Commentary on the "A multidisciplinary opioid-reduction pathway for robotic prostatectomy: outcomes at year one".

BACKGROUND: Opioid-sparing multimodal analgesia is increasingly emphasized for postoperative pain management. This commentary discusses a study by Manning et al. on an opioid reduction pathway for robotic prostatectomy. METHODS: We reviewed the Manning et al. study, which implemented a multidisciplinary opioid reduction pathway and compared outcomes before and after pathway implementation. Outcomes included opioid use, pain scores, antiemetic use, length of stay, and readmissions. RESULTS: The study found reduced opioid consumption, lower antiemetic use, shorter length of stay, and similar pain scores after pathway implementation. However, the pre-post-study design has limitations in attributing causality to the pathway itself. Key confounders were not fully accounted for. The clinical significance of the small reduction in length of stay is also questionable. CONCLUSIONS: This commentary highlights important limitations of the Manning et al. study, including the retrospective design, potential confounding factors, small effect size, and lack of long-term outcomes. While the study provides early evidence for a multidisciplinary opioid reduction approach, further rigorous prospective research is needed to confirm the observed benefits and long-term impacts. Additional focus on direct opioid consumption, equivalent analgesia assessment, and clinically meaningful outcomes is warranted.

Men's symptom experience throughout androgen deprivation therapy for prostate cancer: A systematic review and meta-aggregation.

BACKGROUND: Androgen deprivation therapy is a common treatment for men with advanced prostate cancer. They have experienced many complex symptoms that affect their quality of life. However, qualitative reviews that synthesize the symptom experience for men with prostate cancer are lacking. OBJECTIVE: To explore the men's symptom experience throughout androgen deprivation therapy for prostate cancer. DESIGN: A qualitative evidence synthesis using meta-aggregation. DATA RESOURCES: Published and unpublished literature between January 2001 and August 2023 were identified from PubMed, Embase (Ovid), Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL), The Cochrane Library, ProQuest, Google Scholar, China National Knowledge Infrastructure (CNKI), Wang Fang, and VIP. REVIEW METHODS: Two reviewers independently conducted screening, study selection and data extraction, and quality appraisal was performed using the Joanna Briggs Institutes Critical Appraisal Checklist for Qualitative Research. Data synthesis was conducted using meta-aggregative approach. RESULTS: 24 articles of moderate to high methodological quality were included. A total of 98 findings were extracted with 59 unequivocal or equivocal findings eligible for meta-aggregation, aggregated into nine categories, and developed four synthesized findings: (1) production of symptoms: unrecognized and underestimated, (2) perception of symptoms: varied and complicated, (3) meaning of symptoms: threatened and affected, and (4) response to symptoms: push and pull. CONCLUSIONS: Men throughout androgen deprivation for prostate cancer experience the four crisis-packed stages in their symptomatic journey. Health care provider need to understand the men's thoughts whether in the process of shared decision-making or in the course of the chosen therapy. Future research should develop individual suitable interventions and offer practical strategies for managing symptom. PROSPERO registration: CRD42023449129.

The prognostic value of prognostic nutritional index and renal function indicators for mortality prediction in severe COVID-19 elderly patients: A retrospective study.

Identifying prognostic factors in elderly patients with severe coronavirus disease 2019 (COVID-19) is crucial for clinical management. Recent evidence suggests malnutrition and renal dysfunction are associated with poor outcome. This study aimed to develop a prognostic model incorporating prognostic nutritional index (PNI), estimated glomerular filtration rate (eGFR), and other parameters to predict mortality risk. This retrospective analysis included 155 elderly patients with severe COVID-19. Clinical data and outcomes were collected. Logistic regression analyzed independent mortality predictors. A joint predictor "L" incorporating PNI, eGFR, D-dimer, and lactate dehydrogenase (LDH) was developed and internally validated using bootstrapping. Decreased PNI (OR = 1.103, 95% CI: 0.78-1.169), decreased eGFR (OR = 0.964, 95% CI: 0.937-0.992), elevated D-dimer (OR = 1.001, 95% CI: 1.000-1.004), and LDH (OR = 1.005, 95% CI: 1.001-1.008) were independent mortality risk factors (all P < .05). The joint predictor "L" showed good discrimination (area under the curve [AUC] = 0.863) and calibration. The bootstrapped area under the curve was 0.858, confirming model stability. A combination of PNI, eGFR, D-dimer, and LDH provides useful prognostic information to identify elderly patients with severe COVID-19 at highest mortality risk for early intervention. Further external validation is warranted.

