QiDongNing induces lung cancer cell apoptosis via triggering P53/DRP1-mediated mitochondrial fission.

Non-small-cell lung cancer (NSCLC) is a major cause of worldwide cancer death, posing a challenge for effective treatment. Our previous findings showed that Chinese herbal medicine (CHM) QiDongNing (QDN) could upregulate the expression of p53 and trigger cell apoptosis in NSCLC. Here, our objective was to investigate the mechanisms of QDN-induced apoptosis enhancement. We chose A549 and NCI-H460 cells for validation in vitro, and LLC cells were applied to form a subcutaneous transplantation tumour model for validation in more depth. Our findings indicated that QDN inhibited multiple biological behaviours, including cell proliferation, cloning, migration, invasion and induction of apoptosis. We further discovered that QDN increased the pro-apoptotic BAX while inhibiting the anti-apoptotic Bcl2. QDN therapy led to a decline in adenosine triphosphate (ATP) and a rise in reactive oxygen species (ROS). Furthermore, QDN elevated the levels of the tumour suppressor p53 and the mitochondrial division factor DRP1 and FIS1, and decreased the mitochondrial fusion molecules MFN1, MFN2, and OPA1. The results were further verified by rescue experiments, the p53 inhibitor Pifithrin-α and the mitochondrial division inhibitor Mdivi1 partially inhibited QDN-induced apoptosis and mitochondrial dysfunction, whereas overexpression of p53 rather increased the efficacy of the therapy. Additionally, QDN inhibited tumour growth with acceptable safety in vivo. In conclusion, QDN induced apoptosis via triggering p53/DRP1-mediated mitochondrial fission in NSCLC cells.

Decafluorinated and Perfluorinated Warped Nanographenes: Synthesis, Structural Analysis, and Properties.

Fluorination is a useful approach for tailoring the physicochemical properties of nanocarbon materials. However, owing to the violent reactivity of fluorination, achieving edge-perfluorination of nanographene while maintaining its original π-conjugated structure is challenging. Instead of using traditional fluorination, here, we employed a bottom-up strategy involving fluorine preinstallation and synthesized decafluorinated and perfluorinated warped nanographenes (DFWNG and PFWNG, respectively) through a 10-fold Suzuki-Miyaura coupling followed by a harsh Scholl reaction, whereby precisely edge-perfluorinated nanographene with an intact π-conjugated structure was achieved for the first time. X-ray crystallography confirmed the intact π-conjugated structure and more twisted saddle-shaped geometry of PFWNG compared to that of DFWNG. Dynamic study revealed that the 26-ring carbon framework of PFWNG is less flexible than that of DFWNG and the pristine WNG, enabling chirality resolution of PFWNG and facilitating the achievement of CD spectra at -10 °C. The edge-perfluorination of PFWNG resulted in improved solubility, lower lowest unoccupied molecular orbital, and a surface electrostatic potentials/dipole moment direction opposite those of the pristine WNG. Likely owing to its intact π-conjugated structure, PFWNG exhibits comparable electron mobility with well-known PC61BM. Furthermore, perfluorination improves thermal stability and hydrophobicity, making PFWNG suitable for use as a thermostable/hydrophobic n-type semiconductor material. In the future, this fluorination strategy can be used to synthesize other perfluorinated nanocarbon materials, such as perfluorinated graphene nanoribbons and porous nanocarbon.

Factors influencing diffusion tensor imaging of knee cartilage in children ages 6-12 years: a prospective study.

