The OsCPK17-OsPUB12-OsRLCK176 module regulates immune homeostasis in rice.

Plant immunity is fine-tuned to balance growth and defense. However, little is yet known about molecular mechanisms underlying immune homeostasis in rice (Oryza sativa). In this study, we reveal that a rice calcium-dependent protein kinase (CDPK), OsCPK17, interacts with and stabilizes the receptor-like cytoplasmic kinase (RLCK) OsRLCK176, a close homolog of Arabidopsis thaliana BOTRYTIS-INDUCED KINASE 1 (AtBIK1). Oxidative burst and pathogenesis-related gene expression triggered by pathogen-associated molecular patterns are significantly attenuated in the oscpk17 mutant. The oscpk17 mutant and OsCPK17-silenced lines are more susceptible to bacterial diseases than the wild-type plants, indicating that OsCPK17 positively regulates rice immunity. Furthermore, the plant U-box (PUB) protein OsPUB12 ubiquitinates and degrades OsRLCK176. OsCPK17 phosphorylates OsRLCK176 at Ser83, which prevents the ubiquitination of OsRLCK176 by OsPUB12 and thereby enhances the stability and immune function of OsRLCK176. The phenotypes of the ospub12 mutant in defense responses and disease resistance show that OsPUB12 negatively regulates rice immunity. Therefore, OsCPK17 and OsPUB12 reciprocally maintain OsRLCK176 homeostasis and function as positive and negative immune regulators, respectively. This study uncovers positive cross talk between CDPK- and RLCK-mediated immune signaling in plants and reveals that OsCPK17, OsPUB12, and OsRLCK176 maintain rice immune homeostasis.

Ustilaginoidea virens secretes a family of phosphatases that stabilize the negative immune regulator OsMPK6 and suppress plant immunity.

Rice false smut caused by Ustilaginoidea virens is emerging as a devastating disease of rice (Oryza sativa) worldwide; however, the molecular mechanisms underlying U. virens virulence and pathogenicity remain largely unknown. Here we demonstrate that the small cysteine-rich secreted protein SCRE6 in U. virens is translocated into host cells during infection as a virulence factor. Knockout of SCRE6 leads to attenuated U. virens virulence to rice. SCRE6 and its homologs in U. virens function as a novel family of mitogen-activated protein kinase phosphatases harboring no canonical phosphatase motif. SCRE6 interacts with and dephosphorylates the negative immune regulator OsMPK6 in rice, thus enhancing its stability and suppressing plant immunity. Ectopic expression of SCRE6 in transgenic rice promotes pathogen infection by suppressing the host immune responses. Our results reveal a previously unidentified fungal infection strategy in which the pathogen deploys a family of tyrosine phosphatases to stabilize a negative immune regulator in the host plant to facilitate its infection.

Capsaicin Enhanced the Efficacy of Photodynamic Therapy Against Osteosarcoma via a Pro-Death Strategy by Inducing Ferroptosis and Alleviating Hypoxia.

Ferroptosis, a novel form of nonapoptotic cell death, can effectively enhance photodynamic therapy (PDT) performance by disrupting intracellular redox homeostasis and promoting apoptosis. However, the extremely hypoxic tumor microenvironment (TME) together with highly expressed hypoxia-inducible factor-1α (HIF-1α) presents a considerable challenge for clinical PDT against osteosarcoma (OS). Hence, an innovative nanoplatform that enhances antitumor PDT by inducing ferroptosis and alleviating hypoxia is fabricated. Capsaicin (CAP) is widely reported to specifically activate transient receptor potential vanilloid 1 (TRPV1) channel, trigger an increase in intracellular Ca2+ concentration, which is closely linked with ferroptosis, and participate in decreased oxygen consumption by inhibiting HIF-1α in tumor cells, potentiating PDT antitumor efficiency. Thus, CAP and the photosensitizer IR780 are coencapsulated into highly biocompatible human serum albumin (HSA) to construct a nanoplatform (CI@HSA NPs) for synergistic tumor treatment under near-infrared (NIR) irradiation. Furthermore, the potential underlying signaling pathways of the combination therapy are investigated. CI@HSA NPs achieve real-time dynamic distribution monitoring and exhibit excellent antitumor efficacy with superior biosafety in vivo. Overall, this work highlights a promising NIR imaging-guided "pro-death" strategy to overcome the limitations of PDT for OS by promoting ferroptosis and alleviating hypoxia, providing inspiration and support for future innovative tumor therapy approaches.

