Genomic characteristics and evolution of Multicentric Esophageal and gastric Cardiac Cancer.

BACKGROUND: Esophageal carcinoma (EC) and gastric cardiac adenocarcinoma (GCA) have high incidence rates in the Chaoshan region of South China. Multifocal esophageal and cardiac cancer (MECC) is commonly observed in this region in clinical practice. However, the genomic characteristics of MECC remains unclear. MATERIALS AND METHODS: In this study, a total of 2123 clinical samples of EC and GCA were analyzed to determine the frequency of multifocal tumors, as well as their occurrence sites and pathological types. Cox proportional hazards regression was used to model the relationship between age, sex, and tumor state concerning survival in our analysis of the cohort of 541 patients with available follow-up data. We performed whole-genome sequencing on 20 tumor foci and 10 normal samples from 10 MECC patients to infer clonal structure on 6 MECC patients to explore genome characteristics. RESULT: The MECC rate of EC and GCA was 5.65% (121 of 2123). Age and sex were potential factors that may influence the risk of MECC (p < 0.001). Furthermore, MECC patients showed worse survival compared with single tumor patients. We found that 12 foci from 6 patients were multicentric origin model (MC), which exhibited significant heterogeneity of variations in paired foci and had an increased number of germline mutations in immune genes compared to metastatic model. In MC cases, different lesions in the same patient were driven by distinct mutation and copy number variation (CNV) events. Although TP53 and other driver mutation genes have a high frequency in the samples, their mutation sites show significant heterogeneity in paired tumor specimens. On the other hand, CNV genes exhibited higher concordance in paired samples, especially in the amplification of oncogenes and the deletion of tumor suppressor genes. CONCLUSIONS: The extent of inter-tumor heterogeneity suggests both monoclonal and polyclonal origins of MECC, which could provide insight into the genome diversity of MECC and guide clinical implementation.

Correlation between degeneration of cervical intervertebral disc and degeneration of paravertebral muscle.

Objective: To investigate the relationship between degeneration of cervical intervertebral disc and degeneration of paravertebral muscles[multifidus (MF), cervical semispinalis (SCer), semispinalis capitis (SCap) and splenius capitis (SPL)]. Methods: 82 patients with chronic neck pain were randomly selected, including 43 males and 39 females, with 50.73 0.7.51 years old. All patients were scanned by 3.0T MRI Philips Ingenia performed conventional MRI sequence scanning and fat measurement sequence mDIXON-Quant scanning of cervical. Fat infiltration (FI) and cross-sectional area (CSA) of cervical paravertebral muscle (MF, SCer, SCap and SPL) at central level of C5-6 disc were measured by Philips 3.0T MRI image post-processing workstation. According to Pfirrmann grading system, there was no grade I in the included cases. The number of grade IIr IV cases were n=16, 40, 19 and 7 respectively. CSA and FI of cervical paravertebral muscles were compared with t test or one-way ANOVA, Spearman correlation analysis was used to evaluate the correlation between age, disc degeneration, and CSA, FI of cervical paravertebral muscles, and multiple linear regression analysis was used to analyze the independent influencing factors of CSA and FI. Results: CSA of cervical paravertebral muscles in male patients was significantly higher than that in female patients (all P<0.001), but there was no significant difference in FI (all P>0.05). Age was weakly correlated with CSA of MF+SCer, moderately correlated with CSA of SCap and SPL (r=-0.256, -0.355 and -0.361, P<0.05), weakly correlated with FI of SCap and SPL (r= 0.182 and 0.264, P<0.001), moderately correlated with FI of MF+SCer (r=0.408, P<0.001). There were significant differences in FI with disc degeneration (P<0.001, P=0.028 and P=0.005). Further correlation analysis showed that disc degeneration was strongly correlated with FI of MF+SCer (r=0.629, P<0.001), and moderately correlated with FI of SCap and SPL (r=0.363, P=0.001; r=0.345, P=0.002). Multiple linear regression analysis showed that sex and age were the influencing factors of CSA of SCap and SPL, sex was the independent influencing factor of CSA of MF+SCer, and disc degeneration was the independent influencing factor of FI. Conclusions: Age is negatively correlated with CSA and positively correlated with FI. Disc degeneration was correlated with FI of paravertebral muscles, especially with FI of MF and SCer. Sex and age were the influencing factors of CSA, while disc degeneration was the independent influencing factor of FI.

