Comprehensive analysis of gene mutations and mismatch repair in Chinese colorectal cancer patients.

BACKGROUND: RAS, BRAF, and mismatch repair (MMR)/microsatellite instability (MSI) are crucial biomarkers recommended by clinical practice guidelines for colorectal cancer (CRC). However, their characteristics and influencing factors in Chinese patients have not been thoroughly described. AIM: To analyze the clinicopathological features of KRAS, NRAS, BRAF, and PIK3CA mutations and the DNA MMR status in CRC. METHODS: We enrolled 2271 Chinese CRC patients at the China-Japan Friendship Hospital. MMR proteins were tested using immunohistochemical analysis, and the KRAS/NRAS/BRAF/PIK3CA mutations were determined using quantitative polymerase chain reaction. Microsatellite status was determined using an MSI detection kit. Statistical analyses were conducted using SPSS software and logistic regression. RESULTS: The KRAS, NRAS, BRAF, and PIK3CA mutations were detected in 44.6%, 3.4%, 3.7%, and 3.9% of CRC patients, respectively. KRAS mutations were more likely to occur in patients with moderate-to-high differentiation. BRAF mutations were more likely to occur in patients with right-sided CRC, poorly differentiated, or no perineural invasion. Deficient MMR (dMMR) was detected in 7.9% of all patients and 16.8% of those with mucinous adenocarcinomas. KRAS, NRAS, BRAF, and PIK3CA mutations were detected in 29.6%, 1.1%, 8.1%, and 22.3% of patients with dMMR, respectively. The dMMR was more likely to occur in patients with a family history of CRC, aged < 50 years, right-sided CRC, poorly differentiated histology, no perineural invasion, and with carcinoma in situ, stage I, or stage II tumors. CONCLUSION: This study analyzed the molecular profiles of KRAS, NRAS, BRAF, PIK3CA, and MMR/MSI in CRC, identifying key influencing factors, with implications for clinical management of CRC.

Short-chain fatty acids mitigate Methamphetamine-induced hepatic injuries in a Sigma-1 receptor-dependent manner.

Methamphetamine (Meth) is a potent psychostimulant with well-established hepatotoxicity. Gut microbiota-derived short-chain fatty acids (SCFAs) have been reported to yield beneficial effects on the liver. In this study, we aim to further reveal the mechanisms of Meth-induced hepatic injuries and investigate the potential protective effects of SCFAs. Herein, mice were intraperitoneally injected with 15 mg/kg Meth to induce hepatic injuries. The composition of fecal microbiota and SCFAs was profiled using 16 S rRNA sequencing and Gas Chromatography/Mass Spectrometry (GC/MS) analysis, respectively. Subsequently, SCFAs supplementation was performed to evaluate the protective effects against hepatic injuries. Additionally, Sigma-1 receptor knockout (S1R-/-) mice and fluvoxamine (Flu), an agonist of S1R, were introduced to investigate the mechanisms underlying the protective effects of SCFAs. Our results showed that Meth activated S1R and induced hepatic autophagy, inflammation, and oxidative stress by stimulating the MAPK/ERK pathway. Meanwhile, Meth disrupted SCFAs product-related microbiota, leading to a reduction in fecal SCFAs (especially Acetic acid and Propanoic acid). Accompanied by the optimization of gut microbiota, SCFAs supplementation normalized S1R expression and ameliorated Meth-induced hepatic injuries by repressing the MAPK/ERK pathway. Effectively, S1R knockout repressed Meth-induced activation of the MAPK/ERK pathway and further ameliorated hepatic injuries. Finally, the overexpression of S1R stimulated the MAPK/ERK pathway and yielded comparable adverse phenotypes to Meth administration. These findings suggest that Meth-induced hepatic injuries relied on the activation of S1R, which could be alleviated by SCFAs supplementation. Our study confirms the crucial role of S1R in Meth-induced hepatic injuries for the first time and provides a potential preemptive therapy.

