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Background Video-assisted thoracoscopic surgery (VATS) has been widely used as an alternative for thoracotomy, but the reported incidence of chronic postsurgical pain (CPSP) following VATS varied widely. The purpose of this study was to investigate the incidence and risk factors for CPSP after VATS. Methods We retrospectively collected preoperative demographic, anesthesiology, and surgical factors in a cohort of patients undergoing VATS between January 2018 and October 2020. Patients were interviewed via phone survey for pain intensity, and related medical treatment 3 months after VATS. Univariate and multivariate analysis were used to explore independent risk factors associated with CPSP. Results 2348 patients were included in our study. The incidence of CPSP after VATS were 43.99% (n = 1033 of 2348). Within those suffering CPSP, 14.71% (n = 152 of 1033) patients reported moderate or severe chronic pain. Only 15.23% (n = 23 of 152) patients with moderate to severe chronic pain sought active analgesic therapies. Age < 65 years (OR 1.278, 95% CI 1.057–1.546, P  = 0.011), female (OR 1.597, 95% CI 1.344–1.898, P  < 0.001), education level less than junior school (OR 1.295, 95% CI 1.090–1.538, P  = 0.003), preoperative pain (OR 2.564, 95% CI 1.696–3.877, P  < 0.001), consumption of rescue analgesia postoperative (OR 1.248, 95% CI 1.047–1.486, P  = 0.013), consumption of sedative hypnotic postoperative (OR 2.035, 95% CI 1.159–3.574, P  = 0.013), and history of postoperative wound infection (OR 5.949, 95% CI 3.153–11.223, P  < 0.001) were independent risk factors for CPSP development. Conclusions CPSP remains a challenge in clinic because half of patients may develop CPSP after VATS. Trial registration Chinese Clinical Trial Registry (ChiCTR2100045765), 2021/04/24

Key summary points Aim Total knee arthroplasty (TKA) is an important therapy for OA, but control of postoperative pain is a clinical challenge. We assumed that frailty could predict post-surgical pain after TKA, especially in older patients. Findings Preoperative frailty in older patients is an important risk factor for both acute and chronic pain after TKA, suggesting that frailty assessment should become a necessary procedure before operation, especially in older patients. Message As a risk factor for post-surgical pain after TKA, timely intervention for preoperative frailty may be able to reduce the incidence of pain in older patients Purpose Frailty is reportedly associated with postoperative adverse outcomes and may increase the risk of post-surgical pain. Our study aimed to explore whether frailty was an independent risk factor for pain after total knee arthroplasty (TKA) in older patients. Methods Included in this prospective observational study were patients aged 65 or older who underwent primary TKA. Frailty of the patients was assessed before surgery using the comprehensive geriatric assessment-frailty index and pain was evaluated before and after surgery using the Numerical Rating Scale. Results Of the 164 patients including 125 females with a mean age of 71.4 ± 4.6 years, 51 patients were identified as being frail. Patients with chronic post-surgical pain had a significantly higher frailty index than those without chronic post-surgical pain, which was the same in patients with acute post-surgical pain. After adjusting for other confounding factors, frailty was shown to be an independent risk factor for both acute (OR: 13.23, 95% CI 3.73–46.93, P  < 0.001) and chronic post-surgical pain (OR: 4.24, 95% CI 1.29–14.00, P  = 0.02). The area under the receiver operating characteristic curve for frailty predicting chronic post-surgical pain was 0.73 ( P  < 0.001, 95% CI 0.65–0.81). Conclusions Our findings demonstrated that preoperative frailty in older patients was a predictor of acute and chronic post-surgical pain after TKA, suggesting that frailty assessment should become a necessary procedure before operations, especially in older patients.

