Low-intensity ultrasound ameliorates brain organoid integration and rescues microcephaly deficits.

Human brain organoids represent a remarkable platform for modeling neurological disorders and a promising brain repair approach. However, the effects of physical stimulation on their development and integration remain unclear. Here, we report that low-intensity ultrasound significantly increases neural progenitor cell proliferation and neuronal maturation in cortical organoids. Histological assays and single-cell gene expression analyses reveal that low-intensity ultrasound improves the neural development in cortical organoids. Following organoid grafts transplantation into the injured somatosensory cortices of adult mice, longitudinal electrophysiological recordings and histological assays reveal that ultrasound-treated organoid grafts undergo advanced maturation. They also exhibit enhanced pain-related gamma-band activity and more disseminated projections into the host brain than the untreated groups. Finally, low-intensity ultrasound ameliorates neuropathological deficits in a microcephaly brain organoid model. Hence, low-intensity ultrasound stimulation advances the development and integration of brain organoids, providing a strategy for treating neurodevelopmental disorders and repairing cortical damage.

Ternary Passivation for Enhanced Carrier Transport and Recombination Suppression in Highly Efficient Sn-Based Perovskite Solar Cells.

The exploration of nontoxic Sn-based perovskites as a viable alternative to their toxic Pb-based counterparts has garnered increased attention. However, the power conversion efficiency of Sn-based perovskite solar cells lags significantly behind their Pb-based counterparts. This study presents a ternary passivation strategy aimed at enhancing device performance, employing [6,6]-phenyl-C61-butyric-acid-methyl-ester (PCBM), poly(3-hexylthiophene) (P3HT), and indene C60 bisadduct (ICBA). These components play crucial roles in managing energy levels and enhancing carrier transportation, respectively. The results reveal that the introduction of the ternary system leads to improvements in carrier collection and transportation, accompanied by a suppression of the recombination process. Ultimately, the champion device achieves a remarkable performance with an efficiency of 14.64%. Notably, the device also exhibits robust operational and long-term stored stability.

Autophagy inhibitors 3-MA and BAF may attenuate hippocampal neuronal necroptosis after global cerebral ischemia-reperfusion injury in male rats by inhibiting the interaction of the RIP3/AIF/CypA complex.

Our previous study found that receptor interacting protein 3 (RIP3) and apoptosis-inducing factor (AIF) were involved in neuronal programmed necrosis during global cerebral ischemia-reperfusion (I/R) injury. Here, we further studied its downstream mechanisms and the role of the autophagy inhibitors 3-methyladenine (3-MA) and bafilomycin A1 (BAF). A 20-min global cerebral I/R injury model was constructed using the 4-vessel occlusion (4-VO) method in male rats. 3-MA and BAF were injected into the lateral ventricle 1 h before ischemia. Spatial and activation changes of proteins were detected by immunofluorescence (IF), and protein interaction was determined by immunoprecipitation (IP). The phosphorylation of H2AX (γ-H2AX) and activation of mixed lineage kinase domain-like protein (p-MLKL) occurred as early as 6 h after reperfusion. RIP3, AIF, and cyclophilin A (CypA) in the neurons after I/R injury were spatially overlapped around and within the nucleus and combined with each other after reperfusion. The survival rate of CA1 neurons in the 3-MA and BAF groups was significantly higher than that in the I/R group. Autophagy was activated significantly after I/R injury, which was partially inhibited by 3-MA and BAF. Pretreatment with both 3-MA and BAF almost completely inhibited nuclear translocation, spatial overlap, and combination of RIP3, AIF, and CypA proteins. These findings suggest that after global cerebral I/R injury, RIP3, AIF, and CypA translocated into the nuclei and formed the DNA degradation complex RIP3/AIF/CypA in hippocampal CA1 neurons. Pretreatment with autophagy inhibitors could reduce neuronal necroptosis by preventing the formation of the RIP3/AIF/CypA complex and its nuclear translocation.

Metal ions steer the duality in microbial community recovery from nitrogen enrichment by shaping functional groups.