Full-endoscopic lumbar discectomy via lateral superior articular process approach for treating far lateral lumbar disc herniation: a retrospective study and technical note.

PURPOSE: This study aims to evaluate the efficacy and safety of the full-endoscopic lumbar discectomy (FELD) via lateral superior articular process (LSAP) approach and full-endoscopic transforaminal discectomy (FETD) for treating far lateral lumbar disk herniation (FFLDH). METHODS: From January 2020 to June 2022, patients who were diagnosed as FLLDH underwent the FELD via LSAP approach or FETD. The operation time, estimated blood loss, length of hospital stays, and complications were recorded. The visual analog scale (VAS) for back pain, VAS for leg pain, and the Oswestry Disability Index (ODI) scores was measured during preoperative and postoperative follow-up. RESULTS: Thirty-two patients were enrolled in this study, of which 12 patients were treated with the FELD via LSAP approach (LSAP-FELD group) and 20 patients underwent FETD (FETD group). The LSAP-FELD group exhibited significantly shorter operation times and hospital stays compared to the FETD group, while no statistically significant differences were observed in intraoperative blood loss and complication rates. There were no significant differences in the VAS for back pain, the VAS for leg pain, and the ODI score between the two groups preoperatively and three days, three months, and the last follow-up postoperatively. CONCLUSIONS: Both the FELD via LSAP approach and FETD have demonstrated favourable clinical efficacy in the treatment of FLLDH. Notably, the FELD via LSAP approach shows the advantages of shorter operation time and hospital stays.

Homologous targeting nanoparticles for enhanced PDT against osteosarcoma HOS cells and the related molecular mechanisms.

BACKGROUND: No prominent advancements in osteosarcoma (OS) treatment have been made in the past 20 years. Although photodynamic therapy (PDT) is an emerging technique for cancer therapy, the lack of targeted photosensitizers for OS treatment severely limits its applications. RESULTS: In this study, we constructed a potential theranostic nanoplatform by using (poly (lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) encapsulating IR780 into the shell (PLGA-IR780 NPs), which were further camouflaged with human OS cell membranes from the HOS cell line (MH-PLGA-IR780 NPs). These constructed NPs showed the capacity for homologous targeting with excellent photoacoustic (PA)/fluorescence (FL) imaging ability. Benefitting from their homologous targeting capacity, MH-PLGA-IR780 NPs obviously promoted cell endocytosis in vitro and tumor accumulation in vivo, which could further improve PDT performance under near-infrared (NIR) irradiation. In addition, to their homologous targeting and PA/FL dual-mode imaging ability, MH-PLGA-IR780 NPs had advantages in penetrating deeper into tumor tissues and in real-time dynamic distribution monitoring in vivo, which laid a foundation for further clinical applications in OS. Moreover, we demonstrated that PDT guided by the constructed NPs could significantly induce HOS cells apoptosis and ferroptosis via excessive accumulation of reactive oxygen species (ROS), and further determined that the potential anticancer molecular mechanism of apoptosis was triggered by the release of cytochrome c-activated mitochondrial apoptosis (endogenous apoptosis), and that ferroptosis caused the activation of nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy and the inactivation of glutathione peroxidase 4 (GPX4), synergistically leading to excessive accumulation of Lipid-ROS and Lipid peroxides (LPOs). Concurrently, MH-PLGA-IR780 NPs-guided PDT also showed an obvious inhibitory effect on tumor growth in vivo. CONCLUSION: These results suggest that this homologous targeting-based theranostic nanoplatform provides an effective method to improve PDT performance in OS and contributes a new and promising approach for OS therapy.

Gene expression and immune infiltration in melanoma patients with different mutation burden.