Clinical features and surgical management of traumatic acquired isolated superior rectus palsy.

PURPOSE: Isolated acquired superior rectus palsy (ASRP) is extremely rare. The goal of this report is to describe the clinical manifestations and surgical protocols for treatment of isolated traumatic ASRP. DESIGN: Retrospective observational case series. METHOD: Records of patients presenting with traumatic isolated ASRP from 2011 to 2020 were retrospectively reviewed. Variables analyzed included nature of the damage, ocular alignment, ocular motility, binocular vision, fundus photography, imaging and surgical treatment. RESULT: Of the 23,498 strabismus surgeries performed, 16 (0.07%) were identified as being attributable to traumatic isolated ASRP. Iatrogenic injury during orbital/brain tumorectomy was the most common cause for ASRP, followed by injury resulting from a sharp object, blunt instrument, car accident, dog bite, accidental fall and explosion. The main clinical features were hypotropia and deficient supraduction of the affected eye, accompanied by exotropia, extorsion, decreased vision and ptosis. The imaging examination showed the superior orbital wall fracture in 3 cases and superior rectus rupture in 7 cases. Inferior rectus recession and/or superior rectus resection comprised the major surgical procedures employed for these cases. Vertical deviations were reduced from 45.60 ± 17.52 PD preoperatively to 12.20 ± 12.97 PD postoperatively after an average of 22.70 months at follow-up, with a success rate of 50%. CONCLUSION: Traumatic isolated ASRP comprised only 0.07% of cases receiving strabismus surgery at our hospital. Orbital imaging is essential to identify whether muscle rupture, orbital fractures and/or other possible disorders are present. Superior rectus resection and inferior rectus recession represented the most frequently used surgical procedures.

CPK1-HSP90 phosphorylation and effector XopC2-HSP90 interaction underpin the antagonism during cassava defense-pathogen infection.

Cassava is one of the most important tropical crops, but it is seriously affected by cassava bacteria blight (CBB) caused by the bacterial pathogen Xanthomonas phaseoli pv manihotis (Xam). So far, how pathogen Xam infects and how host cassava defends during pathogen-host interaction remains elusive, restricting the prevention and control of CBB. Here, the illustration of HEAT SHOCK PROTEIN 90 kDa (MeHSP90.9) interacting proteins in both cassava and bacterial pathogen revealed the dual roles of MeHSP90.9 in cassava-Xam interaction. On the one hand, calmodulin-domain protein kinase 1 (MeCPK1) directly interacted with MeHSP90.9 to promote its protein phosphorylation at serine 175 residue. The protein phosphorylation of MeHSP90.9 improved the transcriptional activation of MeHSP90.9 clients (SHI-RELATED SEQUENCE 1 (MeSRS1) and MeWRKY20) to the downstream target genes (avrPphB Susceptible 3 (MePBS3) and N-aceylserotonin O-methyltransferase 2 (MeASMT2)) and immune responses. On the other hand, Xanthomonas outer protein C2 (XopC2) physically associated with MeHSP90.9 to inhibit its interaction with MeCPK1 and the corresponding protein phosphorylation by MeCPK1, so as to repress host immune responses and promote bacterial pathogen infection. In summary, these results provide new insights into genetic improvement of cassava disease resistance and extend our understanding of cassava-bacterial pathogen interaction.

Association between nocturnal blood pressure phenotype and adverse cardiovascular prognosis in patients with coronary heart disease and hypertension.