Dual auxotrophy coupled red labeling strategy for efficient genome editing in Saccharomyces cerevisiae.

The homologous recombination strategy has a long history of editing Saccharomyces cerevisiae target genes. The application of CRISPR/Cas9 strategy to editing target genes in S. cerevisiae has also received a lot of attention in recent years. All findings seem to indicate that editing relevant target genes in S. cerevisiae is an extremely easy event. In this study, we systematically analyzed the advantages and disadvantages of homologous recombination (HR) strategy, CRISPR/Cas9 strategy, and CRISPR/Cas9 combined homology-mediated repair (CRISPR/Case9-HDR) strategy in knocking out BY4742 ade2. Our data showed that when the ade2 was knocked out by HR strategy, a large number of clones appeared to be off-target, and 10 %-80 % of the so-called knockout clones obtained were heteroclones. When the CRISPR/Cas9 strategy was applied, 60% of clones were off-target and the rest were all heteroclones. Interestingly, most of the cells were edited successfully, but at least 60 % of the clones were heteroclones, when the CRISPR/Cas9-HDR strategy was employed. Our results clearly showed that the emergence of heteroclone seems inevitable regardless of the strategies used for editing BY4742 ade2. Given the characteristics of BY4742 defective in ade2 showing red on the YPD plate, we attempted to build an efficient yeast gene editing strategy, in which the CRISPR/Cas9 combines homology-mediated repair template carrying an ade2 expression cassette, BY4742(ade2Δ0) as the start strain. We used this strategy to successfully achieve 100 % knockout efficiency of trp1, indicating that technical challenges of how to easily screen out pure knockout clones without color phenotype have been solved. Our data showed in this study not only establishes an efficient yeast gene knockout strategy with dual auxotrophy coupled red labeling but also provides new ideas and references for the knockout of target genes in the monokaryotic mycelium of macrofungi.

Comparative Metabolome Profiling for Revealing the Effects of Different Cooking Methods on Glutinous Rice Longjing57 (Oryza sativa L. var. Glutinosa).

Glutinous rice (GR), an important food crop in Asia, provides prolonged energy for the human body due to its high amylopectin content. The non-volatile metabolites generated by different cooking methods that affect the nutritional value and color of GR are still poorly understood. Herein, a widely targeted metabolomics approach was used to understand the effects of different cooking methods (steaming, baking, and frying) on the metabolite profiles of GR. Compared with other treatments, steamed GR had a brighter color and significantly lower contents of total sugar, starch, amylopectin, and amylose, at 40.74%, 14.13%, 9.78%, and 15.18%, respectively. Additionally, 70, 108, and 115 metabolites were significantly altered in the steaming, baking, and frying groups respectively, and amino acid and carbohydrate metabolism were identified as the representative metabolic pathways based on KEGG annotations. Further evaluation of 14 amino acids and 12 carbohydrates in steamed GR, especially 4-aminobutyric acid, suggested its high nutraceutical value. Additionally, multivariate analysis indicated that total sugar content, amylose content, beta-alanine methyl ester hydrochloride, and 4-aminobutyric acid played a critical role in color formation in raw and cooked GR. Finally, the levels of major amino acids and carbohydrates were quantified by conventional methods to verify the reliability of the metabolome. Consequently, this in-depth understanding of metabolite profiling in normal cooking methods has provided a foundation for the processing of GR products.

Design and evaluation of an efficient mosquito trap.

BACKGROUND: Vector mosquito control is important for preventing and controlling mosquito-borne infectious diseases. This study designed and developed a mosquito killer (MK) with a specific light wavelength, simulated human body temperature, human odor, and a photocatalyst to stimulate CO2 based on the physiological characteristics and ecological habits of mosquitoes. We tested the trapping effect of individual and multiple mosquito-trapping elements of the MK through two-way selection experiments and compared them with several commercial mosquito traps. RESULTS: The 365 nm wavelength MK was significantly more effective than the 395 nm (Cx. quinquefasciatus: 62.00% vs. 34.25%; Ae. albopictus: 50.75% vs 45.00%, An. sinensis: 49.75% vs 39.00%). Mosquitoes captured by the MK with heaters at 365 nm were significantly more than those captured by the MK without heaters at 365 nm. A trap with a 365 nm wavelength, heating element, and lure showed significantly better capture effectiveness than MK with a 365 nm wavelength, heating element, but without lure (Cx. quinquefasciatus: 67.00% vs. 29.75%, Ae. albopictus: 60.25% vs 36.25%, An. sinensis: 49.75% vs 39.75%). The coated photocatalyst trap with a 365 nm wavelength, heating element, and lure showed significantly better capture effectiveness than the trap without coating (Cx. quinquefasciatus: 54.25% vs. 42.50%; Ae. albopictus: 53.50% vs 44.00%, An. sinensis: 50.00% vs 41.25%). This trap demonstrated a significantly better capture advantage for Cx. quinquefasciatus and Ae. albopictus compared to the three commercial products. CONCLUSION: The developed mosquito trap with multiple attractant factors significantly enhanced the capture effectiveness of common mosquitoes. © 2024 Society of Chemical Industry.

