14 can produce 25, 34 and 18 alternative splice variants, respectively. In this study, through Illumina sequencing, we identified additional splice variants for exons 6 and 14, hence there may be > 50,000 Dscam protein variants. Sequencing of exons 4, 6 and 14 showed that alternative splicing was altered after bacterial stimulation. Therefore, we expressed and purified the extracellular variable region of Dscam (EsDscam-Ig1-Ig7). Exons 4.3, 6.46 and 14.18, three variable exons of the recombinant protein, were randomly selected. The functions of EsDscam-Ig1-Ig7 in immune defences of E. sinensis were subsequently explored. EsDscam-Ig1-Ig7 was discovered to bind to both Gram-positive Staphylococcus aureus and Gram-negative Vibrio parahaemolyticus, but it did not exhibit antibacterial activity. By promoting hemocyte phagocytosis and bacterial removal, EsDscam-Ig1-Ig7 can also shield the host from bacterial infection. The findings highlight the immunological activities of Dscam alternative splicing and reveal the potential for many more Dscam isoforms than were previously predicted in E. sinensis.

Short- and long-term outcomes of laparoscopic versus open liver resection for large hepatocellular carcinoma: a propensity score study.

PURPOSE: Laparoscopic liver resection (LLR) for hepatocellular carcinoma (HCC) remains controversial, especially for tumors larger than 5 cm. We compared the short- and long-term outcomes of laparoscopic and open liver resection (OLR) for large HCC. METHODS: Patients with large HCC after curative hepatectomy were enrolled. To compare the short-term outcomes, propensity score matching (PSM) and inverse probability treatment weighting (IPTW) were performed to reduce the effect of confounding factors, respectively. Subsequently, Cox-regression analyses were conducted to identify the independent risk factors associated with decreased recurrence-free survival (RFS) and poor overall survival (OS). RESULT: There were 265 patients enrolled in the final analysis: 146 who underwent OLR and 119 who underwent LLR. There was no significant difference between the OLR and LLR groups according to PSM and IPTW analysis (all P > 0.05). Multivariable analysis revealed that LLR was not independently associated with poorer OS (HR 1.15, 95% CI 0.80-1.67, P = 0.448) or RFS (HR 1.22, 95% CI 0.88-1.70, P = 0.238). CONCLUSION: There were no significant differences in perioperative complications or long-term prognosis between LLR and OLR for large HCC, which provides evidence for standard laparoscopic surgical practice with adequate surgeon experience and careful patient selection.

The clinical application effects of artificial dermis scaffold and autologous split-thickness skin composite grafts combined with vacuum-assisted closure in refractory wounds.