BACKGROUND: Magnetic resonance diffusion tensor imaging (DTI) has recently been used to evaluate the developing cartilage of children, but the influencing factors have not been well studied. OBJECTIVE: The objective of this study was to investigate the influence of the diffusion gradient strength (b value), diffusion gradient direction, age and sex on knee cartilage DTI in healthy children aged 6-12 years. MATERIALS AND METHODS: A total of 30 healthy child volunteers, with an average age of 8.9 ± 1.6 (mean ± standard deviation) years, were enrolled in this study. They were categorized into three groups according to their age range: 6-8 years, 8-10 years and 10-12 years, ensuring equal sex distribution in each group (5 boys and 5 girls). These volunteers underwent routine left knee joint magnetic resonance imaging (MRI) and serial DTI scans. DTI parameters were altered as follows: when b value = 600 s/mm2, diffusion gradient direction was set to 6, 15, 25, 35 and 45; and when diffusion gradient direction = 25, b value was set to 300, 600, 900 and 1200 s/mm2. The values of fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were separately acquired using image post-processing techniques. The correlation between various b values, diffusion gradient directions, age and sex on the one hand and FA and ADC values on the other, was investigated. RESULTS: (1) When diffusion gradient direction was fixed and the b value was varied, both FA and ADC exhibited a decreasing trend as the b value increased (P < 0.001). (2) When the b value was fixed and diffusion gradient direction was varied, the FA of knee cartilage showed a decreasing trend with increasing diffusion gradient direction (P < 0.001). (3) The FA value increased with age (P < 0.05). CONCLUSION: The b value, diffusion gradient direction value and age exert a significant impact on both FA and ADC values in MR DTI of knee cartilage in children aged 6-12 years. In order to obtain a stable DTI, it is recommended to select a b value ≥ 600 s/mm2 and a diffusion gradient direction ≥ 25 during scanning.

Divergent roles of Rad4 and Rad23 homologs in Metarhizium robertsii's resistance to solar ultraviolet damage.

The anti-ultraviolet (UV) role of a Rad4-Rad23-Rad33 complex in budding yeast relies on nucleotide excision repair (NER), which is mechanistically distinct from photorepair of DNA lesions generated under solar UV irradiation but remains poorly known in filamentous fungi. Here, two nucleus-specific Rad4 paralogs (Rad4A and Rad4B) and nucleocytoplasmic shuttling Rad23 ortholog are functionally characterized by multiple analyses of their null mutants in Metarhizium robertsii, an entomopathogenic fungus lacking Rad33. Rad4A was proven to interact with Rad23 and contribute significantly more to conidial UVB resistance (90%) than Rad23 (65%). Despite no other biological function, Rad4A exhibited a very high activity in photoreactivation of UVB-impaired/inactivated conidia by 5-h light exposure due to its interaction with Rad10, an anti-UV protein clarified previously to have acquired a similar photoreactivation activity through its interaction with a photolyase in M. robertsii. The NER activity of Rad4A or Rad23 was revealed by lower reactivation rates of moderately impaired conidia after 24-h dark incubation but hardly observable at the end of 12-h dark incubation, suggesting an infeasibility of its NER activity in the field where nighttime is too short. Aside from a remarkable contribution to conidial UVB resistance, Rad23 had pleiotropic effect in radial growth, aerial conidiation, antioxidant response, and cell wall integrity but no photoreactivation activity. However, Rad4B proved redundant in function. The high photoreactivation activity of Rad4A unveils its essentiality for M. robertsii's fitness to solar UV irradiation and is distinct from the yeast homolog's anti-UV role depending on NER. IMPORTANCE Resilience of solar ultraviolet (UV)-impaired cells is crucial for the application of fungal insecticides based on formulated conidia. Anti-UV roles of Rad4, Rad23, and Rad33 rely upon nucleotide excision repair (NER) of DNA lesions in budding yeast. Among two Rad4 paralogs and Rad23 ortholog characterized in Metarhizium robertsii lacking Rad33, Rad4A contributes to conidial UVB resistance more than Rad23, which interacts with Rad4A rather than functionally redundant Rad4B. Rad4A acquires a high activity in photoreactivation of conidia severely impaired or inactivated by UVB irradiation through its interaction with Rad10, another anti-UV protein previously proven to interact with a photorepair-required photolyase. The NER activity of either Rad4A or Rad23 is seemingly extant but unfeasible under field conditions. Rad23 has pleiotropic effect in the asexual cycle in vitro but no photoreactivation activity. Therefore, the strong anti-UV role of Rad4A depends on photoreactivation, unveiling a scenario distinct from the yeast homolog's NER-reliant anti-UV role.

Protective effects of polydatin against bone and joint disorders: the in vitro and in vivo evidence so far.

Polydatin is an active polyphenol displaying multifaceted benefits. Recently, growing studies have noticed its potential therapeutic effects on bone and joint disorders (BJDs). Therefore, this article reviews recent in vivo and in vitro progress on the protective role of polydatin against BJDs. An insight into the underlying mechanisms is also presented. It was found that polydatin could promote osteogenesis in vitro, and symptom improvements have been disclosed with animal models of osteoporosis, osteosarcoma, osteoarthritis and rheumatic arthritis. These beneficial effects obtained in laboratory could be mainly attributed to the bone metabolism-regulating, anti-inflammatory, antioxidative, apoptosis-regulating and autophagy-regulating functions of polydatin. However, studies on human subjects with BJDs that can lead to early identification of the clinical efficacy and adverse effects of polydatin have not been reported yet. Accordingly, this review serves as a starting point for pursuing clinical trials. Additionally, future emphasis should also be devoted to the low bioavailability and prompt metabolism nature of polydatin. In summary, well-designed clinical trials of polydatin in patients with BJD are in demand, and its pharmacokinetic nature must be taken into account.