Analysis of fungal diversity in the gut feces of wild takin (Budorcas taxicolor).

Introduction: The composition of the intestinal microbiome correlates significantly with an animal's health status. Hence, this indicator is highly important and sensitive for protecting endangered animals. However, data regarding the fungal diversity of the wild Budorcas taxicolor (takin) gut remain scarce. Therefore, this study analyzes the fungal diversity, community structure, and pathogen composition in the feces of wild B. taxicolor. Methods: To ensure comprehensive data analyses, we collected 82 fecal samples from five geographical sites. Amplicon sequencing of the internal transcribed spacer (ITS) rRNA was used to assess fecal core microbiota and potential pathogens to determine whether the microflora composition is related to geographical location or diet. We further validated the ITS rRNA sequencing results via amplicon metagenomic sequencing and culturing of fecal fungi. Results and discussion: The fungal diversity in the feces of wild Budorcas taxicolor primarily comprised three phyla (99.69%): Ascomycota (82.19%), Fungi_unclassified (10.37%), and Basidiomycota (7.13%). At the genus level, the predominant fungi included Thelebolus (30.93%), Functional_unclassified (15.35%), and Ascomycota_unclassified (10.37%). Within these genera, certain strains exhibit pathogenic properties, such as Thelebolus, Cryptococcus, Trichosporon, Candida, Zopfiella, and Podospora. Collectively, this study offers valuable information for evaluating the health status of B. taxicolor and formulating protective strategies.

Effects of a Modified Long-Acting Cocktail on Analgesia and Enhanced Recovery After Total Hip Arthroplasty: A Double-Blinded Randomized Clinical Trial.

BACKGROUND: We compared the efficacy and safety of a modified cocktail for postoperative analgesia and early functional rehabilitation in patients undergoing total hip arthroplasty (THA). METHODS: Magnesium sulfate and sodium bicarbonate were added to a cocktail of ropivacaine, epinephrine, and dexamethasone. Primary outcome measures were visual analog scale (VAS) pain scores at various intervals after surgery, morphine consumption for rescue analgesia after surgery, and time to first rescue analgesia. Secondary outcomes were hip function after surgery, daily walking distance, quadriceps muscle strength, and the incidence of postoperative adverse reactions. RESULTS: Morphine consumption was significantly lower in the modified cocktail group than in the control group in the first 24 hours after surgery (6.2 ± 6.0 versus 14.2 ± 6.4 mg, P < .001), as was total morphine consumption (10.0 ± 8.6 versus 19.2 ± 10.1 mg, P < .001). The duration of the first rescue analgesia was significantly prolonged (23.7 ± 10.3 versus 11.9 ± 5.8 mg, P < .001). Morphine consumption was also reduced in the magnesium sulfate and sodium bicarbonate groups over a 24-hour period compared to the control group (P < .001). The modified cocktail group had significantly lower resting VAS pain scores than the control group within 24 hours after surgery (P < .050). The VAS pain scores during movement within 12 hours after surgery were also lower (P < .050). The experimental groups showed better hip range of motion (P < .050) and longer walking distance (P < .050) on the first postoperative day, and levels of inflammatory markers were significantly reduced. The incidence of postoperative adverse reactions was similar among the 4 groups. CONCLUSIONS: The modified cocktail with a new adjuvant can prolong the duration of postoperative analgesia, reduce the dosage of rescue analgesics, and accelerate early postoperative functional recovery in patients undergoing THA.

