Electroencephalographic depression after abruptly increasing partial pressure of end-tidal carbon dioxide: a case series.

BACKGROUND: Prolonged electroencephalographic depression during surgery is associated with poor outcomes for patients. However, the published literature on electroencephalographic depression caused by a sudden increase in the partial pressure of end-tidal carbon dioxide (PETCO2) is lacking. CASE PRESENTATION: We report four patients who were scheduled for laparoscopic liver surgery under general anesthesia. During the process of EEG monitoring with Sedline, four patients experienced electroencephalographic depression closely after a sudden increase in PETCO2. The four patients showed that electroencephalographic depression mainly manifested as a slow in EEG frequency, a reduction in the amplitude and power of EEG, and a decrease in spectral edge frequency. Patient state index was elevated in three cases. CONCLUSIONS: To summarize, our patients showed EEG depression when PETCO2 suddenly increased, which suggests that clinical doctors should be alert to electroencephalographic depression when the PETCO2 abruptly increases. EEG monitoring devices should be applied in patients with possible hypercapnia. Anesthesiologists must comprehensively interpret the raw EEG, spectral edge frequency, and density spectral array data, in addition to patient sedation index values.

Therapeutic targets of armored chimeric antigen receptor T cells navigating the tumor microenvironment.

Chimeric antigen receptor (CAR) T cell therapy, which targets tumors with high specificity through the recognition of particular antigens, has emerged as one of the most rapidly advancing modalities in immunotherapy, demonstrating substantial success against hematological malignancies. However, previous generations of CAR-T cell therapy encountered numerous challenges in treating solid tumors, such as the lack of suitable targets, high immunosuppression, suboptimal persistence, and insufficient infiltration owing to the complexities of the tumor microenvironment, all of which limited their efficacy. In this review, we focus on the current therapeutic targets of fourth-generation CAR-T cells, also known as armored CAR-T cells, and explore the mechanisms by which these engineered cells navigate the tumor microenvironment by targeting its various components. Enhancing CAR-T cells with these therapeutic targets holds promise for improving their effectiveness against solid tumors, thus achieving substantial clinical value and advancing the field of CAR-T cell therapy. Additionally, we discuss potential strategies to overcome existing challenges and highlight novel targets that could further enhance the efficacy of CAR-T cell therapy in treating solid tumors.

Preconditioning with ß-hydroxybutyrate attenuates lung ischemia-reperfusion injury by suppressing alveolar macrophage pyroptosis through the SIRT1-FOXO3 signaling pathway.

The complex pathogenesis of lung ischemia-reperfusion injury (LIRI) was examined in a murine model, focusing on the role of pyroptosis and its exacerbation of lung injury. We specifically examined the levels and cellular localization of pyroptosis within the lung, which revealed alveolar macrophages as the primary site. The inhibition of pyroptosis by VX-765 reduced the severity of lung injury, underscoring its significant role in LIRI. Furthermore, the therapeutic potential of ß-hydroxybutyrate (ß-OHB) in ameliorating LIRI was examined. Modulation of ß-OHB levels was evaluated by ketone ester supplementation and 3-hydroxybutyrate dehydrogenase 1 (BDH-1) gene knockout, along with the manipulation of the SIRT1-FOXO3 signaling pathway using EX-527 and pCMV-SIRT1 plasmid transfection. This revealed that ß-OHB exerts lung-protective and anti-pyroptotic effects, which were mediated through the upregulation of SIRT1 and the enhancement of FOXO3 deacetylation, leading to decreased pyroptosis markers and lung injury. In addition, ß-OHB treatment of MH-S cells in vitro showed a concentration-dependent improvement in pyroptosis, linking its therapeutic benefits to specific cell mechanisms. Overall, this study highlights the significance of alveolar macrophage pyroptosis in the exacerbation of LIRI and indicates the potential of ß-OHB in mitigating injury by modulating the SIRT1-FOXO3 signaling pathway.

Liposomes delivery systems of functional substances for precision nutrition.

