Mesenchymal Stem Cell Exosomes Enhance Posterolateral Spinal Fusion in a Rat Model.

Spinal fusion, a common surgery performed for degenerative lumbar conditions, often uses recombinant human bone morphogenetic protein 2 (rhBMP-2) that is associated with adverse effects. Mesenchymal stromal/stem cells (MSCs) and their extracellular vesicles (EVs), particularly exosomes, have demonstrated efficacy in bone and cartilage repair. However, the efficacy of MSC exosomes in spinal fusion remains to be ascertained. This study investigates the fusion efficacy of MSC exosomes delivered via an absorbable collagen sponge packed in a poly Ɛ-caprolactone tricalcium phosphate (PCL-TCP) scaffold in a rat posterolateral spinal fusion model. Herein, it is shown that a single implantation of exosome-supplemented collagen sponge packed in PCL-TCP scaffold enhanced spinal fusion and improved mechanical stability by inducing bone formation and bridging between the transverse processes, as evidenced by significant improvements in fusion score and rate, bone structural parameters, histology, stiffness, and range of motion. This study demonstrates for the first time that MSC exosomes promote bone formation to enhance spinal fusion and mechanical stability in a rat model, supporting its translational potential for application in spinal fusion.

Secular trends in the prevalence of meeting 24-hour movement guidelines among U.S. adolescents: evidence from NHANES 2007-2016.

Background: The 24-Hour Movement Guidelines (24-HMG) recommend a balanced combination of physical activity (PA), sedentary behavior (SB) and sleep (SLP) for optimal health. However, there is limited understanding of how well U.S. adolescents adhere to these guidelines. This study aims to analyze the prevalence trends of meeting the 24-HMG among a nationally representative sample of U.S. general adolescents. Methods: The study included 2,273 adolescents (55.3% boys) aged 16-19 who participated in the National Health and Nutrition Examination Surveys (NHANES) from 2007 to 2016. The researchers categorized the adolescents based on whether they met various PA, SB, and SLP recommendations, as well as different combinations of these recommendations, separately for boys and girls. The prevalence rate, weighted by survey data, was calculated along with a 95% confidence interval (CI) to assess the changes in meeting the 24-HMG among U.S. adolescents across different survey years and sociodemographic subgroups. Results: In the 2015-2016 cycle, approximately 6.3% of adolescents did not meet any of the three recommendations, while only 19.2% of adolescents achieved all three guidelines. Compliance with PA and SB recommendations among adolescents has decreased over time, from 72.5% (65.9% to 79.2%) to 64.2% (57.4% to 70.9%) for PA, and from 59.0% (49.6% to 68.4%) to 46.6% (37.8% to 55.5%) for SB, respectively, from 2007-2008 cycle to 2015-2016 cycle. Boys exhibited more favorable patterns in meeting different sets of recommendations compared to girls (p-value <0.001). This includes meeting both PA and SB guidelines (15.5% for boys and 11.1% for girls) and meeting both PA and SLP guidelines (19.5% for boys and 15.7% for girls). The level of parental education was found to have effect on meeting all three guidelines (Ptrend < 0.05). Conclusion: We analyzed ten consecutive years of representative NHANES data to evaluate the prevalence meeting 24-HMG and found that the proportion of adolescents aged 16-19 in the U.S. who adhered to all three movement guidelines simultaneously has consistently remained low throughout each survey cycle. Notably, there has been a significant decline in the proportion of adolescents meeting the SB guideline.

Increased matrix metalloproteinase-2 in ligamentum flavum hypertrophy and the regulation of MMP-2/TIMPs by elastin-derived peptides.