Polystyrene nanoplastics induce cardiotoxicity by upregulating HIPK2 and activating the P53 and TGF-ß1/Smad3 pathways.

Nanoplastics (NPs) pollution has become a global environmental problem, raising numerous health concerns. However, the cardiotoxicity of NPs exposure and the underlying mechanisms have been understudied to date. To address this issue, we comprehensively evaluated the cardiotoxicity of polystyrene nanoplastics (PS-NPs) in both healthy and pathological states. Briefly, mice were orally exposed to four different concentrations (0 mg/day, 0.1 mg/day, 0.5 mg/day, and 2.5 mg/day) of 100-nm PS-NPs for 6 weeks to assess their cardiotoxicity in a healthy state. Considering that individuals with underlying health conditions are more vulnerable to the adverse effects of pollution, we further investigated the cardiotoxic effects of PS-NPs on pathological states induced by isoprenaline. Results showed that PS-NPs induced cardiomyocyte apoptosis, cardiac fibrosis, and myocardial dysfunction in healthy mice and exacerbated cardiac remodeling in pathological states. RNA sequencing revealed that PS-NPs significantly upregulated homeodomain interacting protein kinase 2 (HIPK2) in the heart and activated the P53 and TGF-beta signaling pathways. Pharmacological inhibition of HIPK2 reduced P53 phosphorylation and inhibited the activation of the TGF-ß1/Smad3 pathway, which in turn decreased PS-NPs-induced cardiotoxicity. This study elucidated the potential mechanisms underlying PS-NPs-induced cardiotoxicity and underscored the importance of evaluating nanoplastics safety, particularly for individuals with pre-existing heart conditions.

The gut microbiota contributes to methamphetamine-induced reproductive toxicity in male mice.

Methamphetamine (METH) is a psychostimulant drug belonging to the amphetamine-type stimulant class, known to exert male reproductive toxicity. Recent studies suggest that METH can disrupt the gut microbiota. Furthermore, the gut-testis axis concept has gained attention due to the potential link between gut microbiome dysfunction and reproductive health. Nonetheless, the role of the gut microbiota in mediating the impact of METH on male reproductive toxicity remains unclear. In this study, we employed a mouse model exposed to escalating doses of METH to assess sperm quality, testicular pathology, and reproductive hormone levels. The fecal microbiota transplantation method was employed to investigate the effect of gut microbiota on male reproductive toxicity. Transcriptomic, metabolomic, and microbiological analyses were conducted to explore the damage mechanism to the male reproductive system caused by METH. We found that METH exposure led to hormonal disorders, decreased sperm quality, and changes in the gut microbiota and testicular metabolome in mice. Testicular RNA sequencing revealed enrichment of several Gene Ontology terms associated with reproductive processes, as well as PI3K-Akt signaling pathways. FMT conveyed similar reproductive damage from METH-treated mice to healthy recipient mice. The aforementioned findings suggest that the gut microbiota plays a substantial role in facilitating the reproductive toxicity caused by METH, thereby highlighting a prospective avenue for therapeutic intervention in the context of METH-induced infertility.

Male reproductive function before and after the adjustment of the COVID-19 prevention policy: a multicenter study in China.

At the end of 2022, the adjustment of the coronavirus disease 2019 (COVID-19) pandemic control policy in China resulted in a large-scale increase in public infection. To compare the fertility parameters of male patients before and after the adjustments of the COVID-19 pandemic control policy in China, we collected data on patients' medical histories and laboratory examinations on their first visits between June 2022 and March 2023 in five different hospitals. Data were divided into five groups according to the timeline of the policy adjustment. The data we collected from male patients included semen quality and serum reproductive hormone levels, and intergroup comparisons were made using the Mann-Whitney U and Chi-square tests. In total, 16 784 cases underwent regular semen analysis, 11 180 had sperm morphology assessments, and 7200 had reproductive hormone analyses. The data showed declining trends in semen volume, sperm motility, and the progressive sperm motility rate after the policy adjustment. Subgroup comparison revealed an initial decrease and gradual recovery in progressive motility rate. Sperm morphology analysis showed increased neck and tail abnormalities after the policy adjustment. No significant change in hormone levels was observed. Following the adjustment of the COVID-19 prevention policy in China, a decline in sperm motility and morphology was observed. This trend may gradually recover over 2 months. After the policy adjustment, reproductive hormone levels were relatively stable throughout, except for an increase in luteinizing hormone (LH). These changes in semen parameters suggest that the policy adjustment had a short- to medium-term impact on male reproductive function.

