Causal inference of the effect of plasma proteins on the incidence of oral cancer: two-sample Mendelian randomization.

OBJECTIVE: This study is aimed to investigate the causal relationship between plasma proteins and oral cancer risk using two-sample MR (Mendelian randomization). METHODS: Summary-level GWAS (genome-wide association study) data on plasma protein levels (4,907 proteins) and oral cancer (6,034 cases, 6,585 controls) of European ancestry were utilized. SNPs (single nucleotide polymorphisms) associated with proteins at genome-wide significance were selected as instrumental variables. Multiple MR methods including IVW (inverse-variance weighted), MR-Egger, weighted median, simple mode and weighted mode were applied to estimate causal effects. Sensitivity analyses were conducted. RESULTS: Eight plasma proteins (CCDC167, MID2, NDRG4, PEAR1, PIAS4, RCAN1, SAMHD1 and TNMD) were identified to have significant causal associations with oral cancer risk. NDRG4, RCAN1, SAMHD1 and TNMD were associated with increased oral cancer risk while PEAR1 was associated with decreased risk. The causal estimates were consistent across different methods. Sensitivity analyses indicated the results were robust without significant heterogeneity or horizontal pleiotropy. Multivariable MR adjusting for smoking, alcohol intake and periodontal disease showed CCDC167, MID2, NDRG4, PEAR1, PIAS4 and SAMHD1 still had direct effects on oral cancer. CONCLUSION: This two-sample MR study provides evidence for potentially causal effects of several plasma proteins on oral cancer risk. The identified proteins may serve as biomarkers and shed light on biological mechanisms underlying oral carcinogenesis. Further research is warranted to validate and extend these findings.

The antitumor effects of herbal medicine Triphala on oral cancer by inactivating PI3K/Akt signaling pathway: based on the network pharmacology, molecular docking, in vitro and in vivo experimental validation.

BACKGROUND: This research aimed to investigate the anti-tumor effects and underlying genetic mechanisms of herbal medicine Triphala (TRP) in oral squamous cell carcinoma (OSCC). METHODS: The target genes of Triphala (TRP) in oral squamous cell carcinoma (OSCC) were identified, and subsequent functional enrichment analysis was conducted to determine the enriched signaling pathways. Based on these genes, a protein-protein interaction network was constructed to identify the top 10 genes with the highest degree. Genes deregulated in OSCC tumor samples were identified to be hub genes among the top 10 genes. In vitro experiments were performed to investigate the influence of TRP extracts on the cell metabolic activity, migration, invasion, apoptosis, and proliferation of two OSCC cell lines (CAL-27 and SCC-9). The functional rescue assay was conducted to investigate the effect of applying the inhibitor and activator of an enriched pathway on the phenotypes of cancer cells. In addition, the zebrafish xenograft tumor model was established to investigate the influence of TRP extracts on tumor growth and metastasis in vivo. RESULTS: The target genes of TRP in OSCC were prominently enriched in the PI3K-Akt signaling pathway, with the identification of five hub genes (JUN, EGFR, ESR1, RELA, and AKT1). TRP extracts significantly inhibited cell metabolic activity, migration, invasion, and proliferation and promoted cell apoptosis in OSCC cells. Notably, the application of TRP extracts exhibited the capacity to downregulate mRNA and phosphorylated protein levels of AKT1 and ESR1, while concomitantly inducing upregulation of mRNA and phosphorylated protein levels in the remaining three hub genes (EGFR, JUN, and RELA). The functional rescue assay demonstrated that the co-administration of TRP and the PI3K activator 740Y-P effectively reversed the impact of TRP on the phenotypes of OSCC cells. Conversely, the combination of TRP and the PI3K inhibitor LY294002 further enhanced the effect of TRP on the phenotypes of OSCC cells. Remarkably, treatment with TRP in zebrafish xenograft models demonstrated a significant reduction in both tumor growth and metastatic spread. CONCLUSIONS: Triphala exerted significant inhibitory effects on cell metabolic activity, migration, invasion, and proliferation in OSCC cell lines, accompanied by the induction of apoptosis, which was mediated through the inactivation of the PI3K/Akt pathway.

Controllable Adaptive Molybdate-Oligosaccharide Nanoparticles Regulate M2 Macrophage Mitochondrial Function and Promote Angiogenesis via PI3K/HIF-1α/VEGF Pathway to Accelerate Diabetic Wound Healing.