The study aimed to examine matrix metalloproteinase-2 (MMP-2) expression in a rat ligamentum flavum (LF) hypertrophy model in vivo, and the effect of elastin-derived peptides (EDPs) on MMP-2 and tissue inhibitors of metalloproteinases (TIMPs) in rat LF cells in vitro. Surgical destabilization was performed at the rat spinal L3/4 level to induce increased mechanical stress. Rats were killed at 6- and 12-weeks postsurgery for histological staining, immunohistochemical staining, RT-qPCR and western blot. 100 µg/mL EDPs were applied to isolated normal rat LF cells, with or without pretreatment of elastin receptor complex (ERC) inhibitors, to assess the expression of MMP-2, TIMP-1, and TIMP-2. Spinal destabilization led to LF hypertrophy, observed through increased LF thickness and area, along with histological changes of chondrometaplasia and elastic fiber degradation. LF was also stained positively for Col I and Col II, where elastic fiber has broken down. MMP-2 expression was notably elevated in the hypertrophied LF, accompanied by increased TIMP-2 and TIMP-3 levels. EDPs were found to suppress MMP-2 expression and reduce TIMP-1 and TIMP-2 levels in rat LF cells. Interestingly, exposure to EDPs led to a significant rise in MMP-2/TIMP-1 and MMP-2/TIMP-2 ratios, dependent on the ERC. Collectively, the study suggests that increased MMP-2 activity contributes to elastic fiber degradation in hypertrophied LF, generating EDPs that further enhance the MMP-2/TIMPs ratio in LF cells in an ERC-dependent manner. Further research is essential to delve into the mechanisms of EDPs in LF hypertrophy.

Quantitative anatomical analysis of lumbar interspaces based on 3D CT imaging: optimized segment selection for lumbar puncture in different age groups.

BACKGROUND: Optimal lumbar puncture segment selection remains controversial. This study aims to analyze anatomical differences among L3-4, L4-5, and L5-S1 segments across age groups and provide quantitative evidence for optimized selection. METHODS: 80 cases of CT images were collected with patients aged 10-80 years old. Threedimensional models containing L3-S1 vertebrae, dural sac, and nerve roots were reconstructed. Computer simulation determined the optimal puncture angles for the L3-4, L4-5, and L5-S1 segments. The effective dural sac area (ALDS), traversing nerve root area (ATNR), and area of the lumbar inter-laminar space (ALILS) were measured. Puncture efficacy ratio (ALDS/ALILS) and nerve injury risk ratio (ATNR/ALILS) were calculated. Cases were divided into four groups: A (10-20 years), B (21-40 years), C (41-60 years), and D (61-80 years). Statistical analysis was performed using SPSS. RESULTS: 1) ALDS was similar among segments; 2) ATNR was greatest at L5-S1; 3) ALILS was greatest at L5-S1; 4) Puncture efficacy ratio was highest at L3-4 and lowest at L5-S1; 5) Nerve injury risk was highest at L5-S1. In group D, L5-S1 ALDS was larger than L3-4 and L4-5. ALDS decreased after age 40. Age variations were minimal across parameters. CONCLUSION: The comprehensive analysis demonstrated L3-4 as the optimal first-choice segment for ages 10-60 years, conferring maximal efficacy and safety. L5-S1 can serve as an alternative option for ages 61-80 years when upper interspaces narrow. This study provides quantitative imaging evidence supporting age-specific, optimized lumbar puncture segment selection.

A time-continuous land surface temperature (LST) data fusion approach based on deep learning with microwave remote sensing and high-density ground truth observations.