Inulin alleviates perinatal 2-ethylhexyl diphenyl phosphate (EHDPHP) exposure-induced intestinal toxicity by reshaping the gut microbiota and suppressing the enteric-origin LPS/TLR4/NF-κb pathway in dams and pups.

Organophosphorus flame retardants (OPFRs), such as 2-ethylhexyl diphenyl phosphate (EHDPHP), are ubiquitously used, leading to pervasive environmental contamination and human health risks. While associations between EHDPHP and health issues such as disruption of hormones, neurotoxic effects, and toxicity to reproduction have been recognized, exposure to EHDPHP during perinatal life and its implications for the intestinal health of dams and their pups have largely been unexplored. This study investigated the intestinal toxicity of EHDPHP and the potential for which inulin was effective. Dams were administered either an EHDPHP solution or a corn oil control from gestation day 7 (GD7) to postnatal day 21 (PND21), with inulin provided in their drinking water. Our results indicate that inulin supplementation mitigates damage to the intestinal epithelium caused by EHDPHP, restores mucus-secreting cells, suppresses intestinal hyperpermeability, and abates intestinal inflammation by curtailing lipopolysaccharide leakage through reshaping of the gut microbiota. A reduction in LPS levels concurrently inhibited the inflammation-associated TLR4/NF-κB pathway. In conclusion, inulin administration may ameliorate intestinal toxicity caused by EHDPHP in dams and pups by reshaping the gut microbiota and suppressing the LPS/TLR4/NF-κB pathway. These findings underscore the efficacy of inulin as a therapeutic agent for managing health risks linked to EHDPHP exposure.

Association Between Dyadic Coping and Quality of Life in Breast Cancer Patients and Their Spouses: An Actor-partner Interdependence Mediation Model.

PURPOSE: This study aims to examine the relationship between dyadic coping (DC), intimate relationship, and quality of life (QOL), and to explore the mediating role of intimate relationship in patients with breast cancer (BC) and their spouses from a dyadic perspective. METHODS: A cross-sectional design was used in this present study, and 205 dyads of BC patients and their spouses who completed a sociodemographic and clinical questionnaire and self-reported measures assessing their DC, intimate relationship, and QOL were recruited. The actor-partner interdependence mediation model (APIMeM) was adopted for dyadic distinguished data analysis. The paired t-test, Pearson's correlation coefficients, and the structural equation model were employed for data analysis by using SPSS 22.0 and Amos 24.0. RESULTS: The current study revealed that, for BC patients and their spouses, intimate relationship mediates completely the actor effect of DC on QOL. That is to say, DC was positively related to intimate relationship and then improved QOL. It was interesting to find that, for both patients and their spouses, the intimate relationship could exert a partner-actor complete mediation effect between DC and QOL. CONCLUSIONS: The DC perceived by both BC patients and their spouses has significant actor effects on QOL by improving the level of an intimate relationship. Furthermore, intimate relationship has significant actor-actor and partner-actor complete mediation effects for both patients and their spouses. Given the vital role of patient-spouse dyads, nursing staff should take patients' spouses into account when conducting related psychosocial interventions aiming to improve the QOL of BC patients and their spouses.

Perioperative corticosteroids for reducing postoperative complications following esophagectomy: an updated systematic review and meta-analysis.