BACKGROUND: Immunotherapy is a vital component in cancer treatment. However, due to the complex genetic bases of cancer, a clear prediction index for efficacy has not been established. Tumor mutation burden (TMB) is one of the essential factors that affect immunotherapeutic efficacies, but it has not been determined whether the mutation is associated with the survival of Skin Cutaneous Melanoma (SKCM) patients. This study aimed at evaluating the correlation between TMB and immune infiltration. METHODS: Somatic mutation profiles (n = 467), transcriptome data (n = 471), and their clinical information (n = 447) of all SKCM samples were downloaded from The Cancer Genome Atlas (TCGA) database. For each sample, TMB was calculated as the number of variants per megabase. Based on K-M survival analysis, they were allocated into the high-TMB and low-TMB groups (the optimal cutoff was determined by the 'surv_cutpoint' algorithm of survival R package). Then, Gene ontology (GO) and Gene Set Enrichment Analyses (GSEA) were performed, with immune-associated biological pathways found to be significantly enriched in the low-TMB group. Therefore, immune genes that were differentially expressed between the two groups were evaluated in Cox regression to determine their prognostic values, and a four-gene TMB immune prognostic model (TMB-IP) was constructed. RESULTS: Elevated TMB levels were associated with better survival outcomes in SKCM patients. Based on the cutoff value in OS analysis, they were divided into high-TMB and low-TMB groups. GSEA revealed that the low-TMB group was associated with immunity while intersection analysis revealed that there were 38 differentially expressed immune-related genes between the two groups. Four TMB-associated immune genes were used to construct a TMB-IP model. The AUC of the ROC curve of this model reached a maximum of 0.75 (95%CI, 0.66-0.85) for OS outcomes. Validation in each clinical subgroup confirmed the efficacy of the model to distinguish between high and low TMB-IP score patients. CONCLUSIONS: In SKCM patients, low TMB was associated with worse survival outcomes and enriched immune-associated pathways. The four TMB-associated immune genes model can effectively distinguish between high and low-risk patients.

Intraoperative cell salvage for obstetrics: a prospective randomized controlled clinical trial.

BACKGROUND: The latest basic studies and clinical evidence have confirmed the safety and efficacy of intraoperative autologous blood cell transfusion in cardiac surgery and orthopaedics. However, in caesarean section, there are still concerns about the contamination of amniotic fluid and foetal components, and consequently the application of intraoperative autologous blood cell transfusion is not universal. Therefore, this study aimed to evaluate the clinical value of intraoperative autologous blood cell transfusion in obstetric surgery. METHODS: A prospective, randomized, controlled, feasibility study was performed in women undergoing caesarean section. One hundred sixteen participants were randomly assigned at a 1:1 ratio into either the intraoperative cell salvage group or the control group. Allogeneic blood cells were transfused into patients with haemoglobin concentrations < 80 g/dL in both the intraoperative cell salvage group and the control group. RESULTS: No significant differences were found between the two groups in age, weight, maternal parity, history of previous caesarean section, gestational weeks of delivery, etc. However, compared with the control group, patients in the intraoperative cell salvage group had a significantly lower amount of allogeneic blood cell transfusion, lower incidence of postoperative incision infection, delayed wound healing, perioperative allergy, adverse cardiovascular events, hypoproteinaemia and shorter hospital stay. CONCLUSION: The results of this study suggest that the use of autologous blood cell transfusion is safe and effective for patients with obstetric haemorrhage. TRIAL REGISTRATION: All procedures performed in studies involving human participants were in accordance with the ethical standards of the Institutional and/or National Research Committee of Beijing Obstetrics and Gynecology Hospital, Capital Medical University (2016-XJS-003-01) as well as the 1964 Helsinki Declaration and its later amendments or other comparable ethical standards. The clinical trials were registered (ChiCTR-ICC-15,007,096) on September 28, 2015.

Changes in the gut microbiota during and after commercial helium-oxygen saturation diving in China.

OBJECTIVES: The influence of commercial helium-oxygen saturation diving on divers' gut microbiotas was assessed to provide dietary suggestion. METHODS: Faecal samples of 47 divers working offshore were collected before (T1), during (T2) and after (T3) saturation diving. Their living and excursion depths were 55-134 metres underwater with a saturation duration of 12-31 days and PaO2 of 38-65 kPa. The faecal samples were examined through 16S ribosomal DNA amplicon sequencing based on the Illumina sequencing platform to analyse changes in the bacteria composition in the divers' guts. RESULTS: Although the α and ß diversity of the gut microbiota did not change significantly, we found that living in a hyperbaric environment of helium-oxygen saturation decreased the abundance of the genus Bifidobacterium, an obligate anaerobe, from 2.43%±3.83% at T1 to 0.79%±1.23% at T2 and 0.59%±0.79% at T3. Additionally, the abundance of some short-chain fatty acid (SCFA)-producing bacteria, such as Fusicatenibacter, Faecalibacterium, rectale group and Anaerostipes, showed a decreased trend in the order of before, during and after diving. On the contrary, the abundance of species, such as Lactococcus garvieae, Actinomyces odontolyticus, Peptoclostridium difficile, Butyricimonas virosa, Streptococcus mutans, Porphyromonas asaccharolytica and A. graevenitzii, showed an increasing trend, but most of them were pathogens. CONCLUSIONS: Occupational exposure to high pressure in a helium-oxygen saturation environment decreased the abundance of Bifidobacterium and some SCFA-producing bacteria, and increased the risk of pathogenic bacterial infection. Supplementation of the diver diet with probiotics or prebiotics during saturation diving might prevent these undesirable changes.