Nocturnal blood pressure and nighttime dipping patterns are associated with the occurrence of cardiovascular events. However, there is few research on whether riser pattern is associated with the poor prognosis of patients with coronary heart disease (CHD) and hypertension independent of nighttime systolic blood pressure (SBP). This prospective and observational clinical study included 568 hospitalized patients with CHD and hypertension. All patients underwent 24-h ambulatory blood pressure (BP) monitoring during their hospitalization. Multivariate adjusted Cox proportional hazard models were utilized to examine the associations of nocturnal blood pressure and dipping status with primary endpoint events. Additionally, Harrell's C-statistics were employed to compare the discriminative ability of each model. During the 1-year follow-up period, 64 (11.3%) primary endpoint events were recorded, including 55 (9.7%) atherosclerotic cardiovascular disease (ASCVD) events. After adjusting for demographic and clinical risk variables, nighttime SBP was significantly related to the risk of incident primary endpoint events [per 20 mm Hg increase: hazard ratio (HR) = 1.775, 95% confidence interval (CI) 1.256-2.507]. The riser pattern group exhibited a significantly higher risk for primary endpoint events compared to the dipper pattern group, even after adjusting for office SBP (HR: 2.687, 95% CI: 1.015-7.110, p = .047). Furthermore, the addition of nighttime SBP or dipping status to the base model yielded statistically significant increments in C-statistic values (p = .036 and p = .007). However, adding both nighttime SBP and dipping status did not significantly enhance the model's performance in predicting the risk of primary endpoint events and ASCVD events according to the C-index (p = .053 and p = .054), which meant that the riser pattern group did not exhibit a significantly higher risk for primary endpoint events compared to the dipper pattern group after adjusting for nighttime SBP. In conclusion, nocturnal SBP and riser pattern demonstrated an association with adverse prognosis in patients with CHD and hypertension. Notably, nocturnal SBP proved to be a more reliable predictor than dipping status.

circ_0039787 promotes cervical cancer cell tumorigenesis by regulation of the miR-877-5p-KRAS axis.

Circular RNA (circRNA) is a novel type of RNA that plays an important role in the occurrence and development of many malignant tumors. However, the potential regulatory role and molecular mechanisms of circRNAs in cervical cancer (CC) are still not clear. Here, we explored circRNAs associated with CC from the Gene Expression Omnibus (GEO) datasets GSE113696 and GSE102686. We initially identified circ_0039787, which is derived from exons 2 to 3 of the C16orf70 gene. We observed that circ_0039787 is mainly located in the cytoplasm and is more stable than its linear counterpart, C16orf70. circ_0039787 is significantly upregulated in CC tissues and cells. In addition, functional gain and loss experiments demonstrated that circ_0039787 promotes the proliferation, migration, and invasion of CC cells in vitro and the growth of CC tumors in vivo. Mechanistically, circ_0039787 promotes CC tumor progression by competitively absorbing miR-877-5p to alleviate the inhibitory effect of miR-877-5p on Kirsten Rat Sarcoma viral oncogene homolog (KRAS) expression. Overall, our results suggest that circ_0039787 could serve as a promising diagnostic biomarker and potential therapeutic target for CC patients.

Association between apolipoprotein B/A1 ratio and quantities of tissue prolapse on optical coherence tomography examination in patients with atherosclerotic cardiovascular disease.