To investigate the clinical application effects of artificial dermis scaffold and autologous split-thickness skin composite grafts combined with vacuum-assisted closure (V.A.C) in refractory wounds. A retrospective analysis was performed on 70 patients with refractory wounds admitted to the First Affiliated Hospital of Soochow University from June 2019 to December 2021 (44 males and 25 females, with an average age of 49.3 ± 21.4 years). There were 26 patients with chronic ulcers; 3 patients with cancerous wounds; 16 patients with hot crush injuries; and 25 patients with traumatic wounds, including 21 cases of hands, 33 cases of feet, 6 cases of upper limbs, and 10 cases of lower limbs. The patients were divided into an artificial dermis scaffold group (35 patients, including 21 males and 14 females, aged 49.5 ± 21.3 years) and a skin graft group (35 patients, including 23 males and 11 females, aged 49.1 ± 21.5 years). In the artificial dermis scaffold group, after debridement, the artificial dermis scaffold was transplanted for approximately 2 weeks until the wound surface was well vascularized, after which the autologous split-thick skin graft was transplanted. Negative pressure wound therapy was performed throughout the treatment. In the skin grafting group, after debridement, the autologous split-thickness skin graft (aSTSG) was transplanted, and negative pressure wound therapy was performed continuously. The wound healing rate; skin graft survival rate; postoperative wound infection; exudative fluid volume; subcutaneous haematoma; hospitalisation time; hospitalisation cost; Vancouver Scar Scale (VSS) score, used to evaluate the scar of the recipient area at 6 months after the operation; and the sensory disorder grading method, used to evaluate the sensory recovery of the recipient area, were compared between the two groups. All 70 refractory wounds healed. In the artificial dermis scaffold group, the skin graft survival rate was 90% (86%-95%), the hospitalisation time was 38 (29-45) days, the hospitalisation cost was 148 102 (118242-192327) yuan, and the VSS score was 1.9 ± 1.3. There were significant differences in skin graft survival rate (70% [60%-80%]), length of hospital stay (21 [14-28] days), hospitalisation cost (76 201 [39228-135 919] yuan) and VSS score [6.1 ± 3.6] between the skin graft group and the artificial dermis scaffold group (P < .05). The skin graft survival rate, scar hyperplasia and sensory recovery of the recipient area in the artificial dermis scaffold group were better than those in the skin graft group, but the hospitalisation time was relatively longer, and the hospitalisation cost was relatively higher. Wound healing rate, postoperative wound infection, exudate volume, and subcutaneous haematoma of patients in the two groups were similar, and there were no significant differences (P > .05). The artificial dermis scaffold and composite transplantation of autologous aSTSG with V.A.C can promote painless wound healing and improve the skin survival rate, skin colour and lustre, and flexible smooth texture and is conducive to less scar hyperplasia and postoperative functional exercise and recovery. This method provides a reasonable and effective scheme for the treatment of clinical refractory wounds.

[Prescription and medication rules of traditional Chinese medicine for prevention and treatment of diabetic microangiopathy based on literature mining].

This study explored the prescription and medication rules of traditional Chinese medicine(TCM) in the prevention and treatment of diabetic microangiopathy based on literature mining. Relevant literature on TCM against diabetic microangiopathy was searched and prescriptions were collected. Microsoft Excel 2021 software was used to establish a prescription database, and an analysis was conducted on the frequency, properties, flavors, meridian tropism, and efficacy classifications of drugs. Association rule analysis, cluster analysis, and factor analysis were performed using SPSS Modeler 18.0 and SPSS Statistics 26.0 software. The characteristic active components and mechanisms of action of medium-high frequency drugs in the analysis of medication rules were explored through li-terature mining. A total of 1 327 prescriptions were included in this study, involving 411 drugs, with a total frequency reaching 19 154 times. The top five high-frequency drugs were Astragali Radix, Angelicae Sinensis Radix, Poria, Salviae Miltiorrhizae Radix et Rhizoma, and Rehmanniae Radix. The cold and warm drugs were used in combination. Drugs were mainly sweet, followed by bitter and pungent, and acted on the liver meridian. The majority of drugs were effective in tonifying deficiency, clearing heat, activating blood, and resolving stasis. Association rule analysis identified the highly supported drug pair of Astragali Radix-Angelicae Sinensis Radix and the highly confident drug combination of Poria-Alismatis Rhizoma-Corni Fructus. The strongest correlation was found among Astragali Radix, Angelicae Sinensis Radix, Poria, and Salviae Miltiorrhizae Radix et Rhizoma through the complex network analysis. Cluster analysis identified nine categories of drug combinations, while factor analysis identified 16 common factors. The analysis of active components in high-frequency drugs for the treatment of diabetic microangiopathy revealed that these effective components mainly exerted their effects by inhibiting oxidative stress and suppressing inflammatory reactions. The study found that the pathogenesis of diabetic microangiopathy was primarily characterized by deficiency in origin, with a combination of deficiency and excess. Deficiency was manifested as Qi deficiency and blood deficiency, while excess as phlegm-heat and blood stasis. The key organ involved in the pathological changes was the liver. The treatment mainly focused on supplementing Qi and nourishing blood, supplemented by clearing heat, coo-ling blood, activating blood, and dredging collaterals. Commonly used formulas included Danggui Buxue Decoction, Liuwei Dihuang Pills, Erzhi Pills, and Buyang Huanwu Decoction. The mechanisms of action of high-frequency drugs in the treatment of diabetic microangiopathy were often related to the inhibition of oxidative stress and suppression of inflammatory reactions. These findings can provide references for the clinical treatment of diabetic microangiopathy and the development of targeted drugs.