Subacromial osteolysis following hook plate fixation for acromioclavicular dislocation: a systematic review and meta-analysis.

BACKGROUND: Clavicular hook plates are extensively used in the treatment of acromioclavicular (AC) dislocation. Subacromial osteolysis is a typical complication following hook plate fixation. We performed a systematic review and meta-analysis to determine the incidence of subacromial osteolysis and analyzed the associated characteristics of subacromial osteolysis to guide surgeons. METHODS: PubMed, EMBASE, and Cochrane Library databases were comprehensively searched for relevant literature. We screened the literature based on the eligibility criteria, extracted relevant data and assessed the quality of the included studies. Pooled odds ratios (ORs) or mean differences (MDs) with 95% confidence intervals were calculated by a fixed-effects or random-effects model. Heterogeneity was evaluated by the chi-squared test and I2 statistics. A meta-regression analysis was performed to explore the potential source of heterogeneity. RESULTS: Thirty-two studies met the inclusion criteria. The total pooled incidence of subacromial osteolysis was 29%, and the only covariate that could influence the incidence of subacromial osteolysis was the radiological measurement method (P=0.017). Patients in the hook plate fixation with coracoclavicular (CC) ligament reconstruction group had lower odds of subacromial osteolysis (OR, 2.54, 95% CI 1.54 to 4.18; P < 0.001). There were no significant differences in the Constant-Murley scores at the final follow-up between patients with and without subacromial osteolysis (SMD, -0.17; 95% CI, -0.50 to 0.15; P= 0.294). CONCLUSIONS: Subacromial osteolysis has a relatively high and variable incidence, and the primary factor influencing the reported incidence is the radiological assessment method. The current analysis suggests CC ligament reconstruction as an effective surgical approach for decreasing the incidence of subacromial osteolysis. The presence or absence of subacromial osteolysis did not significantly impact the functional outcomes observed during the final follow-up period.

miR-2940-1 is involved in the circadian regulation of oviposition in Aedes albopictus.

The vast majority of all global species have circadian rhythm cycles that allow them to adapt to natural environments. These regular rhythms are regulated by core clock genes and recent studies have also implicated roles for microRNAs in this regulation. Oviposition is an important circadian behavior in the reproductive cycle of insect vectors of diseases, and little is known about the rhythm or its regulation in mosquitoes. Aedes albopictus is a diurnal mosquito that transmits arboviruses and is the major cause of outbreaks of dengue fever in China. We analyzed the oviposition rhythm patterns of A. albopictus under different light/dark conditions and show that the mosquitoes have an oviposition peak between zeitgeber time 9 (ZT 9) and ZT 12. Furthermore, the antagomir-mediated knockdown of expression of the microRNA miR-2940-1 affected the oviposition rhythm of A. albopictus. These data support the conclusion that miR-2940-1 is involved in the regulation of oviposition rhythm in A. albopictus and provide a foundation for using oviposition rhythms as a new target for vector mosquito control.

The Effect of Unintended Facet Arthrodesis on the Treatment Outcome of Dynamic Neutralization System for Lumbar Degenerative Diseases.

Purpose: This study aimed to examine the influence of unintended facet arthrodesis on the therapeutic effectiveness of the dynamic neutralization system (Dynesys). Methods: This retrospective study enrolled consecutive patients who underwent posterior decompression and dynamic stabilization for lumbar spondylosis or spinal stenosis. Follow-up assessments included lumbar radiography, lumbar vertebral computerized tomography (CT), visual analog scale (VAS), and Oswestry disability index (ODI). Patients were classified into the facet fusion and non-fusion groups. The differences in the VAS scores for back pain and leg pain, ODI, intervertebral range of motion (ROM) at the surgical segments, and upper adjacent segments were assessed before and after treatment. Results: A total of 49 patients (29 males and 20 females) aged 31-65 years were enrolled and followed-up for over 40 months. Among the patients, 16 (32.7%) experienced unintended facet arthrodesis and were assigned to the fusion group, whereas the remaining patients were assigned to the non-fusion group. There was a significant increase in the incidence of facet arthrodesis in the surgical segments over time post-surgery (χ2 = 6.2, p < 0.05). The ROM of the surgical and upper adjacent segments, VAS scores for back pain and leg pain, and ODI were all significantly different before and after the operation (p < 0.05), but not between the fusion and non-fusion groups (p > 0.05). Conclusion: Although unintended facet arthrodesis is common after Dynesys procedure, the presence of facet arthrodesis does not significantly affect the efficacy of Dynesys in treating lumbar degenerative diseases.