BACKGROUND: This updated systematic review and meta-analysis aims to evaluate the efficacy and safety of perioperative corticosteroid administration versus placebo for esophageal cancer patients following scheduled esophagectomy. METHODS: We searched databases through June 30, 2023. We included articles on randomized controlled trials (RCTs) comparing perioperative corticosteroid administration with placebo in esophageal cancer patients with esophagectomy. The outcomes were the death rate during hospitalization, length of hospital stay, and short-term complications. Risk ratios (RRs) and corresponding 95% confidence interval (CIs) for each estimated effect size were applied for dichotomous outcomes, and the mean difference (MD) and corresponding 95% CIs for each estimated effect size were applied for continuous outcomes. We used GRADE to evaluate the quality of each of the outcome and the level of recommendations. RESULTS: Nine RCTs with 508 participants were included in this study. Severe outcomes, including the length of hospital stay, leakage, mortality during the hospitalization period in the corticosteroid group was comparable to that in the control group, but positive effects of corticosteroid administration were observed on the length of intensive care unit stay (MD -3.1, 95% CI - 5.43 to - 0.77), cardiovascular disorders (RR 0.44, 95% CI 0.21-0.94) and other general complications (RR 0.49, 95% CI 0.29-0.85). CONCLUSIONS: Peri-operative intravenous corticosteroid administration may reduce cardiovascular disorders, other general complications and the length of ICU stay without carrying severe outcomes. More high quality RCTs are warranted to further investigate the effects of corticosteroids on postoperative mortality and complications for esophageal cancer patients with esophagectomy. SYSTEMATIC REVIEW REGISTRATION: Cochrane, registration number: 196.

Maternal inulin supplementation ameliorates prenatal methamphetamine exposure-induced hepatotoxicity and restores gut microbiota in mouse offspring.

Prenatal exposure to methamphetamine (METH) is an issue of global concern due to its adverse effects on offspring, particularly its impact on liver health, an area still not fully understood. Inulin, a recognized prebiotic, is thought to potentially ameliorate these developmental disorders and toxic injuries in progeny. To investigate the effects of prenatal METH exposure on the liver and the role of gut microbiota, we established a murine model, the subjects of which were exposed to METH prenatally and subsequently treated with inulin. Our findings indicate that prenatal METH exposure causes liver damage in offspring, as evidenced by a decreased liver index, histopathological changes, diminished glycogen synthesis, hepatic dysfunction, and alterations in mRNA profiles. Furthermore, it impairs the antioxidant system and induces oxidative stress, possibly due to changes in cecal microbiota and dysregulation of bile acid homeostasis. However, maternal inulin supplementation appears to restore the gut microbiota in offspring and mitigate the hepatotoxic effects induced by prenatal METH exposure. Our study provides definitive evidence of METH's transgenerational hepatotoxicity and suggests that maternal inulin supplementation could be an effective preventive strategy.

Anti-COVID-19 mechanism of Anoectochilus roxburghii liquid based on network pharmacology and molecular docking / 药学学报

italic>Anoectochilus roxburghii liquid (spray, a hospital preparation of Wu Mengchao Hepatobiliary Hospital of Fujian Medical University) has shown a good clinical treatment effect during the COVID-19 pandemic, but its material basis and mechanism of action are still unclear. In this study, network pharmacology and molecular docking methods were used to predict the molecular mechanism of A. roxburghii liquid against COVID-19, and pharmacodynamic experiments in vitro were conducted to study the interaction between the current targets with clear preventive and therapeutic effects and the key components of A. roxburghii liquid. UPLC-MS and database were used to compare and analyze the active ingredients in the liquid, and 17 potential active ingredients with good drug-like properties were screened by in vivo pharmacokinetics process in SwissADME database. SwissTargetPrediction and GeneCards were searched to find 93 common targets. Cytoscape 3.8.2 software was used to construct the "component-target" network map, and the Metascape platform was used for gene function annotation and pathway enrichment analysis. It was found that the extract could regulate the positive response to external stimuli, inflammatory response, cytokine production and other biological processes by binding the active ingredients such as isorhamnetin, kaempferol, luteolin, quercetin and apigenin to the common targets (NOS3, MPO, MMP3, etc.), and play an anti-COVID-19 role. In the angiotensin-converting enzyme 2 (ACE2) activity inhibition assay, it was found that the stock solution of A. roxburghii liquid (for spray), and the supernatant after removing polysaccharides (mainly containing flavonoids) could to some extent inhibit the activity of ACE2. Crucially, in the experiment of 2019-nCOV-S pseudovirus infecting HEK-293T-ACE2 cells, we found that A. roxburghii liquid may exert anti-COVID-19 effects by blocking the binding of SARS-CoV-S protein to ACE2.