Natural bioactive compounds with antioxidant, antimicrobial, anticancer, and other biological activities are vital for maintaining the body's physiological functions and enhancing immunity. These compounds have great potential as nutritional therapeutic agents, but they can be limited due to their poor flavor, color, unstable nature, and poor water solubility, and degradation by gastrointestinal enzymes. Liposomes, as ideal carriers, can encapsulate both water-soluble and fat-soluble nutrients, enhance the bioavailability of functional substances, promote the biological activity of functional substances, and control the release of nutrients. Despite their potential, liposomes still face obstacles in nutrient delivery. Therefore, the design of liposomes for special needs, optimization of the liposome preparation process, enhancement of liposome encapsulation efficiency, and industrial production are key issues that must be addressed in order to develop food-grade liposomes. Moreover, the research on surface-targeted modification and surface functionalization of liposomes is valuable for expanding the scope of application of liposomes and achieving the release of functional substances from liposomes at the appropriate time and site. The establishment of in vivo and in vitro digestion models of nutrient-loaded liposomes, in-depth study of gastrointestinal digestive behavior after liposome ingestion, targeted nutrient release, and deciphering the nutritional intervention of human diseases and positive health promotion are promising fields with broad development prospects.

Risk factors for postoperative urinary retention in patients underwent surgery for benign anorectal diseases: a nested case-control study.

BACKGROUND: Postoperative urinary retention (POUR) is a common complication of anorectal surgery. This study was to determine the incidence of POUR in anorectal surgery for benign anorectal diseases, identify its risk factors, and establish a nomogram for prediction of POUR. METHODS: A nested case-control study was conducted. The clinical data of patients were collected, and the incidence of POUR was analyzed. Univariate analysis was used to identify the risk factors associated with POUR, and multivariate logistic regression analysis was used to determine independent risk factors for POUR. A nomogram for the preoperative prediction of POUR using a logistic regression model was developed (n = 609). RESULTS: The incidence of POUR after anorectal surgery for benign anorectal diseases was 19.05%. The independent risk factors for POUR were: female (P = 0.007); male with benign prostatic hyperplasia (BPH) (P = 0.001); postoperative visual analogue scale (VAS) score > 6 (P = 0.002); patient-controlled epidural analgesia (PCEA) (P = 0.016); and a surgery time > 30 min (P = 0.039). In the nomogram, BPH is the most important factor affecting the occurrence of POUR, followed by a postoperative VAS score > 6, PCEA, surgery time > 30 min, and sex has the least influence. CONCLUSION: For patients undergoing anorectal surgery for benign anorectal diseases, preventive measures can be taken to reduce the risk of POUR, taking into account the following risk factors: female or male with BPH, severe postoperative pain, PCEA, and surgery time > 30 min. Furthermore, we developed and validated an easy-to-use nomogram for preoperative prediction of POUR in anorectal surgery for benign anorectal diseases. TRIAL REGISTRATION: China Clinical Trial Registry: ChiCTR2000039684, 05/11/2020.

The impact of combined administration of ropivacaine and dexamethasone on postoperative analgesia in perianal surgery with pudendal nerve block under ultrasound guidance: a prospective randomized controlled study.

Background: In recent years, severe pain after perianal surgery has seriously affected the prognosis of hospitalized patients. How to maximize the improvement of postoperative pain and perioperative comfort becomes particularly important. Methods: This study was a double-blind randomized controlled trial (Registration No.: ChiCTR2100048760, Registration Date: 16 July 2021, Link: www.chictr.org.cn/showproj.html?proj=130226), and patients were randomly divided into two groups: one group underwent postoperative 20 mL bilateral pudendal nerve block with 0.5% ropivacaine (P group), and the other group underwent postoperative 20 mL bilateral pudendal nerve block with 0.5% ropivacaine + 8 mg dexamethasone (PD group). The primary outcome was the incidence of moderate to severe pain at the first postoperative dressing change. Secondary outcomes included Quality of recovery-15 (QoR-15) score at 3 days after surgery, sleep quality, pain score at 3 days after surgery, and incidence of adverse events. Results: In the main outcome indicators, the incidence was 41.7% in the P group and 24.2% in the PD group (p = 0.01). The QoR-15 score and sleep quality in PD group were better than those in P group 2 days before surgery. The incidence of postoperative urinary retention was significantly decreased in PD group (p = 0.01). Conclusion: Local anesthesia with dexamethasone combined with pudendal nerve block after perianal surgery can reduce the incidence of moderate to severe pain during the first dressing change. This may be one of the approaches to multimodal analgesia after perianal surgery. Clinical Trial Registration: https://www.chictr.org.cn/, identifier ChiCTR2100048760.

