Sorafenib plus transarterial chemoembolization vs sorafenib alone for patients with advanced hepatocellular carcinoma: A systematic review and meta-analysis.

BACKGROUND: Although the past decade has seen remarkable advances in treatment options for hepatocellular carcinoma (HCC), the dismal overall prognosis still envelops HCC patients. Several comparative trials have been conducted to study whether transarterial chemoembolization (TACE) could improve clinical outcomes in patients receiving sorafenib for advanced HCC; however, the findings have been inconsistent. AIM: To study the potential synergies and safety of sorafenib plus TACE vs sorafenib alone for treating advanced HCC, by performing a systematic review and meta-analysis. METHODS: This study was conducted following the PRISMA statement. A systematic literature search was conducted using the Cochrane Library, Embase, PubMed, and Web of Science databases. Data included in the present work were collected from patients diagnosed with advanced HCC receiving sorafenib plus TACE or sorafenib alone. Data synthesis and meta-analysis were conducted using Review Manager software. RESULTS: The present study included 2780 patients from five comparative clinical trials (1 was randomized control trial and 4 were retrospective studies). It was found that patients receiving sorafenib plus TACE had better prognoses in terms of overall survival (OS), with a combined hazard ratio (HR) of 0.65 [95% confidence interval (95%CI): 0.46-0.93, P = 0.02, n = 2780]. Consistently, progression free survival (PFS) and time to progression (TTP) differed significantly between the sorafenib plus TACE arm and sorafenib arm (PFS: HR = 0.62, 95%CI: 0.40-0.96, P = 0.03, n = 443; TTP: HR = 0.73, 95%CI: 0.64-0.83, P < 0.00001, n = 2451). Disease control rate (DCR) was also significantly increased by combination therapy (risk ratio = 1.36, 95%CI: 1.02-1.81, P = 0.04, n = 641). Regarding safety, the incidence of any adverse event (AE) was increased due to the addition of TACE; however, no significant difference was found in grade ≥ 3 AEs. CONCLUSION: The combination of sorafenib with TACE has superior efficacy to sorafenib monotherapy, as evidenced by prolonged OS, PFS, and TTP, as well as increased DCR. Additional high-quality trials are essential to further validate the clinical benefit of this combination in the treatment of advanced HCC.

Identification of hydrochemical fingerprints, quality and formation dynamics of groundwater in western high Himalayas.

Identifying hydrochemical fingerprints of groundwater is a challenge in areas with complex geological settings. This study takes the Gilgit-Baltistan, a complex geological area in west high Himalayas, Pakistan, as the study area to get insights into the hydrochemcial genesis and quality of groundwater in complex geological mountainous regions. A total of 53 samples were collected across the area to determine the hydrochemical characteristics and formation of groundwater. Results revealed groundwater there is characterized by slightly alkaline and soft fresh feature. Groundwater is dominated by the hydrochemical facies of HCO3·SO4-Ca·Mg type. The factor method yields three components (PCs) of principal component analysis, which together explain 75.71% of the total variances. The positive correlation of EC, TDS, Ca2+, SO42-, K+ in PC1, and NO3-, Cl- in PC2 indicate that a combination of natural and anthropogenic activities influences groundwater hydrochemistry. Water-rock interaction is the main mechanism governing the natural hydrochemistry of groundwater. The negative correlation of Cl-, SO42-, Ca2+, and Na+ with NDVI attributes to inorganic salt uptake by plant roots. Groundwater chemical composition is also affected by the type of land use. Groundwater is characterized as excellent and good water quality based on the entropy-weighted water quality index assessment, and is suitable for drinking purposes except for very few samples, while aqueous fluoride would pose potential health threats to water consumers in western high Himalayas, and infants are most at risk compared to other populations. This study will help to deepen the hydrochemial formation mechanism and exploitation suitability of groundwater resources in the mountainous areas that undergone the combined actions of nature and human activities, and provide insights into the characteristics of water environmental quality in western Himalayas area.