Land surface temperature (LST) is a crucial parameter in the circulation of water, exchange of land-atmosphere energy, and turbulence. Currently, most LST products rely heavily on thermal infrared remote sensing, which is susceptible to cloud and rain interference, leading to inferior temporal continuity. Microwave remote sensing has the advantage of being available "all-weather" due to strong penetration capability, which provides the possibility to simulate time-continuous LST data. In addition, the continuous increase in high-density station observations (>10,000 stations) provides reliable measured data for the remote sensing monitoring of LST in China. This study aims to adopt the "Earth big data" generated from high-density station observation and microwave remote sensing data to monitor LST based on deep learning (U-Net family) for the first time. Given the significant spatial and temporal variability of LST and its sensitivity to various factors according to radiation transmission equations, this study incorporated climatic, anthropogenic, geographical, and vegetation datasets to facilitate a multi-source data fusion approach for LST estimation. The results showed that the U-Net++ model with modified skip connections better minimized the semantic discrepancy between the feature maps of the encoder and decoder subnetworks for 0.1° daily LST mapping across China than the U-Net and U2-Net deep learning models. The accuracy of the LST simulation exhibited favorable outcomes in the spatial and temporal dimensions. The station density met the requirements of monitoring air-ground integration monitoring in China. Additionally, the temporal change in the simulation accuracy fluctuated in a W-shape owing to the limited simulation capability of deep learning in extreme scenarios. Anthropogenic factors had the largest influence on LST changes in China, followed by climate, geography, and vegetation. This study highlighted the application of deep learning in remote sensing monitoring against the background of "big data" and provided a scientific foundation for the response of climate change to human activities, ecological environmental protection, and sustainable social and economic development.

Selection and application of aptamers for p-hydroxybenzyl hydrogen sulfite after Gastrodia elata Bl. fumigated with sulfur.

Gastrodia elata Bl. is a widely used traditional Chinese medicine known for its medicinal properties. However, during the drying process, G. elata is often fumigated with sulfur to prevent corrosion and improve its appearance. Sulfur-fumigation can result in a reduction in the effective components of the herb and can also be hazardous to human health due to the remaining sulfur dioxide. Sulfur-fumigation of G. elata poses a significant challenge to both end-users and researchers. The detection of p-hydroxybenzyl hydrogen sulfite (p-HS) is a useful tool in determining whether G. elata has been fumigated with sulfur. Unfortunately, the current method for detecting p-HS is costly and requires sophisticated instruments. Therefore, there is a need to develop a more cost-effective and user-friendly method for the detection of p-HS. This study utilized the Capture-SELEX technique to screen high-affinity aptamers for p-HS, which were subsequently characterized by isothermal titration calorimetry (ITC). An aptamer sequence (seq 6) with a high affinity of Kd = 26.5 µM was obtained following 8 rounds of selection against p-HS. With the aptamer serving as the recognition element and gold nanoparticles as the colorimetric indicator, a simple and efficient colorimetric sensor was developed for the specific detection of p-HS. This detection method exhibited a limit of detection of 1 µg/ml, while the p-HS recoveries demonstrated a range of between 88.5 % and 105 % for samples of G. elata obtained in the market. In summary, the aptamer exhibited a high affinity for p-HS, and the sensor developed through the use of a colloidal gold detector based on nucleic acid aptamer can be utilized for rapid detection of sulfur-fumigated G. elata. With these findings, this research paper provides valuable scientific insights and highlights significant potential for future studies in this area.

Protective Effects and Mechanism of Polysaccharides from Edible Medicinal Plants in Alcoholic Liver Injury: A Review.

Alcohol use accounts for a large variety of diseases, among which alcoholic liver injury (ALI) poses a serious threat to human health. In order to overcome the limitations of chemotherapeutic agents, some natural constituents, especially polysaccharides from edible medicinal plants (PEMPs), have been applied for the prevention and treatment of ALI. In this review, the protective effects of PEMPs on acute, subacute, subchronic, and chronic ALI are summarized. The pathogenesis of alcoholic liver injury is analyzed. The structure-activity relationship (SAR) and safety of PEMPs are discussed. In addition, the mechanism underlying the hepatoprotective activity of polysaccharides from edible medicinal plants is explored. PEMPs with hepatoprotective activities mainly belong to the families Orchidaceae, Solanaceae, and Liliaceae. The possible mechanisms of PEMPs include activating enzymes related to alcohol metabolism, attenuating damage from oxidative stress, regulating cytokines, inhibiting the apoptosis of hepatocytes, improving mitochondrial function, and regulating the gut microbiota. Strategies for further research into the practical application of PEMPs for ALI are proposed. Future studies on the mechanism of action of PEMPs will need to focus more on the utilization of multi-omics approaches, such as proteomics, epigenomics, and lipidomics.