Ct-based diagnosis of sarcopenia as a prognostic factor for postoperative mortality after elective open-heart surgery in older patients: a cohort-based systematic review and meta-analysis.

Background: Cardiac open-heart surgery, which usually involves thoracotomy and cardiopulmonary bypass, is associated with a high incidence of postoperative mortality and adverse events. In recent years, sarcopenia, as a common condition in older patients, has been associated with an increased incidence of adverse prognosis. Methods: We conducted a search of databases including PubMed, Embase, and Cochrane, with the search date up to January 1, 2024, to identify all studies related to elective cardiac open-heart surgery in older patients. We used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of evidence. Results: A total of 12 cohort studies were included in this meta-analysis for analysis. This meta-analysis revealed that patients with sarcopenia had a higher risk of postoperative mortality. Furthermore, the total length of hospital stay and ICU stay were longer after surgery. Moreover, there was a higher number of patients requiring further healthcare after discharge. Regarding postoperative complications, sarcopenia patients had an increased risk of developing renal failure and stroke. Conclusion: Sarcopenia served as a tool to identify high-risk older patients undergoing elective cardiac open-heart surgery. By identifying this risk factor early on, healthcare professionals took targeted steps to improve perioperative function and made informed clinical decisions.Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023426026.

Adipose Kiss1 controls aerobic exercise-related adaptive responses in adipose tissue energy homeostasis.

Kisspeptin signaling regulates energy homeostasis. Adiposity is the principal source and receiver of peripheral Kisspeptin, and adipose Kiss1 metastasis suppressor (Kiss1) gene expression is stimulated by exercise. However, whether the adipose Kiss1 gene regulates energy homeostasis and plays a role in adaptive alterations during prolonged exercise remains unknown. Here, we investigated the role of Kiss1 role in mice and adipose tissues and the adaptive changes it induces after exercise, using adipose-specific Kiss1 knockout (Kiss1adipoq-/-) and adeno-associated virus-induced adipose tissue Kiss1-overexpressing (Kiss1adipoq over) mice. We found that adipose-derived kisspeptin signal regulates lipid and glucose homeostasis to maintain systemic energy homeostasis, but in a sex-dependent manner, with more pronounced metabolic changes in female mice. Kiss1 regulated adaptive alterations of genes and proteins in tricarboxylic acid (TCA) cycle and oxidative phosphorylation (OxPhos) pathways in female gWAT following prolonged aerobic exercise. We could further show that adipose Kiss1 deficiency leads to reduced peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC-1α) protein content of soleus muscle and maximum oxygen uptake (VO2 max) of female mice after prolonged exercise. Therefore, adipose Kisspeptin may be a novel adipokine that increases organ sensitivity to glucose, lipids, and oxygen following exercise.

The Mechanism of Short-Circuit Oscillations in Automotive-Grade Multi-Chip Parallel Power Modules and an Effective Mitigation Approach.