Low-intensity pulsed ultrasound treatment mitigates ventricular arrhythmias via inhibiting microglia-mediated neuroinflammation in heart failure rat model.

BACKGROUND: Sympathetic overactivation plays an important role in heart failure (HF)-induced ventricular arrhythmias (VAs). Microglia-mediated neuroinflammation could contribute to sympathetic overactivation. A previous study demonstrated that low-intensity pulsed ultrasound (LIPUS) could inhibit neuroinflammation. However, whether LIPUS could attenuate HF-induced VAs via inhibiting microglia-mediated neuroinflammation remains largely unknown. METHODS: Forth Sprague-Dawley male rats were averagely randomized into four groups: CTL (control) group, CTL + LIPUS group, HF group and HF + LIPUS. Surgical ligation of the coronary artery was used for induction of HF. In vivo electrophysiological study was performed to check VAs susceptibility. Left stellate ganglion (LSG) neural activity and heart rate variability (HRV) were used to test sympathetic nerve activity. RESULTS: Compared to the HF group, LIPUS treatment significantly ameliorated HF-induced cardiac hypertrophy, fibrosis, and dysfunction. In addition, LIPUS treatment markedly inhibited HF-induced VAs susceptibility and reversed gap junction remodeling. LIPUS treatment obviously inhibited microglial activation and neuroinflammation in PVN, sympathetic hyperactivity in the LSG and proinflammatory cytokines releases in the ventricle. P2X7/NLRP3 signaling pathway may be involved in the anti-arrhythmic effect of LIPUS treatment following HF. CONCLUSIONS: Our data demonstrated that LIPUS treatment protected against HF-induced VAs via alleviating microglia-mediated neuroinflammation, sympathetic overactivation and proinflammatory cytokines releases through inhibiting P2X7/NLRP3 signaling. This study provides novel insight into the therapeutic potential of LIPUS.

Dapansutrile Ameliorates Atrial Inflammation and Vulnerability to Atrial Fibrillation in HFpEF Rats.

BACKGROUND: Numerous studies have demonstrated that NLRP3 inflammasomes are key players in the progression of atrial fibrillation (AF) in heart failure with preserved ejection fraction (HFpEF). This study aimed to analyse the effect of pharmacological inhibition of NLRP3 inflammasomes using dapansutrile (DAPA), an oral NLRP3-specific inhibitor. METHODS: Dahl salt-sensitive rats were fed a high-salt diet (HSD, 8% NaCl) to induce HFpEF. Either DAPA (200 mg/kg/day) or saline was administered daily via gavage for 4 weeks. Electrophysiological studies were performed to assess the AF inducibility. Confocal fluorescence microscopy and western blot analysis were used to study calcium handling. RESULTS: The DAPA-treated HFpEF rats were less prone to AF induction by programmed electrical stimulation. Atrial fibrosis and inflammation were attenuated in DAPA-treated HFpEF hearts. Dapansutrile treatment showed an increase in the Ca2+ transient sarcoplasmic reticulum-Ca2+ load, and protein expression of SERCA2; NCX1 and phosphorylation of PLB at Thr17 were decreased following DAPA treatment. The increased frequency of spontaneous Ca2+ spark in the HFpEF rats was related to the hyperphosphorylation of RyR2 at Ser2814, which was blunted in DAPA treatment. Dapansutrile treatment also decreased the phosphorylation of CaMKII expression in the HFpEF rats. Mechanistically, DAPA exerts an anti-arrhythmic effect, mainly by inhibiting activation of the NLRP3 inflammasome. CONCLUSION: These data provide evidence that the beneficial cardiac effects of DAPA are associated with reduced atrial inflammation and improved CaMKII-dependent Ca2+-handling abnormalities via blunting activation of the NLRP3 inflammasome, and DAPA may be beneficial in a rat model of HFpEF-induced AF.