Atmospheric nitrogen (N) deposition has been substantially reduced due to declines in the reactive N emission in major regions of the world. Nevertheless, the impact of reduced N deposition on soil microbial communities and the mechanisms by which they are regulated remain largely unknown. Here, we examined the effects of N addition and cessation of N addition on plant and soil microbial communities through a 17-year field experiment in a temperate grassland. We found that extreme N input did not irreversibly disrupt the ecosystem, but ceasing high levels of N addition led to greater resilience in bacterial and fungal communities. Fungi exhibited diminished resilience compared to bacteria due to their heightened reliance on changes in plant communities. Neither bacterial nor fungal diversity fully recovered to their original states. Their sensitivity and resilience were mainly steered by toxic metal ions and soil pH differentially regulating on functional taxa. Specifically, beneficial symbiotic microbes such as N-fixing bacteria and arbuscular mycorrhizal fungi experienced detrimental effects from toxic metal ions and lower pH, hindering their recovery. The bacterial functional groups involved in carbon decomposition, and ericoid mycorrhizal and saprotrophic fungi were positively influenced by soil metals, and demonstrated gradual recovery. These findings could advance our mechanistic understanding of microbial community dynamics under ongoing global changes, thereby informing management strategies to mitigate the adverse effects of N enrichment on soil function.

Magnetic tuning with minimal thermal drift in high-Q microspheres coated with magnetorheological polydimethylsiloxane.

Integration of whispering-gallery-mode (WGM) resonators with high-quality factors (Q) into advanced timing, oscillator, and sensing systems demands a platform that enables precise resonance frequency modulation. This study investigates the tuning characteristics of magnetorheological polydimethylsiloxane (MR-PDMS) coated microspheres (µ-spheres) employed as magnetic microresonators, achieving a Q value of 107 at the 1550 nm wavelength. Magnetic WGM resonators not only endow the device with magnetic adjustability but also markedly improve thermal resistance. Experimental findings reveal that the magnetic µ-sphere demonstrates a sensitivity of -32.53 MHz/mT, outperforming conventional magnetic WGM resonators. Furthermore, analysis of the temperature dependence shows a reduction in fluctuation to -2.85 MHz/K, thereby greatly enhancing the sensor's practical detection limit.

Comparison of the Clinical Outcomes of Vesselplasty vs. Percutaneous Vertebroplasty for the Treatment of Neurologically Intact Osteoporotic Kümmell's Disease: A Retrospective Study.

Kummell's disease (KD) is a rare clinical complication of osteoporotic vertebral compression fractures (OVCFs). Minimally invasive surgery is an important way to treat KD. In this paper, we used Percutaneous Vertebroplasty (PVP) and Vesselplasty (VP) to treat KD. 125 patients with KD were admitted to our hospital. Among them, 89 patients received PVP and 36 received VP. All patients underwent operations successfully. VAS scores and ODI of both groups at each postoperative time point were lower than preoperatively. Postoperative Cobb angle of both groups postoperatively was lower than preoperatively (p < 0.05). The anterior height and ratio of vertebra compression of both groups postoperatively was lower than preoperatively (p < 0.05). Cement leakage occurred in 16 vertebrae (16/89) in PVP group and one (1/36) in VP group. Two patients suffered from transient paraplegia in PVP group immediately after operation. Adjacent vertebral fractures occurred in one patient in PVP group and one in VP group. Re-fracture of affected vertebra occurred in one patient in PVP group. Besides, four patients suffered from bone cement loosening in PVP group while one in VP group. Both PVP and VP play an important effect in pain relief and functional recovery for the treatment of KD. And VP is more effective than PVP in preventing cement leakage.

Identification of bHLH transcription factors and screening of anthocyanin-related genes in Lagerstroemia indica.