This paper presents an in-depth analysis of the oscillation phenomenon occurring in multi-chip parallel automotive-grade power modules under short-circuit conditions and investigates three suppression methods. We tested and analyzed two commercial automotive-grade power modules, one containing two chips and the other containing a single chip, and found that short-circuit gate oscillations were more likely to occur in multi-chip parallel packaged modules than in single-chip packaged modules. Through experimental and simulation analyses, we observed that gate oscillations were mainly caused by the interaction between internal parasitic parameters of the module and the external drive circuit, and we found that high drive resistance and low common emitter inductance between parallel chips could effectively suppress gate voltage oscillations. We also analyzed the two mainstream suppression schemes, increasing the drive gate resistance and placing the drive capacitors in parallel. Unfortunately, we found that these suppression schemes were not ideal solutions because both schemes changed the switching characteristics of the power module. As an alternative, we propose a simple and effective solution that involves adding parallel connections between the parallel chips. Simulation calculations showed that this optimized method reduced the emitter inductance between parallel chips in the upper bridge arm by about 30% and in the lower bridge arm by 35%. Through short-circuit experiments conducted at different DC bus voltages, it has been verified that the new optimized solution effectively resolves gate oscillation issues without affecting the switching characteristics of the power module.

Combined vaccines against angiotensin II receptor type 1 and alpha 1D-adrenergic receptor for hypertension.

PURPOSE: Compared with monotherapy, combination therapy with multiple antihypertensive drugs has demonstrated superior efficacy in the management of hypertension. The aim of this study was to explore the efficacy of multitarget combined vaccines in achieving simultaneous antihypertensive and target organ protection effects. METHODS: Our team has developed ATRQß-001 and ADRQß-004 vaccines targeting Ang II type 1 receptor (AT1R) and α1D-adrenergic receptor (α1D-AR), respectively. In NG-nitroarginine methyl ester ( l -NAME) + abilities spontaneously hypertensive rats (SHRs) model, SHRs were simultaneously inoculated with ATRQß-001 and ADRQß-004 vaccines. Histological and biochemical analyses were performed to evaluate the antihypertensive effects and target organ protection of the ATRQß-001 and ADRQß-004 combined vaccines in comparison with those of the single vaccine. RESULTS: Both ATRQß-001 and ADRQß-004 vaccines induced robust antibody production, resulting in persistent high antibody titers in rats. Notably, the combined administration of both vaccines significantly decreased SBP in SHRs compared with treatment with a single vaccine, both before and after l -NAME administration. Furthermore, the combined vaccine regimen demonstrated superior efficacy in protecting against vascular remodeling, myocardial hypertrophy and fibrosis, and kidney injury in SHRs. Mechanistically, the combined vaccines exhibited significantly downregulated the expression of angiotensin II type 1 receptor (AT1R) and α1D-adrenergic receptor (α1D-AR). Importantly, no apparent immune-related adverse effects were observed in animals immunized with the combined vaccines. CONCLUSION: Preliminary findings from this investigation suggest that co-administration of the novel ATRQß-001 and ADRQß-004 vaccines holds potential as a groundbreaking therapeutic strategy for managing hypertension.

Efficacy of ganglion impar block combined with pudendal nerve pulsed radiofrequency for pudendal neuralgia management-a randomized clinical trial.

BACKGROUND: Pudendal neuralgia is a chronic and debilitating condition. Its prevalence ranges from 5 to 26%. Currently, therapeutic approaches to treat pudendal neuralgia include patient education, medication management, psychological and physical therapy, and procedural interventions, such as nerve block, trigger point injections, and surgery. Drug therapy has a limited effect on pain relief. A pudendal nerve block may cause a significant decrease in pain scores for a short time; however, its efficacy significantly decreases over time. In contrast, pudendal nerve pulsed radiofrequency can provide pain relief for 3 months, and ganglion impar block has been widely used for treating chronic perineal pain and chronic coccygodynia. This study aimed to determine the efficacy and safety of monotherapy (pudendal nerve pulsed radiofrequency) and combination therapy (pudendal nerve pulsed radiofrequency plus ganglion impar block) in patients with pudendal neuralgia. METHODS: This randomized, controlled clinical trial will include 84 patients with pudendal neuralgia who failed to respond to drug or physical therapy. Patients will be randomly assigned into one of the two groups: mono or combined treatment groups. The primary outcome will be a change in pain intensity measured using the visual analog scale. The secondary outcomes will include a Self-Rating Anxiety Scale score, Self-Rating Depression Scale score, the use of oral analgesics, the Medical Outcomes Study Health Survey Short Form-36 Item score, and the occurrence of adverse effects. The study results will be analyzed using intention-to-treat and per-protocol analyses. Primary and secondary outcomes will be evaluated between the mono and combined treatment groups. Subgroup analyses will be conducted based on the initial ailment, age, and baseline pain intensity. The safety of the treatment will be assessed by monitoring adverse events, which will be compared between the two groups. DISCUSSION: This study protocol describes a randomized, controlled clinical trial to determine the efficacy and safety of mono and combination therapies in patients with pudendal neuralgia. The study results will provide valuable information on the potential benefits of this combination therapy and contribute to the development of more effective and safer treatments for patients with pudendal neuralgia. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2200061800).