The complex wound environment of diabetic wounds leads to poor treatment efficacy, and the inflammatory disorders and vascular injury are the primary causes of death in such patients. Herein, a sprayable, controllable adaptive, pH-responsive nanosystem of molybdate and oligosaccharide (CMO) is specially developed as an immunomodulatory and angiogenesis-promotion material for diabetic wound healing. CMO exhibited pH-responsive release of Mo2+ and oligosaccharide (COS), specifically in response to the alkalescent environment observed in diabetic wounds. CMO provide an anti-inflammatory environment by promoting M2 polarization through significantly stimulating macrophage mitochondrial function. Specifically, CMO with a certain concentration reduce reactive oxygen species (ROS) and tumor necrosis factor α (TNF-α) expression, and upregulated mitochondrial membrane potential (MMP), superoxide dismutase (SOD), and interleukin 10 (IL-10) expression in macrophages. Moreover, CMO facilitate angiogenesis via upregulating the PI3K/HIF-1α/VEGF pathway-a critical process for the formation of new blood vessels that supply nutrients and oxygen to the healing tissue. Remarkably, CMO promote cell viability and migration of endothelial cells, and enhance the expression of angiogenic genes. In vitro and in vivo studies suggest this simple but powerful nanosystem targeting mitochondrial function has the potential to become an effective treatment for diabetic wound healing.

The genes regulating sensitivity of tumor cells to T cell-mediated killing: could they be potential personalized immunotherapeutic targets in head and neck squamous cell carcinoma?

OBJECTIVE: To identify the pivotal genes, specifically the STTK genes, that govern the sensitivity of tumor cells to T cell-mediated killing in Head and Neck Squamous Cell Carcinoma (HNSC). METHODS: The differentially expressed genes (DEGs) in HNSC and STTK genes were overlapped to obtain the DE-STTK genes. Univariate and LASSO regression analyses were conducted to identify the pivotal DE-STTK genes that serve as hubs in HNSC (i.e., hub DE-STTK genes). The risk model was established to divide HNSC tumor samples into high- and low-risk groups based on the hub DE-STTK genes. Further investigations were carried out by examing the expression level, prognostic values, diagnostic values, enriched signaling pathways, correlation with tumor mutation burden (TMB), and association with tumor immune infiltration cells (TIICs). RESULTS: A total of 71 genes were found to be overlapped between DEGs in HNSC and STTK genes. Lasso regression analysis identified 9 hub genes which were MYF6, AATF, AURKA, CXCL9, DPM2, MYO1B, NCBP2, TNFRSF12A, and TRAF1. The network analysis of hub DE-STTK genes-pathway reveals that these 9 hub genes exhibit enrichment in multiple signaling pathways, including toll-like receptor signaling, TNF signaling, NF-kappa B signaling, cytokine-cytokine receptor interaction, spliceosome, mRNA surveillance pathway, nucleocytoplasmic transport, GPI-anchor biosynthesis, as well as N-Glycan biosynthesis. The Pearson correlation analysis showed that the majority of correlations between 9 hub DE-STTK genes and immune cells were positive. CONCLUSION: The 9 identified hub DE-STTK genes (MYF6, AATF, AURKA, CXCL9, DPM2, MYO1B, NCBP2, TNFRSF12A, and TRAF1) are presumptively implicated in the modulation of tumor immunity in HNSC. These genes, along with their enriched pathways, hold promise as potential personalized immunotherapeutic targets for the treatment of HNSC, thereby offering novel avenues for therapeutic intervention in this malignancy.

[Clinical analysis of distal radius core decompression for chronic wrist pain].