[Mechanism of pregnancy-induced thymus involution and regeneration and medication rules of postpartum prescriptions].

In order to prevent the maternal immune defenses to the semi-allogeneic fetus, the maternal body will present a special adaptive immune system change represented by acute thymic involution(ATI) during pregnancy, which can be quickly regenerated after delivery. The ATI during pregnancy is related to the level of sex hormones, which is mainly caused by progesterone. Pregnancy-induced ATI is manifested as the continuous shrinkage of thymus volume, especially the cortex, and the wrinkle and phagocytosis of the subcapsular cortical thymic epithelial cells(cTECs), while other thymic epithelial cells(TECs) remain unchanged. The postpartum thymus is regenerated by the co-mediation of forkhead box N1(FOXN1) as well as its target genes chemokine(C-C motif) ligand 25(CCL25), chemokine(C-X-C motif) ligand 12(CXCL12), δ-like ligand 4(DLL4), cathepsin L(CTSL), and serine protease 16(PRSS16). Once the postpartum thymus is poorly repaired, immune dysfunction of the maternal body and several puerperal diseases will be induced, seriously endangering the survival of the mother and the newborn. In traditional Chinese medicine(TCM), Qi and blood are the cornerstone of pregnancy, and the thymus plays a key role in regulating Qi and blood. The deficiency of Qi and blood during pregnancy and childbirth is closely related to the abnormal ATI during pregnancy and the poor regeneration of the postpartum thymus. Based on this theory, TCM has profound academic ideas and rich clinical experience in postpartum recuperation. Based on the systematic description of the mechanism of ATI regeneration during pregnancy, as well as data mining and analysis of two classic gynecological works of TCM, Wan's Gynecology and Fu Qing-zhu's Treatise on Gynecology, this study found that the commonly used TCM for postpartum included Angelicae Sinensis Radix, Ginseng Radix et Rhizoma, Glycyrrhizae Radix et Rhizoma, and Chuanxiong Rhizoma. Among them, Ginseng Radix et Rhizoma, Angelicae Sinensis Radix, and Chuanxiong Rhizoma are high-frequency TCMs with positive effects on postpartum recovery.However, the mechanism of these TCMs in promoting postpartum thymus regeneration needs further investigation.

Real-world evidence of osimertinib in Chinese patients with EGFR T790M-positive non-small cell lung cancer: a subgroup analysis from ASTRIS study.

PURPOSE: ASTRIS study aimed the largest to evaluate the effectiveness and safety of second- or higher-line osimertinib in patients with advanced/metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer (NSCLC) in the real-world setting. Here we report the results of Chinese patients in ASTRIS study. METHODS: Adults with EGFR T790M-positive advanced NSCLC pretreated with EGFR-tyrosine kinase inhibitor (EGFR-TKI), having a WHO performance status score of 0-2 and asymptomatic, stable central nervous system (CNS) metastases were included. All patients received once-daily osimertinib 80 mg orally. The outcomes included investigator-assessed clinical response, progression-free survival (PFS), time-to-treatment discontinuation (TTD), and safety. RESULTS: A total of 1350 patients were included. Response rate was 55.7% (95% confidence interval [CI] 0.53-0.58). The median PFS and the median TTD were 11.7 months (95% CI 11.1-12.5) and 13.9 months (95% CI 13.1-15.2), respectively. Overall, 389 patients (28.8%) had at least one protocol-specified adverse event (AE); AEs of interstitial lung diseases/pneumonitis-like events and QT prolongation were reported in 3 (0.2%) and 59 (4.4%) patients, respectively. CONCLUSION: Osimertinib was effective in Chinese patients with T790M-positive NSCLC who had progressed after first- or second-generation EGFR-TKI in real-word setting and the results were consistent with ASTRIS study overall population and AURA studies. No new safety signals or events were identified. CLINICAL TRIAL NUMBER: NCT02474355.

Photobiomodulation provides neuroprotection through regulating mitochondrial fission imbalance in the subacute phase of spinal cord injury.