AEGNN-M:A 3D Graph-Spatial Co-Representation Model for Molecular Property Prediction.

Improving the drug development process can expedite the introduction of more novel drugs that cater to the demands of precision medicine. Accurately predicting molecular properties remains a fundamental challenge in drug discovery and development. Currently, a plethora of computer-aided drug discovery (CADD) methods have been widely employed in the field of molecular prediction. However, most of these methods primarily analyze molecules using low-dimensional representations such as SMILES notations, molecular fingerprints, and molecular graph-based descriptors. Only a few approaches have focused on incorporating and utilizing high-dimensional spatial structural representations of molecules. In light of the advancements in artificial intelligence, we introduce a 3D graph-spatial co-representation model called AEGNN-M, which combines two graph neural networks, GAT and EGNN. AEGNN-M enables learning of information from both molecular graphs representations and 3D spatial structural representations to predict molecular properties accurately. We conducted experiments on seven public datasets, three regression datasets and 14 breast cancer cell line phenotype screening datasets, comparing the performance of AEGNN-M with state-of-the-art deep learning methods. Extensive experimental results demonstrate the satisfactory performance of the AEGNN-M model. Furthermore, we analyzed the performance impact of different modules within AEGNN-M and the influence of spatial structural representations on the model's performance. The interpretability analysis also revealed the significance of specific atoms in determining particular molecular properties.

Do Patients with Borderline Anemia Need Treatment before Total Hip Arthroplasty? A Propensity Score-Matched Cohort Study.

OBJECTIVE: Preoperative anemia has been identified as a modifiable risk factor for multiple adverse outcomes. In real clinical practice, considering treatment of anemia would increase costs and delay surgery. Patients undergoing total hip arthroplasty (THA) with mild anemia are usually neglected and still underdiagnosed or inadequately treated. This study investigated the effects of preoperative borderline anemia and anemia intervention before THA on perioperative outcomes. METHODS: We screened 706 patients from those receiving THA at our hospital from January 2020 to January 2022, with 112 in the borderline anemia group and 594 in the non-anemia group. The cohort for this retrospective study was created by using propensity score matching (PSM) and subgroup analysis. The primary outcome was perioperative blood loss, while secondary outcomes were the rate of allogeneic blood transfusion and human serum albumin transfusion, perioperative laboratory indicators, postoperative length of stay, and complications. The independent sample t-test and the Mann-Whitney U-test were used to analyze continuous data, and the Pearson χ2 -test or the Fisher exact test was used to analyze categorical variables. RESULTS: After PSM, there was no significant difference in perioperative blood loss between patients in the borderline anemia group and the non-anemia group. The primary outcomes of hidden (p = 0.004) and total (p = 0.005) blood loss were significantly lower in the intervention group than in the control group. No statistical differences were found in allogeneic blood transfusion, human serum albumin transfusion, postoperative length of stay, or complications (p > 0.05). CONCLUSIONS: Anemia treatments for patients with borderline anemia before THA significantly reduced hidden blood loss and total blood loss in the perioperative period and decreased the drop of hemoglobin and hematocrit without increasing postoperative complications.

Efficacy of Diosmin in Reducing Lower-Extremity Swelling and Pain After Total Knee Arthroplasty: A Randomized, Controlled Multicenter Trial.

BACKGROUND: Many patients experience lower-extremity swelling following total knee arthroplasty (TKA), which impedes recovery. Diosmin is a semisynthetic flavonoid that is often utilized to treat swelling and pain caused by chronic venous insufficiency. We aimed to evaluate the efficacy and safety of diosmin in reducing lower-extremity swelling and pain as well as in improving functional outcomes following TKA. METHODS: This study was designed as a randomized, controlled multicenter trial and conducted in 13 university-affiliated tertiary hospitals. A total of 330 patients undergoing TKA were randomized to either receive or not receive diosmin postoperatively. The diosmin group received 0.9 g of diosmin twice per day for 14 consecutive days starting on the day after surgery, whereas the control group received neither diosmin nor a placebo postoperatively. The primary outcome was lower-extremity swelling 1, 2, 3, and 14 days postoperatively. The secondary outcomes were postoperative pain assessed with use of a visual analogue scale, Hospital for Special Surgery score, range of knee motion, levels of the inflammatory biomarkers C-reactive protein and interleukin-6, and complications. RESULTS: At all postoperative time points, diosmin was associated with significantly less swelling of the calf, thigh, and upper pole of the patella as well as with significantly lower pain scores during motion. However, no significant differences in postoperative pain scores at rest, Hospital for Special Surgery scores, range of motion, levels of inflammatory biomarkers, or complication rates were found between the diosmin and control groups. CONCLUSIONS: The use of diosmin after TKA reduced lower-extremity swelling and pain during motion and was not associated with an increased incidence of short-term complications involving the outcomes studied. However, further studies are needed to continue exploring the efficacy and safety of diosmin use in TKA. LEVEL OF EVIDENCE: Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.

