Reduced motor cortex GABABR function following chronic alcohol exposure.

The GABAB receptor (GABABR) agonist baclofen has been used to treat alcohol and several other substance use disorders (AUD/SUD), yet its underlying neural mechanism remains unclear. The present study aimed to investigate cortical GABABR dynamics following chronic alcohol exposure. Ex vivo brain slice recordings from mice chronically exposed to alcohol revealed a reduction in GABABR-mediated currents, as well as a decrease of GABAB1/2R and G-protein-coupled inwardly rectifying potassium channel 2 (GIRK2) activities in the motor cortex. Moreover, our data indicated that these alterations could be attributed to dephosphorylation at the site of serine 783 (ser-783) in GABAB2 subunit, which regulates the surface expression of GABABR. Furthermore, a human study using paired-pulse-transcranial magnetic stimulation (TMS) analysis further demonstrated a reduced cortical inhibition mediated by GABABR in patients with AUD. Our findings provide the first evidence that chronic alcohol exposure is associated with significantly impaired cortical GABABR function. The ability to promote GABABR signaling may account for the therapeutic efficacy of baclofen in AUD.

Sinus tarsi approach versus the extended lateral approach for displaced intra-articular calcaneal fractures: a systematic review and meta-analysis.

BACKGROUND: The goal of this study was to review eligible randomized controlled trials to determine the efficacy of the sinus tarsi approach (STA) versus the extended lateral approach (ELA) for the treatment of displaced intra-articular calcaneal fractures (DIACF). METHODS: Using appropriate keywords, we identified relevant studies using PubMed, the Cochrane Library, Embase, CNKI, VANFUN, and VIP. Key pertinent sources in the literature were also reviewed, and all articles published through June 2020 were considered for inclusion. For each study, we assessed odds ratios (ORs), mean difference (MD), and 95% confidence interval (95% CI) to assess and synthesize the outcomes. RESULTS: We included 15 RCTs, with a total of 847 patients in the STA group and 959 in the ELA group. The results found that after STA and ELA, no significant difference in changes of Böhler's angle (WMD: 0.746, 95% CI: - 0.316-1.809), Gissane angle (WMD: - 0.710, 95% CI: - 2.157-0.737), calcaneal heights (WMD: 0.378, 95% CI: - 1.973-2.728), calcaneal widths (SMD: - 0.431, 95% CI: - 1.604- 0.742), calcaneal lengths (WMD: 0.691, 95% CI: - 0.749-2.131). Besides, there was no significant difference in the incidence of complications between the STA group and the ELA group (RR: 0.592, 95% CI: 0.336-1.045). CONCLUSION: There was no difference in clinical efficacy between STA and ELA in treating DIACF. Besides, there is still a need of large-sample, high-quality, long-term randomized controlled trials to confirm the conclusion. LEVEL OF EVIDENCE: Level I-High-Quality Prospective Randomized Study.

Retracted: Downregulation of microRNA-367 promotes osteoblasts growth and proliferation of mice during fracture by activating the PANX3-mediated Wnt/ß-catenin pathway.

A majority of people suffering from bone fractures fail to heal and develop a nonunion, which is a challenging orthopedic complication requiring complex and expensive treatment. Previous data showed the inhibition of some microRNAs (miRNAs or miRs) can enhance fracture healing. The objective of the present study is to explore effects of miR-367 on the osteoblasts growth and proliferation of mouse during fracture via the Wnt/ß-catenin pathway by targeting PANX3. Primarily, the femur fracture model was successfully established in 66 (C57BL/6) 6-week-old male mice. To verify whether miR-367 target PANX3, we used the target prediction program and performed luciferase activity determination. Subsequently, to figure out the underlying regulatory roles of miR-367 in fracture, osteoblasts were elucidated by treatment with miR-367 mimic, miR-367 inhibitor, or siRNA against PANX3 to determine the expression of miR-367, siPANX3, ß-catenin, and Wnt5b as well as cell proliferation and apoptosis. The results demonstrated that PANX3 was verified as a target gene of miR-367. MiR-367 was found to highly expressed but PANX3, ß-catenin, and Wnt5b were observed poorly expressed in fracture mice. downregulated miR-367 increased the mRNA and protein expression of PANX3, ß-catenin, and Wnt5b, increased cell growth, proliferation, and migration, while decreased cell apoptosis in osteoblasts. Altogether, our study demonstrates that the downregulation of miR-367 may promote osteoblasts growth and proliferation in fracture through the activation of the PANX3-dependent Wnt/ß-catenin pathway.