Increasing evidence indicates that mitochondrial fission imbalance plays an important role in delayed neuronal cell death. Our previous study found that photobiomodulation improved the motor function of rats with spinal cord injury. However, the precise mechanism remains unclear. To investigate the effect of photobiomodulation on mitochondrial fission imbalance after spinal cord injury, in this study, we treated rat models of spinal cord injury with 60-minute photobiomodulation (810 nm, 150 mW) every day for 14 consecutive days. Transmission electron microscopy results confirmed the swollen and fragmented alterations of mitochondrial morphology in neurons in acute (1 day) and subacute (7 and 14 days) phases. Photobiomodulation alleviated mitochondrial fission imbalance in spinal cord tissue in the subacute phase, reduced neuronal cell death, and improved rat posterior limb motor function in a time-dependent manner. These findings suggest that photobiomodulation targets neuronal mitochondria, alleviates mitochondrial fission imbalance-induced neuronal apoptosis, and thereby promotes the motor function recovery of rats with spinal cord injury.

Correlative increasing expressions of KIF5b and Nav1.7 in DRG neurons of rats under neuropathic pain conditions.

Nav1.7, one of tetrodotoxin-sensitive voltage-gated sodium channels, mainly expressed in the small diameter dorsal root ganglion (DRG) neurons. The expression and accumulation on neuronal membrane of Nav1.7 increased following peripheral tissue inflammation or nerve injury. However, the mechanisms for membrane accumulation of Nav1.7 remained unclear. We report that KIF5b, a highly expressed member of the kinesin-1 family in DRGs, promoted the translocation of Nav1.7 to the plasma membrane in DRG neurons of the rat. Following nociceptive behaviors in rats induced by peripheral spared nerve injury (SNI), synchronously increased KIF5b and Nav1.7 expressions were observed in DRGs. Immunohistochemistry staining demonstrated the co-expressions of KIF5b and Nav1.7 in the same DRG neurons. Immunoprecipitation experiments further confirmed the interactions between KIF5b and Nav1.7. Moreover, intrathecal injections of KIF5b shRNA moderated the SNI-induced both mechanical and thermal hyperalgesia. The rescued analgesic effects also alleviated SNI-induced anxiety-like behaviors. In sum, KIF5b was required for the membrane localizations of Nav1.7, which suggests a novel mechanism for the trafficking of Nav1.7 involved in neuropathic pain.

Potential targets and mechanisms of photobiomodulation for spinal cord injury.

As a classic noninvasive physiotherapy, photobiomodulation, also known as low-level laser therapy, is widely used for the treatment of many diseases and has anti-inflammatory and tissue repair effects. Photobiomodulation has been shown to promote spinal cord injury repair. In our previous study, we found that 810 nm low-level laser therapy reduced the M1 polarization of macrophages and promoted motor function recovery. However, the mechanism underlying this inhibitory effect is not clear. In recent years, transcriptome sequencing analysis has played a critical role in elucidating the progression of diseases. Therefore, in this study, we performed M1 polarization on induced mouse bone marrow macrophages and applied low-level laser therapy. Our sequencing results showed the differential gene expression profile of photobiomodulation regulating macrophage polarization. We analyzed these genes using gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. Networks of protein-protein interactions and competing RNA endogenous networks were constructed. We found that photobiomodulation inhibited STAT3 expression through increasing the expression of miR-330-5p, and that miR-330-5p binding to STAT3 inhibited STAT3 expression. Inducible nitric oxide synthase showed trends in changes similar to the changes in STAT3 expression. Finally, we treated a mouse model of spinal cord injury using photobiomodulation and confirmed that photobiomodulation reduced inducible nitric oxide synthase and STAT3 expression and promoted motor function recovery in spinal cord injury mice. These findings suggest that STAT3 may be a potential target of photobiomodulation, and the miR-330-5p/STAT3 pathway is a possible mechanism by which photobiomodulation has its biological effects.

Effect of Digitalis on ICD or CRT-D Recipients: A Systematic Review and Meta-Analysis.