A radiomics model based on T2WI and clinical indexes for prediction of lateral lymph node metastasis in rectal cancer.

OBJECTIVE: The aim of this study was to explore the clinical value of a radiomics prediction model based on T2-weighted imaging (T2WI) and clinical indexes in predicting lateral lymph node (LLN) metastasis in rectal cancer patients. METHODS: This was a retrospective analysis of 106 rectal cancer patients who had undergone LLN dissection. The clinical risk factors for LLN metastasis were selected by multivariable logistic regression analysis of the clinical indicators of the patients. The LLN radiomics features were extracted from the pelvic T2WI of the patients. The least absolute shrinkage and selection operator algorithm and backward stepwise regression method were adopted for feature selection. Three LLN metastasis prediction models were established through logistic regression analysis based on the clinical risk factors and radiomics features. Model performance was assessed in terms of discriminability and decision curve analysis in the training, verification and test sets. RESULTS: The model based on the combined T2WI radiomics features and clinical risk factors demonstrated the highest accuracy, surpassing the models based solely on either T2WI radiomics features or clinical risk factors. Specifically, the model achieved an AUC value of 0.836 in the test set. Decision curve analysis revealed that this model had the greatest clinical utility for the vast majority of the threshold probability range from 0.4 to 1.0. CONCLUSION: Combining T2WI radiomics features with clinical risk factors holds promise for the noninvasive assessment of the biological characteristics of the LLNs in rectal cancer, potentially aiding in therapeutic decision-making and optimizing patient outcomes.

Prediction of ROS1 and TRKA/B/C occupancy in plasma and cerebrospinal fluid for entrectinib alone and in DDIs using physiologically based pharmacokinetic (PBPK) modeling approach.

PURPOSE: Entrectinib (ENT) is a potent c-ros oncogene 1(ROS1) and neurotrophic tyrosine receptor kinase (NTRKA/B/C) inhibitor. To determine the optimum dosage of ENT using ROS1 and NTRKA/B/C occupancy in plasma and cerebrospinal fluid (CSF) in drug-drug interactions (DDIs), physiologically-based pharmacokinetic (PBPK) models for healthy subjects and cancer population were developed for ENT and M5 (active metabolite). METHODS: The PBPK models were built using the modeling parameters of ENT and M5 that were mainly derived from the published paper on the ENT PBPK model, and then validated by the observed pharmacokinetics (PK) in plasma and CSF from healthy subjects and patients. RESULTS: The PBPK model showed that AUC, Cmax, and Ctrough ratios between predictions and observations are within the range of 0.5-2.0, except that the M5 AUC ratio is slightly above 2.0 (2.34). Based on the efficacy (> 75% occupancy for ROS1 and NTRKA/B/C) and safety (AUC < 160 µM·h and Cmax < 8.9 µM), the appropriate dosing regimens were identified. The appropriate dosage is 600 mg once daily (OD) when administered alone, reduced to 200 mg and 400 mg OD with itraconazole and fluconazole, respectively. ENT is not recommended for co-administration with rifampicin or efavirenz, but is permitted with fluvoxamine or dexamethasone. CONCLUSION: The PBPK models can serve as a powerful approach to predict ENT concentration as well as ROS1 and NTRKA/B/C occupancy in plasma and CSF.

Case report of radiotherapy combined with anlotinib and immunotherapy for a patient with esophageal cancer and esophageal fistula.