Impact of perioperative blood transfusion on survival of patients undergoing laparoscopic gastrectomy for gastric cancer.

PURPOSE: Previous studies have suggested that perioperative blood transfusion is associated with poor prognosis in patients undergoing radical gastrectomy for gastric cancer. The purpose of this study was to evaluate the impact of blood transfusion on the long-term survival of such patients. METHODS: Short- and long-term outcomes were retrieved from a prospectively collected database of patients who underwent laparoscopic gastrectomy with radical intent for gastric cancer. RESULTS: A total of 309 patients who underwent laparoscopic radical gastrectomy were evaluated. Sixty-one (19.7%) received blood transfusions during or within 30 days after gastrectomy. These patients were typically older, had lower preoperative hemoglobin levels, had a more advanced cancer stage, had more than two comorbidities, had a higher rate of postoperative 30-day complications, and had a higher conversion rate. The overall survival (OS) (p=0.040) and disease-free survival (DFS) (p=0.004) were significantly decreased in patients who received blood transfusions. Multivariate analysis revealed that perioperative blood transfusion was not independently associated with decreased OS and DFS but that cancer stage and having more than two comorbidities were independent risk factors. CONCLUSION: Perioperative blood transfusion was associated with decreased OS and DFS in this patient series, but this apparently reflected the relatively poor medical condition of these patients requiring gastrectomy and was not a causative relationship.

Effect of direct current pulse stimulating acupoints of JiaJi (T10-13) and Ciliao (BL 32) with Han's Acupoint Nerve Stimulator on labour pain in women: a randomized controlled clinical study.

OBJECTIVE: To assess the clinical effect and safety of direct current (DC) pulse produced by Han's Acupoint Nerve Stimulator in reduction (HANS) of labor pain. METHODS: Totally 120 participants were enrolled in this clinical trial, and were randomly divided into 4 groups including: HANS group, patient controlled intravenous analgesia (PCIA) group, patient-controlled epidural analgesia (PCEA) group and control group. The HANS group was treated by stimulating the acupoints of JiaJi (T10-L3) and Ciliao (BL 32) with DC pulse of 100 Hz and 15-30 mA produced by a portable battery-powered Han's Acupoint Nerve Stimulator for 30 min. The PCIA group was intravenously infused Ondansetron (8 mg) for 5 min, then tramadol injection (1.5 mg/kg) was slowly dripped by using BaxterAP II electronic pump with 50 mL tramadol (0.70%) + ondansetron (8 mg), background infusion 2 mL/h, PCA dose of 2 mL, lockout interval of 10 min. In PCEA group, women received intrathecal injection ropivacaine (3 mg) in L2-3, and epidural catheter was connected to BaxterAP II electronic pump, with 100 mL Ropivacaine (0.1%) and Sufentanil (50 ug), background infusion 5 mL, Patient controlled analgesia (PCA) dose of 5 mL, lockout interval of 10 min. The control group was not received analgesia. The visual analogue scale (VAS), stage and manner of labor, Apgar score of newborn, neonatal weights, oxytocin dosage, postpartum hemorrhage and side effects were monitored in all groups. RESULTS: The vital signs were all stable in the four analgesic groups. After analgesia, there was statistical difference in VAS score between HANS group and control group, between PCEA group and the control group, between PCIA group and control group. The analgesic effect in the PCEA group was significantly better than that of other two groups. The second stage of labor in the PCEA group was longer than the other three groups, showing significant difference between them. The Apgar score of newborn 1 min after birth in the PCIA group was slightly lower than that of the other two groups, showing significant difference between them. The neonatal weights between four groups were not significantly different. The rate of cesarean section in the control group was significantly higher than that of the labor analgesia group, there was statistically difference in four groups. The number of PCIA group that used oxytocin was lower than that of other three groups. There was no significant difference in postpartum hemorrhage between four groups. The side effects of the PCEA group were itching, uroschesis and neonatal asphyxia and PCIA group were nausea and vomiting and neonatal asphyxia. However, fewer side-effects were observed in the HANS group. CONCLUSION: The DC pulse produced by HANS may be a non-pharmacological alternative to labor pain with fewer side effects.

