Comprehensive application of AI algorithms with TCR NGS data for glioma diagnosis.

T-cell receptor (TCR) detection can examine the extent of T-cell immune responses. Therefore, the article analyzed characteristic data of glioma obtained by DNA-based TCR high-throughput sequencing, to predict the disease with fewer biomarkers and higher accuracy. We downloaded data online and obtained six TCR-related diversity indices to establish a multidimensional classification system. By comparing actual presence of the 602 correlated sequences, we obtained two-dimensional and multidimensional datasets. Multiple classification methods were utilized for both datasets with the classification accuracy of multidimensional data slightly less to two-dimensional datasets. This study reduced the TCR ß sequences through feature selection methods like RFECV (Recursive Feature Elimination with Cross-Validation). Consequently, using only the presence of these three sequences, the classification AUC value of 96.67% can be achieved. The combination of the three correlated TCR clones obtained at a source data threshold of 0.1 is: CASSLGGNTEAFF_TRBV12_TRBJ1-1, CASSYSDTGELFF_TRBV6_TRBJ2-2, and CASSLTGNTEAFF_TRBV12_TRBJ1-1. At 0.001, the combination is: CASSLGETQYF_TRBV12_TRBJ2-5, CASSLGGNQPQHF_TRBV12_TRBJ1-5, and CASSLSGNTIYF_TRBV12_TRBJ1-3. This method can serve as a potential diagnostic and therapeutic tool, facilitating diagnosis and treatment of glioma and other cancers.

Efficacy of Tetracycline Three Times Daily was Comparable to That of Four Times Daily for Helicobacter pylori Rescue Treatment: A Multicenter, Noninferiority, Randomized Controlled Trial.

BACKGROUND: The optimal dosage of tetracycline remains unclear for Helicobacter pylori eradication. Frequent dosing requirements may decrease patient adherence and increase the incidence of adverse events, potentially reducing treatment efficacy. This study aimed to compare the efficacy of different tetracycline dosages in rescue treatment for H. pylori infection. METHODS: A total of 406 patients needing H. pylori rescue treatment were enrolled. Patients were randomized into two groups and received bismuth-containing quadruple therapies as follows: esomeprazole 40 mg twice daily, bismuth 220 mg twice daily, amoxicillin 1000 mg twice daily, and tetracycline 500 mg either three (TET-T group) or four (TET-F group) times daily. At least 6 weeks after treatment completion, a 13C-urea breath test was performed to evaluate H. pylori eradication. RESULTS: The intention-to-treat (ITT) eradication rates were 91.13% (185/203) and 90.15% (183/203) (p = 0.733), the modified ITT (MITT) eradication rates were 94.87% (185/195) and 95.31% (183/192) (p = 0.841), and the per-protocol (PP) eradication rates were 94.79% (182/192) and 95.21% (179/188) (p = 0.851) in the TET-T group and TET-F group, respectively. The eradication rates for the TET-T group were not inferior to those of the TET-F group in ITT, MITT, and PP analyses. The incidence of adverse effects was significantly lower in the TET-T group than in the TET-F group (23.65% vs. 33.50%, p = 0.028). No significant differences were observed in treatment compliance between the groups. CONCLUSIONS: The dose of tetracycline administered three times daily showed comparable efficacy to that administered four times daily, while significantly reducing the incidence of adverse events. The combination of tetracycline and amoxicillin in bismuth-containing quadruple therapy achieved a high eradication rate in H. pylori rescue treatment.

SLC44A2 regulates vascular smooth muscle cell phenotypic switching and aortic aneurysm.