Atherosclerotic cardiovascular disease (ASCVD) continues to be a major health concern globally. Apolipoprotein (Apo) B/A1 ratio is a reliable predictor of ASCVD and an important factor in assessing the risk of myocardial infarction. Tissue prolapse (TP) is defined as the tissue extrusion into the lumen through the stent struts after implantation, which is a significant factor for poor short-term outcomes such as acute and subacute thrombosis, severe myocardial necrosis, and vulnerable plaque. Therefore, the aim of this study was to investigate the relationship between Apo B/A1, plaque vulnerability, and tissue prolapse on optical coherence tomography (OCT). This study enrolled 199 patients with atherosclerotic cardiovascular disease (ASCVD) who underwent percutaneous coronary intervention (PCI). Both pre- and post-procedural optical coherence tomography (OCT) examinations were conducted to assess TP volume and plaque morphology. Logistic regression analyses were performed to identify potential risk factors for tissue prolapse volume. Receiver operator characteristic (ROC) curve analysis was carried out to evaluate the value of the Apo B/A1 ratio for tissue prolapse volume. The high Apo B/A1 ratio group showed a larger TP volume (P = 0.001) and a higher percentage of plaque rupture and erosion in comparison to the low Apo B/A1 ratio group (P = 0.022 and P = 0.008). The high Apo B/A1 ratio group and the high TP volume group also had a higher proportion of thin-cap fibroatheroma (TCFA) (P = 0.046, P = 0.021). Multivariate logistic regression analysis revealed that both Apo B/A1 ratio (odds ratio [OR]: 1.041, 95% confidence interval [CI] 1.007-1.076; P = 0.019) and TCFA (OR: 3.199, 95%CI 1.133-9.031; 0.028) were significantly related to high TP volume. Furthermore, the area under the curve (AUC) for predictive value of TP volume was 0.635 for Apo B/A1 (95% CI 0.554-0.717, P = 0.002) compared to 0.615 for low density lipoprotein cholesterol (LDL-C) (95% CI 0.533-0.697, P = 0.008). The Apo B/A1 ratio is an independent predictor of TP volume on OCT and is related to plaque vulnerability.

BPSegSys: A Brachial Plexus Nerve Trunk Segmentation System Using Deep Learning.

OBJECTIVE: Ultrasound-guided nerve block anesthesia (UGNB) is a high-tech visual nerve block anesthesia method that can be used to observe the target nerve and its surrounding structures, the puncture needle's advancement and local anesthetics spread in real time. The key in UGNB is nerve identification. With the help of deep learning methods, the automatic identification or segmentation of nerves can be realized, assisting doctors in completing nerve block anesthesia accurately and efficiently. METHODS: We established a public data set containing 320 ultrasound images of brachial plexus (BP). Three experienced doctors jointly produced the BP segmentation ground truth and labeled brachial plexus trunks. We designed a brachial plexus segmentation system (BPSegSys) based on deep learning. RESULTS: BPSegSys achieves experienced-doctor-level nerve identification performance in various experiments. We evaluated BPSegSys performance in terms of intersection-over-union (IoU). Considering three data set groups in our established public data set, the IoUs of BPSegSys were 0.5350, 0.4763 and 0.5043, respectively, which exceed the IoUs 0.5205, 0.4704 and 0.4979 of experienced doctors. In addition, we determined that BPSegSys can help doctors identify brachial plexus trunks more accurately, with IoU improvement up to 27%, which has significant clinical application value. CONCLUSION: We establish a data set for brachial plexus trunk identification and designed a BPSegSys to identify the brachial plexus trunks. BPSegSys achieves the doctor-level identification of the brachial plexus trunks and improves the accuracy and efficiency of doctors' identification of the brachial plexus trunks.

Coat protein of cassava common mosaic virus targets RAV1 and RAV2 transcription factors to subvert immunity in cassava.

Cassava common mosaic virus (CsCMV, genus Potexvirus) is a prevalent virus associated with cassava mosaic disease, so it is essential to elucidate the underlying molecular mechanisms of the coevolutionary arms race between viral pathogenesis and the cassava (Manihot esculenta Crantz) defense response. However, the molecular mechanism underlying CsCMV infection is largely unclear. Here, we revealed that coat protein (CP) acts as a major pathogenicity determinant of CsCMV via a mutant infectious clone. Moreover, we identified the target proteins of CP-related to abscisic acid insensitive3 (ABI3)/viviparous1 (VP1) (MeRAV1) and MeRAV2 transcription factors, which positively regulated disease resistance against CsCMV via transcriptional activation of melatonin biosynthetic genes (tryptophan decarboxylase 2 (MeTDC2), tryptamine 5-hydroxylase (MeT5H), N-aceylserotonin O-methyltransferase 1 (MeASMT1)) and MeCatalase6 (MeCAT6) and MeCAT7. Notably, the interaction between CP, MeRAV1, and MeRAV2 interfered with the protein phosphorylation of MeRAV1 and MeRAV2 individually at Ser45 and Ser44 by the protein kinase, thereby weakening the transcriptional activation activity of MeRAV1 and MeRAV2 on melatonin biosynthetic genes, MeCAT6 and MeCAT7 dependent on the protein phosphorylation of MeRAV1 and MeRAV2. Taken together, the identification of the CP-MeRAV1 and CP-MeRAV2 interaction module not only illustrates a molecular mechanism by which CsCMV orchestrates the host defense system to benefit its infection and development but also provides a gene network with potential value for the genetic improvement of cassava disease resistance.