Macrophage hitchhiking for systematic suppression in postablative multifocal HCC.

BACKGROUND AND AIMS: HCC, particularly the multifocal HCC, features aggressive invasion and dismal prognosis. Locoregional treatments were often refractory to eliminate tumor tissue, resulting in residual tumor cells persisting and subsequent progression. Owing to problematic delivery to the tumor tissue, systemic therapies, such as lenvatinib (LEN) therapy, show limited clinical benefit in preventing residual tumor progression. Therefore, more advanced strategies for postablative multifocal HCC are urgently needed. APPROACH AND RESULTS: Motivated by the chemotaxis in tumor penetration of macrophages, we report a strategy named microinvasive ablation-guided macrophage hitchhiking for the targeted therapy toward HCC. In this study, the strategy leverages the natural inflammatory gradient induced by ablation to guide LEN-loaded macrophages toward tumor targeting, which increased by ~10-fold the delivery efficiency of LEN in postablative HCC in vivo. Microinvasive ablation-guided macrophage hitchhiking has demonstrated significant antitumor activity in various HCC models, including the hydrodynamic tail vein injection multifocal HCC mouse model and the orthotopic xenograft HCC rabbit model, systematically inhibiting residual tumor progression after ablation and prolonging the median survival of tumor-bearing mice. The potential antitumor mechanism was explored using techniques such as flow cytometry, ELISA, and immunohistochemistry. We found that the strategy significantly suppressed tumor cell proliferation and neovascularization, and such enhanced delivery of LEN stimulated systemic immune responses and induced durable immune memory. CONCLUSIONS: The macrophage hitchhiking strategy demonstrates exceptional therapeutic efficacy and biosafety across various species, offering promising prospects for clinical translation in controlling residual tumor progression and improving outcomes following HCC ablation.

Bioturbation analysis of microbial communities and flavor metabolism in a high-yielding cellulase Bacillus subtilis biofortified Daqu.

In this study, a fortified Daqu (FF Daqu) was prepared using high cellulase-producing Bacillus subtilis, and the effects of in situ fortification on the physicochemical properties, flavor, active microbial community and metabolism of Daqu were analyzed. The saccharification power, liquefaction power, and cellulase activity of the FF Daqu were significantly increased compared with that of the traditional Daqu (CT Daqu). The overall differences in flavor components and their contents were not significant, but the higher alcohols were lower in FF Daqu. The relative abundance of dominant active species in FF Daqu was 85.08% of the total active microbiota higher than 63.42% in CT Daqu, and the biomarkers were Paecilomyces variotii and Aspergillus cristatus, respectively. The enzymes related to starch and sucrose metabolic pathways were up-regulated and expressed in FF Daqu. In the laboratory level simulation of baijiu brewing, the yield of baijiu was increased by 3.36% using FF Daqu.

Short-term resistance training combined with cheese supplementation can optimize body parameters and intestinal microbiota in healthy adults.