Extracellular vesicles from human umbilical cord mesenchymal stem cells reduce lipopolysaccharide-induced spinal cord injury neuronal apoptosis by mediating miR-29b-3p/PTEN.

OBJECTIVE: This study investigated the molecular mechanism of whether hUC-MSCs-EVs repressed PTEN expression and activated the PI3K/AKT pathway through miR-29b-3p, thus inhibiting LPS-induced neuronal injury. METHODS: hUC-MSCs were cultured and then identified. Cell morphology was observed. Alizarin red, oil red O, and alcian blue staining were used for inducing osteogenesis, adipogenesis, and chondrogenesis. EVs were extracted from hUC-MSCs and identified by transmission electron microscope observation and Western blot. SCI neuron model was established by 24h lipopolysaccharide (LPS) induction. After the cells were cultured with EVs without any treatment, uptake of EVs by SCI neurons, miR-29b-3p expression, cell viability, apoptosis, caspase-3, cleaved caspase-3, caspase 9, Bcl-2, PTEN, PI3K, AKT, and p-Akt protein levels, caspase 3 and caspase 9 activities, and inflammatory factors IL-6 and IL-1ß levels were detected by immunofluorescence labeling, RT-qPCR, MTT, flow cytometry, Western blot, caspase 3 and caspase 9 activity detection kits, and ELISA. The binding sites between PTEN and miR-29b-3p were predicted by the database and verified by dual-luciferase assay. RESULTS: LPS-induced SCI cell model was successfully established, and hUC-MSCs-EVs inhibited LPS-induced apoptosis of injured spinal cord neurons. EVs transferred miR-29b-3p into LPS-induced injured neurons. miR-29b-3p silencing reversed EV effects on reducing LPS-induced neuronal apoptosis. miR-29b-3p reduced LPS-induced neuronal apoptosis by targeting PTEN. After EVs-miR-inhi and si-PTEN treatment, inhibition of the PI3K/AKT pathway reversed hUC-MSCs-EVs effects on reducing LPS-induced neuronal apoptosis. CONCLUSION: hUC-MSCs-EVs activated the PI3K/AKT pathway by carrying miR-29b-3p into SCI neurons and silencing PTEN, thus reducing neuronal apoptosis.

A comparison of three bone graft struts for interbody fusion using a posterior approach for lower lumbar spinal tuberculosis in adults: a midterm follow-up study.

BACKGROUND: This retrospective observational study was conducted to compare midterm outcomes of three bone graft struts for interbody fusion using a posterior approach in adults with lower lumbar spinal tuberculosis. METHODS: A total of 126 lower lumbar spinal tuberculosis patients were treated by one-stage posterior debridement, interbody fusion, and instrumentation. Forty-one patients (group A) were treated with autogenous bone graft for interbody fusion, 45 patients (group B) were treated with allogeneic bone grafting, and the remaining 40 (group C) patients were treated with titanium mesh cage. In addition, clinical and radiographic data were gathered and analyzed. RESULTS: At the final follow-up, all patients were completely cured. The operation period and intraoperative blood loss for groups B and C were significantly less than in group A (P = 0.000). Post-operation, neurological performance and quality of life were remarkably improved at the final follow-up. The preoperative lordosis angles of three groups were significantly improved, as evidenced by the values immediately after the operation or those at the final follow-up. The correction loss of the group C was lower than those of groups A and B (P = 0.000). All the patients obtained bone graft fusion, the fusion period of group B was longer than that of the other two groups (P = 0.000). No significant differences among the three groups in adjacent segment degeneration rates were found at the last visit (P = 0.922). CONCLUSIONS: This midterm follow-up study established that one-stage posterior debridement, interbody fusion, and instrumentation, combined with medical therapy, can effectively treat lower lumbar spinal tuberculosis. In addition, the intervertebral titanium mesh cage bone graft can provide better outcomes with regard to maintaining lordosis and preventing collapse.