Objective: To investigate the effectiveness of distal radius core decompression in the treatment of chronic wrist pain caused by various etiologies. Methods: A retrospective analysis was performed for the clinical data of 10 patients with chronic wrist pain treated with distal radial core decompression between January 2018 and December 2021. There were 6 males and 4 females with an average age of 37.4 years (range, 21-55 years). The disease duration ranged from 7 to 72 months, with an average of 26.5 months. Preoperative MRI examination showed that 10 cases had bone marrow edema at the distal radius on the affected side, and 8 cases had bone marrow edema in the carpal bones such as scaphoid and lunate bone. Among them, 3 patients had a history of wrist fracture, and 2 patients had Kienböck diseases (1 case each in stage ⅡB and stage ⅢA). Three cases were combined with triangular fibrocartilage complex (TFCC) type 1A injury. Two cases were combined with osteoarthritis, 1 of them was complicated with severe traumatic arthritis, the wrist arthroscopy showed that the TFCC was completely lost and could not be repaired, and the cartilage of the lunate bone and the ulnar head were severely worn.Visual analogue scale (VAS) score was used to evaluate the relief of wrist pain before operation, at 6 months after operation, and at last follow-up, and the range of motion of the affected wrist in dorsiflexion, palmar flexion, ulnar deviation, and radial deviation was measured. The degree of bone marrow edema was evaluated according to T1WI, T2WI, and STIR sequences of MRI. Results: All the patients were followed up 12-22 months, with an average of 16.4 months. Except for 1 patient who experienced persistent wrist joint pain and limited mobility after operation, the remaining 9 patients showed significant improvement in pain symptoms and wrist joint mobility. The VAS score and range of motion of wrist dorsiflexion, palmar flexion, ulnar deviation, and radial deviation at 6 months after operation and at last follow-up were significantly improved when compared with those before operation, the VAS score and the range of motion of wrist ulnar deviation and radial deviation at last follow-up were further improved when compared with those at 6 months after operation, all showing significant differences ( P<0.05). There was no significant difference in wrist dorsiflexion and palmar flexion between at 6 months after operation and at last follow-up ( P>0.05). Bone marrow edema was improved in 6 patients on MRI at 6 months after operation, and was also improved in other patients at last follow-up. Conclusion: For chronic wrist pain caused by a variety of causes, distal radius core decompression can directly reduce the pressure of the medullary cavity of the distal radius, improve the blood supply of the corresponding distal structure, significantly alleviate chronic wrist pain, and provide an option for clinical treatment.

Ultrasound-induced cavitation renders prostate cancer cells susceptible to hyperthermia: Analysis of potential cellular and molecular mechanisms.

Background: Focused ultrasound (FUS) has become an important non-invasive therapy for prostate tumor ablation via thermal effects in the clinic. The cavitation effect induced by FUS is applied for histotripsy, support drug delivery, and the induction of blood vessel destruction for cancer therapy. Numerous studies report that cavitation-induced sonoporation could provoke multiple anti-proliferative effects on cancer cells. Therefore, cavitation alone or in combination with thermal treatment is of great interest but research in this field is inadequate. Methods: Human prostate cancer cells (LNCap and PC-3) were exposed to 40 s cavitation using a FUS system, followed by water bath hyperthermia (HT). The clonogenic assay, WST-1 assay, and Transwell® invasion assay, respectively, were used to assess cancer cell clonogenic survival, metabolic activity, and invasion potential. Fluorescence microscopy using propidium iodide (PI) as a probe of cell membrane integrity was used to identify sonoporation. The H2A.X assay and Nicoletti test were conducted in the mechanism investigation to detect DNA double-strand breaks (DSBs) and cell cycle arrest. Immunofluorescence microscopy and flow cytometry were performed to determine the distribution and expression of 5α-reductase (SRD5A). Results: Short FUS shots with cavitation (FUS-Cav) in combination with HT resulted in, respectively, a 2.2, 2.3, and 2.8-fold decrease (LNCap) and a 2.0, 1.5, and 1.6-fold decrease (PC-3) in the clonogenic survival, cell invasiveness and metabolic activity of prostate cancer cells when compared to HT alone. FUS-Cav immediately induced sonoporation in 61.7% of LNCap cells, and the combination treatment led to a 1.4 (LNCap) and 1.6-fold (PC-3) increase in the number of DSBs compared to HT alone. Meanwhile, the combination therapy resulted in 26.68% of LNCap and 31.70% of PC-3 with cell cycle arrest in the Sub-G1 phase and 35.37% of PC-3 with cell cycle arrest in the G2/M phase. Additionally, the treatment of FUS-Cav combined with HT block the androgen receptor (AR) signal pathway by reducing the relative Type I 5α-reductase (SRD5A1) level to 38.28 ± 3.76% in LNCap cells, and decreasing the relative Type III 5α-reductase 3 (SRD5A3) level to 22.87 ± 4.88% in PC-3 cells, in contrast, the relative SRD5A level in untreated groups was set to 100%. Conclusion: FUS-induced cavitation increases the effects of HT by interrupting cancer cell membranes, inducing the DSBs and cell cycle arrest, and blocking the AR signal pathway of the prostate cancer cells, with the potential to be a promising adjuvant therapy in prostate cancer treatment.