Naples prognostic score: a novel predictor of survival in patients with HER2-positive breast cancer.

Purpose: The predictive significance of the Naples prognostic score (NPS) in HER2-positive breast cancer is unclear. Hence we sought to evaluate the relationship between NPS and the clinical outcomes in HER2-positive breast cancer patients. Methods: This study retrospectively collected and analyzed data from 173 HER2-positive breast cancer patients between August 2004 and February 2014. The Cox regression model was applied in univariate and multivariate statistical analysis. Results: In multivariate analysis, increased NPS score correlated significantly with poor overall survival (p = 0.001) and disease-free survival (p < 0.001). Conclusion: Our findings may point to NPS being a novel and reliable prognostic score system with favorable predictive ability for HER2-positive breast cancer patients.

Breast cancer is one of the most frequent cancers in females and the second leading cause of death among women worldwide. HER2-positive breast cancer has the characteristics of rapid growth, high risk of relapse and cancer migration and spreading. The predictive significance of the Naples prognostic score (NPS) in HER2-positive breast cancer is unknown. We hypothesized that NPS may improve prediction of outcomes in HER2-positive patients. A statistical analysis was conducted. Our results revealed that NPS was an independent predictive factor of overall survival and disease-free survival in patients with HER2-positive breast cancer.

The prevalence of chronic medication therapy problems and pharmacists' interventions among hospitalized perioperative patients: a retrospective observational study.

BACKGROUND: Inadequate preoperative management of chronic medications can place perioperative patients at risk and cause unnecessary delays in surgical procedures. This study aims to investigate the prevalence of chronic medication therapy problems (CMTPs) in hospitalized perioperative patients and assess the relevance of pharmacists' interventions. METHODS: We conducted a retrospective study of pharmacist-led preoperative management of chronic medications in hospitalized adult patients from November 2018 to April 2019. The recorded drug-related problems (DRPs) were retrospectively reviewed and categorized according to the Pharmaceutical Care Network Europe classification V9.1 and were analyzed with a multinomial regression model to identify risk factors. RESULTS: A total of 254 DRPs were recorded, with an average of 0.52 DRPs per patient. Treatment safety (66.9%) was the most common DRP. The most frequent causes of perioperative DRPs and nonperioperative DRPs were drug selection (72.9%) and patient related (50.8%), respectively. Of the 292 documented interventions, 71.6% were fully accepted by the clinicians and patients. The majority (68.9%) of the recorded problems were completely resolved. The number of comorbidities (OR = 3.815) and the number of chronic medications taken (OR = 1.539) were risk factors for the occurrence of DRPs. CONCLUSION: The findings of this study suggest that pharmacist-led chronic medication therapy management in surgical wards may be an effective method to help reduce medication-related surgical risks and optimize the medication therapies used for the long-term treatment of chronic diseases.

[Rapid prediction of flavonoid content in Epimedium sagittatum by infrared spectroscopy].