Background: Resistance training (RT) and protein supplementation have beneficial effects on the human body. However, it is unknown if RT's health-promoting benefits are enhanced by food-borne protein, such as cheese supplements. This study investigated at how the body composition, lipid profile, muscle strength and intestinal microbiota changed following four weeks of RT combined with cheese supplementation. Methods: Thirty-five male and untrained adults were divided into 4 groups [control group (CON), low-dose group (LG), medium-dose group (MG), and high-dose group (HG)] and underwent a 4-week RT (3 times/week) in combination with cheese supplementation. Participants received 108 g (LG), 216 g (MG), or 324 g (HG) of cheese on the day of RT, and each serving (108 g) of cheese contained 6.7 g of food-borne protein. The RT program was a whole-body program with movements such as chest presses, leg presses, seated rowing, knee extensions and triceps pushdown. The exercise consisted of 3 sets of 8-12 repetitions at 70%RM, with a 120-s break in between. Body parameters (body composition, lipid profile and muscle strength) were assessed at baseline and after the 4 weeks of the intervention. The feces sample was taken every weekend. A two-way (group × time) mixed-design ANOVA was used to examine the body parameters. Independent one-way ANOVA was used to analyze the differences between groups in baseline characteristics and different values of each parameter. Results: HDL-C level was higher in MG than in LG. In comparison to LG, MG had lower levels of total cholesterol, low-density lipoprotein cholesterol, body weight, body mass index, body fat mass and body fat percentage. However, there was no difference in muscle strength between in the four groups. The abundance of Actinobacteria was higher in LG and Erysipelotrichaceae was lower in MG and HG. Conclusion: The findings suggest that cheese could be a readily available food-borne protein supplement to enhance the beneficial effects of RT on health. It may improve body composition and lipid profile by altering the proportion of intestinal microbiota. During the 4-week RT intervention, 13.4 g of foodborne protein in the form of cheese 3 times per week was the ideal dosage.

A real-world study of antifibrotic drugs-related adverse events based on the United States food and drug administration adverse event reporting system and VigiAccess databases.

Objectives: This study aims to investigate adverse events (AEs) and adverse drug reactions (ADRs) associated with pirfenidone and nintedanib, two antifibrotic drugs used to treat idiopathic pulmonary fibrosis (IPF). Methods: Reporting odds ratio (ROR) and proportional reporting ratio (PRR) analyses were conducted to assess the association between these drugs and signals at both the preferred term (PT) and system organ class (SOC) levels. Results: 55,949 reports for pirfenidone and 35,884 reports for nintedanib were obtained from the FAERS database. The VigiAccess database provided 37,187 reports for pirfenidone and 23,134 reports for nintedanib. Male patients and individuals over the age of 65 were more likely to report AEs. Gastrointestinal disorders emerged as the most significant signal at SOC level for both drugs. Furthermore, nausea, diarrhoea, and decreased appetite were observed at the PT level. We further identified notable signals, including hemiplegic migraine for pirfenidone and asthenia, constipation, and flatulence for nintedanib, which were previously unknown or underestimated ADRs. Conclusion: This study has identified AEs and ADRs associated with pirfenidone and nintedanib, confirming that the majority of the corresponding label information indicates relative safety. However, it is essential to take unexpected risk signals seriously, necessitating further research to manage the safety profiles of these drugs.

Real-world incidence and risk factors of pneumonitis in chemoradiation plus immune checkpoint inhibitors compared with chemoradiation alone in lung cancer: a retrospective cohort study.