Periodontal Inflamed Surface Area Is Associated With Increased Gestational Blood Pressure and Uric Acid Levels Among Pregnant Women From Rural North China.

Background: Periodontal disease has been associated with gestational complications and both conditions have a high prevalence in rural populations from developing regions. A cross-sectional study was carried out to explore the relationship between periodontal inflamed surface area (PISA), blood pressure (BP), and, serum uric acid levels (UA) in a group of rural North Chinese pregnant women in the third trimester of pregnancy. Methods: Three hundred and thirty-five rural women aged 20-34 years, with normal body mass index (BMI) were examined in a cross-sectional study during their third trimester of gestation. Exclusion criteria were history of pregnancy complications, multiple pregnancy, smoking habits, diabetes, hypertension or any known infectious disease. Socio-demographic variables, including age and socioeconomic status (SES), systolic blood pressure (SBP) and diastolic blood pressure (DBP) readings, serum UA levels, and PISA values were recorded. A structural equation model was implemented with two constructed latent variables including "Dem" (comprising of age and SES category to represent unobserved demographic variables) and, "BP" (comprising of SBP and DBP to account for measurement error and lack of multiple BP readings). The model accounted for co-variance of BP and UA, and implemented simultaneous regressions for BP and UA as outcomes, upon Dem and PISA values as exogenous variables. Results: The median PISA score was 1,081.7 (IQR = 835.01), reflecting high levels of periodontal inflammation in the sample. SEM showed a significant association of PISA with BP (estimate = 0.011, 95% CI = 0.009-0.012 p < 0.001) and UA (estimate = 0.001, 95% CI = 0.001-0.001, p < 0.001). Conclusion: Higher PISA values were significantly associated with higher blood pressure and uric acid levels among rural pregnant women in a cross-sectional sample from a center in North China after accounting for a latent demographic construct derived from age and SES.

Implications of Human Antimicrobial Peptide Defensin Beta-1 in Clinical Oral Squamous Cell Carcinoma Patients via an Integrated Bioinformatics Approach.

BACKGROUND: The human antimicrobial peptide defensin beta 1 (DEFB1) has been found to play antimicrobial and anti-inflammatory roles in oral diseases; however, its tumor-regulating role in oral squamous cell carcinoma (OSCC) has not yet been researched by using an integrative bioinformatics approach. OBJECTIVE: To investigate the regulating mechanisms of the DEFB1 gene in OSCC in terms of its expression patterns, prognostic values, biological functions, and implication for tumor immunity. METHODS: The DEFB1 gene expression pattern and regulatory involvement in OSCC were investigated using publically accessible data from TCGA database. R software tools and public web servers were utilized to conduct statistical analysis of data from cancer and noncancerous samples. RESULTS: DEFB1 was found to be significantly downregulated in OSCC tumor samples compared with healthy control oral samples. The DEFB1 gene was found associated with the prognostic outcomes of OSCC, and its upregulation represented better survival outcome. Gene set enrichment analysis (GSEA) results showed that DEFB1-significantly correlated genes were mainly enriched in four signaling pathways mediating the antitumor role of DEFB1 in OSCC, including extracellular matrix-related pathway, RTK/PI3K/AKT/mTOR pathway, keratinization, and cytokine-related pathway. The gene-gene interaction network showed that DEFB1 was closely correlated with several genes, for example, CCR6 (C-C motif chemokine receptor 6), CXCL1 (C-X-C motif chemokine ligand 1), MAP4K2 (mitogen-activated protein kinase kinase kinase kinase 2), PTGER3 (prostaglandin E receptor 3), and MMP7 (matrix metallopeptidase 7). Moreover, DEFB1 was found to be involved in the tumor immunity of OSCC by regulating the function of tumor macrophage cells, mast cells, T cells, and NK cells. CONCLUSIONS: Given the dysregulation, prognostic value, and tumor progression-related biological pathway alteration, indicating the tumor immune-modulatory role of DEFB1 in OSCC, the DEFB1 gene should be regarded as a potential therapeutic target for treating oral cancer.

Protective Effect of Triphala against Oxidative Stress-Induced Neurotoxicity.