Epimedii Folium is a well-known Chinese herbal medicine with the effect of nourishing kidney and strengthening Yang. Its main active ingredients are flavonoids. In this study, 60 samples of Epimedium sagittatum were collected for the determination of total flavonoids(TF) including the total amount of epimedin A, epimedin B, epimedin C, and icariin(abbreviated as ABCI) specified in the Chinese Pharmacopoeia as well as rhamnosylicariside Ⅱ and icariside Ⅱ. The calibration parameters of "first derivativemultiva-riate scattering correction in 1 900-650 cm~(-1) band(4-point smoothing)" and "first derivativestandard normal variable correction in 4 000-650 cm~(-1) full band(4-point smoothing)" were confirmed respectively. The quantitative model was established via Fourier infrared spectroscopy plus attenuated total reflection(FTIR-ATR) accessory combined with partial least squares(PLS) method and then used to predict the flavonoid content of 11 validation sets. The average prediction accuracy for ABCI in calibration set and validation set was 98.985% and 96.087%, respectively. The average prediction accuracy for TF in calibration set and validation set was 98.998% and 94.771%, respectively. These results indicated that FTIR-ATR combined with PLS model could be used for rapid prediction of flavonoid content in E. sagittatum, with the prediction accuracy above 94.7%. The establishment of this method provides a new solution for the detection of a large number of E. sagittatum samples.

[Content correlation of eight phenolic acids and flavonoids in different medicinal parts of PA-type Perilla germplasms].

In this study, 10 PA-type Perilla germplasms were selected to detect the content of two phenolic acids, i.e., rosmarinic acid(RA) and caffeic acid(CA), and six flavonoids, including scutellarin-7-O-diglucuronoside(SDG), luteolin-7-O-diglucuronoside(LDG), apigenin-7-O-diglucuronoside(ADG), scutellarin-7-O-glucuroside(SG), luteolin-7-O-glucuroside(LG), and apigenin-7-O-glucuroside(AG) in leaves, stems, and fruits. The total content of phenolic acids and flavonoids in leaves was 3.991-12.028 mg·g~(-1) and 12.309-25.071 mg·g~(-1), respectively, which was much higher than that in stems(0.586-2.015 mg·g~(-1) and 0.879-1.413 mg·g~(-1), respectively) and fruits(0.004-2.222 mg·g~(-1) and 0.651-1.936 mg·g~(-1), respectively). RA was detected in five fruit samples, and RA content between leaves and fruits showed a significant negative correlation in the other five samples. For flavonoids, only LG and LDG could be detected in stems, and SG and SDG were not detected in fruits, while other flavonoids were not detected in some samples. The content of total flavonoids and LG in leaves and fruits was significantly positively correlated, and the content of LG in stems and fruits was significantly positively correlated. In 10 stem samples, seven met the standard that the content of RA in the stem should be not less than 0.1% specified in the Chinese Pharmacopoeia(2020 edition). Only one fruit sample reached the standard of RA content in the fruit not less than 0.25% specified in the Chinese Pharmacopoeia.

Acupuncture for functional gastrointestinal disorders: A systematic review and meta-analysis.

OBJECTIVES: The therapeutic effect of acupuncture treatments (AT) on functional gastrointestinal disorders (FGIDs) is contentious. A meta-analysis was conducted to assess the efficacy and safety of acupuncture for FGIDs. METHODS: The Cochrane Library, EMBASE, PUBMED, Web of Science, Wanfang Database, China National Knowledge Infrastructure, and VIP Database were searched through December 31, 2019 with no language restrictions. Risk ratio (RR) with 95% confidence interval (CI) was calculated to determine the improvement in symptom severity after treatment. RESULTS: A total of 61 randomized controlled trials (RCTs) on FGIDs were included. The pooled results illustrated the following: compared to pharmacotherapy (RR 1.13, 95% CI 1.09-1.17), placebo acupuncture (RR 1.69, 95% CI 1.37-2.08), no specific treatment (RR 1.86, 95% CI 1.31-2.62), and AT as an adjuvant intervention to other active treatments (RR 1.25, 95% CI 1.21-1.30), AT had more favorable improvements in symptom severity; sub-group analysis results classified according to functional dyspepsia, irritable bowel syndrome, and functional constipation also supported this finding; and the incidence of adverse events was lower in AT than in other treatments (RR 0.75, 95% CI 0.56-0.99). CONCLUSIONS: This meta-analysis found that AT was significantly associated with relief of FGIDs symptoms; however, the evidence level was moderate or low. Further data from rigorously designed and well powered RCTs are needed to verify the effectiveness and safety of AT as a FGIDs treatment. PROSPERO PROTOCOL NUMBER: CRD42020169508.