Aortic aneurysm is a life-threatening disease with limited interventions, closely related to vascular smooth muscle cells (VSMCs) phenotypic switching. SLC44A2, a member of solute carrier series 44 (SLC44) family, remains under-characterized in the context of cardiovascular diseases. Venn diagram analysis based on microarray and single-cell RNA sequencing identified SLC44A2 as a major regulator of VSMCs phenotypic switching in aortic aneurysm. Screening for Slc44a2 amongst aortic cell lineages demonstrated its predominant location in VSMCs. Elevated levels of SLC44A2 were evidenced in the aorta of both abdominal aortic aneurysm patients and angiotensin II (Ang II)-infused Apoe-/- mice. In vitro, SLC44A2 silencing promoted VSMCs towards a synthetic phenotype, while SLC44A2 overexpression attenuated VSMCs phenotypic switching. VSMCs-specific SLC44A2 knockout mice were more susceptible to aortic aneurysm under Ang II infusion, while SLC44A2 overexpression showed protective effects. Mechanistically, SLC44A2 interaction with NRP1 and ITGB3 activates TGF-ß/SMAD signaling, thereby promoting contractile genes expression. Elevated SLC44A2 in aortic aneurysm is associated with upregulated runt-related transcription factor 1 (RUNX1). Furthermore, low dose of lenalidomide (LEN) suppressed aortic aneurysm progression by enhancing SLC44A2 expression. These findings reveal SLC44A2/NRP1/ITGB3 complex is a major regulator of VSMCs phenotypic switching and provide potential therapeutic approach (LEN) for aortic aneurysm treatment.

Shape-fixing hydrogel promotes scarless healing of wounds under tension.

The healing of a wound under tension (hereafter, "tension wound") often coincides with the development of hypertrophic scars in clinical settings. Currently, compress bandages offer a potential alternative for the healing of tension wounds; however, their application in surgery is limited due to their prefabricated patch form. To overcome this, a tension-shielding hydrogel system was designed using photocurable catechol-grafted hyaluronic acid and tannic-acid silver nanoparticles (hereafter, "HTA system"). The hydrogel exhibited tension-shielding capacity, reducing wound tension via shape-fixation and ultimately reducing scar formation. The HTA hydrogel exhibited superior photothermal antibacterial efficacy, self-healing properties, and effective dissipation of energy, thereby promoting tissue regeneration. The hydrogel significantly inhibited the mechanotransduction pathway, thus preventing Engrailed-1 activation and reducing the fibrotic response. The HTA hydrogel system, therefore, provides a treatment strategy for tension wounds, burn wounds and other wounds that are prone to form hypertrophic scars via creating a tension-free local environment. STATEMENT OF SIGNIFICANCE: In our study, we presented a wound-dressing hydrogel system (HTA) that exhibit shape-fixing capacity in tension wound model. Here, we designed and modified a tension regulator, applied it to mice, and furthermore, established a tension wound model in mice with adjustable tension. Outcomes showed that the HTA hydrogel system can effectively form a shape-fixed environment on tension wounds and dynamic wounds, thus promoting scarless healing. Additionally, HTA performs injectability, rapid crosslinking, biocompatibility, wet adhesion, hemostasis and photothermal antibacterial properties. We believe this research has various potential clinical applications, including scarless-healing in tension wounds, treatment of acute bleeding, treatment of infected wounds, and even internal organ repair.

Clarifying varied Helicobacter pylori eradication therapies: A comprehensive review.

Current global variations exist in Helicobacter pylori (H. pylori) eradication regimens. Triple therapy (TT), bismuth quadruple therapy (BQT), and high-dose dual therapy (HDDT) currently represent the predominant regimens. These regimens diverge in terms of treatment duration, the utilization of susceptibility testing, acid-inhibiting drug administration, and patient education. We conducted a comprehensive systematic literature review on these H. pylori treatment regimens. Our review aims to provide standardized treatment recommendations for H. pylori, reducing the risk of amalgamating findings from diverse eradication regimens. Recent research suggests that the optimal treatment duration for TT and BQT may be 14 and 10 days, respectively. Selecting the appropriate treatment duration for HDDT should rely on regional research evidence, and 14 days may be the optimal duration. The incorporation of susceptibility testing in TT is of paramount importance. In the case of BQT, the absence of susceptibility testing may be considered as an option, contingent upon cost and availability, and should be determined based on local antibiotic resistance patterns and the efficacy of empirical regimens. The type and dosage of acid-inhibiting drug would affect the efficacy of these regimens. Acid-inhibiting drugs should be selected and applied reasonably according to the population and therapies. Adequate patient education plays a pivotal role in the eradication of H. pylori. In regions with accessible local research evidence, the 10-day empirical BQT regimen may be considered a preferred choice for H. pylori eradication.