BACKGROUND: Oxidative stress is implicated in the progression of many neurological diseases, which could be induced by various chemicals, such as hydrogen peroxide (H2O2) and acrylamide. Triphala is a well-recognized Ayurvedic medicine that possesses different therapeutic properties (e.g., antihistamine, antioxidant, anticancer, anti-inflammatory, antibacterial, and anticariogenic effects). However, little information is available regarding the neuroprotective effect of Triphala on oxidative stress. MATERIALS AND METHODS: An in vitro H2O2-induced SH-SY5Y cell model and an in vivo acrylamide-induced zebrafish model were established. Cell viability, apoptosis, and proliferation were examined by MTT assay, ELISA, and flow cytometric analysis, respectively. The molecular mechanism underlying the antioxidant activity of Triphala against H2O2 was investigated dose dependently by Western blotting. The in vivo neuroprotective effect of Triphala on acrylamide-induced oxidative injury in Danio rerio was determined using immunofluorescence staining. RESULTS: The results indicated that Triphala plays a neuroprotective role against H2O2 toxicity in inhibiting cell apoptosis and promoting cell proliferation. Furthermore, Triphala pretreatment suppressed the phosphorylation of the mitogen-activated protein kinase (MARK) signal pathway (p-Erk1/2, p-JNK1/2, and p-p38), whereas it restored the activities of antioxidant enzymes (superoxide dismutase 1 (SOD1) and catalase) in the H2O2-treated SH-SY5Y cells. Consistently, similar protective effects of Triphala were observed in declining neuroapoptosis and scavenging free radicals in the zebrafish central neural system, possessing a critical neuroprotective property against acrylamide-induced oxidative stress. CONCLUSION: In summary, Triphala is a promising neuroprotective agent against oxidative stress in SH-SY5Y cells and zebrafishes with significant antiapoptosis and antioxidant activities.

Focused Ultrasound-Induced Cavitation Sensitizes Cancer Cells to Radiation Therapy and Hyperthermia.

Focused ultrasound (FUS) has become an important non-invasive therapy for solid tumor ablation via thermal effects. The cavitation effect induced by FUS is thereby avoided but applied for lithotripsy, support drug delivery and the induction of blood vessel destruction for cancer therapy. In this study, head and neck cancer (FaDu), glioblastoma (T98G), and prostate cancer (PC-3) cells were exposed to FUS by using an in vitro FUS system followed by single-dose X-ray radiation therapy (RT) or water bath hyperthermia (HT). Sensitization effects of short FUS shots with cavitation (FUS-Cav) or without cavitation (FUS) to RT or HT (45 °C, 30 min) were evaluated. FUS-Cav significantly increases the sensitivity of cancer cells to RT and HT by reducing long-term clonogenic survival, short-term cell metabolic activity, cell invasion, and induction of sonoporation. Our results demonstrated that short FUS treatment with cavitation has good potential to sensitize cancer cells to RT and HT non-invasively.

Focus on Notoginsenoside R1 in Metabolism and Prevention Against Human Diseases.

Notoginsenoside (NG)-R1 is one of the main bioactive compounds from Panax notoginseng (PN) root, which is well known in the prescription for mediating the micro-circulatory hemostasis in human. In this article, we mainly discuss NG-R1 in metabolism and the biological activities, including cardiovascular protection, neuro-protection, anti-diabetes, liver protection, gastrointestinal protection, lung protection, bone metabolism regulation, renal protection, and anti-cancer. The metabolites produced by deglycosylation of NG-R1 exhibit higher permeability and bioavailability. It has been extensively verified that NG-R1 may ameliorate ischemia-reperfusion (IR)-induced injury in cardiovascular and neuronal systems mainly by upregulating the activity of estrogen receptor α-dependent phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) and nuclear factor erythroid-2-related factor 2 (NRF2) pathways and downregulating nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. However, no specific targets for NG-R1 have been identified. Expectedly, NG-R1 has been used as a main bioactive compound in many Traditional Chinese Medicines clinically, such as Xuesaitong, Naodesheng, XueShuanTong, ShenMai, and QSYQ. These suggest that NG-R1 exhibits a significant potency in drug development.

Transfers of the Ipsilateral C7 Plus the Spinal Accessory Nerve Versus Triple Nerve Transfers for Treatment of C5-C6 Avulsion of the Brachial Plexus.