Background: Immune checkpoint inhibitors (ICIs) have shown high efficacy in lung cancer. Adding ICIs to chemoradiation might increase the treatment efficacy, while the application of ICIs or chemoradiation alone can induce treatment-related pneumonitis, so whether combination therapy would increase the risk of pneumonitis needs careful evaluation. This study aimed to retrospectively analyze the incidence of pneumonitis in patients who underwent chemoradiation combined with ICIs compared with chemoradiation alone and explore the risk factors of pneumonitis in combination therapy. Methods: This was a retrospective cohort study. Patients who received conventional thoracic radiation with a minimum total dose of 50 Gy for lung cancer between January 2020 and December 2021 at West China Hospital were retrospectively reviewed and followed up for at least 6 months after radiation. Patients were divided into two groups according to whether chemoradiation was administered with or without ICIs. Pneumonitis was evaluated by chest computed tomography (CT) at least every 2 months in outpatient department. The clinical characteristics, including sex, age, smoking history, pathological diagnosis, baseline pulmonary disease [including chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD)], treatment strategy, location of primary tumor and radiological dosimetric parameters were recorded. Chi-squared tests or Fisher's exact tests were performed to analyze the difference between the combination group and control group for categorical variables and Mann-Whitney U test for continuous variables. Univariate and multivariate analyses were performed by logistic regression. Results: A total of 152 patients who received chemoradiation were enrolled. The median age was 59 years. A total of 115 (75.7%) patients were non-small cell lung cancer (NSCLC), 22 (14.5%) were small cell lung cancer (SCLC), and 15 (9.9%) were other pathological types. Among them, 58 received chemoradiation combined with ICIs and 94 received chemoradiation alone. The rate of grade ≥2 pneumonitis was significantly higher in the combination therapy group (39.7% vs. 22.3%, P=0.028) and was associated with the use of ICIs [odds ratio (OR): 2.641, 95% confidence interval (CI): 1.244-5.608, P=0.011] and percent volume of the lung receiving ≥30 Gy (V30) (OR: 1.728, 95% CI: 1.214-2.460, P=0.002). The history of chronic lung disease was the independent risk factor (OR: 6.359, 95% CI: 1.953-20.705, P=0.002) of grade ≥3 pneumonitis. In the combination group, univariate and multivariate analyses revealed that V5, V20, V30, and mean lung dose (MLD) were not associated with pneumonitis, whereas the history of chronic lung disease was an independent risk factor of grade ≥3 pneumonitis (OR: 8.351, 95% CI: 1.469-47.484, P=0.017). Conclusions: The incidence of pneumonitis of ICIs combined with chemoradiation was higher than chemoradiation alone, but manageable. The combination therapy should be applied with caution especially in patients with history of chronic lung disease.

Efficacy and Safety of Celiac Plexus Neurolysis Versus Splanchnic Nerve Neurolysis in the Management of Abdominal Cancer Pain: A Meta-analysis of 359 Patients.

BACKGROUND: Splanchnic nerve neurolysis (SNN) is commonly used as an alternative pain control technique to celiac plexus neurolysis (CPN) in patients with distortion of anatomy, but the analgesic effect and relative risks of the 2 procedures remain controversial in general condition. OBJECTIVES: The aim of this study was to evaluate the pain condition, safety, and symptom burden of SNN compared with CPN. STUDY DESIGN: A systematic review and meta-analysis of neurolysis therapy for intractable cancer-related abdominal pain. METHODS: A systematic search was performed for randomized controlled trials comparing SNN and CPN using the PubMed, Medline, Cochrane Library, Web of Science, Google Scholar, and China National Knowledge Infrastructure databases. Meta-analysis was performed using Stata Version 15.0. Outcomes included pain condition, opioid consumption, adverse effects, quality of life (QOL), and survival rate. Standardized mean difference (SMD) was calculated for continuous outcomes with its corresponding 95% CI. LIMITATIONS: Study limitations include challenges to make subgroup analysis by intervention measures and addressing inevitable heterogeneity. Larger studies are needed for survival rates and further insights. RESULTS: Seven studies involving 359 patients were included. No significant difference was found in pain condition at 2 weeks [SMD = 0.75, 95% CI (-0.25, 1.74), P > 0.05], 2 months [SMD = 1.10, 95% CI (-0.21, 2.40), P > 0.05] and 6 months [SMD = 0.53, 95% CI (-0.02, 1.08), P > 0.05] between SNN and CPN. Opioid consumption was comparable at 2 weeks [SMD = 0.57, 95% CI (-1.21, 2.34), P > 0.05] and one month [SMD = 0.37, 95% CI (-1.33, 2.07), P > 0.05]. However, SNN was associated with a statistically significant reduction in the opioid consumption at 2 months postoperatively [SMD = 0.99, 95% CI (0.68, 1.30), P < 0.05]. A systematic review was performed for adverse effects and QOL. CONCLUSIONS: Our evidence supports that the analgesic effect of SNN is equivalent to that of CPN, independent of changes in the anatomical structure of the abdominal nerve plexus. SNN requires less use of opioids at 2 months and does not show greater improvement in pain burden compared to CPN.