BACKGROUND: Esophageal cancer (EC) is a frequent gastrointestinal malignancy. The most common types of EC pathology worldwide are esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). Although surgical resection is still the main treatment modality for EC, most patients are already lost to surgery at the time of presentation due to the late stage. In recent years, the development of radiation therapy (RT) combined with targeted therapy (TT) and immunization therapy (IT) has brought more options for the treatment of EC. During radiation therapy, the radiation therapy area is very close to the trachea and esophagus, so radiation therapy may cause damage to the tissues of the trachea and esophagus, which is also known as a tracheoesophageal fistula (TF). We present the case of an EC patient who developed TF during radiation therapy and gradually improved after a combination of anlotinib and immunotherapy. METHODS: The patient was diagnosed with poorly differentiated ESCC by pathological biopsy and treated with "lobaplatin + Tegafur Gimeracil Oteracil Porassium Capsule" for 5 cycles. RESULTS: CT scan of the chest showed progression after treatment. During RT, the patient developed radiotherapy-related adverse effects, which were relieved by symptomatic support therapy. At the end of RT, the patient developed TF, but we chose to let the patient continue his radiation treatment plan with the anti-angiogenic drug "anlotinib." CONCLUSION: After radiation therapy, the patient continued to be treated with anlotinib and immunotherapy with camrelizumab, and the patient's lesion improved.

An Analysis of the Gene Expression Associated with Lymph Node Metastasis in Colorectal Cancer.

Objective: This study aimed to explore the genes regulating lymph node metastasis in colorectal cancer (CRC) and to clarify their relationship with tumor immune cell infiltration and patient prognoses. Methods: The data sets of CRC patients were collected through the Cancer Gene Atlas database; the differentially expressed genes (DEGs) associated with CRC lymph node metastasis were screened; a protein-protein interaction (PPI) network was constructed; the top 20 hub genes were selected; the Gene Ontology functions and the Kyoto Encyclopedia of Genes and Genomes pathways were enriched and analyzed. The Least Absolute Shrinkage and Selection Operator (LASSO) regression method was employed to further screen the characteristic genes associated with CRC lymph node metastasis in 20 hub genes, exploring the correlation between the characteristic genes and immune cell infiltration, conducting a univariate COX analysis on the characteristic genes, obtaining survival-related genes, constructing a risk score formula, conducting a Kaplan-Meier analysis based on the risk score formula, and performing a multivariate COX regression analysis on the clinical factors and risk scores. Results: A total of 62 DEGs associated with CRC lymph node metastasis were obtained. Among the 20 hub genes identified via PPI, only calcium-activated chloride channel regulator 1 (CLCA1) expression was down-regulated in lymph node metastasis, and the rest were up-regulated. A total of nine characteristic genes associated with CRC lymph node metastasis (KIF1A, TMEM59L, CLCA1, COL9A3, GDF5, TUBB2B, STMN2, FOXN1, and SCN5A) were screened using the LASSO regression method. The nine characteristic genes were significantly related to different kinds of immune cell infiltration, from which three survival-related genes (TMEM59L, CLCA1, and TUBB2B) were screened. A multi-factor COX regression showed that the risk scores obtained from TMEM59L, CLCA1, and TUBB2B were independent prognostic factors. Immunohistochemical validation was performed in tissue samples from patients with rectal and colon cancer. Conclusion: TMEM59L, CLCA1, and TUBB2B were independent prognostic factors associated with lymphatic metastasis of CRC.

Influence laws of air gap structure manipulation of covalent organic frameworks on dielectric properties and exciton effects for photopolymerization.

Boosting the dissociation of excitons is essential to enhance the photocatalytic efficiency. However, the relationship between the structure of the catalyst and the exciton effect on the photocatalytic activity is still unclear as the main problem. Here, it is proposed that as a descriptive factor, an experimentally measurable dielectric constant (εr) is available to quantitatively describe its relationship with exciton binding energy (Eb) and photocatalytic activity. With tuning the linker of covalent organic frameworks (COFs), the "air gap" structure is oriented to shrink, leading to an increased εr of COFs and a lower Eb to facilitate exciton dissociation. Meanwhile, taking "water-/oxygen-fueled" photo-induced electron transfer reversible addition-fragmentation chain transfer (PET-RAFT) polymerization as a demonstration platform, it can be seen that COFs with a small "air gap" structure have relatively superior photocatalytic activity. This provides important implications for the evolution of efficient photocatalysts.