Selenocysteine inhibits human osteosarcoma cells growth through triggering mitochondrial dysfunction and ROS-mediated p53 phosphorylation.

Osteosarcoma represents the most common primary malignant bone tumor in children and adolescents, which shows severe resistance toward standard chemotherapy because of high invasive capacity and growing incidence. Selenocysteine (SeC) is a naturally available Se-containing amino acid that displays splendid anticancer activities against several human tumors. However, little information about SeC-induced growth inhibition against human osteosarcoma is available. Herein, the anticancer efficiency and underlying mechanism of SeC against human osteosarcoma were evaluated in vitro and in vivo. The results revealed that SeC significantly inhibited MG-63 human osteosarcoma cells growth in vitro through induction of S-phase arrest and apoptosis, as reflected by the decrease of cyclin A and CDK-2, PARP cleavage, and caspases activation. SeC treatment also resulted in mitochondrial dysfunction through affecting Bcl-2 family expression. Moreover, SeC triggered p53 phosphorylation by inducing reactive oxygen species (ROS) overproduction. ROS inhibition effectively blocked SeC-induced cytotoxicity and p53 phosphorylation. Importantly, MG-63 human osteosarcoma xenograft growth in nude mice was significantly suppressed in vivo through triggering apoptosis and p53 phosphorylation. These results indicated that SeC had the potential to inhibit human osteosarcoma cells growth in vitro and in vivo through triggering mitochondrial dysfunction and ROS-mediated p53 phosphorylation, which validated the potential application of Se-containing compounds in treatment of human osteosarcoma.

Combined treatment with alendronate and Drynaria rhizome extracts : Effect on fracture healing in osteoporotic rats.

The effects of both alendronate (ALN) and Drynaria rhizome extracts (DRE) alone could promote bone healing in osteoporotic fractures but there are no reports about the combined use of ALN and DRE for promotion of bone healing of fractures in osteoporotic settings. This study investigated the effects of ALN plus DRE on fractures in osteopenic rats. Osteopenic rats underwent unilateral transverse osteotomy on the femur fixed by a sterilized Kirschner wire 2 weeks after intragastric administration of retinoic acid (80 mg/kg body weight/day). Subsequently, the animals were randomly divided into four groups: control, ALN, DRE and ALN + DRE. All rats from groups ALN, DRE and ALN + DRE received ALN (40 mg/kg, weekly), DRE (90 mg/kg/day), or both for 2, 4 and 6 weeks. The results of our study indicated that all treatment promoted fracture healing and callus formation compared to controls but ALN + DRE treatment showed significantly stronger effects than ALN or DRE alone in histological, X­ray and biomechanical tests. These results seem to indicate that combined treatment with ALN and DRE has an additive effect on fracture healing and callus formation in osteoporotic rats.

A histomorphometric study of necrotic femoral head in rabbits treated with extracorporeal shock waves.

[Purpose] This study aimed to determine the effectiveness and mechanisms of extracorporeal shock wave therapy in the treatment of femoral head osteonecrosis. [Subjects and Methods] Histomorphometric analysis of necrotic femoral head in rabbits treated with shock waves was performed. Bilateral osteonecrosis of femoral heads was induced with methylprednisolone and lipopolysaccharide in eight rabbits. The left limb (study side) received shock waves to the femoral head. The right limb (control side) received no shock waves. Biopsies of the femoral heads were performed at 12 weeks after shock wave therapy. [Results] Necrotic femoral heads treated with shock waves, compared with controls, had higher bone volume per tissue volume, trabecular thickness, trabecular number, osteoblast surface/bone surface, osteoid surface/bone surface, osteoid thickness, mineralizing surface/bone surface, mineralizing apposition rate, and bone formation rate. However, trabecular separation was lower in shock wave-treated femoral heads than in controls. Eroded surface/bone surface and osteoclast surface/bone surface did not differ significantly between groups. [Conclusion] The bone mass of necrotic femoral heads treated with shock waves increases. Extracorporeal shock wave may promote bone repair in necrotic femoral heads through the proliferation and activation of osteoblasts.

Antinociceptive effects of fisetin against diabetic neuropathic pain in mice: Engagement of antioxidant mechanisms and spinal GABAA receptors.