Association between serum total bilirubin and diabetic kidney disease in US diabetic patients.

Background: Bilirubin has been widely reported to be a protective factor against diabetic kidney disease (DKD) in Asian populations. However, few large-sample analyses have been conducted in American populations. This study aimed to investigate the association between serum total bilirubin (STB) level and DKD in a US diabetic cohort. Methods: This cross-sectional study enrolled participants from the National Health and Nutrition Examination Survey (NHANES) 2003-2018. Univariate and multivariate logistic regression analyses were performed to assess the association between STB level and DKD. Three models were conducted to control the potential confounding factors. Subgroup analysis was carried out for further validation. Results: Among the 5,355 participants, the median age [interquartile range (IQR)] was 62 [52-71] years; 2,836 (52.96%) were male, and 1,576 (29.43%) were diagnosed with DKD. In the entire cohort, no significant association between STB level and DKD was observed in any logistic regression models (p > 0.05). Subgroup analysis revealed that, in U.S. diabetic males, STB levels > 11.98 µmol/L were associated with a nearly 30% lower risk of DKD than STB levels ≤ 8.55 µmol/L. Additionally, a moderate STB level (8.56-11.98 µmol/L) was found associated with a nearly 25% lower risk of DKD in U.S. diabetic patients over 65 years old. Conclusion: The association of STB level with DKD may depict differences across diverse populations, among which the impact of race, sex, and age requires thorough consideration and relevant inferences should be interpreted cautiously.

[Risk factors and prognosis of preoperative herat failure after hip fracture].

OBJECTIVE: To explore incidence, risk factors and the relationship between preoperative heart failure and prognosis in elderly patients with hip fracture. METHODS: A retrospective analysis was performed on 1 569 elderly patients with hip fracture treated from January 2012 to December 2019, including 522 males and 1 047 females, aged 81.00 (75.00, 90.00) years old;896 intertrochanteric fractures and 673 femoral neck fractures. Patients were divided into heart failure and non-heart failure groups according to whether they developed heart failure before surgery, and heart failure was set as the dependent variable, with independent variables including age, gender, fracture type, comorbidities and hematological indicators, etc. Univariate analysis was performed at first, and independent variables with statistical differences were included in multivariate Logistic regression analysis. Independent risk factors for preoperative heart failure were obtained. The length of hospital stay, perioperative complications, mortality at 30 days and 1 year after surgery were compared between heart failure and non-heart failure groups. RESULTS: There were 91 patients in heart failure group, including 40 males and 51 females, aged 82.00 (79.00, 87.00) years old;55 patients with intertrochanteric fracture and 36 patients with femoral neck fracture. There were 1 478 patients in non-heart failure groups, including 482 males and 996 females, aged 81.00(75.00, 86.00) years old;841 patients with intertrochanteric fracture and 637 patients with femoral neck fracture. There were significant differences in age, sex, coronary heart disease, arrhythmia and dementia between two groups(P<0.05). Multivariate Logistic analysis of statistically significant factors showed that males(OR=1.609, P=0.032), age(OR=1.032, P=0.031), arrhythmia(OR=2.045, P=0.006), dementia (OR=2.106, P=0.014) were independent risk factor for preoperative heart failure. The 30-day and 1-year mortality rates were 9.9% and 26.4% in heart failure group and 3.6% and 13.8% in non-heart failure group, respectively;and had statistical significance between two groups (P<0.05). There were significant differences in pulmonary infection, cerebrovascular complications and cardiovascular complications between two groups (P<0.05). The duration of hospitalization in heart failure group was (16.21±10.64) d compared with that in non-heart failure group (13.26±8.00) d, and the difference was statistically significant (t=2.513, P=0.012). CONCLUSION: Male, old age, arrhythmia and dementia are independent risk factors for heart failure after hip fracture in elderly patients. Patients with preoperative heart failure have a higher incidence of postoperative pulmonary infection, cerebrovascular and cardiovascular complications, higher mortality at 30 d and 1 year after surgery, and longer hospital stay.