Proteoglycan Extracted from Ganoderma lucidum Ameliorated Diabetes-Induced Muscle Atrophy via the AMPK/SIRT1 Pathway In Vivo and In Vitro.

Muscle atrophy often occurs in type 2 diabetes (T2D) and leads to an increase in physical disability and insulin resistance. However, there are very few studies that have investigated potential natural products used for this condition. In this study, we demonstrated that FYGL (Fudan-Yueyang-G. lucidum), a proteoglycan extracted from Ganoderma lucidum, ameliorated muscle atrophy in rat and mouse models of diabetes. Histopathological analysis of muscle revealed that oral administration of FYGL significantly prevented reduction of the cross-sectional area of muscle fibers and overexpression of muscle atrophic factors in diabetic rats and mice. Muscle RNA-seq analysis in vivo indicated that FYGL regulated genes related to myogenesis, muscle atrophy, and oxidative phosphorylation. Also, FYGL activated AMPK in vivo. Furthermore, the underlying molecular mechanisms were studied in palmitate-induced C2C12 muscle cells using immunofluorescence staining and Western blotting, which revealed that FYGL inhibited muscle atrophy by stimulating ATP production and activating the AMPK/SIRT1 pathway, thus promoting oxidative metabolism. This result rationalized the in vivo findings. These results suggest FYGL as a promising functional food ingredient for the prevention of T2D-induced muscle atrophy.

Balancing adipocyte production and lipid metabolism to treat obesity-induced diabetes with a novel proteoglycan from Ganoderma lucidum.

Obesity is often accompanied by metabolic disorder and insulin resistance, resulting in type 2 diabetes. Based on previous findings, FYGL, a natural hyperbranched proteoglycan extracted from the G. lucidum fruiting body, can decrease blood glucose and reduce body weight in diabetic mice. In this article, the underlying mechanism of FYGL in ameliorating obesity-induced diabetes was further investigated both in vivo and in vitro. FYGL upregulated expression of metabolic genes related to fatty acid biosynthesis, fatty acid ß-oxidation and thermogenesis; downregulated the expression of insulin resistance-related genes; and significantly increased the number of beige adipocytes in db/db mice. In addition, FYGL inhibited preadipocyte differentiation of 3T3-L1 cells by increasing the expression of FABP-4. FYGL not only promoted fatty acid synthesis but also more significantly promoted triglyceride degradation and metabolism by activating the AMPK signalling pathway, therefore preventing fat accumulation, balancing adipocyte production and lipid metabolism, and regulating metabolic disorders and unhealthy obesity. FYGL could be used as a promising pharmacological agent for the treatment of metabolic disorder-related obesity.

Dynamic human retinal pigment epithelium (RPE) and choroid architecture based on single-cell transcriptomic landscape analysis.

The retinal pigment epithelium (RPE) and choroid are located behind the human retina and have multiple functions in the human visual system. Knowledge of the RPE and choroid cells and their gene expression profiles are fundamental for understanding retinal disease mechanisms and therapeutic strategies. Here, we sequenced the RNA of about 0.3 million single cells from human RPE and choroids across two regions and seven ages, revealing regional and age differences within the human RPE and choroid. Cell-cell interactions highlight the broad connectivity networks between the RPE and different choroid cell types. Moreover, the transcription factors and their target genes change during aging. The coding of somatic variations increases during aging in the human RPE and choroid at the single-cell level. Moreover, we identified ELN as a candidate for improving RPE degeneration and choroidal structure during aging. The mapping of the molecular architecture of the human RPE and choroid improves our understanding of the human vision support system and offers potential insights into the intervention targets for retinal diseases.

Diagnostic value of a radiomics model based on CT and MRI for prediction of lateral lymph node metastasis of rectal cancer.