Endoscopy-assisted anterior cervical debridement combined with posterior fixation and fusion for the treatment of upper cervical spine tuberculosis: a retrospective feasibility study.

BACKGROUND: This retrospective study aimed to determine the feasibility and efficacy of endoscopy-assisted anterior cervical debridement combined with posterior fixation and fusion in patients with upper cervical spine tuberculosis. METHODS: Between June 2008 and January 2016, 17 patients (10 men and 7 women) with upper cervical spine tuberculosis underwent endoscopy-assisted anterior cervical debridement combined with posterior fixation and fusion. Anti-tuberculosis treatment was administered for 2-4 weeks preoperatively and 12-18 months postoperatively. The clinical and radiographic data of the patients were analyzed. RESULTS: The operation was successfully completed in all patients. Neck pain and stiffness were relieved after the surgery in all patients. The mean operation time was 210.0 ± 21.2 min, and the mean intraoperative blood loss was 364.7 ± 49.6 mL. The mean follow-up duration was 68.1 ± 6.7 months. The erythrocyte sedimentation rate returned to normal by 3 months postoperatively. Visual analog scale scores for neck pain were significantly lower postoperatively than preoperatively. All patients had significant postoperative neurological improvement. Patient-reported outcomes, as measured using the Kirkaldy-Willis criteria, were as follows: excellent, 12 patients; good, 4 patients; fair, 1 patient; and poor, 0 patients. Bone fusion was achieved at 10.9 ± 1.9 months after the surgery; no cases of instrument loosening or fracture occurred. CONCLUSION: Endoscopy-assisted anterior cervical debridement combined with posterior fixation and fusion is a feasible and effective surgical method for the treatment of upper cervical spine tuberculosis. It can be used to restore upper cervical spine stability and facilitate spinal healing.

The binding of an anti-PD-1 antibody to FcγRΙ has a profound impact on its biological functions.

Antibodies targeting PD-1 have been demonstrated durable anti-cancer activity in certain cancer types. However, the anti-PD-1 antibodies are less or not efficacious in many situations, which might be attributed to co-expression of multiple inhibitory receptors or presence of immunosuppressive cells in the tumor microenvironment. Most of the anti-PD-1 antibodies used in clinical studies are of IgG4 isotype with the S228P mutation (IgG4S228P). The functional impact by the interaction of anti-PD-1 IgG4S228P antibody with Fc gamma receptors (FcγRs) is poorly understood. To assess the effects, we generated a pair of anti-PD-1 antibodies: BGB-A317/IgG4S228P and BGB-A317/IgG4-variant (abbreviated as BGB-A317), with the same variable regions but two different IgG4 Fc-hinge sequences. There was no significant difference between these two antibodies in binding to PD-1. However, BGB-A317/IgG4S228P binds to human FcγRI with high affinity and mediates crosslinking between PD-1 and FcγRI. In contrast, BGB-A317 does neither. Further cell-based assays showed that such crosslinking could reverse the function of an anti-PD-1 antibody from blocking to activating. More importantly, the crosslinking induces FcγRI+ macrophages to phagocytose PD-1+ T cells. In a mouse model transplanted with allogeneic human cancer cells and PBMCs, BGB-A317 showed significant tumor growth inhibition, whereas BGB-A317/IgG4S228P had no such inhibition. Immunohistochemistry study revealed an inverse correlation between FcγRI+ murine macrophage infiltration and the density of CD8+PD-1+ human T cells within tumors in the BGB-A317/IgG4S228P-treated group. These evidences suggested that FcγRI+ binding and crosslinking had negative impact on the anti-PD-1 antibody-mediated anti-cancer activity.

An overview of the American trauma system.

The American trauma system is designed to provide an organized response to injury. It draws its foundations from lessons learned from America's involvement in the wars of the 20th century as well as principles developed in urban community hospitals. Although run at the local and state government level, it is guided by national societies and has become a world class example. It also currently faces challenges with declining reimbursement and providing equal access to care for all Americans. Professional societies and legislative bodies are continuing to work together for fair and equitable solutions to these issues.

Lithium-titanate-nanotube-supported WO3 for enhancing transmittance contrast in electrochromics.