Exploring the causal relationship between female reproductive traits and frailty: a two-sample mendelian randomization study.

Background: The impact of female reproductive factors, including age at menarche (AAM), age at first birth (AFB), age at first sexual intercourse (AFS), age at natural menopause (ANM), and pregnancy abortion (PA), on the risk of developing frailty remains uncertain. Our objective is to examine the potential causal relationship between female reproductive traits and frailty through the utilization of two-sample univariable Mendelian Randomization (UVMR) and multivariable Mendelian Randomization (MVMR) analyses. Methods: Leveraging large-scale Genome-Wide Association Study (GWAS) data from individuals of European ancestry, we performed two-sample UVMR and MVMR analyses to examine the causal relationship between female reproductive traits and frailty. The primary analysis employed inverse-variance-weighted (IVW) estimation, and sensitivity analyses were conducted to assess the robustness of the findings. Results: The UVMR analysis revealed a significant causal relationship between female reproductive traits (AFS, AFB, AAM) and frailty [IVW: OR = 0.74, 95%CI(0.70-0.79), p = 0.000; OR = 0.93, 95%CI(0.92-0.95), p = 0.000; OR = 0.96, 95%CI(0.95-0.98), p = 0.000]. However, there was no significant effect of ANM and PA on frailty (p > 0.05). The sensitivity analysis results were robust, supporting the findings. Furthermore, this association remained significant even after adjusting for body mass index (BMI) and educational attainment (EA) in the MVMR analysis [IVW: OR = 0.94, 95%Cl (0.91-0.97), p = 0.000; OR = 0.77, 95%Cl (0.70-0.86), p = 0.000; OR = 0.95, 95%Cl (0.94-0.97), p = 0.000]. BMI and EA serve as mediators in this process. Conclusion: Our research has established a significant causal relationship between female reproductive traits (AFS, AFB, AAM) and frailty, with BMI and EA acting as mediating factors in this process. However, further research is warranted to validate our findings and elucidate the underlying biological mechanisms.

Nitrogen-doped substrate material ion imprinting-capacitive deionization selective recovery of lithium ions from acidic solutions.

With the continuous development of global industry and the increasing demand for lithium resources, recycling valuable lithium from industrial solid waste is necessary for sustainable development and environmental friendliness. Herein, we employed ion imprinting and capacitive deionization to prepare a new electrode material for lithium-ion selective recovery. The material morphology and structure were characterized using scanning electron microscopy, Fourier-transform infrared spectroscopy, and other characterization methods, and the adsorption mechanism and water clusters were correlated using the density functional theory. The electrode material exhibited a maximum adsorption capacity of 36.94 mg/g at a Li+ concentration of 600 mg/L. The selective separation factors for Na+, K+, Mg2+, and Al3+ in complex solution environments were 2.07, 9.82, 1.80, and 8.45, respectively. After undergoing five regeneration cycles, the material retained 91.81% of the initial Li+ adsorption capacity. Meanwhile, the electrochemical adsorption capacity for Li+ was more than twice the corresponding conventional physical adsorption capacity because electrochemical adsorption provides the energy needed for deprotonation, enabling exposure of the cavities of the crown ether molecules to enrich the active sites. The proposed environment-friendly separation approach offers excellent selectivity for Li+ recovery and addresses the growing demand for Li+ resources.

Most suitable plant communities for the slope reclamation of the Zhengzhou-Xinxiang section of the Beijing-Hong Kong-Macao expressway.