The basic helix-loop-helix (bHLH) family is one of the three major transcription factor families that play important transcriptional regulatory roles in plant growth and development. One of the most crucial elements in defining Lagerstroemia indica's decorative qualities is flower color. However, the function of the bHLH transcription factor family in L. indica anthocyanin glycoside synthesis has not been clarified. Using the transcriptome data of flower color, 79 LibHLH genes were found in this study. Phylogenetic analysis showed that the LibHLH genes can be divided into 16 subfamilies, and most of the genes in the same subfamily have similar conserved motifs. The total anthocyanin glycoside content of L. indica 'Zihua Guifei' petals was determined during three developmental stages of the petals' growth. The results showed that the total anthocyanin glycoside content grew gradually with growth and development, and that it accumulated most during the full bloom stage. By using gene expression analysis, protein interaction network analysis, and bioinformatics, it was possible to determine which member of the III f family, LibHLH29, is important for the synthesis of anthocyanin glycosides in L. indica. Its expression was confirmed by qRT-PCR, and the results were essentially compatible with the transcriptome data. It was more prominent in the light-colored bloom stage the color-transition stage of L. indica 'Zihua Guifei'. It can be further investigated as a major candidate gene for regulating anthocyanin glycoside synthesis in L. indica, thus laying the foundation for an in-depth study of the interactions among transcription factors.

Phenethyl isothiocyanate inhibits metastasis potential of non-small cell lung cancer cells through FTO mediated TLE1 m6A modification.

N6-methyladenosine (m6A) modification is a prevalent RNA epigenetic modification, which plays a crucial role in tumor progression including metastasis. Isothiocyanates (ITCs) are natural compounds and inhibit the tumorigenesis of various cancers. Our previous studies show that ITCs inhibit the proliferation and metastasis of non-small cell lung cancer (NSCLC) cells, and have synergistic effects with chemotherapy drugs. In this study, we investigated the molecular mechanisms underlying the inhibitory effects of ITCs on cancer cell metastasis. We showed that phenethyl isothiocyanate (PEITC) dose-dependently inhibited the cell viability of both NSCLC cell lines H1299 and H226 with IC50 values of 17.6 and 15.2 µM, respectively. Furthermore, PEITC dose-dependently inhibited the invasion and migration of H1299 and H226 cells. We demonstrated that PEITC treatment dose-dependently increased m6A methylation levels and inhibited the expression of the m6A demethylase fat mass and obesity-associated protein (FTO) in H1299 and H226 cells. Knockdown of FTO significantly increased m6A methylation in H1299 and H226 cells, impaired their abilities of invasion and migration in vitro, and enhanced the inhibition of PEITC on tumor growth in vivo. Overexpression of FTO promoted the migration of NSCLC cells, and also mitigated the inhibitory effect of PEITC on migration of NSCLC cells. Furthermore, we found that FTO regulated the mRNA m6A modification of a transcriptional co-repressor Transducin-Like Enhancer of split-1 (TLE1) and further affected its stability and expression. TCGA database analysis revealed TLE1 was upregulated in NSCLC tissues compared to normal tissues, which might be correlated with the metastasis status. Moreover, we showed that PEITC suppressed the migration of NSCLC cells by inhibiting TLE1 expression and downstream Akt/NF-κB pathway. This study reveals a novel mechanism underlying ITC's inhibitory effect on metastasis of lung cancer cells, and provided valuable information for developing new therapeutics for lung cancer by targeting m6A methylation.

Association between Silva pattern-based classification and endocervical adenocarcinoma: a systematic review and meta-analysis.

OBJECTIVE: To determine the relationship between the Silva pattern-based classification system and endocervical adenocarcinoma. METHODS: The PubMed, Embase, Central Cochrane Library, and Web of Science databases were systematically searched for studies that investigated the correlation between the Silva classification system and the oncology prognosis or pathological features of endocervical adenocarcinoma, published in the period from January 2013 to March 2024. RESULTS: A total of 19 eligible studies including 3122 cases were included in this systematic review and meta-analysis. The combined death rate in the Silva A, Silva B, and Silva C patterns was 0% (95% CI 0.0% to 0.4%), 2.6% (95% CI 0.4% to 5.9%), and 14.0% (95% CI 9.4% to 19.2%), respectively; the combined recurrence rate in the Silva A, Silva B, and Silva C patterns was 0.1% (95% CI 0.0% to 1.2%), 5.1% (95% CI 1.6% to 10.0%), and 19.4% (95% CI 14.7% to 24.4%), respectively; the combined lymphovascular invasion rate in the Silva A, Silva B, and Silva C patterns was 0% (95% CI 0.0% to 0.5%), 21.0% (95% CI 16.9% to 25.4%), and 58.8% (95% CI 50.1% to 67.3%), respectively; and the combined International Federation of Gynecology and Obstetrics (FIGO) I rate in the Silva A, Silva B, and Silva C patterns was 99.3% (95% CI 97.6% to 100%), 93.7% (95% CI 86.4% to 98.7%), and 82.4% (95% CI 74.9% to 88.9%), respectively. CONCLUSION: Our study found that Silva A was negatively correlated with death rate, while Silva C was positively correlated. There was no correlation regarding the death rate for Silva B. Based on these findings, it is suggested that the Silva pattern-based classification system can predict the prognosis of human papillomavirus (HPV)-related endocervical adenocarcinoma and assist in guiding patient treatment.