[Molecular mechanism of sleep deprivation-induced body injury and traditional Chinese medicine prevention and treatment: a review].

Sleep occupies one-third of a person's lifetime and is a necessary condition for maintaining physiological function and health. With the increase in social and economic pressures, the growing use of electronic devices and the accelerated aging process of the population, insufficient sleep and its hazards have drawn widespread attention from researchers in China and abroad. Sleep deprivation refers to a decrease in sleep or a severe lack of sleep due to various reasons. Previous studies have found that sleep deprivation can cause extensive damage to the body, including an increased incidence and mortality rate of neuropathic diseases in the brain, cardiovascular diseases, imbalances in the gut microbiota, and other multi-organ diseases. The mechanisms underlying the occurrence of multi-system and multi-organ diseases due to sleep deprivation mainly involve oxidative stress, inflammatory responses, and impaired immune function in the body. According to traditional Chinese medicine(TCM), sleep deprivation falls into the category of sleepiness, and long-term sleepiness leads to Yin-Yang imbalance, resulting in the consumption of Qi and damage to the five Zang-organs. The appropriate treatment should focus on tonifying deficiency, reinforcing healthy Qi, and harmonizing Yin and Yang. TCM is characterized by a wide variety and abundant resources, and it has minimal side effects and a broad range of applications. Numerous studies have shown that TCM drugs and prescriptions not only improve sleep but also have beneficial effects on liver nourishment, intelligence enhancement, and kidney tonification, effectively preventing and treating the body injury caused by sleep deprivation. Given the increasing prevalence of sleep deprivation and its significant impact on body health, this article reviewed sleep deprivation-mediated body injury and its mechanism, summarized and categorized TCM compound prescriptions and single drugs for preventing and treating body injury, with the aim of laying the foundation for researchers to develop effective drugs for preventing and treating body injury caused by sleep deprivation and providing references for further exploration of the molecular mechanisms underlying the body injury caused by sleep deprivation.

[Intracytoplasmic sperm injection for patients with special types of teratozoospermia: Analysis of outcomes].

OBJECTIVE: To investigate the outcomes of intracytoplasmic sperm injection (ICSI) in the treatment of special types of teratozoospermia such as globozoospermia, acephalic spermatozoa syndrome (ASS) and multiple morphological abnormalities of sperm flagella (MMAF). METHODS: We retrospectively analyzed the clinical data on 7 cases of globozoospermia (group A), 6 cases of ASS (group B) and 21 cases of MMAF (group C) treated by ICSI from January 2011 to January 2021, all confirmed with pathogenic or likely pathogenic gene variations. We compared the age, body mass index (BMI), sperm parameters, number of mature oocytes, and rates of fertilization, high-quality embryos, clinical pregnancy, live birth and spontaneous abortion among the three groups of patients. RESULTS: There were no statistically significant differences in the age, BMI and number of metaphase Ⅱ (MⅡ) oocytes among the three groups (P > 0.05). Sperm concentration and motility were dramatically higher (P < 0.01) while the rates of fertilization, clinical pregnancy and live birth remarkably lower in group A than in B and C (P < 0.01). No statistically significant difference was observed in the spontaneous abortion rate among the three groups (P > 0.05). CONCLUSION: ICSI can achieve relatively satisfactory outcomes of clinical pregnancy in patients with ASS or MMAF, but only a low fertilization rate or no fertilization at all in those with globozoospermia even if treated by artificial oocyte activation.