The construction of expressways in China has produced diverse habitats along slopes characterized by steep gradients, uneven water distribution, poor soil conditions, and no routine maintenance. Manually planting beneficial species is an essential method of effectively improving slope soils to prevent soil erosion. However, few studies have evaluated the reclamation effects and plant community composition and structure used to restore slopes along expressways. This study focused on the Zhengzhou-Xinxiang section of the Beijing-Hong Kong-Macao Expressway. A total of 10 representative plant communities were evaluated using the analytic hierarchy process (AHP)-fuzzy integrated evaluation method. The sites were divided into four layers, namely, plant communities, soil nutrients, soil physical properties, and other ecological factors, and 14 indicators were assessed. The evaluation results showed that four of these plant communities (PCs) were excellent, three PCs were good, one PC was normal, two PCs were poor. The four excellent PCs had high Shannon-Wiener index, pielou index, richness index or community productivity. It is worth noting that most excellent plant community structures were tree + shrub + herb. Based on these results, we recommend that fill slopes should be restored using a combination of trees, herbs, and shrubs; also, the vegetation should include native plants, such as B. papyrifera, U. pumila, A. fruticosa, and Cynodon dactylon (L.). This study could provide ideas for plant community composition and structure of new highway slopes in similar climate environment, and provide theoretical support for plant community composition and structure and soil improvement for the existing slope.

Biomimetic biphasic microsphere preparation based on the thermodynamic incompatibility of glycosaminoglycan with gelatin methacrylate for hair regeneration.

Hair follicle (HF) tissue engineering is promising for hair loss treatment especially for androgenetic alopecia. Physiologically, the initiation of HF morphogenesis relies on the interactions between hair germ mesenchymal and epithelial layers. To simulate this intricate process, in this study, a co-flowing microfluidic-assisted technology was developed to produce dual aqueous microdroplets capturing growth factors and double-layer cells for subsequent use in hair regeneration. Microspheres, called G/HAD, were generated using glycosaminoglycan-based photo-crosslinkable biological macromolecule (HAD) shells and gelatin methacrylate (GelMA) cores to enclose mesenchymal cells (MSCs) and mouse epidermal cells (EPCs). The findings indicated that the glycosaminoglycan-based HAD shells display thermodynamic incompatibility with GelMA cores, resulting in the aqueous phase separation of G/HAD cell spheres. These G/HAD microspheres exhibited favorable characteristics, including sustained growth factor release and wet adhesion properties. After transplantation into the dorsal skin of BALB/c nude mice, G/HAD cell microspheres efficiently induced the regeneration of HFs. This approach enables the mass production of approximately 250 dual-layer microspheres per minute. Thus, this dual-layer microsphere fabrication method holds great potential in improving current hair regeneration techniques and can also be combined with other tissue engineering techniques for various regenerative purposes.

Neuroprotection and Mechanism of Gas-miR36-5p from Gastrodia elata in an Alzheimer's Disease Model by Regulating Glycogen Synthase Kinase-3ß.

Alzheimer's disease (AD) is currently the most common neurodegenerative disease. Glycogen synthase kinase 3ß (GSK-3ß) is a pivotal factor in AD pathogenesis. Recent research has demonstrated that plant miRNAs exert cross-kingdom regulation on the target genes in animals. Gastrodia elata (G. elata) is a valuable traditional Chinese medicine that has significant pharmacological activity against diseases of the central nervous system (CNS). Our previous studies have indicated that G. elata-specific miRNA plays a cross-kingdom regulatory role for the NF-κB signaling pathway in mice. In this study, further bioinformatics analysis suggested that Gas-miR36-5p targets GSK-3ß. Through western blot, RT-qPCR, and assessments of T-AOC, SOD, and MDA levels, Gas-miR36-5p demonstrated its neuroprotective effects in an AD cell model. Furthermore, Gas-miR36-5p was detected in the murine brain tissues. The results of the Morris water maze test and western blot analysis provided positive evidence for reversing the learning deficits and hyperphosphorylation of Tau in AD mice, elucidating significant neuroprotective effects in an AD model following G. elata RNA administration. Our research emphasizes Gas-miR36-5p as a novel G. elata-specific miRNA with neuroprotective properties in Alzheimer's disease by targeting GSK-3ß. Consequently, our findings provide valuable insights into the cross-kingdom regulatory mechanisms underlying G. elata-specific miRNA, presenting a novel perspective for the treatment of Alzheimer's disease.

Gastrodia elata specific miRNA attenuates neuroinflammation via modulating NF-κB signaling pathway.