Background Thoracoscopic surgical techniques continue to advance, yet the intensity of postoperative pain remains significant, impeding swift patient recovery. This study aimed to evaluate the differences in postoperative pain and recuperation between patients receiving intrathecal morphine paired with low-dose bupivacaine and those administered general anesthesia exclusively. Methods This randomized controlled trial enrolled 100 patients, who were allocated into three groups: Group M (5 μg/kg morphine intrathecal injection), Group B (5 μg/kg morphine combined with bupivacaine 3 mg intrathecal injection) and Group C (intrathecal sham injection). The primary outcome was the assessment of pain relief using the Numeric Rating Scale (NRS). Additionally, intraoperative remifentanil consumption was quantified at the end of the surgery, and postoperative opioid use was determined by the number of patient-controlled analgesia (PCIA) compressions at 48 h post-surgery. Both the efficacy of the treatments and any complications were meticulously recorded. Results Postoperative NRS scores for both rest and exercise at 6, 12, 24, and 48 h were significantly lower in groups M and B than in group C ( P <0.05). The intraoperative remifentanil dosage was significantly greater in groups M and C than in group B ( P <0.05), while there was no significant difference between groups M and C ( P >0.05). There was no significant difference in intraoperative propofol dosage across all three groups ( P >0.05). Postoperative dosages of both sufentanil and Nonsteroidal anti‐inflammatory drugs (NSAIDs) were significantly less in groups M and B compared to group C ( P <0.05). The time of first analgesic request was later in both groups M and B than in group C ( P <0.05). Specific and total scores were elevated at 2 days postoperative when compared to scores at 1 day for all groups ( P <0.05). Furthermore, at 1 day and 2 days postoperatively, both specific scores and total scores were higher in groups M and B compared to group C ( P <0.05). Conclusion Intrathecal administration of morphine combined with bupivacaine has been shown to effectively ameliorate acute pain in patients undergoing thoracoscopic surgery. Trial registration The trial was registered on ClinicalTrials.gov: ChiCTR2200058544, registered 10/04/2022.

Background Hip or knee osteoarthritis (OA) is one of the main causes of disability worldwide and occurs mostly in the older adults. Total hip or knee arthroplasty is the most effective method to treat OA. However, severe postsurgical pain leading to a poor prognosis. So, investigating the population genetics and genes related to severe chronic pain in older adult patients after lower extremity arthroplasty is helpful to improve the quality of treatment. Methods We collected blood samples from elderly patients who underwent lower extremity arthroplasty from September 2020 to February 2021 at the Drum Tower Hospital Affiliated to Nanjing University Medical School. The enrolled patients provided measures of pain intensity using the numerical rating scale on the 90th day after surgery. Patients were divided into the case group (Group A) and the control group (Group B) including 10 patients respectively by the numerical rating scale. DNA was isolated from the blood samples of the two groups for whole-exome sequencing. Results In total, 661 variants were identified in the 507 gene regions that were significantly different between both groups ( P  < 0.05), including CASP5, RASGEF1A, CYP4B1, etc. These genes are mainly involved in biological processes, including cell–cell adhesion, ECM–receptor interaction, metabolism, secretion of bioactive substances, ion binding and transport, regulation of DNA methylation, and chromatin assembly. Conclusions The current study shows some variants within genes are significantly associated with severe postsurgical chronic pain in older adult patients after lower extremity arthroplasty, indicating a genetic predisposition for chronic postsurgical pain. The study was registered according to ICMJE guidelines. The trial registration number is ChiCTR2000031655 and registration date is April 6th, 2020.

Epistasis is one of important genetic components for a quantitative trait in plant. Eshed and Zamir found negative epistatic interactions of quantitative trait loci in Tomato first. We detected that positive (negative) QTLs generated mostly negative (positive) epistatic interactions on heading date in rice, and then proposed the hypothese that QTL epistasis plays a role of homeostasis in one of our recent papers. In order to further provide additional evidence, the effects of QTLs and their epistatic effects on two quantitative traits of plant height (ph) and thousand kernel weight (tkw) were analyzed in this study. The same regularity was verified again. We detected that positive ph QTLs and negative tkw QTLs always generated reverse epistatic effects, respectively. Moreover, high-order epistatic effects were estimated on these two traits. The sum of all epistatic effects would partially neutralize the additive of constitutive QTL effects. This feature of epistsis would be the mechanism for bionts to maintain homeostasis while the obstacle for human to achieve the pyramiding breeding objectives. More evidences are still being collected to support our assumption.