Splenectomy as a part of cytoreductive surgery in ovarian cancer: systematic review and meta-analysis.

OBJECTIVE: The role of splenectomy on cytoreductive surgery in patients with ovarian cancer remains controversial. We conducted this meta-analysis to evaluate the safety and impact of survival outcome of splenectomy in patients with ovarian cancer. METHODS: In this meta-analysis we analyzed studies published in PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), International Clinical Trials Registry Platform (ICTRP), and Clinical Trials. gov that appeared in our search from inception to November 10, 2023. RESULT: This meta-analysis included 10 studies, totaling 6297 patients, comprising one prospective and nine retrospective analyses. The results indicated no significant disparity in overall survival and mortality (OR 1.14, 95% CI 0.69 to 1.87, p=0.62) between the splenectomy cohort and the no splenectomy (required) cohort. Furthermore, relative to the no splenectomy (required) cohort, the splenectomy group showed a heightened incidence of overall post-operative complications (odds ratio (OR) 1.66, 95% CI 1.65 to 2.61, p=0.03), an extended duration of hospitalization (mean difference (MD) 2.88 days, 95% CI 2.09 to 3.67), an increased interval from surgery to the initiation of adjuvant chemotherapy (MD 4.44 days, 95% CI 2.41 to 6.07, p<0.0001), and a greater probability of undergoing reoperation (OR 4.7, 95% CI 1.91 to 11.55, p=0.0007). However, concerning the occurrence of specific post-operative complications such as anastomotic leakage (OR 0.97, 95% CI 0.33 to 2.84, p=0.95), pancreatic fistula (OR 3.25, 95% CI 0.63 to 16.7, p=0.16), abdominal abscess (OR 1.75, 95% CI 0.25 to 12.33, p=0.57), sepsis (OR 1.46, 95% CI 0.77 to 2.77, p=0.25), and thrombotic events (OR 1.82, 95% CI 0.93 to 3.57, p=0.08), no significant differences were observed between the two cohorts. CONCLUSION: Splenectomy does not impact the overall survival and mortality of patients with ovarian cancer. Thus, it can be considered an acceptably safe procedure to obtain optimal cytoreduction. However, caution should be taken when selecting patients for splenectomy because it is associated with an increased incidence of overall post-operative complications, prolonged hospital stays, delayed initiation of adjuvant chemotherapy, and an increased probability of requiring subsequent surgical interventions.

Disability trajectories individuals with spinal cord injury in mainland China: do psychosocial resources and diseases factors predict trajectories?

STUDY DESIGN: Observational cohort study. OBJECTIVE: To identify classes of disability trajectories from 1 month post-injury (acute hospital) to 6 months post-injury (individuals with SCI individuals who stay in rehabilitation setting or back in the community), and to investigate whether psychosocial resources and disease factors can predict disability trajectory. SETTING: Spinal surgery in three Class III hospitals. Hospitals in China are divided into three classes (Class I, II and III). METHODS: All the participants were submitted to WHO Disability Assessment Schedule (WHO-DAS 2.0) at three times; and personal data anamnesis, level of hope, level of PTSD, level of social support were recorded at first time. All the data collected by the master's students who participated in this study. RESULTS: Two disability trajectories were identified using the latent class growth model: the continuous high disability group (N = 196, 93.3%) and the low starting point stabilization group (N = 14, 6.7%). Complete injury(ASIA-A) with SCI and more depression in the stable condition after SCI surgery were more likely to be classified as having higher disability than those with a lower disability trajectory. Occupation, annual family income, hope, social support, and Post-traumatic Stress Disorder (PTSD) cannot predict individuals belonging to trajectory classes. CONCLUSION: These findings emphasize the importance of ASIA and depression in the early recovery stage after SCI and support the opinion that strengthening psychological nursing and rehabilitation management at an early stage after SCI will benefit individuals with a lower disability trajectory.