The application of weighted gene co-expression network analysis and support vector machine learning in the screening of Parkinson's disease biomarkers and construction of diagnostic models.

Background: This study aims to utilize Weighted Gene Co-expression Network Analysis (WGCNA) and Support Vector Machine (SVM) algorithm for screening biomarkers and constructing a diagnostic model for Parkinson's disease. Methods: Firstly, we conducted WGCNA analysis on gene expression data from Parkinson's disease patients and control group using three GEO datasets (GSE8397, GSE20163, and GSE20164) to identify gene modules associated with Parkinson's disease. Then, key genes with significantly differential expression from these gene modules were selected as candidate biomarkers and validated using the GSE7621 dataset. Further functional analysis revealed the important roles of these genes in processes such as immune regulation, inflammatory response, and cell apoptosis. Based on these findings, we constructed a diagnostic model by using the expression data of FLT1, ATP6V0E1, ATP6V0E2, and H2BC12 as inputs and training and validating the model using SVM algorithm. Results: The prediction model demonstrated an AUC greater than 0.8 in the training, test, and validation sets, thereby validating its performance through SMOTE analysis. These findings provide strong support for early diagnosis of Parkinson's disease and offer new opportunities for personalized treatment and disease management. Conclusion: In conclusion, the combination of WGCNA and SVM holds potential in biomarker screening and diagnostic model construction for Parkinson's disease.

Complicated Bosworth fracture-dislocation: A case report and review of the literature.

Bosworth fracture and dislocation is relatively rare, accounting for about 1% of ankle fractures. It is characterized by the proximal fibula fracture embedded in the posterolateral distal tibia. Due to an insufficient understanding of this fracture, it is easy to cause missed diagnosis and misdiagnosis in clinical practice. Due to the insertion of the fracture, it is challenging to perform closed reduction, and improper treatment is easy to cause complications. Surgical treatment is recommended for this type of fracture. In order to improve the understanding of orthopedic surgeons about Bosworth fracture and dislocation, this paper reports the diagnosis and treatment of 2 cases of Bosworth fracture and dislocation, and reviews the literature on Bosworth fracture's mechanism, diagnosis, classification, complications, and treatment options in recent years.

Near-Infrared-II-Driven Pollen Micromotors for Inflammatory Bowel Disease Treatment.

Inflammatory bowel disease (IBD) is a common inflammatory bowel disease with a high incidence rate and serious consequences. Attempts in this area are focusing on developing efficient delivery systems for relieving IBD. Herein, we present a kind of near-infrared-II (NIR-II)-activated pollen-derived micromotor (PDMM) as an efficient delivery system for treating IBD. These PDMMs are pollen grains with half of them covered by a gold (Au) layer, which can result in an asymmetric thermal gradient around the PDMMs under NIR-II irradiation, thereby forming a thermophoretic force to drive PDMMs to move spontaneously. Besides, the inherent spiny and hollow architectures of pollen grains endowed the PDMMs with outstanding capacity of adherence and drug delivery, respectively. Based on these features, we have demonstrated that the PDMMs could move actively in vivo with the irradiation of NIR-II light and adhere to the surrounding tissues for drug delivery. Thus, the PDMMs loaded with dexamethasone show desirable curative effects on treating IBD. These results indicated that the proposed PDMM-based delivery system has great potential in clinic gastrointestinal administration.

Designing self-triggered micro/milli devices for gastrointestinal tract drug delivery.