This study aimed to develop a radiomics model for predicting lateral lymph node (LLN) metastasis in rectal cancer patients using MR-T2WI and CT images, and assess its clinical value. This prospective study included rectal cancer patients with complete MR-T2WI and portal enhanced CT images who underwent LLN dissection at Tianjin Union Medical Center between June 2017 and November 2022. Primary lesions and LLN were segmented using 3D slicer. Radiomics features were extracted from the region of interest using pyradiomics in Python. Least absolute shrinkage and selection operator algorithm and backward stepwise regression were employed for feature selection. Three LLN metastasis radiomics prediction models were established via multivariable logistic regression analysis. The performance of the model was evaluated using receiver operating characteristic curve analysis, and the area under the curve (AUC), sensitivity, specificity were calculated for the training, validation, and test sets. A nomogram was constructed for visualization, and decision curve analysis (DCA) was performed to evaluate clinical value. We included 94 eligible patients in the analysis. For each patient, we extracted a total of 1344 radiomics features. The CT combined with MR-T2WI model had the highest AUC for all sets compared to CT and MR-T2WI models. AUC values for the CT combined with MR-T2WI model in the training, validation, and test sets were 0.957, 0.901, and 0.936, respectively. DCA revealed high prediction value for the combined MR-T2WI and CT model. A radiomics model based on CT and MR-T2WI data effectively predicted LLN metastasis in rectal cancer patients preoperatively.

The effect of posterior cruciate ligament tibial avulsion fracture on functional outcomes in knees with concomitant ipsilateral lower limb fractures: a matched-cohort analysis.

BACKGROUND: At present, the optimal treatment for posterior cruciate ligament tibial avulsion fracture (PCLTAF) combined with concomitant ipsilateral lower limb fractures remains unclear. The present study aimed to assess the preliminary outcomes of treatment for PCLTAF with concomitant ipsilateral lower limb fractures by open reduction and internal fixation (ORIF). MATERIALS AND METHODS: The medical records of patients who sustained PCLTAF with concomitant ipsilateral lower limb fractures between March 2015 and February 2019 and underwent treatment at a single institution were retrospectively reviewed. Imaging examinations performed at the time of injury were applied to identify concomitant ipsilateral lower limb fractures. We used 1:2 matching between patients with PCLTAF combined with concomitant ipsilateral lower limb fractures (combined group; n = 11) and those with isolated PCLTAF (isolated group; n = 22). Outcome data were collected, including the range of motion (ROM) and visual analogue scale (VAS), Tegner, Lysholm, and International Knee Documentation Committee (IKDC) scores. At the final follow-up, the clinical outcomes were compared between the combined and isolated groups and between patients who underwent early-stage surgery and those who underwent delayed treatment for PCLTAF. RESULTS: Thirty-three patients (26 males, 7 females) were included in this study, with eleven patients having PCLTAF and concomitant ipsilateral lower limb fractures and a follow-up of 3.1 to 7.4 years (average, 4.8 years). Compared to patients in the isolated group, patients in the combined group demonstrated significantly worse Lysholm scores (85.7 ± 5.8 vs. 91.5 ± 3.9, p = 0.040), Tegner scores (4.4 ± 0.9 vs. 5.4 ± 0.8, p = 0.006), and IKDC scores (83.6 ± 9.3 vs. 90.5 ± 3.0, p = 0.008). Inferior outcomes were found in patients with delayed treatment. CONCLUSIONS: Inferior results were found in patients with concomitant ipsilateral lower limb fractures, while better outcomes were obtained in patients with PCLTAF through early-stage ORIF using the posteromedial approach. The present findings may help determine the prognoses of patients with PCLTAF combined with concomitant ipsilateral lower limb fractures treated through early-stage ORIF.

Effects of a Ganoderma lucidum Proteoglycan on Type 2 Diabetic Rats and the Recovery of Rat Pancreatic Islets.