PURPOSE: To compare the long-term results of transfers of the ipsilateral C7 (IC7) plus spinal accessory nerve (SAN) with those of triple nerve transfers (TNT) using one fascicle of the ulnar nerve to the biceps motor branch (Oberlin's procedure), SAN transferred to the suprascapular nerve, and transfer of the long head of triceps nerve branch to the anterior branch of axillary nerve to treat C5-C6 avulsion of the brachial plexus. METHODS: The IC7 group included 9 patients undergoing transfers of IC7 to the upper trunk and SAN to the suprascapular nerve. Median age at surgery was 26 years and interval between injury and surgery was 2.8 months. Patients were observed for a median of 118 months. The TNT group contained 13 patients, median age 33 years; interval between injury and surgery was 3.1 months. Patients were observed for a median of 103 months. RESULTS: In the IC7 group, median shoulder abduction was 105° and median external rotation of the shoulder was 64°, which was similar to that of the TNT group (89° abduction and 58° external rotation). Eight of nine patients recovered at least M3 (Modified Narakas scale) strength of deltoid in the IC7 group, which was similar to that in the TNT group (11 of 13 patients). Six of nine patients achieved at least Medical Research Council grade 3 (MRC3) strength of biceps in the IC7 group, which was similar to that in the TNT group (11 of 13 patients). Of 4 patients in the IC7 group with a preoperative latissimus dorsi strength of MRC3 or less, 3 gained a deltoid strength of M3 or less, and 3 a biceps strength of MRC2 or less. CONCLUSIONS: Transfers of IC7 plus SAN provide results comparable to those of TNT for treatment of C5-C6 avulsion. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

[Advances in diagnosis and treatment of acute scaphoid fractures].

OBJECTIVE: To review the advances in diagnosis and treatment of acute scaphoid fractures. METHODS: The characteristic, classification, diagnosis, and treatment of acute scaphoid fractures were reviewed and summarized. RESULTS: As one of the common fracture in hand, scaphoid fractures are generally classified as either undisplaced and stable or displaced and unstable. CT and MRI has best diagnostic specificity and sensitivity respectively. Most undisplaced and stable fractures can be treated successfully by plaster immobilization, whereas the displaced and unstable fractures have great prognosis after open reduction and internal fixation. CONCLUSION: Acute scaphoid fractures should be diagnosed and treated at an early stage, and choose the appropriate treatment according to the location and stability of the fracture.

Panax notoginseng Saponins Protect Cerebral Microvascular Endothelial Cells against Oxygen-Glucose Deprivation/Reperfusion-Induced Barrier Dysfunction via Activation of PI3K/Akt/Nrf2 Antioxidant Signaling Pathway.

Oxidative stress plays a critical role in cerebral ischemia/reperfusion (I/R)-induced blood-brain barrier (BBB) disruption. Panax notoginseng saponins (PNS) possess efficient antioxidant activity and have been used in the treatment of cerebral ischemic stroke in China. In this study, we determined the protective effects of PNS on BBB integrity and investigated the underlying mechanism in cerebral microvascular endothelial cells (bEnd.3) exposed to oxygen-glucose deprivation/reperfusion (OGD/R). MTT and LDH release assays revealed that PNS mitigated the OGD/R-induced cell injury in a dose-dependent manner. TEER and paracellular permeability assays demonstrated that PNS alleviated the OGD/R-caused disruption of BBB integrity. Fluorescence probe DCFH-DA showed that PNS suppressed ROS generation in OGD/R-treated cells. Immunofluorescence and western blot analysis indicated that PNS inhibited the degradation of tight junction proteins triggered by OGD/R. Moreover, mechanism investigations suggested that PNS increased the phosphorylation of Akt, the activity of nuclear Nrf2, and the expression of downstream antioxidant enzyme HO-1. All the effects of PNS could be reversed by co-treatment with PI3K inhibitor LY294002. Taken together, these observations suggest that PNS may act as an extrinsic regulator that activates Nrf2 antioxidant signaling depending on PI3K/Akt pathway and protects against OGD/R-induced BBB disruption in vitro.

Dual Nerve Transfers for Restoration of Shoulder Function After Brachial Plexus Avulsion Injury.