Lithium titanate nanotubes (Li-TNTs) have been successfully synthesized. The inner and outer diameters of the nanotubes are 5 nm and 8 nm with an interlayer spacing of 0.83 nm. The nanotubes were in accordance with the Li1.81H0.19Ti2O5 · xH2O phase. The chemical component was Li0.9H1.1Ti2O5 · H2O as determined by ICP-AES. The Li-TNT-supported WO3 nanoparticle (WO3/Li-TNTs) thin film was prepared onto ITO glass via spin-coating and then fabricated with an electrochromic device. The Li ion diffusion coefficient in the WO3/Li-TNT film was 6.1 × 10(-10) cm(2) s(-1), which is eight times higher than that for the pure WO3 film. The transmittance contrast of the pure WO3-based ECD was 53.3% at 600 nm. However, this increased to 74.1% for the WO3/Li-TNT-based ECD. Meanwhile, the color-switching times of the WO3/Li-TNT-based ECD were apparently shorter than the ones for the WO3-based ECD.

Rad2, Rad14 and Rad26 recover Metarhizium robertsii from solar UV damage through photoreactivation in vivo.

Rad2, Rad14 and Rad26 recover ultraviolet (UV) damage by nucleotide excision repair (NER) in budding yeast but their functions in filamentous fungi have not been elucidated. Here, we report mechanistically different anti-UV effects of nucleus-specific Rad2, Rad14 and Rad26 orthologs in Metarhizium robertsii, an insect-pathogenic fungus. The null mutants of rad2, rad14 and rad26 showed a decrease of ∼90% in conidial resistance to UVB irradiation. When conidia were impaired at a UVB dose of 0.15 J/cm2, they were photoreactivated (germinated) by only 6-13% through a 5-h light plus 19-h dark incubation, whereas 100%, 80% and 70% of the wild-type conidia were photoreactivated at 0.15, 0.3 and 0.4 J/cm2, respectively. The dose-dependent photoreactivation rates were far greater than the corresponding 24-h dark reactivation rates and were largely enhanced by the overexpression (OE) of rad2, rad14 or rad26 in the wild-type strain. The OE strains exhibited markedly greater activities in photoreactivation of conidia inactivated at 0.5-0.7 J/cm2 than did the wild-type strain. Confirmed interactions of Rad2, Rad14 and Rad26 with photolyase regulators and/or Rad1 or Rad10 suggest that each of these proteins could have evolved into a component of the photolyase regulator-cored protein complex to mediate photoreactivation. The interactions inhibited in the null mutants resulted in transcriptional abolishment or repression of those factors involved in the complex. In conclusion, the anti-UV effects of Rad2, Rad14 and Rad26 depend primarily on DNA photorepair-dependent photoreactivation in M. robertsii and mechanistically differ from those of yeast orthologs depending on NER.

Predicting the mechanism of action of YQYYJD prescription in the treatment of non-small cell lung cancer using transcriptomics analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: The efficacy of the herbal formula Yiqi Yangyin Jiedu (YQYYJD) in the treatment of advanced lung cancer has been reported in clinical trials. However, the key anti-lung cancer herbs and molecular mechanisms underlying its inhibition of lung cancer are not well-understood. AIM OF THE STUDY: To identify the key anti-lung cancer herbs in the YQYYJD formula and investigate their therapeutic effect and potential mechanism of action in non-small cell lung cancer (NSCLC) using transcriptomics and bioinformatics techniques. MATERIALS AND METHODS: A mouse Lewis lung carcinoma (LLC) subcutaneous inhibitory tumor model was established with 6 mice in each group. Mice were treated with the YQYYJD split formula: Yiqi Formula (YQ), Yangyin Formula (YY), and Ruanjian Jiedu Formula (RJJD) for 14 days. The tumor volume and mouse weight were recorded, and the status of tumor occurrence was further observed by taking photos. The tumor was stained with hematoxylin-eosin to observe its histopathological changes. Immunohistochemistry was used to detect the expression of the proliferation marker Ki67 and the apoptotic marker Caspase-3 in tumor tissues. Flow cytometry was used to detect the number of CD4+ and CD8+ T cells and cytokines interleukin-2 (IL-2) and interferon-gamma (IFN-γ) in the spleen and tumor tissues. The differential genes of key drugs against tumors were obtained by transcriptome sequencing of tumors. Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genomes (KEGG) enrichment analyses were performed on differential genes to obtain pathways and biological processes where targets were aggregated. TIMER2.0 and TISIDB databases were used to evaluate the impact of drugs on immune cell infiltration and immune-related genes. The binding activity of the key targets and compounds was verified by molecular docking. RESULTS: YQ, YY, and RJJD inhibited the growth of subcutaneous transplanted tumors in LLC mice to varying degrees and achieved antitumor effects by inhibiting the expression of tumor cell proliferation, apoptosis, and metastasis-related proteins. Among the three disassembled prescriptions, YQ better inhibited the growth of subcutaneous transplanted tumors in LLC mice, significantly promoted tumor necrosis, significantly increased the expression of Caspase-3 protein in tumor tissue, and significantly decreased the expression of Ki-67 (P < 0.05), thereby increasing the infiltration of CD8+ T cells. YQ significantly increased the expression of CD4+ and CD8+ T cells in tumor and splenic tissues of tumor-bearing mice and up-regulated the expression of IL-2 and IFN-γ. Transcriptome sequencing and bioinformatics results showed that after YQ intervention, differentially expressed genes were enriched in more than one tumor-related pathway and multiple immune regulation-related biological functions. There were 12 key immune-related target genes. CONCLUSION: YQ was the key disassembled prescription of YQYYJD, exerting significant antitumor effects and immune regulation effects on NSCLC. It may have relieved T cell exhaustion and regulated the immune microenvironment to exert antitumor effects by changing lung cancer-related targets, pathways, and biological processes.