Genome-wide association study identifies genetic susceptibility loci and pathways of radiation-induced acute oral mucositis.

BACKGROUND: Radiation-induced oral mucositis (OM) is one of the most common acute complications for head and neck cancer. Severe OM is associated with radiation treatment breaks, which harms successful tumor management. Radiogenomics studies have indicated that genetic variants are associated with adverse effects of radiotherapy. METHODS: A large-scale genome-wide scan was performed in 1467 nasopharyngeal carcinoma patients, including 753 treated with 2D-CRT from Genetic Architecture of the Radiotherapy Toxicity and Prognosis (GARTP) cohort and 714 treated with IMRT (192 from the GARTP and 522 newly recruited). Subgroup analysis by radiotherapy technique was further performed in the top associations. We also performed physical and regulatory mapping of the risk loci and gene set enrichment analysis of the candidate target genes. RESULTS: We identified 50 associated genomic loci and 64 genes via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping and gene-based analysis, and 36 of these loci were replicated in subgroup analysis. Interestingly, one of the top loci located in TNKS, a gene relevant to radiation toxicity, was associated with increased OM risk with OR = 3.72 of the lead SNP rs117157809 (95% CI 2.10-6.57; P = 6.33 × 10-6). Gene set analyses showed that the 64 candidate target genes were enriched in the biological processes of regulating telomere capping and maintenance and telomerase activity (Top P = 7.73 × 10-7). CONCLUSIONS: These results enhance the biological understanding of radiotherapy toxicity. The association signals enriched in telomere function regulation implicate the potential underlying mechanism and warrant further functional investigation and potential individual radiotherapy applications.

Identification of immune-related biomarkers associated with tumorigenesis and prognosis in cutaneous melanoma patients.

BACKGROUND: Skin cutaneous melanoma (SKCM) is one of the most malignant and aggressive cancers, causing about 72% of deaths in skin carcinoma. Although extensive study has explored the mechanism of recurrence and metastasis, the tumorigenesis of cutaneous melanoma remains unclear. Exploring the tumorigenesis mechanism may help identify prognostic biomarkers that could serve to guide cancer therapy. METHOD: Integrative bioinformatics analyses, including GEO database, TCGA database, DAVID, STRING, Metascape, GEPIA, cBioPortal, TRRUST, TIMER, TISIDB and DGIdb, were performed to unveil the hub genes participating in tumor progression and cancer-associated immunology of SKCM. Furthermore, immunohistochemistry (IHC) staining was performed to validate differential expression levels of hub genes between SKCM tissue and normal tissues from the First Affiliated Hospital of Soochow University cohort. RESULTS: A total of 308 differentially expressed genes (DEGs) and 12 hub genes were found significantly differentially expressed between SKCM and normal skin tissues. Functional annotation indicated that inflammatory response, immune response was closely associated with SKCM tumorigenesis. KEGG pathways in hub genes include IL-10 signaling and chemokine receptors bind chemokine signaling. Five chemokines members (CXCL9, CXCL10, CXCL13, CCL4, CCL5) were associated with better overall survival and pathological stages. IHC results suggested that significantly elevated CXCL9, CXCL10, CXCL13, CCL4 and CCL5 proteins expressed in the SKCM than in the normal tissues. Moreover, our findings suggested that IRF7, RELA, NFKB1, IRF3 and IRF1 are key transcription factors for CCL4, CCL5, CXCL10. In addition, the expressions of CXCL9, CXCL10, CXCL13, CCL4 and CCL5 were positively correlated with infiltration of six immune cells (B cell, CD8+T cells, CD4+T cells, macrophages, neutrophils, dendritic cells) and 28 types of TILs. Among them, high levels of B cells, CD8+T cells, neutrophils and dendritic cells were significantly related to longer SKCM survival time. CONCLUSION: In summary, this study mainly identified five chemokine members (CXCL9, CXCL10, CXCL13, CCL4, CCL5) associated with SKCM tumorigenesis, progression, prognosis and immune infiltrations, which might help us evaluate several immune-related targets for cutaneous melanoma therapy.