The purpose of this study was to investigate the effectiveness of shoulder function restoration by dual nerve transfers, spinal accessory nerve to the suprascapular nerve and 2 intercostal nerves to the anterior branch of the axillary nerve, in patients with shoulder paralysis that resulted from brachial plexus avulsion injury. It was a retrospective analysis to assess the impact of a variety of factors on reanimation of shoulder functions with dual nerve transfers. A total of 19 patients were included in this study. Most of these patients sustained avulsions of C5, C6, and C7 nerve roots (16 patients). Three of them had avulsions of C5 and C6 roots only. Through a posterior approach, direct coaptation of the intercostal nerves and the anterior branch of the axillary nerve was performed, along with accessory nerve transfer to the suprascapular nerve. Satisfactory shoulder function recovery (93.83° of shoulder abduction and 54.00° of external rotation on average) was achieved after a 62-month follow-up. This dual nerve transfer procedure provided us with a reliable and effective method for shoulder function reconstruction after brachial plexus root avulsion, especially C5/C6/C7 avulsion. The level of evidence is therapeutic IV.

[ADVANCES IN NERVE RECONSTRUCTION OF OBSTETRIC BRACHIAL PLEXUS PALSY].

OBJECTIVE: To review the advances in the diagnosis and treatment of obstetric brachial plexus palsy (OBPP). METHODS: The incidence, risk factors, classification, and imaging tests of OBPP and indication, technique, and results of surgery were reviewed and summarized. RESULTS: The incidence of OBPP is not declining in recent years. Birth weight of ≥4 kg, forceps delivery, and prepregnancy body mass index of ≥21 are considered to be major risk factors, and caesarean section delivery seems to be a protective factor. Neurophysiological investigations can be applied to qualitative diagnosis of OBPP, but can not to quantitative one. Sensitivity and specificity of both CT and MRI myelography are about 0.7 and 0.97, respectively. Narakas classification is widely used:C5, 6 injury as type I, C5-7 injury as type Ⅱ, C5-T1 injury as type Ⅲ, C5-T1 injury with Horner's syndrome as type IV. It is generally considered that the brachial plexus exploration should be undertaken for infants without spontaneous recovery of elbow flexion by a maximum of 3 months old; and 10% to 30% of patients may need nerve reconstruction surgery. It is advocated that traumatic neuroma of the upper trunk should be resected with nerve reconstruction. The final evaluation for surgical results should be at minimal 4 years for upper roots and 8 years for total roots. Scales of Mallet, Gilbert, and Raimondi are mostly used for assessing shoulder function, elbow function, and hand function. CONCLUSIONS: Brachial plexus exploration should be undertaken for infants without flexion of elbow at the age of 3 months. Traumatic neuroma (even neuroma-in-continuity) resection followed by microsurgical reconstruction of the brachial plexus is favored.

Sensorimotor cortical changes assessed with resting-state fMRI following total brachial plexus root avulsion.

OBJECTIVE: Peripheral nerve injury can induce immediate and long-standing remodelling of the brain cortex, which may affect outcomes of nerve repair. This study examined changes of corresponding cortical representations in patients with brachial plexus injuries. METHODS: Resting-state fMRI was acquired for 13 adult patients with total brachial plexus root avulsion, three of whom underwent second scans 7 or 8 months later. The time of examination ranged from 1 to 16 months after injuries. Nine healthy adults were enrolled as control. Seed-based functional connectivity was performed for all subjects. RESULTS: For nine patients whose first fMRI was performed from 1 to 4 months after brachial plexus injuries, images showed that their cortical maps of sensorimotor areas corresponding to the hand and arm in the hemisphere contralateral to the injured side had much weaker correlation with the supplementary motor area (SMA) than those ipsilateral to the injured side. Symmetrical maps of bilateral cortical sensorimotor areas corresponding to the hand and arm were observed in other four cases with fMRI tested from 7 to 16 months after injuries. For three of the nine patients with asymmetrical cortical representations, second scans indicated symmetric results or even stronger correlation with SMA in the cerebral cortex contralateral to the injured side. CONCLUSIONS: Total brachial plexus root avulsion causes cortical representations of the brachial plexus to undergo a change from an inactive to an active state. This implies that peripheral deafferentation after brachial plexus injuries will induce corresponding cortical representations to be occupied by adjacent non-deafferented cortical territories.

Optimal time-point for neural stem cell transplantation to delay denervated skeletal muscle atrophy.