AIMS: Based on our previous research on the specific miRNAs identified from Gastrodia elata, we selected Gas-miR2-3p to investigate its effects on neuroinflammation via in vitro and in vivo experiments. RESULTS: RT-qPCR analysis indicated that G. elata specific Gas-miR2-3p was detected in all murine tissues post-oral administration, suggesting their potential as orally bioavailable miRNA. The analysis of RT-qPCR, Western blotting and ELISA assays consistently demonstrate that the expression of inflammatory factors as TNF-α, IL-6, IL-1ß was decreased and the expression levels of p-p65 and p-IκBα were downregulated after the action of Gas-miR2-3p in both cell and animal experiments. CONCLUSION: Gas-miR2-3p can attenuate neuroinflammation by regulating the inflammation factors and suppressing the activation of the NF-κB signaling pathway. Our findings indicate that G. elata miRNAs, as novel active components, perform a modulatory role in the NF-κB signaling pathway associated with neuroinflammation in a cross-species way.

Comparison of Percutaneous Endoscopic Transforaminal and Interlaminar Approaches in Treating Adjacent Segment Disease Following Lumbar Decompression Surgery: A Clinical Retrospective Study.

BACKGROUND: Adjacent segment disease (ASD) is a common complication following posterior disc decompression and fusion surgery. Percutaneous endoscopic lumbar decompression surgery (PELD) has been used to treat ASD through either a transforaminal or interlaminar approach. However, to our limited knowledge there are no reports comparing the 2 approaches for treating ASD. OBJECTIVE: To evaluate clinical outcomes of PELD in treating ASD and comparing the surgical results and complications between the 2 approaches. This may be helpful for spinal surgeons when decision-making ASD treatment. STUDY DESIGN: A clinical retrospective study. SETTING: This study was conducted at the Department of Orthopedics of the Affiliated Hospital of Qingdao University. METHODS: From January 2015 through December 2019, a total of 68 patients with ASD who underwent PELD after lumbar posterior decompression with fusion surgery were included in this study. The patients were divided into a percutaneous endoscopic transforaminal decompression (PETD) group and a percutaneous endoscopic interlaminar decompression (PEID) group according to the approach used. The demographic characteristics, radiographic and clinical outcomes, and complications were recorded in both groups through a chart review. RESULTS: Of the 68 patients, 40 underwent PEID and 28 patients underwent PETD. Compared with their preoperative Visual Analog Scale (VAS) pain score and Oswestry Disability Index (ODI) score, all patients had significant postoperative improvement at 3 months, 6 months, one year and at the latest follow-up. There were no significant statistical differences in the VAS and ODI scores between PETD and PEID groups with a P value > 0.05. There was a significant statistical difference in the average fluoroscopy times between the PETD and PEID groups with a P value = 0.000. Revision surgery occurred in 8 patients: 6 patients who underwent PETD and 2 patients who underwent PEID. The revision rate showed a significant statistical difference between the 2 approaches with a P value = 0.039. LIMITATIONS: Firstly, the number of patients included in this study was small. More patients are needed in a further study. Secondly, the follow-up time was limited in this study. There is still no conclusion about whether the primary decompression with instruments will increase the reoperation rate after a PELD, and a longer follow-up is needed in the future. Thirdly, this study was a clinical retrospective study. Randomized or controlled trials are needed in the future in order to achieve a higher level of evidence. Fourthly, there were debates about PELD approach choices for ASDs, which may affect the comparison results between PETD and PEID. In our study, the approaches were mainly determined by the level and types of disc herniation, and the surgeons' preference. More patients with an ASD with different levels and types of disc herniation and surgical approaches are needed in the future to eliminate these biases. CONCLUSION: Percutaneous endoscopic lumbar decompression surgery is a feasible option for ASD following lumbar decompression surgery with instruments. Compared with PETD, PEID seems to be a better approach to treat symptomatic ASDs.

Photocurable injectable Janus hydrogel with minimally invasive delivery for all-in-one treatment of gastric perforations and postoperative adhesions.