The Impact of Sarcopenia on the Clinical Outcomes of Percutaneous Kyphoplasty in Patients With Osteoporotic Vertebral Compression Fracture: A Retrospective Cohort Study.

Objective: This study aimed to explore the impact of sarcopenia on clinical outcomes after percutaneous kyphoplasty (PKP) for osteoporotic vertebral compression fracture (OVCF). Methods: We retrospectively analyzed the medical records of patients with single-segment OVCF who underwent percutaneous kyphoplasty (PKP) between September 2021 and August 2022. Patients were categorized into a sarcopenia group (43 patients) and a non-sarcopenia group (125 patients) based on their Advanced Skeletal Muscle Index (ASMI). Clinical and radiological data were collected and analyzed. Results: There were no significant differences between the sarcopenia and non-sarcopenia groups in age, sex, bone mineral density (BMD), body mass index (BMI), fractured segment, fracture type, surgical approach, bone cement volume, bone cement distribution, comorbidities, preoperative and immediate postoperative VAS and ODI scores (P > .05). However, the time to ambulation, hospital stays, VAS and ODI scores at follow-up, excellent/good rate, and the incidence of residual pain and re-fractures in the non-sarcopenia group were significantly better than those in the sarcopenia group (P < .05). Meanwhile, radiological outcomes, including regional kyphosis and vertebral height loss rate, were significantly better in the non-sarcopenia group than in the sarcopenia group at 6 and 12 month follow-ups (P < .05). Conclusion: Clinical outcomes after PKP in patients with OVCF could be negatively affected by sarcopenia. Therefore, prevention and treatment of sarcopenia should be actively considered in the management of patients with OVCF.

Comparison of clinical outcomes between unilateral biportal endoscopic discectomy and percutaneous endoscopic interlaminar discectomy for migrated lumbar disc herniation at lower lumbar spine: a retrospective controlled study.

BACKGROUND: Both Unilateral Biportal Endoscopic Discectomy (UBED) and Percutaneous Endoscopic Interlaminar Discectomy (PEID) have resulted in favorable clinical outcomes in the management of LDH. The aim of this study is to comprehensively compare the efficacy of UBED and PEID in treating migrated LDH in the lower lumbar spine, with a specific focus on high-grade migrated LDH. METHODS: 96 patients who underwent UBED (31 cases) and PEID (65 cases) procedures were enrolled in the study. All patients received a minimum follow-up period of 6 months. Clinical outcomes of the patients were assessed with incision length, operation time, total hemoglobin loss, hospital stay, intraoperative fluoroscopy times, visual analogue scale (VAS) for lower back and leg pain, Oswestry disability index (ODI), modified MacNab criteria, complications, area of lamina loss and increased intervertebral height. RESULTS: The VAS scores for lower back and leg pain and ODI significantly decreased in both groups after the operation. Preoperatively, at 1 day, 1 month, and 6 months after the procedure, the VAS and ODI scores exhibited no significant differences between the two groups. There was no significant difference in terms of modified MacNab criteria, area of lamina loss, and increased intervertebral height. The UBED group had a longer incision length, operation time and postoperative hospital stay, and fewer intraoperative fluoroscopy times than to the PEID group. Complications were noted in both groups throughout the follow-up period, but there was no significant difference in the rate of complications. Moreover, there were no notable differences in clinical outcomes between the two groups in the high-grade migrated LDH. CONCLUSIONS: Both UBED and PEID could achieve favorable clinical outcomes for treating migrated LDH at the lower lumbar spine. Despite the longer operative time and postoperative hospital stay associated with the UBED group, UBED remains safe and innovative for treating migrated LDH at the lower lumbar spine.

The therapeutic effect of sufficient oxygen-rich PRP injection in facial rejuvenation by multiple objective evaluations in 26 cases.