Type 2 diabetes (T2D) results from both insulin resistance and pancreatic ß-cell dysfunction. A natural proteoglycan extracted from Ganoderma lucidum, namely, FYGL, has been demonstrated to be capable of ameliorating insulin resistance in previous work. In this work, a T2D rat model induced by streptozocin (STZ) and a high-fat diet was used to investigate the effects of FYGL on pancreatic functions, and the transcriptomics of the rat pancreas was used to investigate the biological processes (BP) and signal pathways influenced by FYGL on the gene basis. Furthermore, the results of transcriptomics were verified both by histopathological analyses and protein expression. The studies showed that FYGL positively regulated T2D-related BP and signaling pathways and recovered the pancreatic function, therefore ameliorating hyperglycemia and hyperlipidemia in vivo. Importantly, the recovery of the pancreatic function suggested a crucial strategy to radically treat T2D.

The effect of intravenous unit-dose tranexamic acid on visible and hidden blood loss in posterior lumbar interbody fusion: a randomized clinical trial.

There are few reports of intravenous unit-dose tranexamic acid (TXA) on the relationship between visible blood loss (VBL) and hidden blood loss (HBL) in posterior lumbar interbody fusion (PLIF). Therefore, the objective of this randomized, prospective, double-blind, single center study was to investigate the effect of intravenous unit-dose TXA on VBL and HBL in patients who underwent PLIF. Among 100 patients, 11 were excluded due to failue to comply with the study, 1 was excluded due to non-conpliance with the study, and 88 were eligible for inclusion in the study. 46 patients who treated with PLIF received unit-dose of TXA (1 g/100 mL) intravenously 15 min before skin incision after general anesthesia (observation group) and 42 patients were given 100 mL of normal saline (control group). The operation time, intraoperative blood loss, postoperative drainage, VBL, HBL, blood transfusion rate, and adverse events were recorded in the two groups. Besides, activated partial prothrombin time (APTT), prothrombin time (PT), thrombin time (TT), fibrinogen (FIB), platelets (PLT), red blood cells (RBC), hemoglobin (HB), hematocrit (HCT), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) on the 1st postoperative day; and RBC, HB, HCT, CRP, ESR on the 4th postoperative day were recorded. All 88 patients successfully completed the operation, the incision healed well, and there was no deep vein thrombosis of the lower extremity after operation. The intraoperative blood loss, postoperative drainage, VBL, HBL, and blood transfusion rate in the observation group were lower than those in the control group, and the differences were statistically significant (p < 0.05). There was no significant difference in operation time between the two groups (p > 0.05). There was no significant difference in postoperative APTT, PT, TT, FIB, PLT, RBC, HB, HCT, CRP and ESR between the two groups (p > 0.05). Intravenous unit-dose TXA is safe and feasible in PLIF, and it can effectively reduce perioperative VBL and HBL.