INTRODUCTION: Transplantation of neural stem cells (NSCs) is a promising treatment to delay denervated skeletal muscle atrophy; however, the optimal time-point between peripheral nerve injury and NSC transplantation needs to be determined. METHODS: Improvement in rat gastrocnemius muscle function was evaluated after NSCs were transplanted into sectioned distal tibial nerves. We also assessed survival and differentiation. ANOVA was used to compare the mean value of the number of neuron-like cells, cross-sectional area amelioration, the amount of activated fibers, and latency and amplitude of the gastrocnemius compound muscle action potential. RESULTS: The group in which the NSCs were transplanted 1 week after tibial nerve transection had the largest number of neuron-like cells, maximum cross-sectional area amelioration, and maximum amount of activated gastrocnemius fibers compared with all other groups (P < 0.01). CONCLUSIONS: The optimal time-point for NSC transplantation for delaying denervated skeletal muscle atrophy is 1 week after severing the nerve.

[Anatomic study on intercostal nerve transfer to suprascapular nerve].

OBJECTIVE: To investigate the feasibility of the 3rd-6th intercostal nerve transfer to the suprascapular nerve for reconstruction of shoulder abduction. METHODS: Fifteen thoracic walls (30 sides) were collected from cadavers. The 3rd-6th intercostal nerve length which can be dissected between the midaxillary line and midclavicular the transfer distance between the midaxillary line and midpoint of the clavicular bone (prepared point for neurotization) measured. RESULTS: In 30 sides of specimens, the 3rd and 4th intercostal nerves could be obtained between the midaxillary and midclavicular line, the available length of which was significantly greater than the transfer distance (P < 0.01). Six 5th intercostal nerve and 16 sides of 6th intercostal nerve were covered by the costal cartilage before reaching the midclavicular line. The available length of the 5th intercostal nerve was similar to the transfer distance (P > 0.01), while the available the 6th intercostal nerve was significantly less than transfer distance (P < 0.01). The suprascapular nerve could be dissociated turned to the clavicular bone of more than 2 cm. The whole length of the available 5th intercostal nerve length and length (2 cm) of suprascapular nerve was significantly greater than the transfer distance (P < 0.01), but for the 6th nerve, the whole length was still less than transfer distance (P < 0.01). CONCLUSION: It could be an alternative method the 3rd, 4th, and 5th intercostal nerve transfer to the suprascapular nerve for reconstruction of shoulder abduction. And 6th intercostal nerve, longer dissociated length may be required for direct coaptation or using a graft for nerve repair.

Results of intercostal nerve transfer to the musculocutaneous nerve in brachial plexus birth palsy.

BACKGROUND: Intercostal nerve (ICN) transfer has been one of the main extraplexal nerve transfers in treating brachial plexus root avulsion. This retrospective study evaluated results of ICN transfer for reconstruction of the musculocutaneous nerve (MCN) in brachial plexus birth palsy (BPBP). METHODS: Eighteen boys and 6 girls with BPBP, who had avulsion of at least 2 spinal nerves of the plexus, underwent ICN transfer for reconstruction of MCN, from March 2003 to October 2005. The brachial plexus lesion was diagnosed by clinical assessment, surgical exploration, and intraoperative neurophysiological investigations. The age at surgery ranged from 3 to 11 months of life, with a mean of 5 months. Two intercostals were used for one, 3 intercostals for 9, and 4 intercostals for 14 patients. The intercostals were transferred to MCN in 12 and to the anterior division of the upper trunk in the other 12 cases. RESULTS: Twenty-four children were followed up for 24 to 79 months, with an average of 53 months. No complications were found in the respiratory system. Of 14 transfers with 4 intercostals, biceps gained M4 strength in 8, M3 in 4, and M2 in 2. Of 9 transfers with 3 intercostals, biceps obtained M4 strength in 8 and M3 in 1. One transfer with 2 intercostals got M4 strength of biceps. Twelve patients whose intercostals were transferred to MCN, gained M4 strength of biceps in 11 and M3 in 1, whereas the other 12 patients with intercostals transferred to anterior division of the upper trunk, obtained M4 strength of biceps in 6, M3 in 4, and M2 in 2. The rate of M3 strength or more was 92% and that of M4 was 71%. CONCLUSIONS: ICN transfer is a safe and reliable procedure for reconstruction of the MCN in BPBP. There seems to be no difference of effects between transfers with 3 and those with 4 intercostals. The transferred nerves should be coapted to MCN, rather than a more proximal portion of the plexus. LEVEL OF EVIDENCE: Level III: retrospective comparative study.