BACKGROUND: Digitalis has been widely utilized for heart failure therapy and several studies have demonstrated an association of digitalis and adverse outcome events in patients receiving implantable cardioverter defibrillators (ICDs) or cardiac resynchronization therapy defibrillators (CRT-Ds). Hence, we conducted this meta-analysis to assess the effect of digitalis on ICD or CRT-D recipients. METHODS: We systematically retrieved relevant studies using the Cochrane Library, PubMed, and Embase database. A random effect model was used to pool the effect estimates (hazard ratios (HRs) and 95% confidence intervals (CIs)) when the studies were of high heterogeneity, otherwise a fixed effect model was used. RESULTS: Twenty-one articles containing 44,761 ICD or CRT-D recipients were included. Digitalis was associated with an increased rate of appropriate shocks (HR = 1.65, 95% CI: 1.46-1.86, p < 0.001) and a shortened time to first appropriate shock (HR = 1.76, 95% CI: 1.17-2.65, p = 0.007) in ICD or CRT-D recipients. Furthermore, the all-cause mortality increased in ICD recipients with digitalis therapy (HR = 1.70, 95% CI: 1.34-2.16, p < 0.01), but the all-cause mortality was unchanged in CRT-D recipients (HR = 1.55, 95% CI: 0.92-2.60, p = 0.10) or patients who received ICD or CRT-D therapy (HR = 1.09, 95% CI: 0.80-1.48, p = 0.20). The sensitivity analyses confirmed the robustness of the results. CONCLUSION: ICD recipients with digitalis therapy may tend to have higher mortality rates, but digitalis may not be associated with the mortality rate of CRT-D recipients. Further studies are required to confirm the effects of digitalis on ICD or CRT-D recipients.

U-shaped association between body mass index and ejection fraction in intensive care unit patients with heart failure.

AIMS: There are limited data about the relationship between body mass index (BMI) and left ventricular ejection fraction (EF) in patients with heart failure (HF). The study aims to assess the correlation between BMI and left ventricular EF under HF conditions. METHODS AND RESULTS: We derived the data from the Dryad Digital Repository for analysis, and the information of the original patients was obtained from the MIMIC-III database by the data uploader. We performed smooth curve and two piecewise linear regression analyses to evaluate the association between BMI and EF in HF patients. A total of 962 participants were included in this study, with age of 73.7 ± 13.5 years, and 475 participants were male (49.4%). The results of the smooth curve supported a U-shaped relationship between BMI and EF, and the inflection point was found to be a BMI of 23.3 kg/m2 in these HF patients. After adjusting for potential confounders, we found that EF decreased with increasing BMI up to the inflection point (ß = -0.7, 95% CI -1.3 to -0.1, P = 0.028), whereas beyond the turning point, the relationship between EF and BMI showed a positive correlation (ß = 0.2, 95% CI 0.1-0.3 P < 0.001). Importantly, ischaemic heart disease (interaction P = 0.0499) and hyperlipidaemia (interaction P = 0.0162) affected the association between BMI and EF in the lower BMI group (BMI < 23.3 kg/m2 ), although only diabetes mellitus (interaction P = 0.0255) altered the association between BMI and EF in the higher BMI group (BMI ≥ 23.3 kg/m2 ). CONCLUSIONS: In addition to higher BMI, we also found that lower BMI is related to higher EF in intensive care unit patients with HF, supporting a U-shaped association between BMI and EF.

Effects of acupuncture on microglial polarization and the TLR4/TRIF/MyD88 pathway in a rat model of traumatic brain injury.