Patient-Reported Outcomes of Postoperative NSCLC Patients with or without Staged Chinese Herb Medicine Therapy during Adjuvant Chemotherapy (NALLC 2): A Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVE: To investigate whether the combination of chemotherapy with staged Chinese herbal medicine (CHM) therapy could enhance health-related quality of life (QoL) in non-small-cell lung cancer (NSCLC) patients and prolong the time before deterioration of lung cancer symptoms, in comparison to chemotherapy alone. METHODS: A prospective, double-blind, randomized, controlled trial was conducted from December 14, 2017 to August 28, 2020. A total of 180 patients with stage I B-IIIA NSCLC from 5 hospitals in Shanghai were randomly divided into chemotherapy combined with CHM (chemo+CHM) group (120 cases) or chemotherapy combined with placebo (chemo+placebo) group (60 cases) using stratified blocking randomization. The European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life-Core 30 Scale (QLQ-C30) was used to evaluate the patient-reported outcomes (PROs) during postoperative adjuvant chemotherapy in patients with early-stage NSCLC. Adverse events (AEs) were assessed in the safety analysis. RESULTS: Out of the total 180 patients, 173 patients (116 in the chemo+CHM group and 57 in the chemo+placebo group) were included in the PRO analyses. The initial mean QLQ-C30 Global Health Status (GHS)/QoL scores at baseline were 57.16 ± 1.64 and 57.67 ± 2.25 for the two respective groups (P>0.05). Compared with baseline, the chemo+CHM group had an improvement in EORTC QLQ-C30 GHS/QoL score at week 18 [least squares mean (LSM) change 17.83, 95% confidence interval (CI) 14.29 to 21.38]. Conversely, the chemo+placebo group had a decrease in the score (LSM change -13.67, 95% CI -22.70 to -4.63). A significant between-group difference in the LSM GHS/QoL score was observed, amounting to 31.63 points (95% CI 25.61 to 37.64, P<0.001). The similar trends were observed in physical functioning, fatigue and appetite loss. At week 18, patients in the chemo+CHM group had a higher proportion of improvement or stabilization in GHS/QoL functional and symptom scores compared to chemo+placebo group (P<0.001). The median time to deterioration was longer in the chemo+CHM group for GHS/QoL score [hazard ratio (HR)=0.33, 95% CI 0.23 to 0.48, P<0.0010], physical functioning (HR=0.43, 95% CI 0.25 to 0.75, P=0.0005), fatigue (HR=0.47, 95% CI 0.30 to 0.72, P<0.0001) and appetite loss (HR=0.65, 95% CI 0.42 to 1.00, P=0.0215). The incidence of AEs was lower in the chemo+CHM group than in the chemo+placebo group (9.83% vs. 15.79%, P=0.52). CONCLUSION: The staged CHM therapy could help improve the PROs of postoperative patients with early-stage NSCLC during adjuvant chemotherapy, which is worthy of further clinical research. (Registry No. NCT03372694).