Digital-Twin-Driven Intelligent Insulated-Gate Bipolar Transistor Production Lines.

With the rapid development of novel energy vehicles, power generation, photovoltaics, and other industries, power electronic devices have gained considerable attention. Insulated-gate bipolar transistors (IGBTs) have been widely used in those fields. With the emergence of intelligent manufacturing concepts such as Germany's "Industry 4.0" and China's "Made in China 2025", conventional manufacturing which needs to be upgraded with higher efficiency and yield is rapidly pivoting toward digitalization and intelligence. The digital twin methodology has been extensively used in various industries for constructing virtual models of physical entities, facilitating real-time data interconnection to reduce costs and improve efficiency. This study proposes a modular intelligent IGBT production line based on the digital twin. Real-time data are transmitted from a physical line to a digital line for storage and analysis. The digital line is visualized, and an intelligent management platform containing multiple functions is developed. Additionally, a process simulation database is established to obtain the optimal process parameters. Numerous quality issues that can arise during each process of IGBT packaging are addressed using a problem-solving approach based on the digital twin methodology. Consequently, this digital-twin-based IGBT intelligent production line effectively enhances yield rates and efficiency. IGBT modules with various packaging forms such as ACF, ACE, and ACD are manufactured.

The effects of race and probiotic supplementation on the intestinal microbiota of 10-km open-water swimmers.

This study collected the stools of 10-km open-water swimmers after race and probiotic supplementation, and 16S rRNA sequencing and metabolomic analysis were performed to clarify their intestinal microbiota characteristics. The findings revealed a relatively high proportion of Firmicutes in all the athletes. Firmicutes in female athletes were significantly higher after probiotic supplementation. The intestinal microbiota of athletes was closely associated with the pathways of exercise against cancer, exercise against aging, exercise for improving cognition, sphingolipid metabolism and endocrine resistance. Future research should focus on the relationship between Firmicutes and Proteobacteria with super class metabolites in athletes. This report initially explored the changes in intestinal microbiota involved in metabolic pathways in athletes after race and after probiotic supplementation and provided a theoretical basis for the further improvement of the monitoring of their physical function after race and selection of nutritional strategies during exercise training.

Early versus delayed computed tomography-guided celiac plexus neurolysis for palliative pain management in patients with advanced pancreatic cancer: a retrospective cohort study.

Introduction: Abdominal and back pain is the most frequent symptom in patients with pancreatic cancer, with pain management being extremely challenging. This study aimed to evaluate pain control, opioid consumption, pain-interfered quality of life, and survival after early and delayed computed tomography (CT)-guided celiac plexus neurolysis (CPN). Methods: A retrospective analysis of pancreatic cancer patients receiving CPN for pain (n = 56) between June 2018 and June 2021 was done. The patients were grouped as early group (n = 22) and delayed group (n = 34) on the basis of the presence of persistent refractory pain according to expert consensus on refractory cancer pain. Results: Both groups were comparable in demographic characteristics and baseline pain conditions measured using the numeric rating scale (5.77 ± 1.23 vs. 6.27 ± 1.21; p = 0.141). The pain scores were significantly reduced in both groups; early CPN resulted in significantly lower scores from 3 to 5 months. The opioid consumption gradually decreased to a minimum at 2 weeks but increased at 1 month (35.56 ± 30.14 mg and 50.48 ± 47.90 mg, respectively); significantly larger consumption from 2 to 4 months was seen in the delayed group. The total pain interference was lower than baseline in all patients, with significant improvement after early CPN in sleep, appetite, enjoyment of life, and mood. The average survival time of the two groups was comparable. Conclusion: Early application of CT-guided CPN for patients with advanced pancreatic cancer may help reduce pain exacerbation and opioids consumption, without influencing the survival.