Background: Ozone can enhance the expression of some growth factors (GFs) in platelet rich plasma (PRP), recent study showed oxygen-rich PRP (ozonized PRP) have better therapeutic effects on bone and joint diseases. PRP injection has been widely used in the treatment of facial rejuvenation, but the efficacy of sufficient oxygen-rich PRP in facial rejuvenation has not been studied. Objective: Firstly, we examined whether ozone treatment can increase the concentration of GFs of PRP in vitro. And then a variety of subjective and objective detection methods were used to evaluate the effect of sufficient(10-12 mL each time for the injection of face and neck) oxygen-rich (ozonized PRP) PRP injection in facial rejuvenation by follow-up for 6 months. At last, we investigated the satisfaction, side effects and pain score of the treatment through a questionnaire survey. Methods: The concentration of main GFs in PRP treated with different dose of ozone in vitro was measured by ELISA. Clinical picture, the collagen thickness of dermis by reflectance confocal microscope(RCM), skin conditions (including spots, ultraviolet (UV) spots, brown spots, red area, pores, wrinkles, texture and porphyrin) by VISIA were collected before treatment and each month follow-up visit after treatment until 6-month follow-up period was finished. Patients' satisfaction, side effects and pain score were collected at the end of follow-up period. Results: PRP treated by high-dose ozone (57 µg/mL, ozone/PRP volume ratio:1/1) in vitro showed a significant increase in endothelial growth factor (EGF) and transforming growth factor-ß (TGF-ß) compared to baseline(P < 0.05). Collagen thickness of forehead, cheek and neck improved significantly compare to the baseline until to the 6 months after treatment. Spots, UV spots, brown spots, red area and texture improved significantly compare to the baseline(P < 0.05). All of participants reported improvement and have a median pain score of 4.19. No serious adverse events were observed. Conclusions: Ozone treatment can increase the concentration of GFs such as EGF and TGF-ß in PRP in vitro. Sufficient oxygen-rich PRP injection may be an effective and promising method to treat facial rejuvenation.

Percutaneous Vertebroplasty for Cervical Symptomatic Hemangiomas and Spinal Metastases: A Case Series and Literature Review.

OBJECTIVE: Percutaneous vertebroplasty (PVP) is a commonly used technique for the treatment of spinal diseases, but it is rarely employed for cervical lesions. This study presents a case series and a literature review to evaluate the efficacy of cervical PVP. METHODS: From August 2013 to January 2023, 14 patients underwent cervical PVP in the author's institution. The mean postoperative follow-up time was 20.3 ± 12.1 months (ranging from 5 to 41 months). The pain status and quality of life were assessed preoperatively, postoperatively, and during follow-up using the Visual Analog Scale and Neck Disability Index. Additionally, complications that occurred during the study period were documented. RESULTS: The series of cases included 9 cases of hemangiomas and 5 cases of spinal metastases. The common symptom was axial pain in the neck. All patients were successfully treated with PVP. Visual analog scale scores decreased from 6.6 ± 0.8 preoperatively to 1.9 ± 0.8 at 24 hours postoperatively and to 2.4 ± 1.2 at the last follow-up (P < 0.01). Neck Disability Index decreased from 22.3% ± 8.9% preoperatively to 7.6% ± 8.1% at 24 hours postoperatively and to 6.0% ± 7.2% at 12-month follow-up (P < 0.01). After the operation, a case of dysphagia occurred, but no major complications were observed during the follow-up period. CONCLUSIONS: Cervical PVP via the anterolateral approach is a safe option for the treatment of cervical symptomatic hemangiomas and spinal metastases with limited invasiveness. It is effective in relieving pain and improving quality of life.

Radiology report generation with medical knowledge and multilevel image-report alignment: A new method and its verification.