Efficient Photoreactivation of Solar UV-Injured Metarhizium robertsii by Rad1 and Rad10 Linked to DNA Photorepair-Required Proteins.

Nucleotide excision repair (NER) of ultraviolet (UV)-induced DNA lesions known as cyclobutane pyrimidine dimer (CPD) and (6-4)-pyrimidine-pyrimidone (6-4PP) photoproducts depends on the activities of multiple anti-UV radiation (RAD) proteins in budding yeast. However, NER remains poorly known in filamentous fungi, whose DNA lesions are photorepaired by one or two photolyases, namely CPD-specific Phr1 and/or 6-4PP-specific Phr2. Previously, the white collar proteins WC1 and WC2 were proven to regulate expressions of phr2 and phr1 and photorepair 6-4PP and CDP DNA lesions, respectively, in Metarhizium robertsii, a filamentous entomopathogenic-phytoendophytic fungus. We report here high activities of orthologous Rad1 and Rad10 in 5-h photoreactivation of UVB-injured or UVB-inactivated conidia but a severely compromised capability of their reactivating those conidia via 24-h dark incubation in M. robertsii. The null mutants of rad1 and rad10 were much more compromised in conidial UVB resistance and photoreactivation capability than the previous null mutants of phr1, phr2, wc1 and wc2. Multiple protein-protein (Rad1-Rad10, Rad1-WC2, Rad10-Phr1, WC1-Phr1/2 and WC2-Phr1/2) interactions detected suggest direct/indirect links of Rad1 and Rad10 to Phr1/2 and WC1/2 and an importance of the links for their photoreactivation activities. Conclusively, Rad1 and Rad10 photoreactivate UVB-impaired M. robertsii through their interactions with the DNA photorepair-required proteins.

Novel retro-auricular myocutaneous hemicraniectomy flap: Technical note and cadaveric dissection.

Objective: The hemicraniectomy is a common technique used in a variety of pathologies including some traumatic brain injury and malignant stroke. A novel technique of performing hemicraniectomies using a retro-auricular incision can avoid transgressing the temporalis muscle and superficial temporal artery while providing adequate hemicranial exposure. Methods: This technique was reproduced in a skull base lab using a cadaveric head. The key steps of this approach were illustrated in step-by-step fashion. A post-approach CT scan of the cadaver was performed to evaluate the decompression exposure. Results: This approach can provide sufficient middle fossa decompression and area of exposure, while preserving the temporalis along with the superficial temporal artery. A step-by-step technical illustration is demonstrated in the present note. Conclusions: The modified retro-auricular myocutaneous flap is a novel technique in hemicraniectomy which can provide sufficient middle fossa decompression and exposure while sparing the temporalis muscle and superficial temporal artery during the approach.

Comparing Bone Graft Techniques for Interbody Fusion through a Posterior Approach for Treating Mid-Thoracic Spinal Tuberculosis: A Retrospective Analysis.

OBJECTIVE: Mid-thoracic spinal tuberculosis is prone to kyphotic deformities and neurologic impairment. Posterior approach can effectively restore the spinal stability by reconstructing the anterior and middle spinal columns. Titanium mesh cages (TMC), allogeneic bone (ALB), and autogenous bone (AUB) are three main bone graft struts. We aimed to compare the therapeutic efficacy of three bone graft struts, for anterior and middle column reconstruction through a posterior approach in cases of mid-thoracic spinal tuberculosis. METHODS: Hundred and thirty seven patients with thoracic spinal tuberculosis who had undergone a posterior approach from June 2010 to December 2018 were enrolled. Of them, 46 patients were treated using a titanium mesh cage (TMC group), 44 with allogenic bone grafts (ALB group), and 47 using autogenous bone grafts (AUB group). The following were analyzed to evaluate clinical efficacy: visual analogue scale (VAS) values, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels, kyphotic Cobb's angle, operation duration, intraoperative blood loss, improvement in American Spinal Injury Association (ASIA) grade and in the mental component summary (MCS) and physical component summary (PCS) of Short Form-36 (SF-36), duration of bone graft fusion. The data of the three groups were compared by way of variance analysis, followed by the LSD⁃t test to compare each group. A repeated measures ANOVA was used to analyze the dates of pre-, postoperative and final follow-up. RESULTS: The follow-up duration was at least 3 years. All patients achieved a complete cure for spinal TB. Neurological performance and quality of life were remarkably improved at the final follow-up. The intraoperative blood loss, operation time and VAS values 1 day postoperatively for TMC group and ALB group were significantly lower than those in AUB group (P < 0.05). The duration of bone graft fusion in ALB group (18.1 ± 3.7 months) was longer than that in TMC group and AUB group (9.5 ± 2.8 and 9.2 ± 1.9 months) (P < 0.05). No significant intergroup differences were observed in terms of age or preoperative, 3-months postoperative, and final follow-up indices of ESR and CRP among the three groups (P > 0.05). At the final follow-up, the correction loss was mild (2.1 ± 0.9, 2.2 ± 1.0, 2.1 ± 0.8) and Cobb's angles of the three groups were 20.1 ± 2.9, 20.5 ± 3.2, 20.9 ± 3.4, respectively, which were remarkably rectified in comparison with the preoperative measurements (P < 0.05). CONCLUSIONS: In terms of postoperative recovery and successful fusion rate of bone graft, it seems that posterior instrumentation, debridement, and interbody fusion with titanium mesh cages are more effective and appropriate surgical methods for mid-thoracic spinal tuberculosis.