Multi-Omics Analysis Reveals the Role of Sigma-1 Receptor in a Takotsubo-like Cardiomyopathy Model.

Takotsubo syndrome (TTS) is a stress-induced cardiomyopathy that presents with sudden onset of chest pain and dyspneic and cardiac dysfunction as a result of extreme physical or emotional stress. The sigma-1 receptor (Sigmar1) is a ligand-dependent molecular chaperone that is postulated to be involved in various processes related to cardiovascular disease. However, the role of Sigmar1 in TTS remains unresolved. In this study, we established a mouse model of TTS using wild-type and Sigmar1 knockout mice to investigate the involvement of Sigmar1 in TTS development. Our results revealed that Sigmar1 knockout exacerbated cardiac dysfunction, with a noticeable decrease in ejection fraction (EF) and fractional shortening (FS) compared to the wild-type model. In terms of the gut microbiome, we observed regulation of Firmicutes and Bacteroidetes ratios; suppression of probiotic Lactobacillus growth; and a rise in pathogenic bacterial species, such as Colidextribacter. Metabolomic and transcriptomic analyses further suggested that Sigmar1 plays a role in regulating tryptophan metabolism and several signaling pathways, including MAPK, HIF-1, calcium signaling, and apoptosis pathways, which may be crucial in TTS pathogenesis. These findings offer valuable insight into the function of Sigmar1 in TTS, and this receptor may represent a promising therapeutic target for TTS.

Augmented reality navigation-guided intraoperative pulmonary nodule localization: a pilot study.

Background: With the increasing number of small pulmonary nodules detected, effective localization of pulmonary nodules has become an issue. The goal of this study is to determine the safety and feasibility of a newly developed augmented reality navigation technology for intraoperative localization of small pulmonary nodules. Methods: We conducted a prospective single-center feasibility study of a novel augmented reality navigation system and lung localization (LungBrella) marker on ten patients between July and October 2020. For augmented reality navigation-guided localization, a preoperative chest computed tomography scan was performed to generate 3-dimensional (3D) virtual images and individualized localization plan, which were uploaded into Hololens (a head-mounted augmented reality device). Under the guidance of established procedure plan displayed by HoloLens, localization marker was placed in operating room. Segmentectomy or wedge resection was subsequently performed. The primary endpoint was the localization procedure success rate, and the secondary endpoints were localization time, operation time, and complications. Results: Localization was successful in seven of the ten procedures. Due to different reasons, failures were noted in three cases, after which immediate adjustments were made. In the successful cases, the LungBrella marker was positioned at a median of 5.8 mm (range, 0-10 mm) from the edge of the nodule. Median localization time was 9.4 min (range, 5-19 min), and median operation time was 172.9 min (range, 105-200 min). There were no complications during the entire process. Conclusions: This exploratory study suggests that augmented reality navigation-guided pulmonary nodule localization is a safe and feasible technique (ClinicalTrials.gov identifier, NCT04211051).

Sigma-1 receptor knockout disturbs gut microbiota, remodels serum metabolome, and exacerbates isoprenaline-induced heart failure.