Isolation, identification and characterization of Aeromonas jandaei from diseased Chinese soft-shell turtles.

Aeromonas jandaei is a gram-negative bacterium commonly found in aquatic environments and can induce illnesses in amphibians, reptiles and aquatic animals. In this study, a strain of bacteria was isolated from the diseased Chinese soft-shell turtle (Pelodiscus sinensis), then named strain JDP-FX. This isolate was identified as A. jandaei after analysis of morphological, physiological and biochemical characteristics, as well as 16S rRNA and gyrB gene sequences. Virulence genetic testing further detected temperature-sensitive protease (eprCAI), type III secretion system (TTSS) (ascv), nuclease (nuc), cytotonic enterotoxin (alt) and serine proteinase (ser) in JDP-FX. Compared with healthy Chinese soft-shell turtle, the serum levels of total protein (TP), albumin (ALB) and globulin (GLB) were significantly decreased in the diseased Chinese soft-shell turtle, while, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were significantly increased. Histopathological observations showed that multiple tissues, including intestinal mucosa, liver and kidney, were severely damaged in the diseased Chinese soft-shell turtle. Moreover, the diseased Chinese soft-shell turtle had significant cell degeneration, necrosis, sloughing and interstitial inflammatory cell infiltration. The pathogenicity of JDP-FX was tested via artificial infection. The median lethal dosage (LD50 ) of the strain was 1.05 × 105 colony forming units (CFU/g) per weight of Chinese soft-shell turtle. Drug susceptibility analysis revealed that JDP-FX was susceptible to ceftazidime, minocycline, cefoperazone, ceftriaxone and piperacillin. In addition, JDP-FX was resistant to doxycycline, florfenicol, sulfonamides, gentamicin, ampicillin and neomycin. Therefore, this study may provide guidance for further research into the diagnosis, prevention and treatment of JDP-FX infection.

Multiple omics integration analysis reveals the regulatory effect of chitosan oligosaccharide on testicular development.

Infertility is a global health problem affecting millions of people of reproductive age worldwide, with approximately half caused by males. Chitosan oligosaccharide (COS) has strong antioxidant capacity, but its impact on the male reproductive system has not been effectively evaluated. To address this, we integrated RNA-seq, serum metabolomics and intestinal 16 S rDNA analysis to conduct a comprehensive investigation on the male reproductive system. The results showed that COS has potential targets for the treatment of oligospermia, which can promote the expression of meiotic proteins DDX4, DAZL and SYCP1, benefit germ cell proliferation and testicular development, enhance antioxidant capacity, and increase the expression of testicular steroid proteins STAR and CYP11A1. At the same time, COS can activate PI3K-Akt signaling pathway in testis and TM3 cells. Microbiome and metabolomics analysis suggested that COS alters gut microbial community composition and cooperates with serum metabolites to regulate spermatogenesis. Therefore, COS promotes male reproduction by regulating intestinal microorganisms and serum metabolism, activating PI3K-Akt signaling pathway, improving testicular antioxidant capacity and steroid regulation.

Nuclear access of DNlg3 c-terminal fragment and its function in regulating innate immune response genes.

Neuroligins (NLGNs) are one of the autism susceptibility genes, however, the mechanism that how dysfunction of NLGNs leads to Autism remains unclear. More and more studies have shown that the transcriptome alteration may be one of the important factors to generate Autism. Therefore, we are very concerned about whether Neuroligins would affect transcriptional regulation, which may at last lead to Autism. As a single-transmembrane receptor, proteolytic cleavage is one of the most important posttranslational modifications of NLGN proteins. In this study, we demonstrated the existence of DNlg3 C-terminal fragment. Studies in the S2 cells and HEK293T cells showed the evidence for nuclear access of the DNlg3 C-terminal fragment. Then we identified the possible targets of DNlg3 C-terminal fragment after its nuclear access by RNA-seq. The bioinformatics analysis indicated the transcriptome alteration between dnlg3 null flies and wild type flies focused on genes for the innate immune responses. These results were consistent with the infection hypotheses for autism. Our study revealed the nuclear access ability of DNlg3 c-terminal fragment and its possible function in transcriptional regulation of the innate immune response genes. This work provides the new links between synaptic adhesion molecule NLGNs and immune activation, which may help us to get a deeper understanding on the relationship between NLGNs and Autism.