Background: Surgical sutures for sealing gastric perforations (GP) are associated with severe inflammation and postoperative adhesions. Hydrogel bioadhesives offer a potential alternative for sutureless repair of GP; however, their application in minimally invasive surgery is limited due to their prefabricated patch-form, lacking in situ gelation capability. In this study, we emphasized an all-in-one minimally invasive strategy for sutureless repair of acute GP. Methods: an injectable photocurable Janus hydrogel was synthesized, and their ability to seal GP was performed. A rat GP model was used to verify the wound healing and antiadhesion efficiency of hydrogels, and a rabbit GP model was used to verify their laparoscopic feasibility. A fresh human corpse GP model was further employed to verify the user-friendliness of a minimally invasive deliverable (MID) device. A minipig GP model was utilized to evaluate the all-in-one minimally invasive strategy for the treatment of acute GP. Results: Such injectable Janus hydrogel exhibited asymmetric adhesiveness, where the inner-facing side of the hydrogel displays strong sealing and wound healing abilities for GP, while the outward-facing side prevents postoperative adhesion formation. We further developed a minimally invasive deliverable (MID) device integrating hydrogel-delivery parts and photocrosslinking-gelation parts in a laparoscope system. The precise delivery and rapid fluid-tight sealing process of the injectable Janus hydrogel using the MID device for in situ GP repair were demonstrated in a simulated clinical scenario. The in vivo effectiveness of GP sutureless repair was successfully validated in porcine models, with further exploration of the underlying mechanism. Conclusions: Our findings reveal that the injectable Janus hydrogel offers an all-in-one strategy for sutureless GP repair and concurrent prevention of postoperative adhesion formation by incorporating the MID device in minimally invasive surgery, presenting the significant potential to reduce patient surgical complications.

Effects of rational emotive behavior therapy on alexithymia, anxiety, depression and sleep quality of older people in nursing homes: a quasi-experimental study.

BACKGROUND: Alexithymia, a subclinical cognitive-affective impairment, is prevalent in older people and increases the risk of mental disorders. There is a vast alexithymia treatment gap, with majority of older people in nursing homes lacking access to adequate mental health care. The study aimed to evaluate the effects of rational emotive behavior therapy (REBT) on alexithymia, anxiety, depression and sleep quality of older people in nursing homes. METHODS: This quasi-experimental study was conducted with two groups (the control group and intervention) from March to November 2021. This study enrolled 86 participants, two of whom were lost to follow-up; 42 received usual care (control group) and 42 received REBT based on usual care (intervention group) in nursing homes. The older people in both groups were evaluated at baseline (T0), within one-week post-intervention (T1), and at 3-month follow-up (T3). Generalized estimating equations were used by SPSS version 26 to assess the differential change in the outcomes between the two groups. RESULTS: The intervention group shows significantly greater improvement in alexithymia than the control group at both T1 (ß = -8.167, 95%CI= -10.965, -5.368, P < 0.001) and T2 (ß=-4.119, 95%CI= -7.171, -1.067, P = 0.008). The two groups showed significant differences at both T1 and T2 in both difficulty identifying feelings and difficulty describing feelings. Compared to the control group, the intervention group shows a significant improvement in sleep quality at T2 (ß = -2.048, 95%CI=-4.004, -0.091, P = 0.040). The two groups showed significant differences at both T1 and T2 in both sleep disturbance and daytime dysfunction. For depression and anxiety, no significant differences were found between the intervention and control groups. CONCLUSIONS: REBT showed to be an effective method for improving alexithymia and sleep quality of older people in nursing homes. However, it failed to significantly alleviate anxiety and depression at least in a short-term trial. Refining this intervention may have a broader, more substantial impact on future research.

A modular hydrogel bioink containing microsphere-embedded chondrocytes for 3D-printed multiscale composite scaffolds for cartilage repair.

Articular cartilage tissue engineering is being considered an alternative treatment strategy for promoting cartilage damage repair. Herein, we proposed a modular hydrogel-based bioink containing microsphere-embedded chondrocytes for 3D printing multiscale scaffolds integrating the micro and macro environment of the native articular cartilage. Gelatin methacryloyl (GelMA)/alginate microsphere was prepared by a microfluidic approach, and the chondrocytes embedded in the microspheres remained viable after being frozen and resuscitated. The modular hydrogel bioink could be printed via the gel-in-gel 3D bioprinting strategy for fabricating the multiscale hydrogel-based scaffolds. Meanwhile, the cells cultured in the scaffolds showed good proliferation and differentiation. Furthermore, we also found that the composite hydrogel was biocompatible in vivo. These results indicated that the modular hydrogel-based bioinks containing microsphere-embedded chondrocytes for 3D printing multiscale scaffolds could provide a 3D multiscale environment for enhancing cartilage repairing, which would be encouraging considering the numerous alternative applications in articular cartilage tissue engineering.