MMP-9 inhibition alleviates postoperative cognitive dysfunction by improving glymphatic function via regulating AQP4 polarity.

Postoperative cognitive dysfunction (POCD) is a common complication after surgery, characterized by deficits in memory, attention and cognitive flexibility. However, the underlying mechanisms of POCD remain unclear. Neuroinflammation and blood-brain barrier disruption have been implicated as potential pathological processes. This study explores the neuroprotective effects and mechanisms of the matrix metalloproteinase（MMP-9）inhibitor GM6001 against POCD. We hypothesize GM6001 may reduce neuroinflammation and preserve blood-brain barrier integrity through direct inhibition of MMP-9. Moreover, GM6001 may stabilize aquaporin-4 polarity and glymphatic clearance function by modulating MMP-9-mediated cleavage of dystroglycan, a key protein for aquaporin-4 anchoring. Our results demonstrate GM6001 alleviates postoperative cognitive deficits and neuroinflammation. GM6001 also preserves blood-brain barrier integrity and rescues aquaporin-4 mislocalization after surgery. This study reveals a novel dual role for MMP-9 inhibition in cognitive protection through direct anti-neuroinflammatory effects and regulating aquaporin-4 membrane distribution. Targeting MMP-9 may represent a promising strategy to prevent postoperative cognitive dysfunction by integrating multiple protective mechanisms.

Prevalence of work-related musculoskeletal disorders in neck and shoulder among workers in pharmaceutical and chemical enterprises / 预防医学

Objective@#To investigate the prevalence and influencing factors of work-related musculoskeletal disorders (WMSDs) in neck and shoulder among workers in pharmaceutical and chemical enterprises, so as to provide the basis for prevention of WMSDs.@*Methods@#Workers in 8 pharmaceutical and chemical enterprises in Jinhua City, Zhejiang Province from July to October 2023 were sampled using a stratified random sampling method, and demography, work conditions and WMSDs prevalence were collected using questionnaire surveys. Factors affecting WMSDs in neck and shoulder were analyzed using a multivariable logistic regression model.@*Results@#A total of 1 343 workers were surveyed, including 496 males (36.93%) and 847 females (63.07%). The mean age of workers was 38 (15) years, and the length of service in current posts was 6 (8) years. There were 356 workers with WMSDs (26.51%), with 206 workers with neck WMSDs (15.34%) and 167 workers with shoulder WMSDs (12.43%). Multivariable logistic regression analysis showed that gender (female, OR=1.692, 95%CI: 1.203-2.381), sufficient rest time (OR=0.660, 95%CI: 0.471-0.926) and maintaining same neck posture for a long time (OR=1.690, 95%CI: 1.148-2.510) were factors affecting neck WMSDs; gender (female, OR=1.572, 95%CI: 1.060-2.311), sufficient rest time (OR=0.619, 95%CI: 0.422-0.906), repetitive daily work (OR=1.678, 95%CI: 1.064-2.647), uncomfortable work posture (OR=3.791, 95%CI: 1.330-10.803), multiple repetitive movements per minute (OR: 1.988-2.413, 95%CI: 1.060-4.161) and maintaining same neck posture for a long time (OR=1.926, 95%CI: 1.218-3.043) were factors affecting shoulder WMSDs.@*Conclusion@#The prevalence of WMSDs in neck and shoulder are high among workers in pharmaceutical and chemical enterprises in Jinhua City, and mainly affected by gender, rest time and adverse ergonomics.