Interface Regulation for Efficient and Stable Perovskite Solar Cells through Potassium Citrate Molecules.

Efficiency and stability are key factors determining the final cost of electricity that perovskite solar cells (PSCs) generate. To date, effective strategy to progress in achieving efficient and stable PSCs is still a difficult problem that researchers continue to explore. This study reports a useful way to improve the quality of SnO2 film by introducing potassium citrate (PC) into SnO2 nanoparticles solution. PC passivates interface defects between perovskite and SnO2 layers via the interactions of functional groups (K+ , -COO- ) in PC with undersaturated Pb and I ions in perovskite and Sn4+ in SnO2 . The resultant photovoltaic (PV) device achieves a champion power conversion efficiency (PCE) of 22.79 %. The introduction of PC interface also significantly suppress the degradation of PSCs, by which 87.6 % of initial PCE is maintained after 2850 h storage in ambient environment. Moreover, the devices retained 95.5 % of initial PCE under 1-sun continuous illumination for 1000 h.

The effect of lidocaine intraoperative infusion on quality of postoperative sleep in patients undergoing thyroidectomy: a randomized controlled trial.

BACKGROUND: The incidence of thyroid nodules has increased significantly in recent years, and surgical removal is a common treatment. Postoperative sleep disturbance is still a serious problem in the current surgical environment. In this study, we explored whether intraoperative lidocaine infusion could improve the quality of sleep over 7 days and 30 days after surgery and postoperative recovery for patients undergoing thyroid surgery. METHODS: Seventy patients who underwent thyroid surgery from October 2020 to June 2021 were randomly assigned to the lidocaine or the normal saline group, 35 cases in each group. Patients enrolled in this study were randomized to receive either system lidocaine (a bolus of 1.5 mg·kg- 1, followed by an infusion of 2 mg·kg- 1·h- 1 until the end of the surgical procedure) or identical volumes and rates of normal saline. The primary endpoint was the Pittsburgh Sleep Quality Index (PSQI) scores. Secondary endpoints included intraoperative remifentanil consumption, whether there was a cough within 5 min after extubation and the cough scores, postoperative pain scores, the incidence of postoperative nausea and vomiting (PONV). RESULTS: Totally seventy cases were enrolled and eventually sixty-eight cases were analyzed. PSQI scores did not change significantly over time (F = 2.799, P = 0.069); also, there was no significant difference in PSQI scores between two groups in the entire 30 days follow-up period (F = 0.174, P = 0.678). Further, there was no interaction between the time points and the intervention (F = 0.649, P = 0.513). Similarly, intraoperative remifentanil consumption, the incidence of cough and postoperative pain scores, were comparable between the two groups (all P > 0.05); while patients in the lidocaine group showed significantly lower cough scores (P = 0.042) and lower incidence of PONV (P = 0.015). CONCLUSIONS: Systemic lidocaine infusion might not improve the sleep quality and reduce postoperative pain over 7 days or 30 days after the operation of patients who underwent thyroid surgery, but it can reduce postoperative complications and improve the quality of recovery. Furthermore, sleep quality of patients wasn't impaired significantly in the entire 30 days follow-up period after thyroid surgery compared with baseline values. TRIAL REGISTRATION: Registered in the Chinese Clinical Trial Registry ( http://www.chictr.org.cn , identifier: ChiCTR2000039764, date: 08/11/2020).

Intravenous lidocaine simultaneously infused with sufentanil to accelerate gastrointestinal function recovery in patients after thoracolumbar surgery: a prospective, randomized, double-blind controlled study.