Medical report generation is an integral part of computer-aided diagnosis aimed at reducing the workload of radiologists and physicians and alerting them of misdiagnosis risks. In general, medical report generation is an image captioning task. Since medical reports have long sequences with data bias, the existing medical report generation models lack medical knowledge and ignore the interaction alignment between the two modalities of reports and images. The current paper attempts to mitigate these deficiencies by proposing an approach based on knowledge enhancement with multilevel alignment (MKMIA). To this end, it includes a knowledge enhancement (MKE) module and a multilevel alignment module (MIRA). Specifically, the MKE deals with general medical knowledge (MK) and historical knowledge (HK) obtained via data training. The general knowledge is embedded in the form of a dictionary with characteristic organs (referred to as Key) and organ aliases, disease symptoms, etc. (referred to as Value). It provides explicit exception candidates to mitigate data bias. Historical knowledge ensures the comparison of similar cases to provide a better diagnosis. MIRA furnishes coarse-to-fine multilevel alignment, reducing the gap between image and text features, improving the knowledge enhancement module's performance, and facilitating the generation of lengthy reports. Experimental results on two radiology report datasets (i.e., IU X-ray and MIMIC-CXR) proved the effectiveness of the proposed approach, achieving state-of-the-art performance.

Exosomal LncRNA TM7SF3-AU1 Aggravates White Matter Injury via MiR-702-3p/SARM1 Signaling After Subarachnoid Hemorrhage in Rats.

Subarachnoid hemorrhage (SAH) is a devastating disease associated with a high mortality and morbidity. Exosomes have been considered as a potential therapeutic target for SAH. However, the effect of exosomes in SAH remains to be elucidated. In this study, we focused on investigating the effect of plasma exosomal lncRNA TM7SF3-AU1 in white matter injury after SAH. The SAH model was established by means of endovascular perforation. Exosomes were extracted from rat plasma samples. The expression of RNAs in the exosomes was detected by the transcriptomic microarray. Differentially expressed circRNA, lncRNA, and mRNA were obtained. The ceRNA network showed that the lncRNA TM7SF3-AU1 and miR-702-3p were closely associated with SARM1. Knocking down TM7SF3-AU1 promoted the expression of miR-702-3p and suppressed the expression of SARM1, and knocking down TM7SF3-AU1 also attenuated white matter injury after SAH. In addition, knocking down TM7SF3-AU1 improved the neurological deficits in locomotion, anxiety, learning, memory, and electrophysiological activity after SAH. Mechanistically, TM7SF3-AU1 was able to absorb miR-702-3p, which directly bind the SARM1 mRNA. Furthermore, the white matter injury attenuated by knockdown of TM7SF3-AU1 was partially reversed by the miR-702-3p antagomir in SAH rats. Taken together, this study showed that TM7SF3-AU1 acts as a sponge for miR-702-3p, reducing the inhibitory effect of miR-702-3p on SARM1, resulting in increased SARM1 expression and thus leading to white matter injury after SAH. Our study provides new insights into exosome-associated white matter injury. It also highlights TM7SF3-AU1 as a potential therapeutic target for white matter injury after SAH.

ETAR silencing ameliorated neurovascular injury after SAH in rats through ERK/KLF4-mediated phenotypic transformation of smooth muscle cells.

Subarachnoid haemorrhage (SAH) is a devastating cerebrovascular disease which has a high morbidity and mortality. The phenotypic transformation of smooth muscle cells (SMCs) lead to neurovascular injury after SAH. However, the underlying mechanism remains unclear. In the present study, we aimed to investigate the potential role of ET-1/ETAR on the phenotypic transformation of SMCs after SAH. The models of SAH were established in vivo and vitro. We observed ET-1 secretion by endothelial cells was increased, and the phenotypic transformation of SMCs was aggravated after SAH. Knocking down ETAR inhibited the phenotypic transformation of SMCs, decreased the migration ability of SMCs in vitro. Moreover, Knocking down ETAR ameliorated cerebral ischaemia and alleviated dysfunction of neurological function in vivo. In addition, Exogenous ET-1 increased the migration ability of SMCs and aggravated the phenotypic transformation of SMCs in vitro, which were partly reversed by the antagonist of Erk1/2 - SCH772984. Taken together, our results demonstrated that endothelial ET-1 aggravated the phenotypic transformation of SMCs after SAH. Knocking down ETAR inhibited the phenotypic transformation of SMCs through ERK/KLF4 thus ameliorating neurovascular injury after SAH. We also revealed that ET-1/ETAR is a potential therapeutic target after SAH.

Efficacy of Intrawound Treatments to Prevent Surgical Site Infection after Spine Surgery: A Systematic Review and Network Meta-analysis.