Introduction: Heart failure (HF) is usually the end stage of the continuum of various cardiovascular diseases. However, the mechanism underlying the progression and development of HF remains poorly understood. The sigma-1 receptor (Sigmar1) is a non-opioid transmembrane receptor implicated in many diseases, including HF. However, the role of Sigmar1 in HF has not been fully elucidated. Methods: In this study, we used isoproterenol (ISO) to induce HF in wild-type (WT) and Sigmar1 knockout (Sigmar1-/-) mice. Multi-omic analysis, including microbiomics, metabolomics and transcriptomics, was employed to comprehensively evaluate the role of Sigmar1 in HF. Results: Compared with the WT-ISO group, Sigmar1-/- aggravated ISO-induced HF, including left ventricular systolic dysfunction and ventricular remodeling. Moreover, Sigmar1-/- exacerbated ISO-induced gut microbiota dysbiosis, which was demonstrated by the lower abundance of probiotics g_Akkermansia and g_norank_f_Muribaculaceae, and higher abundance of pathogenic g_norank_f_Oscillospiraceae and Allobaculum. Furthermore, differential metabolites among WT-Control, WT-ISO and Sigmar-/--ISO groups were mainly enriched in bile secretion, tryptophan metabolism and phenylalanine metabolism, which presented a close association with microbial dysbiosis. Corresponding with the exacerbation of the microbiome, the inflammation-related NOD-like receptor signaling pathway, NF-kappa B signaling pathway and TNF signaling pathway were activated in the heart tissues. Conclusion: Taken together, this study provides evidence that a Sigmar1 knockout disturbs the gut microbiota and remodels the serum metabolome, which may exacerbate HF by stimulating heart inflammation.

Inulin alleviates neuroinflammation and oxidative stress induced by perinatal 2-ethylhexyl diphenyl phosphate (EHDPHP) exposure in female mice and offspring.

Organophosphorus flame retardants (OPFRs), including 2-ethylhexyl diphenyl phosphate (EHDPHP), are prevalent in everyday life due to their broad usage in fields such as healthcare, electronics, industry, and sports. These compounds, added to polymers through physical mixing, can leach into the environment, posing a risk to humans through direct contact or the food chain. Despite known associations with health issues like endocrine disruption, neurotoxicity, and reproductive toxicity, the implications of perinatal EHDPHP exposure on both mothers and offspring are still unclear. This study aimed to investigate the neuroinflammatory effects of EHDPHP and the potential mitigating role of inulin. Pregnant C57 mice were administered either a corn oil control or an EHDPHP solution (300 µg/kg bw/d) from gestation day 7 (GD7) to postnatal day 21 (PND21). Concurrently, mice were provided either regular drinking water or water supplemented with 1% inulin. We found that EHDPHP significantly increased the serum levels of IL-1ß, IL-6, and MDA, but decreased SOD levels in both mothers and pups. These effects were reversed by inulin supplementation. RNA-sequencing revealed that EHDPHP induced inflammation and oxidative stress through the TLR4/NF-κB pathway, which was mitigated by inulin. In conclusion, inulin ameliorated EHDPHP-induced neuroinflammation and oxidative stress in both mothers and offspring, highlighting its potential therapeutic role.

[Use a leaflet flap of foot to severed multi-finger with segmental injury].

OBJECTIVE: To explore asurgical methods for replantation of severed finger. METHODS: From January 2018 to November 2022, 8 amputated-finger patients were performed surgical reconstructions by using polyfoliate free flaps with the first dorsal metatarsal artery, including 7 males and 1 female, aged from 20 to 55 years old, and defect areas ranged from (1.0 to 2.0) cm×(3.0 to 4.5) cm. Finger pulp sensation, shape and other relevant parameters were assessed following the upper extremity functional evaluation standard, which was put forward by Hand Surgery Branch of Chinese Medical Association. And maryland foot functional score was used to evaluate foot function. RESULTS: Amputated fingers and flaps of all the 8 patients were survived. All patients were followed up for 4 to 20 months, their finger color and temperature tured to normal, with good wear-resistance and cold-resistance. According to Hand Surgery Branch of Chinese Medical Association, functional score ranged 61 to 92;4 patients got excellent result and 4 good. Maryland foot functional score ranged from 93 to 100;and 8 patients got excellent result. CONCLUSION: It is feasible to repair severed fingers with soft tissue defects using polyfoliate free flaps that driven by the flippers of the first and second toes of the foot. This method ccould bridge blood vessels, increase soft tissue volume of the injured finger, and avoid finger shortening, with high patient satisfaction.