OBJECTIVE: Neuroinflammation caused by traumatic brain injury (TBI) can lead to neurological deficits. Acupuncture can inhibit neuroinflammation and promote nerve repair; however, the specific mechanism is still unclear. The purpose of this study was to explore whether acupuncture could modulate the M1 and M2 phenotypic polarization of microglia in a rat model of TBI via the toll-like receptor 4 (TLR4)/intracellular toll-interleukin-1 receptor (TIR) domain-containing adaptor inducing interferon-ß (TRIF)/myeloid differentiation factor 88 (MyD88) pathway. METHODS: A total of 90 adult male Sprague-Dawley (SD) rats, SPF grade, were randomly divided into a normal group, model group and acupuncture group. Each group was further divided into three subgroups (first, third, and fifth day groups) according to the treatment time (n = 10 rats/subgroup). We used the modified neurological severity score (mNSS) method to quantify neurological deficits before and after modeling. We used Nissl staining to observe the pathological changes in brain tissue, flow cytometry to detect the proportion of M1 and M2 polarized microglia in the injured area on the first, third and fifth day, and co-immunoprecipitation (Co-IP) to examine TLR4/TRIF/MyD88 expression in microglia on the first, third and fifth day, as well as expression of the amount of binding of TLR4 with TRIF and MyD88. RESULTS: Compared to the model group, mNSS in the acupuncture group gradually decreased and pathological morphology improved. The proportion of CD11b/CD86 positive cells was decreased, while that of CD11b/CD206 was increased in the acupuncture group. Expression of IP TLR4, IP TRIF and IP MyD88 also decreased in the acupuncture group. CONCLUSION: The results of this study demonstrate that one of the mechanisms through which acupuncture mitigates neuroinflammation and promotes nerve repair in TBI rats may be inhibition of M1 phenotypic polarization and promotion of M2 phenotypic polarization through inhibition of the TLR4/TRIF/MyD88 signaling pathway.

Lack of evolutionary convergence in multiple primary lung cancer suggests insufficient specificity of personalized therapy.

Multiple primary lung cancer (MPLC) is an increasingly prevalent subtype of lung cancer. According to recent genomic studies, the different lesions of a single MPLC patient exhibit functional similarities that may reflect evolutionary convergence. We perform whole-exome sequencing for a unique cohort of MPLC patients with multiple samples from each lesion found. Using our own and other relevant public data, evolutionary tree reconstruction reveals that cancer driver gene mutations occurred at the early trunk, indicating evolutionary contingency rather than adaptive convergence. Additionally, tumors from the same MPLC patient are as genetically diverse as those from different patients, while within-tumor genetic heterogeneity is significantly lower. Furthermore, the aberrant molecular functions enriched in mutated genes for a sample show a strong overlap with other samples from the same tumor, but not with samples from other tumors or other patients. Overall, there is no evidence of adaptive convergence during the evolution of MPLC. Most importantly, the similar between-tumor diversity and between-patient diversity suggest that personalized therapies may not adequately account for the genetic diversity among different tumors in an MPLC patient. To fully exploit the strategic value of precision medicine, targeted therapies should be designed and delivered on a per-lesion basis.

Abdominal paracentesis drainage improves outcome of acute pancreatitis complicated with intra-abdominal hypertension in early phase.

BACKGROUND: Intra-abdominal hypertension (IAH) is an important risk factor for organ dysfunction, and it occurs in the early phase of severe acute pancreatitis (SAP). We have reported a novel step-up approach and shown the benefit of performing abdominal paracentesis drainage (APD) ahead of percutaneous catheter drainage (PCD) when treating Patients with SAP with fluid collections. This study aimed to evaluate the efficacy of APD in Patients with SAP complicated with IAH in the early phase. METHODS: In the present study, 206 AP patients complicated with IAH in the early phase were enrolled in hospital between June 2017 and December 2020. The patients were divided into two groups: 109 underwent APD (APD group) and 97 were managed without APD (non-APD group). We retrospectively compared the outcomes of the APD and non-APD groups for IAH treatment. The parameters including mortality, infection, organ failure, inflammatory factors, indications for further interventions, and drainage-related complications were observed. RESULTS: The demographic data and severity scores of the two groups were comparable. The mortality rate was lower in the APD group (3.7%) than in the non-APD group (8.2%). Compared with the non-APD group, the intra-abdominal pressure and laboratory parameters of the APD group decreased more rapidly, and the mean number of failed organs was lower. However, there was no significant difference in incidence of infections between the two groups. CONCLUSIONS: Application of APD is beneficial to AP patients. It significantly attenuated inflammation injury, avoided further interventions, and reduced multiple organ failure.