BACKGROUND: Intrawound treatments have been reported to have favorable efficacy for preventing surgical site infection (SSI); however, the best strategy remains unknown. OBJECTIVE: The aim of this systematic review and network meta-analysis was to evaluate the efficacy of intrawound treatments to prevent SSI after spine surgery. STUDY DESIGN: A systematic review and network meta-analysis. METHODS: We searched the Cochrane Library, EMbase, PubMed, Chinese Science and Technology Periodical Database (VIP), China National Knowledge Infrastructure (CNKI), and Wanfang Data from the date of inception to March 2, 2020. The randomized controlled trials (RCTs) and cohort studies were identified and extracted by 2 reviewers independently. We performed a traditional pairwise meta-analysis to evaluate overall efficacy of intrawound treatments. Meanwhile, a network meta-analysis was performed to compare and rank the treatment efficacy using frequentist approach. RESULTS: Thirty-three publications (6 RCTs and 27 retrospective cohort studies) were included, involving 22,763 patients. For pairwise meta-analysis, the combined results showed that the intrawound treatment had a significantly lower SSI rate than the control group (CG) (odds ratio [OR] = 0.41; 95% confidence interval [CI], 0.31-0.55). For network meta-analysis, the treatment of vancomycin (VA) (OR = 0.53; 95% CI, 0.39-0.71), povidone-iodine (PI) (OR = 0.10; 95% CI, 0.04 - 0.23), and vancomycin + povidone-iodine (VA+PI) (OR = 0.25; 95% CI, 0.11-0.58) were found to be significantly more efficacious than CG on reduction of SSI rate. PI ranked first on reducing SSI, followed by PI+HP, VA+PI, gentamicin (GM), VA, and hydrogen peroxide (HP); CG ranked last. LIMITATIONS: Firstly, only 6 RCTs are included in this systematic review. Retrospective cohort studies tend to exaggerate the real results, although most of them are high-quality according to the Newcastle-Ottawa Quality Assessment Scale (NOQAS). More high-quality RCTs need to be included to obtain convincing conclusions. Secondly, the population of this study involves both adult and pediatric cohorts, patients with tumor, congenital disease, or degenerative disease. There is no subgroup analysis for ages and type of diseases, which might have influence on the overall pooled analysis. Thirdly, we define the application of saline solution and no intrawound treatment as the control group, which might ignore their heterogeneity. Fourthly, follow-up periods are variable and the sample size of HP is small. Finally, additional research is needed to compare the complications of different treatments and the benefits of various dosages. CONCLUSION: We found that VA and PI show promising results on reducing SSI. PI is recommended as the most efficacious intrawound treatment to prevent SSI after spine surgery.

[Comparison of clinical efficacy of two different pin arrangements for external fixation of femoral neck fracture].

OBJECTIVE: To retrospectively analyze the clinical efficacy of external fixation in the treatment of femoral neck fracture with two different pin layout. METHODS: From April 2000 to April 2018, 140 cases of femoral neck fracture were treated with closed reduction and percutaneous pin external fixation, among them 121 cases were followed up for more than 1 year, including 31 cases in traditional group, 12 males and 19 females, aged 45 to 74(65.4±8.4) years;90 cases in modified group, 39 males and 51 females, aged 12 to 75 (64.5±7.8) years. In traditional group, the first needle was put on the femoral talus, the second and third needles were put under the tension line, and the three needles were not on the same line in the lateral phase; in modified group, the first needle was drilled into the lateralcortex of the femur, obliquely penetrating the distal and proximal end of the femoral talus fracture, and the other two needles were drilled into the medial cortex of the femoral neck and the femoral talus, respectively. The operation time, hospital stay, postoperative ambulation time, femoral neck shortening rate, fracture healing time, fracture healing rate and femoral head necrosis rate of the two groups were observed and compared. Harris hip function score was used one year after operation. RESULTS: These 121 patients were followed-up, the follow up time of traditional group was 13 to 45(30.5±11.4) months;the follow-up time of modified group was 14 to 120(34.5±12.5) months. There was no significant difference in operation time, hospital stay and femoral head necrosis rate between two groups (P>0.05). There were significant differences between two groups in the time of going to the ground, shortening rate of femoral neck, fracture healing time, fracture healing rate and Harris functional score of the hip 1 year after operation (P<0.05). CONCLUSION: Compared with the traditional group, the modified group has the advantages of lower femoral neck shortening rate, shorter fracture healing time, higher fracture healing rate and higher Harris hip function score.