The efficacy and safety of sodium tanshinone â ¡A sulfonate injection in the treatment of unstable angina pectoris: A systematic review and meta-analysis.

OBJECTIVE: To systematically evaluate the efficacy and safety of Sodium tanshinone ⅡA sulfonate injection (STS) in the treatment of unstable angina pectoris (UAP). METHODS: CNKI, Wanfang, VIP, CBM, PubMed, Cochrane Library, Web of Science, Embase were searched by computer. The research covers the clinical randomized controlled trials of STS in the treatment of unstable angina pectoris published from the establishment of the library to January 31, 2023. Two researchers independently screened the literature, extracted data and evaluated the risk of research bias, and then conducted meta-analysis with RevMan5.3 software. RESULTS: A total of 37 randomized controlled trials were included, involving 3926 patients in total. Meta analysis results showed that, compared with conventional western medicine alone, STS combined with conventional western medicine could reduce the frequency (SMD = -2.61, 95%CI[-4.27, -0.96], P = 0.002) and duration (SMD = -4.01, 95%CI[-6.18, -1.84], P = 0.0003) of angina pectoris, improve ECG efficacy (OR = 3.61, 95%CI[2.79, 4.68], P<0.00001) and clinical symptom efficacy (OR = 4.02, 95%CI[3.32, 4.87], P<0.00001), reduce TG(SMD = -0.60, 95%CI[-1.04, -0.16], P = 0.008), TC(SMD = -3.86, 95%CI[-6.37, -1.34], P = 0.003), and LDL-C(SMD = -1.54, 95%CI[-2.67, -0.42], P = 0.007), decrease plasma viscosity(SMD = -1.02, 95%CI[-1.58, -0.47], P<0.0003), whole blood low shear viscosity(SMD = -0.85, 95%CI[-1.21, -0.49], P<0.00001), whole blood high shear viscosity(SMD = -0.82, 95%CI[-1.44, -0.20], P = 0.009), and erythrocyte aggregation index(SMD = -1.00, 95%CI[-1.75, -0.25], P = 0.009), and bring down CRP(SMD = -1.39, 95%CI[-1.91, -0.86], P<0.00001). The incidence of adverse reactions in the treatment group was higher than that in the control group (OR = 2.26, 95%CI[1.06, 4.85], P = 0.04). Neither of the two groups suffered from abnormal liver and kidney function during the study process. CONCLUSION: STS combined with routine treatment has a definite clinical efficacy and certain safety in the treatment of UAP, but it needs to be further confirmed by high-quality and low-bias randomized controlled trials in the future.

Injectable photocurable Janus hydrogel delivering hiPSC cardiomyocyte-derived exosome for post-heart surgery adhesion reduction.

Postsurgical pericardial adhesions pose increased risks of sequelae, prolonged reoperation time, and reduced visibility in the surgical field. Here, we introduce an injectable Janus hydrogel, which exhibits asymmetric adhesiveness properties after photocrosslinking, sustained delivering induced pluripotent stem cell-derived cardiomyocyte exosomes (iCM-EXOs) for post-heart surgery adhesion reduction. Our findings reveal that iCM-EXOs effectively attenuate oxidative stress in hydrogen peroxide-treated primary cardiomyocytes by inhibiting the activation of the transcription factor nuclear factor erythroid 2-related factor 2. Notably, in rat cardiac postsurgery models, the Janus hydrogels loaded with iCM-EXOs demonstrate dual functionality, acting as antioxidants and antipericardial adhesion agents. These hydrogels effectively protect iCM-EXOs from GATA6+ cavity macrophage clearance by inhibiting the recruitment of macrophages from the thoracic cavity. These results highlight the promising potential of iCM-EXO-laden Janus hydrogels for clinical safety and efficacy validation in trials involving heart surgery patients, with the ultimate goal of routine administration during open-heart surgeries.