Surgical outcomes of bilateral lateral rectus recession versus unilateral recession and resection for the divergence excess type of intermittent exotropia.

Purpose: To compare bilateral lateral rectus recession (BLR) with unilateral recession and resection (RR) for divergence excess intermittent exotropia (IXT). Methods: Retrospective analysis of 66 patients with divergence excess IXT who underwent either BLR or RR from January 2013 to December 2020 was conducted. Data on demographics, pre- and postoperative deviations, fusion, stereopsis, control, and accommodative convergence/accommodation ratio were collected. Success was defined as esodeviation ≤5 PD (prism diopter) to exodeviation ≤10 PD with a follow-up time of at least 8.0 ± 2.0 weeks. Results: BLR (42 cases) and RR (24 cases) groups had the same success rate (83.3%, P = 0.688) and similar reduced postoperative deviations both in distance and at near (P > 0.05). Near-distance disparity decreased significantly in both groups (P = 0.000) with no intergroup difference (P = 0.193). Conclusion: BLR and RR were equally effective for divergence excess IXT with comparable outcomes of both distance and near deviations.

AQP4 is an Emerging Regulator of Pathological Pain: A Narrative Review.

Pathological pain presents significant challenges in clinical practice and research. Aquaporin-4 (AQP4), which is primarily found in astrocytes, is being considered as a prospective modulator of pathological pain. This review examines the association between AQP4 and pain-related diseases, including cancer pain, neuropathic pain, and inflammatory pain. In cancer pain, upregulated AQP4 expression in tumor cells is linked to increased pain severity, potentially through tumor-induced inflammation and edema. Targeting AQP4 may offer therapeutic strategies for managing cancer pain. AQP4 has also been found to play a role in nerve damage. Changes in AQP4 expression have been detected in pain-related regions of the brain and spinal cord; thus, modulating AQP4 expression or function may provide new avenues for treating neuropathic pain. Of note, AQP4-deficient mice exhibit reduced chronic pain responses, suggesting potential involvement of AQP4 in chronic pain modulation, and AQP4 is involved in pain modulation during inflammation, so understanding AQP4-mediated pain modulation may lead to novel anti-inflammatory and analgesic therapies. Recent advancements in magnetic resonance imaging (MRI) techniques enable assessment of AQP4 expression and localization, contributing to our understanding of its involvement in brain edema and clearance pathways related to pathological pain. Furthermore, targeting AQP4 through gene therapies and small-molecule modulators shows promise as a potential therapeutic intervention. Future research should focus on utilizing advanced MRI techniques to observe glymphatic system changes and the exchange of cerebrospinal fluid and interstitial fluid. Additionally, investigating the regulation of AQP4 by non-coding RNAs and exploring novel small-molecule medicines are important directions for future research. This review shed light on AQP4-based innovative therapeutic strategies for the treatment of pathological pain. Dark blue cells represent astrocytes, green cells represent microglia, and red ones represent brain microvasculature.

Design and dynamic analysis of a novel compound bending hollow piezoelectric beam miniature rotary actuator.

In this paper, a miniature hollow piezoelectric beam rotary actuator is proposed and designed based on the compound bending vibration modes. The structure body is designed as an elastic hollow square beam with symmetrical piezoelectric patches attached at both ends, which directly eliminates the step of the frequency tuning. A conical rotor is driven by the hollow piezoelectric beam through the elliptical motions of the points on its inner surface. Based on the Timoshenko beam theory and Lagrange equation, the numerical continuum model is established to analyze the working mechanism. A prototype of the miniature rotary actuator with a size of 50 × 6 × 6 mm (2 mm through-hole) is manufactured and its performance under various excitation parameters is characterized in rotor speed experiments. The experimental results show that the maximum speed of the conical rotor is 913 rpm at the excitation voltage of 400 V. With a maximum load of 70.31 mN, the spherical rotor can achieve a speed of 450 rpm. The numerical results are in great agreement with the experimental results, so the output characteristics of the rotary actuator can be estimated. The simulation and test results demonstrate that the proposed rotary actuator has outstanding output performance and controllability. In addition, the simple structure design is easy to realize the frequency tuning and miniaturization.