If there was no gene interaction, the gene aggregation effect would increase infinitely with the increase of gene number. Epistasis avoids the endless accumulation of gene effects, playing a role of homeostasis. To confirm the role, QTL epistases were analyzed by four single-segment substitution lines with heading date QTLs in this paper. We found that QTLs of three positive effects and one negative effect generated 62.5% negative dual QTL epistatic effects and 57.7% positive triple QTL epistatic effects, forming the relationship “positive QTLs-negative one order interactions-positive two order interactions”. In this way, the aggregation effect of QTLs was partially neutralized by the opposite epistatic effect sum. There also were two exceptions, QTL OsMADS50 and gene Hd3a-2 were always with consistent effect directions with their epistases, implying they could be employed in pyramiding breeding with different objectives. This study elucidated the mechanism of epistatic interactions among four QTLs and provided valuable genetic resources for improving heading date in rice.

Background Propionic acidemia (PA) is a rare autosomal recessive metabolic disorder caused by defects in propionyl-CoA carboxylase (PCC), a mitochondrial enzyme composed of six alpha (PCCA) and six beta (PCCB) subunits. Mutations in PCCA/PCCB genes disrupt PCC function, leading to toxic metabolite accumulation and clinical manifestations. Current research is limited by inadequate patient-derived cellular models and ethical constraints in sample acquisition. Method Using CRISPR/Cas9-mediated gene editing, we established an isogenic human induced pluripotent stem cell (iPSC) line carrying the PCCA c.2002G> A mutation. The mutant iPSCs were further subjected to directed cardiac differentiation. Characteristic metabolites in the iPSC-derived cardiomyocytes (iPSC-CMs) culture medium were analyzed via untargeted metabolomics, and contractile function was assessed by video-based motion analysis under propionate challenge. Results The mutant iPSCs showed sustained expression of pluripotency markers (OCT4, NANOG, SOX-2), maintained normal karyotype (46, XY), and retained trilineage differentiation capacity. Functional characterization demonstrated significantly reduced PCC enzyme activity, accurately modeling PA metabolic pathology. Furthermore, the mutant iPSCs successfully differentiated into cardiomyocytes and exhibited a PA-specific metabolic profile, including significantly elevated propionylcarnitine levels. Upon propionate treatment (2.5 mM), the contractile function of mutant iPSC-CMs was significantly impaired, whereas wild-type iPSC-CMs showed the opposite response with enhanced contraction. Conclusions This isogenic iPSC line provides an ethically unconstrained platform to investigate PA molecular mechanisms and genotype-phenotype relationships. The model enables systematic drug screening and therapeutic development while overcoming patient sample limitations.

Background Wilms tumor is among the most common pediatric malignant tumors. Although m 1 A modification influences the structure and function of RNA and participates in tumorigenesis, the relationship between m 1 A methyltransferase TRMT61B gene polymorphisms and Wilms tumor susceptibility is unclear. Methods We examined the relationship between TRMT61B gene rs4563180 G > C polymorphism (detected by TaqMan probe method) in 414 children with Wilms tumor and 1199 healthy controls. The relationship between the genotype of each sublayer and the risk of Wilms tumor was studied by stratified analysis. The GTEx database was used to analyze the influence of TRMT61B rs4563180 G > C polymorphism on mRNA expression. Results The TRMT61B gene polymorphism significantly reduced the susceptibility to Wilms tumor (GC vs. GG: adjusted odds ratio [AOR] = 0.72, 95% confidence interval [CI] = 0.56–0.93, P  = 0.012; GC/CC vs. GG: AOR = 0.76, 95% CI = 0.60–0.96, P  = 0.021). GC/CC genotype had a protective effect in boys and children with stage III tumors compared with rs4563180 GG genotype. Additionally, the C allele was significantly associated with decreased mRNA expression of TRMT61B gene compared with rs4563180G allele in cultured fibroblasts ( P  = 3.3e − 80), EBV-transformed lymphocytes ( P  = 9.5e − 14), and whole blood ( P  = 6.0e − 12). Conclusions Our results confirm that TRMT61B gene is associated with the development of Wilms tumors, but its underlying mechanism requires further exploration.