Characterization of Nuclear and Mitochondrial Genomes of Two Tobacco Endophytic Fungi Leptosphaerulina chartarum and Curvularia trifolii and Their Contributions to Phylogenetic Implications in the Pleosporales.

The symbiont endophytic fungi in tobacco are highly diverse and difficult to classify. Here, we sequenced the genomes of Curvularia trifolii and Leptosphaerulina chartarum isolated from tobacco plants. Finally, 41.68 Mb and 37.95 Mb nuclear genomes were sequenced for C. trifolii and L. chartarum with the scaffold N50, accounting for 638.94 Kb and 284.12 Kb, respectively. Meanwhile, we obtained 68,926 bp and 59,100 bp for their mitochondrial genomes. To more accurately classify C. trifolii and L. chartarum, we extracted seven nuclear genes and 12 mitochondrial genes from these two genomes and their closely related species. The genes were then used for calculation of evolutionary rates and for phylogenetic analysis. Results showed that it was difficult to achieve consistent results using a single gene due to their different evolutionary rates, while the phylogenetic trees obtained by combining datasets showed stable topologies. It is, therefore, more accurate to construct phylogenetic relationships for endophytic fungi based on multi-gene datasets. This study provides new insights into the distribution and characteristics of endophytic fungi in tobacco.

[Effects of light quality on growth and icariin flavonoid content of Epimedium pseudowushanense under different light intensity].

In this study, the growth index including plant height, compound leaf area, specific leaf area, leaf water content, number of branches, and leaf biomass per plant and the icariin flavonoids such as epimedin A, epimedin B, epimedin C and icariin of Epimedium pseudowushanense were determined on 30 d and 60 d under light intensity(18.2±2.5) µmol·m~(-2)·s~(-1)(L1) and(90.9 ±2.5) µmol·m~(-2)·s~(-1)(L2), and white light as control, red light, blue light and yellow light were used as three light quality treatments, to study the effect of light quality on the growth and flavonoids accumulation of E. pseudowushanense. The E. pseudowushanense was sui-table for growth under L1 light intensity, the blue light treatment significantly reduced the leaf area, but had little effect on the stem height, the red light treatment and the yellow light treatment had no obvious effect on the stem height and leaf area, but the yellow light treatment significantly increased the germination of new branches, and had a sustained promoting effect, and the biomass was significantly higher than the white light treatment at 60 d. The content of icariin flavonoids in red light, blue light and yellow light treatment was higher than that in white light treatment at 30 d and 60 d under L1 light intensity, while yellow light treatment promoted the synthesis of icariin flavonoids to the largest extent, which was 1.8 and 1.9 times of white light treatment(30 d and 60 d).Under L2 light intensity, the effect of strong light on promoting stem germination became the main factor, while the yellow light treatment showed no significant effect on promoting stem germination, and the red light treatment exhibited a significant effect on reducing leaf area. Icariin flavonoids under red light, blue light and yellow light treatment were all lower than that under white light treatment, that is, the effect of white light treatment on the synthesis of icariin flavonoids is better than red light, blue light and yellow light treatment. When the time of strong light treatment was longer, the degradation range of icariin flavonoids in other light treatment appeared, while red light treatment promotes the synthesis of icariin flavonoids. Therefore, the influence of light quality on E. pseudowushanense is quite different under different light intensity, no matter from growth index or flavonoid content index. The results support that the biomass and icariin flavonoid content can be increased by providing appropriate red and yellow light.