Triglyceride-glucose index as a marker of adverse cardiovascular prognosis in patients with coronary heart disease and hypertension.

BACKGROUND: The triglyceride-glucose (TyG) index has been proposed as a potential predictor of adverse prognosis of cardiovascular diseases (CVDs). However, its prognostic value in patients with coronary heart disease (CHD) and hypertension remains unclear. METHODS: A total of 1467 hospitalized patients with CHD and hypertension from January 2021 to December 2021 were included in this prospective and observational clinical study. The TyG index was calculated as Ln [fasting triglyceride level (mg/dL) × fasting plasma glucose level (mg/dL)/2]. Patients were divided into tertiles according to TyG index values. The primary endpoint was a compound endpoint, defined as the first occurrence of all-cause mortality or total nonfatal CVDs events within one-year follow up. The secondary endpoint was atherosclerotic CVD (ASCVD) events, including non-fatal stroke/transient ischemic attack (TIA) and recurrent CHD events. We used restricted cubic spline analysis and multivariate adjusted Cox proportional hazard models to investigate the associations of the TyG index with primary endpoint events. RESULTS: During the one-year follow-up period, 154 (10.5%) primary endpoint events were recorded, including 129 (8.8%) ASCVD events. After adjusting for confounding variables, for per standard deviation (SD) increase in the TyG index, the risk of incident primary endpoint events increased by 28% [hazard ratio (HR) = 1.28, 95% confidence interval (CI) 1.04-1.59]. Compared with subjects in the lowest tertile (T1), the fully adjusted HR for primary endpoint events was 1.43 (95% CI 0.90-2.26) in the middle (T2) and 1.73 (95% CI 1.06-2.82) in highest tertile (T3) (P for trend = 0.018). Similar results were observed in ASCVD events. Restricted cubic spline analysis also showed that the cumulative risk of primary endpoint events increased as TyG index increased. CONCLUSIONS: The elevated TyG index was a potential marker of adverse prognosis in patients with CHD and hypertension.

Combination of a STING Agonist and Photothermal Therapy Using Chitosan Hydrogels for Cancer Immunotherapy.

Cyclic dinucleotides (CDNs) are a promising class of immune agonists that trigger the stimulator of interferon genes (STING) to activate both innate and acquired immunity. However, the efficacy of CDNs is limited by drug delivery barriers. Therefore, we developed a combined immunotherapy strategy based on injectable reactive oxygen species (ROS)-responsive hydrogels, which sustainably release 5,6-dimethylxanthenone-4-acetic acid (DMXAA) as known as a STING agonist and indocyanine green (ICG) by utilizing a high level of ROS in the tumor microenvironment (TME). The STING agonist combined with photothermal therapy (PTT) can improve the biological efficacy of DMXAA, transform the immunosuppressive TME into an immunogenic and tumoricidal microenvironment, and completely kill tumor cells. In addition, this bioreactive gel can effectively leverage local ROS to facilitate the release of immunotherapy drugs, thereby enhancing the efficacy of combination therapy, improving the TME, inhibiting tumor growth, inducing memory immunity, and protecting against tumor rechallenge.

Palladium-catalyzed disilylation of ortho-halophenylethylenes enabled by 2-pyridone ligand.

A palladium-catalyzed disilylation reaction applicable for a variety of non-, α-, or ß-substituted and α,ß-disubstituted ortho-halophenylethylenes has been developed. This reaction proceeds with high yields and very low catalyst loadings. The two C-Si bonds of the disilylated products could be well-differentiated chemoselectively in the reaction with various electrophiles.