PURPOSE: Postoperative gastrointestinal dysfunction is one of the common complications of surgery, especially after surgery for a thoracolumbar spinal fracture. Intravenous lidocaine is a potential method to improve postoperative gastrointestinal function in surgical patients, reduce opioid use and shorten hospital stays. The purpose of this study is to explore the effect of intravenous lidocaine on the recovery of gastrointestinal function in patients after thoracolumbar surgery. METHODS: In this study, 48 eligible patients undergoing elective thoracolumbar spine fractures resection and internal fixation surgery were enrolled to receive intravenous injections of lidocaine in different concentrations during the perioperative period. Patients were randomly divided into three groups: control group (group A), low concentration of lidocaine group (group B) and high concentration of lidocaine group (group C), 16 patients in each group. First postoperative exhaust time, numbers of bowel sound at preoperative and postoperative 3, 6, 12, 24 h, pain scores at postoperative 0, 3, 6, 12, 24, 48 h, total sufentanil use in PACU and perioperative periods, postoperative hospital stay and analgesic remedy within postoperative 48 h were recorded and compared. The primary endpoints include: the time of first flatus passage after the operation, the number of bowel sounds per minute counted with stethoscope at 30 min before anesthesia induction and at 3, 6, 12 and 24 h postoperative. The secondary endpoints included: the pain scores at PACU (after entering into PACU), 3, 6, 12, 24 and 48 h postoperative, the amount of sufentanil administrated by intravenous push during operation and the numbers of patients needed rescuing sufentanil in PACU, and the numbers of patients needed administration of gastric motility drugs or non-steroidal analgesics at ward within 48 h postoperation, length of hospital stay (from the first day after surgery to discharge from hospital) and the incidence of adverse reactions. RESULTS: Compared with group A, the first postoperative exhaust time in group B and C occurred much earlier (23.3 ± 11.0 h vs. 16.0 ± 6.6 h, 16.6 ± 5.1 h, P < 0.05). Compared with preoperation, the numbers of bowel sound significantly increased at 24 h postoperatively in group B, while group B at 6 h and group C at 6 and 24 h postoperatively had significantly more active bowel sounds compared to group A (P < 0.05). There were no remarkable differences in VAS scores within 12 h postoperatively among three groups, and however, significantly lower VAS scores were found at 12, 24 and 48 h postoperatively in group C when comparing to Group A (p < 0.05). There was no statistical significance in the incidence of postoperative flatulence and nausea and vomiting, the number of patients needed rescuing sufentanil in PACU, the length of postoperative hospital stay and the number of patients requiring non-steroidal analgesics at ward within 48 h postoperation. CONCLUSIONS: Intravenous lidocaine infusion together with patient-controlled analgesia of sufentanil expedited the early recovery of gastrointestinal function and improved analgesic quality of sefentanyl in patients undergoing thoracolumbar surgeries.

Biomechanical characteristics of a novel interspinous distraction fusion device in the treatment of lumbar degenerative diseases: a finite element analysis.

BACKGROUND: A novel interspinous distraction fusion (ISDF) device has been used to treat lumbar degenerative diseases. As a minimally invasive technique, ISDF differs from the traditional interspinous process distraction devices. Currently, biomechanical studies on ISDF are rare. OBJECTIVE: To investigate the biomechanical properties of the ISDF device (BacFuse) which is used to treat lumbar degenerative diseases. METHODS: Three-dimensional L3-L5 models were created. The models were divided into four groups: intact (M1), local decompression alone (M2), internal fixation alone (M3) and local decompression combined with internal fixation (M4), based on different surgical procedures. Local laminectomy was performed to resect the lower part of the L4 lamina and the upper part of the L5 lamina at the right lamina of L4/5 in the M2 and M4 groups. After meshing the models elements, Abaqus were used to perform the finite element (FE) analysis. The intervertebral range of motion (ROM) was measured during flexion, extension, left lateral bending, right lateral bending, left rotation and right rotation under a follower load of 400 N with a 7.5Nm moment. The distributions of disc and facet joint stresses were observed and recorded. Spinal vertebral stress was compared, and internal fixation device stress was observed. RESULTS: The ROM of L4/5 in M2 increased in flexion, extension, left lateral bending, right lateral bending, left rotation and right rotation compared with that in M1. In all motion directions, the ROM at L4/5 decreased, and the ROM at L3/4 increased after implantation of the ISDF device in M3 and M4 groups. The disc stress and facet joint stresses in the instrumented segment decreased after implantation of the ISDF device. The spinous process loaded a certain amount of stress in M3 and M4 groups. The spikes of the internal fixation device were loaded with the maximum stress. CONCLUSION: BacFuse exhibited a reduction in intervertebral ROM, as well as decreased stress on the intervertebral disc and facet joint, while also demonstrating a discernible impact on the upper adjacent segment.