Single-cell analyses reveal cannabidiol rewires tumor microenvironment via inhibiting alternative activation of macrophage and synergizes with anti-PD-1 in colon cancer.

Colorectal tumors often create an immunosuppressive microenvironment that prevents them from responding to immunotherapy. Cannabidiol (CBD) is a non-psychoactive natural active ingredient from the cannabis plant that has various pharmacological effects, including neuroprotective, antiemetic, anti-inflammatory, and antineoplastic activities. This study aimed to elucidate the specific anticancer mechanism of CBD by single-cell RNA sequencing (scRNA-seq) and single-cell ATAC sequencing (scATAC-seq) technologies. Here, we report that CBD inhibits colorectal cancer progression by modulating the suppressive tumor microenvironment (TME). Our single-cell transcriptome and ATAC sequencing results showed that CBD suppressed M2-like macrophages and promoted M1-like macrophages in tumors both in strength and quantity. Furthermore, CBD significantly enhanced the interaction between M1-like macrophages and tumor cells and restored the intrinsic anti-tumor properties of macrophages, thereby preventing tumor progression. Mechanistically, CBD altered the metabolic pattern of macrophages and related anti-tumor signaling pathways. We found that CBD inhibited the alternative activation of macrophages and shifted the metabolic process from oxidative phosphorylation and fatty acid oxidation to glycolysis by inhibiting the phosphatidylinositol 3-kinase-protein kinase B signaling pathway and related downstream target genes. Furthermore, CBD-mediated macrophage plasticity enhanced the response to anti-programmed cell death protein-1 (PD-1) immunotherapy in xenografted mice. Taken together, we provide new insights into the anti-tumor effects of CBD.

RNA-sequencing approach for exploring the protective mechanisms of dexmedetomidine on pancreatic injury in severe acute pancreatitis.

Background: Severe acute pancreatitis (SAP) is a severe form of acute pancreatitis with the potential to cause life-threatening complications. Patients with acute SAP require surgical intervention and are admitted to the intensive care unit for non-invasive ventilation. Dexmedetomidine (Dex) is currently used by intensive care clinicians and anaesthesiologists as an adjunctive sedative. Therefore, the clinical availability of Dex makes it easier to implement in SAP treatment than developing new drugs. Methods: Randomly dividing thirty rats into sham-operated (Sham), SAP, and Dex groups. The severity of pancreatic tissue injury in each rat was assessed by Hematoxylin and eosin (HE) staining. Serum amylase activity and inflammatory factor levels were measured using commercially available kits. The expressions of necroptosis-related proteins, myeloperoxidase (MPO), CD68, and 4-hydroxy-trans-2-nonenal (HNE) were detected using immunohistochemistry (IHC). Transferase-mediated dUTP nick-end labeling (TUNEL) staining was utilized to identify pancreatic acinar cell apoptosis. The subcellular organelle structure of pancreatic acinar cells was observed using transmission electron microscopy. The regulatory effect of Dex on the gene expression profile of SAP rat pancreas tissue was investigated using RNA sequencing. We screened for differentially expressed genes (DEGs). Quantitative real-time PCR (qRT-PCR) measured critical DEG mRNA expression in rat pancreatic tissues. Results: Dex attenuated SAP-induced pancreatic injury, infiltration of neutrophils and macrophages, and oxidative stress. Dex inhibited the expression of necroptosis-associated proteins RIPK1, RIPK3, and MLKL and alleviated apoptosis in acinar cells. Dex also mitigated the structural damage caused by SAP to mitochondria and endoplasmic reticulum. Dex inhibited SAP-induced 473 DEGs, as determined by RNA sequencing. Dex may regulate SAP-induced inflammatory response and tissue damage by inhibiting the toll-like receptor/nuclear factor κB (TLR/NF-κB) signaling pathway and neutrophil extracellular trap formation. Conclusion: This study elucidated the remarkable effect of Dex against SAP and investigated the potential mechanism of action, providing an experimental base for the future clinical application of Dex in the treatment of SAP.