Successful Management of Iatrogenic Cranial Pseudomeningocele With Subgaleal Shunt.

Iatrogenic pseudomeningocele is a common complication of cranial surgeries. However, there are no evidence-based guidelines on how to manage this condition. We report two cases of iatrogenic postoperative cranial pseudomeningocele that failed conservative management including compressive head dressing. Subgaleal shunt placement was utilized with successful resolution in both cases. We postulate that subgaleal shunt placement may be an effective method in the management of iatrogenic subgaleal pseudomeningocele.

Irritability and risk of lung cancer: a Mendelian randomization and mediation analysis.

BACKGROUND: There is no research to prove the association between irritability and lung cancer, our study performed a Mendelian randomization (MR) approach to elucidate the causal relationship of irritability with lung cancer risk. METHODS: Genome-wide association studies (GWAS) data of irritability, lung cancer and gastroesophageal reflux disease (GERD) were downloaded from a public database for two-sample MR analysis. Independent single-nucleotide polymorphisms (SNPs) associated with irritability and GERD were selected as instrumental variables (IVs). Inverse variance weighting (IVW) and weighted median method were used to analyze causality. RESULTS: There is an association between irritability and lung cancer risk (ORIVW = 1.01, 95% CI = [1.00, 1.02], P = 0.018; ORweighted median = 1.01, 95% CI = [1.00, 1.02], P = 0.046), and GERD might account for about 37.5% of the association between irritability and lung cancer. CONCLUSIONS: This study confirmed the causal effect between irritability and lung cancer through MR analysis, and found that GERD played an essential mediating role in this relationship, which can partly indicate the role of the "inflammation-cancer transformation" process in lung cancer.

Comparison of two surgical interventions for lumbar brucella spondylitis in adults: a retrospective analysis.

This retrospective study aimed to compare the clinical efficacy of the posterior procedure with the combined anterior and posterior procedure in the surgical management of lumbar Brucella spondylitis. From January 2015 to June 2020, a total of 62 patients presenting with lumbar Brucella spondylitis underwent either one-stage posterior pedicle fixation, debridement, and interbody fusion (Group A, n = 33) or anterior debridement, bone grafting, and posterior instrumentation (Group B, n = 29). All patients were followed up for an average of 25.4 ± 1.5 months and achieved complete resolution of lumbar Brucella spondylitis. No significant differences between the groups were observed in terms of age or pre-operative, three-month postoperative and final follow-up indices of the VAS, ESR, CRP, lordosis angle, ODI scores, fusion time, and time of serum agglutination test conversion to negative (P > 0.05). Each patient exhibited notable improvements in neurological function, as assessed by the JOA score rating system. Group A demonstrated significantly shorter operative duration, intraoperative blood loss, and hospital stay compared to Group B (P < 0.05). Superficial wound infection was observed in one case in Group A, whereas Group B experienced one case each of intraoperative peritoneal rupture, postoperative ileus, iliac vein injury, and superficial wound infection. This study supports the efficacy of both surgical interventions in the treatment of lumbar Brucella spondylitis, with satisfactory outcomes. However, the posterior approach demonstrated advantages, including reduced surgical time, diminished blood loss, shorter hospital stays, and fewer perioperative complications. Consequently, the one-stage posterior pedicle fixation, debridement, and interbody fusion represent a superior treatment option.