INTRODUCTION: Self-triggered micro-/milli-devices (STMDs), which are artificial devices capable of responding to the surrounding environment and transferring external energy into kinetic energy, thus realizing autonomous movement, have come to the forefront as a powerful tool in cargo delivery via gastrointestinal tract. Urgent needs have been raised to overview the development of this area. AREAS COVERED: We summarize the advancement of designing STMDs for delivery via gastrointestinal tract. We first give a brief overview on the opportunities and challenges of delivery via gastrointestinal tract involving gastric barriers and intestinal barriers. Then, emphasis is laid on the design and applications of STMDs for delivery via gastrointestinal tract. We focus on their morphological characteristics and function design, expounding their working mechanisms in the complex gastrointestinal tract. EXPERT OPINION: Although with much progress in STMDs, there is still a huge gap between laboratory researches and clinical applications due to some limitations including latent digestive burden, sophisticated fabrication, unstable delivery, and so on. We give a discussion on the potential, challenges, and prospects of developing STMDs for delivery via gastrointestinal tract.

Lithium prevents glucocorticoid­induced chondrocyte autophagy: An in vitro study.

Glucocorticoids can induce chondrocyte autophagy. Lithium is a classical regulator of autophagy. The present study aimed to determine whether lithium can prevent glucocorticoid­induced chondrocyte autophagy by regulating the PI3K/AKT/mTOR signaling pathway. For this purpose, rat and human chondrocytes were treated with dexamethasone (200 µM) or dexamethasone (200 µM) combined with lithium chloride at various concentrations (0.01, 0.1, 1 and 10 mM). CYTO­ID® autophagy fluorescence staining and transmission electron microscopy were used to detect the levels of autophagy in the chondrocytes. Reverse transcription­quantitative PCR and western blot analysis were used to measure the expression levels of the autophagy marker, LC3B and the autophagy regulatory signaling pathway (PI3K/AKT/mTOR signaling pathways) markers, AKT and mTOR. The viability of chondrocytes was measured using the Cell Counting Kit­8 assay. It was found that compared with that in the control group, dexamethasone induced the autophagy of chondrocytes, decreased the expression levels of AKT and mTOR, and reduced cell viability. Compared with the treatment with dexamethasone alone, lithium chloride (10 mM) + dexamethasone reduced the autophagy levels, increased the expression level of AKT and mTOR, and increased cell viability. In conclusion, the present study demonstrated that lithium can prevent glucocorticoid­induced autophagy by activating the PI3K/AKT/mTOR signaling pathway and preventing the glucocorticoid­induced decrease in chondrocyte viability.

Influencing factors of hidden blood loss after primary total hip arthroplasty through the posterior approach: a retrospective study.

BACKGROUND: Total hip arthroplasty (THA) is an excellent treatment for the end-stage hip disease, and perioperative blood management strategies have been effectively applied to this procedure. However, many patients still experience anemia after the operation, which is usually overlooked by orthopedic surgeons due to the hidden blood loss (HBL) in the perioperative period. Therefore, the objective of this study was to evaluate HBL in patients undergoing primary THA using the posterior approach and to explore its influencing factors. METHODS: A retrospective analysis of 707 patients who underwent primary THA through the posterior approach was conducted in our hospital from January 2020 to January 2022. By applying Gross's and Nadler's formula, the HBL was calculated. Six quantitative variables (age, body mass index, surgical duration, albumin loss, preoperative hemoglobin, and hemoglobin loss) as well as four qualitative variables (gender, American Society of Anesthesiologists class, major preoperative diagnosis, and hypertension) of patients were analyzed using multivariate linear regression. RESULTS: The HBL was recorded at 700.39 ± 368.59 mL. As a result of multivariate linear regression analysis, it was determined that body mass index, surgical duration, and hemoglobin loss were all significant risk factors for HBL, whereas preoperative hemoglobin was considered a protective factor. It has been demonstrated that HBL is not significantly correlated with age, albumin loss, gender, ASA class, or major preoperative diagnosis, but it also did not differ from HBL by hypertension. CONCLUSIONS: Hidden blood Loss (HBL) in patients after primary total hip arthroplasty (THA) using the posterior approach is large and significant. When optimizing the perioperative management of THA, orthopedic surgeons should keep in mind HBL and its influencing factors, especially for patients with high body mass indexes, long surgical durations, and low preoperative hemoglobin levels. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry (ChiCTR2100053888) in 02/12/2021, http://www.chictr.org.cn .