Nephrotic Syndrome Gene TBC1D8B Is Required for Endosomal Maturation and Nephrin Endocytosis in Drosophila.

BACKGROUND: Variants in TBC1D8B cause nephrotic syndrome. TBC1D8B is a GTPase-activating protein for Rab11 (RAB11-GAP) that interacts with nephrin, but how it controls nephrin trafficking or other podocyte functions remains unclear. METHODS: We generated a stable deletion in Tbc1d8b and used microhomology-mediated end-joining for genome editing. Ex vivo functional assays utilized slit diaphragms in podocyte-like Drosophila nephrocytes. Manipulation of endocytic regulators and transgenesis of murine Tbc1d8b provided a comprehensive functional analysis of Tbc1d8b. RESULTS: A null allele of Drosophila TBC1D8B exhibited a nephrocyte-restricted phenotype of nephrin mislocalization, similar to patients with isolated nephrotic syndrome who have variants in the gene. The protein was required for rapid nephrin turnover in nephrocytes and for endocytosis of nephrin induced by excessive Rab5 activity. The protein expressed from the Tbc1d8b locus bearing the edited tag predominantly localized to mature early and late endosomes. Tbc1d8b was required for endocytic cargo processing and degradation. Silencing Hrs, a regulator of endosomal maturation, phenocopied loss of Tbc1d8b. Low-level expression of murine TBC1D8B rescued loss of the Drosophila gene, indicating evolutionary conservation. Excessive murine TBC1D8B selectively disturbed nephrin dynamics. Finally, we discovered four novel TBC1D8B variants within a cohort of 363 patients with FSGS and validated a functional effect of two variants in Drosophila, suggesting a personalized platform for TBC1D8B-associated FSGS. CONCLUSIONS: Variants in TBC1D8B are not infrequent among patients with FSGS. TBC1D8B, functioning in endosomal maturation and degradation, is essential for nephrin trafficking.

Transcriptomics reveals apigenin alleviates airway inflammation and epithelial cell apoptosis in allergic asthma via MAPK pathway.

Persistent chronic inflammation of the lungs and airway remodeling are important pathological features that cannot be ignored in patients with chronic asthma. Apigenin (API) is a natural small molecule compound with good anti-inflammatory and antioxidant activity that has been widely reported in recent years, but its role in chronic asthma is not well defined. Our study began with oral gavage intervention using API (10, 20 mg/kg) or dexamethasone (DEX, 2 mg/kg) in a BALB/c mouse model of ovalbumin (OVA) sensitization. Different doses of API intervention effectively reduced airway resistance in the administered group. Additionally, inflammation was downregulated, mucus secretion was reduced, and airway remodeling was inhibited in the API intervention group compared with the model group. Asthma-related inflammatory cytokines, such as IgE, IL-4, IL-5, IL-13, and IL-17, were downregulated in alveolar lavage fluid. Moreover, the apoptosis level of the administered group was found to be lower than that of the model group in the Tunel staining experiment. By analyzing transcriptome sequencing results, we found that API may exert anti-inflammatory and anti-apoptotic effects by inhibiting the MAPK pathway. Our subsequent results supported this conclusion, showing that the phosphorylation levels of ERKs, JNKs, and p38 MAPKs were inhibited in the administered group relative to the model group. Downstream expression of the apoptosis-related protein B-cell lymphoma-2 (Bcl-2) was upregulated, and the expression of Bcl-2-associated × protein (Bax) and cleaved caspase-3 was downregulated. To further investigate the specific mechanism by which API acted, we established an in vitro model with house dust mite (HDM) stimulation, using API (10, 20 µM) for administration intervention. The results showed that API was able to improve cell viability, inhibit ROS production, and reverse HDM-induced decreases in mitochondrial membrane potential (MMP) and apoptosis in airway epithelial cells via the MAPK pathway.