The incidence of non-suicidal self-injury (NSSI) has been on the rise in recent years. Studies have shown that people with NSSI have difficulties in emotion regulation and cognitive control. In addition, some studies have investigated the cognitive emotion regulation of people with NSSI which found that they have difficulties in cognitive emotion regulation, but there was a lack of research on cognitive emotion regulation strategies and related neural mechanisms. This study included 117 people with NSSI (age = 19.47 ± 5.13, male = 17) and 84 non-NSSI participants (age = 19.86 ± 4.14, male = 16). People with NSSI met the DSM-5 diagnostic criteria, and non-NSSI participants had no mental or physical disorders. The study collected all participants' data of Cognitive Emotion Regulation Questionnaire (CERQ) and functional magnetic resonance imaging (fMRI) to explore the differences in psychological performance and brain between two groups. Afterwards, Machine learning was used to select the found differential brain regions to obtain the highest correlation regions with NSSI. Then, Allen's Human Brain Atlas database was used to compare with the information on the abnormal brain regions of people with NSSI to find the genetic information related to NSSI. In addition, gene enrichment analysis was carried out to find the related pathways and specific cells that may have differences. The differences between NSSI participants and non-NSSI participants were as follows: positive refocusing (t = −4.74, p < 0.01); refocusing on plans (t = −4.11, p < 0.01); positive reappraisal (t = −9.22, p < 0.01); self-blame (t = 6.30, p < 0.01); rumination (t = 3.64, p < 0.01); catastrophizing (t = 9.10, p < 0.01), and blaming others (t = 2.52, p < 0.01), the precentral gyrus (t = 6.04, pFDR < 0.05) and the rolandic operculum (t = −4.57, pFDR < 0.05). Rolandic operculum activity was negatively correlated with blaming others (r = −0.20, p < 0.05). Epigenetic results showed that excitatory neurons (p < 0.01) and inhibitory neurons (p < 0.01) were significant differences in two pathways, “trans-synaptic signaling” (p < −log108) and “modulation of chemical synaptic transmission” (p < −log108) in both cells. People with NSSI are more inclined to adopt non-adaptive cognitive emotion regulation strategies. Rolandic operculum is also abnormally active. Abnormal changes in the rolandic operculum of them are associated with non-adaptive cognitive emotion regulation strategies. Changes in the excitatory and inhibitory neurons provide hints to explore the abnormalities of the neurological mechanisms at the cellular level of them. Trial registration number NCT04094623 •The use of non-adaptive cognitive emotion regulation strategies was associated with abnormal changes in the Rolandic operculum.•Changes in excitatory and inhibitory neurons and abnormal performance of related pathways may be related to changes in brain regions and the use of cognitive emotion regulation strategies.

This study investigated the protective effects and mechanisms of sevoflurane preconditioning (SPC) on neurons in ischemic mice. After SPC, mice were subjected to middle cerebral artery occlusion (MCAO). Cerebral infarction area, cell apoptosis, and metallothionein-1 (MT-1) and metallothionein-2 (MT-2) expressions in MCAO mice were analyzed. Mouse primary neurons were isolated and cultured to determine the location of metallothioneins (MTs) using immunofluorescence. Neurons transfected with MT-siRNA, exogenous MTs, or sh-MTF-1 were subjected to SPC and/or oxygen-glucose deprivation (OGD), and MT-1/MT-2 expression and neurotoxin release were assayed. Meanwhile, neurons were treated with the nitric oxide donor SNAP, degraded SNAP, or the peroxide initiator paraquat, and alterations in MT-1/MT-2 expression and neurotoxicity release were observed. SPC attenuated neuronal injury and apoptosis in MCAO mice. SPC could protect neurons against OGD injury and resulted in upregulated MT-1/MT-2 expression. MT-siRNA transfection led to the downregulated expression of MT-1/MT-2 and increased neurotoxicity, and the expression patterns of these neurons were different from those of neurons transfected with exogenous MTs. The knockdown of MTs could hinder the protective effect of SPC against OGD. Pretreatment with SNAP or paraquat could increase MTF-1 expression in the nucleus of neurons, protecting against OGD injury. The inhibition of nitric oxide and peroxide inhibited the protective role of SPC in OGD by downregulating MTF-1 expression. sh-MTF-1 transfection downregulated MT-1/MT-2 expression and enhanced neurotoxicity in neurons. SPC confers neuroprotection in focal cerebral ischemia mouse models by upregulating the expression of MT-1 and MT-2 by activating NO and peroxide and increasing MTF-1 expression in the nucleus.