A proteoglycan isolated from Ganoderma lucidum attenuates diabetic kidney disease by inhibiting oxidative stress-induced renal fibrosis both in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Ganoderma lucidum (G. lucidum) was regarded as "miraculous herb" by the Chinese and recorded detailly in the "Shen Nong Ben Cao Jing" as a tonic to improve health and prolong life. A proteoglycan (namely, FYGL) was extracted from Ganoderma lucidum, which was a water-soluble hyperbranched proteoglycan, and was found to be able to protect pancreatic tissue against oxidative stress damage. AIM OF THE STUDY: Diabetic kidney disease (DKD) is a complication of diabetes, but the effective treatment is still lack. Chronic hyperglycemia in diabetic patients induce the accumulation of ROS, which injure the renal tissue and lead to the renal dysfunction. In this work, the efficacy and target mechanics of FYGL on diabetic renal function were investigated. MATERIALS AND METHODS: In the present study, the mechanism of the reno-protection of FYGL was analyzed on diabetic db/db mice and rat glomerular mesangial cells (HBZY-1) induced by high glucose (HG) with palmitate (PA) (HG/PA). In vitro, the levels of reactive oxygen species (ROS), malondialdehyde (MDA) and superoxide dismutase (SOD) were evaluated by commercial kits. the expressions of NOX1 and NOX4, phosphorylation of MAPK and NF-κB, and pro-fibrotic proteins were measured by Western blot. In vivo, diabetic db/db mice were gavaged with FYGL for 8 weeks, body weight and fasting blood glucose (FBG) were tested weekly. On 8th week, the serum, urine and renal tissue were collected for glucose tolerance test (OGTT), redox indicator (SOD, CAT, GSH and MDA), lipid metabolism (TC, TG, LDL and HDL), blood urea nitrogen (BUN), serum creatinine (Scr), uric acid (UA), 8-oxo-deoxyguanosine (8-OHdG), and the changes of histopathology and expression of collagen IV and AGEs. RESULTS: The results in vitro showed that FYGL significantly inhibited the HG/PA-induced HBZY-1 cells proliferation, ROS generation, MDA production, promoted SOD activity, and suppressed NOX1, NOX4, MAPK, NF-κB, and pro-fibrotic proteins expression. In addition, FYGL markedly alleviated blood glucose, antioxidant activity and lipid metabolism, improved renal functions, and relieved renal histopathological abnormalities, especially renal fibrosis. CONCLUSIONS: The antioxidant activity of FYGL can reduce ROS caused by diabetes and protect renal from oxidative stress-induced dysfunction, thereby improving renal function. This study shows that FYGL has the potential to treat diabetic kidney disease.

Deep Sc-RNA sequencing decoding the molecular dynamic architecture of the human retina.

The human retina serves as a light detector and signals transmission tissue. Advanced insights into retinal disease mechanisms and therapeutic strategies require a deep understanding of healthy retina molecular events. Here, we sequenced the mRNA of over 0.6 million single cells from human retinas across six regions at nine different ages. Sixty cell sub-types have been identified from the human mature retinas with unique markers. We revealed regional and age differences of gene expression profiles within the human retina. Cell-cell interaction analysis indicated a rich synaptic connection within the retinal cells. Gene expression regulon analysis revealed the specific expression of transcription factors and their regulated genes in human retina cell types. Some of the gene's expression, such as DKK3, are elevated in aged retinas. A further functional investigation suggested that over expression of DKK3 could impact mitochondrial stability. Overall, decoding the molecular dynamic architecture of the human retina improves our understanding of the vision system.

The consequences of laparoscopic fascial space priority approach to lateral lymph node dissection on urinary and sexual functionality.

Introduction: In this prospective observational study, we aimed to evaluate the consequences of laparoscopic fascia space priority lymph node dissection on urination and sexual function. Aim: To assess the consequences of laparoscopic lateral lymph node dissection (LLND) using the fascial space priority approach on urinary and sexual function in patients with advanced middle and low rectal cancer. Material and methods: Consecutive patients undergoing laparoscopic LLND using the fascial space priority approach from December 2020 to November 2022 were identified from Tianjin Union Medical Center. Clinical data including patient characteristics, surgical details, and pathology were analysed. The urinary function was assessed by international prostate symptom score (IPSS) questionnaire and residual urine volume. The sexual function was investigated using the international index of erectile function (IIEF) questionnaire. Results: A total of 51 patients, mean age 60.5 ±10.9 years, were identified. The lymph nodes were positive in 70.6% (36/51) of the patients. There was no significant difference between the preoperative IPSS score and that at 6 months (5.2 ±2.1 vs. 5.6 ±1.5; p = 0.16). And there was no significant difference between the residual urine volume and that at 6 months (9.5 ±10.6 vs. 8.6 ±6.3; p = 0.61). The IIEF score before the surgery showed no significant difference from that at 6 months after the surgery (21.1 ±2.2 vs. 20.6 ±2.3; p = 0.26). Conclusions: Laparoscopic LLND using a fascial space priority approach can effectively protect the autonomic nerves. The procedure reduces short-term urination and sexual function, but it has little effect on long-term function.