Mechanism of pregnancy-induced thymus involution and regeneration and medication rules of postpartum prescriptions / 中国中药杂志

In order to prevent the maternal immune defenses to the semi-allogeneic fetus, the maternal body will present a special adaptive immune system change represented by acute thymic involution(ATI) during pregnancy, which can be quickly regenerated after delivery. The ATI during pregnancy is related to the level of sex hormones, which is mainly caused by progesterone. Pregnancy-induced ATI is manifested as the continuous shrinkage of thymus volume, especially the cortex, and the wrinkle and phagocytosis of the subcapsular cortical thymic epithelial cells(cTECs), while other thymic epithelial cells(TECs) remain unchanged. The postpartum thymus is regenerated by the co-mediation of forkhead box N1(FOXN1) as well as its target genes chemokine(C-C motif) ligand 25(CCL25), chemokine(C-X-C motif) ligand 12(CXCL12), δ-like ligand 4(DLL4), cathepsin L(CTSL), and serine protease 16(PRSS16). Once the postpartum thymus is poorly repaired, immune dysfunction of the maternal body and several puerperal diseases will be induced, seriously endangering the survival of the mother and the newborn. In traditional Chinese medicine(TCM), Qi and blood are the cornerstone of pregnancy, and the thymus plays a key role in regulating Qi and blood. The deficiency of Qi and blood during pregnancy and childbirth is closely related to the abnormal ATI during pregnancy and the poor regeneration of the postpartum thymus. Based on this theory, TCM has profound academic ideas and rich clinical experience in postpartum recuperation. Based on the systematic description of the mechanism of ATI regeneration during pregnancy, as well as data mining and analysis of two classic gynecological works of TCM, Wan's Gynecology and Fu Qing-zhu's Treatise on Gynecology, this study found that the commonly used TCM for postpartum included Angelicae Sinensis Radix, Ginseng Radix et Rhizoma, Glycyrrhizae Radix et Rhizoma, and Chuanxiong Rhizoma. Among them, Ginseng Radix et Rhizoma, Angelicae Sinensis Radix, and Chuanxiong Rhizoma are high-frequency TCMs with positive effects on postpartum recovery.However, the mechanism of these TCMs in promoting postpartum thymus regeneration needs further investigation.

Mechanisms of ferroptosis in chronic kidney disease.

Ferroptosis is a newly identified form of regulated cell death characterized by iron accumulation and lipid peroxidation. Ferroptosis plays an essential role in the pathology of numerous diseases and has emerged as a key area of focus in studies of chronic kidney disease (CKD). CKD is a major public health problem with high incidence and mortality that is characterized by a gradual loss of kidney function over time. The severity and complexity of CKD combined with the limited knowledge of its underlying molecular mechanism(s) have led to increased interest in this disease area. Here, we summarize recent advances in our understanding of the regulatory mechanism(s) of ferroptosis and highlight recent studies describing its role in the pathogenesis and progression of CKD. We further discuss the potential therapeutic benefits of targeting ferroptosis for the treatment of CKD and the major hurdles to overcome for the translation of in vitro studies into the clinic.

Nickel-Catalyzed Direct Cross-Coupling of Diaryl Sulfoxide with Aryl Bromide.

The direct cross-couplings of diaryl sulfoxides with aryl bromides via C-S bond cleavage could be readily accomplished using nickel(II) as the catalyst, 1,2-bis(diphenylphosphino)ethane (dppe) as the ligand, and magnesium turnings as the reducing metal in THF, leading to the corresponding biaryls in moderate to good yields. The reaction exhibited a broad substrate scope and could be applied to a gram-scale synthesis. The "one-pot" reaction, which avoids the utility of presynthesized and moisture-labile organometallic compounds, is operationally simple and step-economic.