Peripheral painful neuropathy is one of the most common complications in diabetes and necessitates improved treatment. Fisetin, a naturally occurring flavonoid, has been reported to exert antidepressant-like effect in previous studies. As antidepressant drugs are employed clinically to treat neuropathic pain, this work aimed to investigate whether fisetin possess beneficial effect on diabetic neuropathic pain and explore the mechanism(s). We subjected mice to diabetes by a single intraperitoneal (i.p.) injection of streptozotocin (200mg/kg), and von Frey test or Hargreaves test was used to assess mechanical allodynia or thermal hyperalgesia, respectively. Chronic treatment of diabetic mice with fisetin not only ameliorated the established symptoms of thermal hyperalgesia and mechanical allodynia, but also arrested the development of neuropathic pain when given at low doses. Although chronic fisetin administration did not impact on the symptom of hyperglycemia in diabetic mice, it reduced exacerbated oxidative stress in tissues of spinal cord, dorsal root ganglion (DRG) and sciatic verve. Furthermore, the analgesic actions of fisetin were abolished by repetitive co-treatment with the reactive oxygen species (ROS) donor tert-butyl hydroperoxide (t-BOOH), but potentiated by the ROS scavenger phenyl-N-tert-butylnitrone (PBN). Finally, acute blockade of spinal GABAA receptors by bicuculline totally counteracted such fisetin analgesia. These findings indicate that chronic fisetin treatment can delay or correct neuropathic hyperalgesia and allodynia in mice with type 1 diabetes. Mechanistically, the present fisetin analgesia may be associated with its antioxidant activity, and spinal GABAA receptors are likely rendered as downstream targets.

Long-term therapy with sorafenib is associated with pancreatic atrophy.

BACKGROUND: Although the short-term adverse effects of sorafenib are well known, few data exist on long-term toxicity. The objective of the present study was to investigate the prevalence of pancreatic atrophy among a cohort of patients with hepatocellular carcinoma (HCC) who were treated with sorafenib for ≥2 y. METHODS: Between March 2007 and December 2013, 31 patients with HCC who were treated with sorafenib for ≥2 y were identified. The effect of pancreatic atrophy and enhancement on incidence of adverse events, tumor response, and overall survival (OS) were assessed. RESULTS: Thirty-one patients with HCC were treated with sorafenib for ≥2 y and met inclusion criteria; 11 patients (35.5%) were Barcelona-clinic liver cancer stage B, whereas 20 patients (64.5%) were Barcelona-clinic liver cancer stage C. Median duration of treatment with sorafenib was 35.2 mo. Pancreatic atrophy and a decrease in pancreatic enhancement occurred in 24 patients (77.4%) and 15 patients (48.4%), respectively. On the basis of the modified response evaluation criteria in solid tumors, four patients (12.9%) had a complete response, 10 patients (32.3%) had a partial response, and 17 patients (54.8%) had stable disease. Patients treated with sorafenib with pancreatic atrophy had a median OS of 49.4 mo (95% confidence interval, 41.2-57.5 mo) compared with 31.2 mo (95% confidence interval, 25.7-36.7 mo) among patients who did not develop pancreatic atrophy (P = 0.009). In contrast, survival was not associated with decreased versus normal enhancement of the pancreas (OS, 47.7 mo versus 41.7 mo, respectively; P = 0.739). CONCLUSIONS: Pancreatic atrophy occurred in many HCC patients after 2 y of treatment with sorafenib. Patients who experienced pancreatic atrophy had a better tumor response and OS.

Association of periodontal disease with oral cancer: a meta-analysis.

The objective is to evaluate the association of periodontal disease with the risk of oral cancer. Literature retrieval, selection and assessment, data extraction, and meta-analyses were performed according to the RevMan 5.0 guidelines. In the meta-analysis, we utilized random-effect model to pool the odds ratio (OR) according to the test of heterogeneity. A total of five eligible studies included 1,191 oral cancer patients and 1,992 healthy control subjects were analyzed. By meta-analysis, we found a significant association of periodontal disease with oral cancer [OR = 3.53, 95 % CI (1.52-8.23); P = 0.003]. Patients with periodontal disease have increased susceptibility to oral cancer.

Association of toll-like receptor 4 signaling pathway with steroid-induced femoral head osteonecrosis in rats.

Osteonecrosis of the femoral head is frequently observed in patients treated with excessive corticosteroids. However, the pathogenesis of corticosteroid-induced osteonecrosis remains unclear. The purpose of this study was to investigate the role of Toll-like receptor 4 (TLR4) signaling pathway in steroid-induced femoral head osteonecrosis in rats. Male Sprague-Dawley rats were injected intramuscularly with 20 mg/kg methylprednisolone (MP) for 8 weeks, twice per week. The animals were sacrificed at 2, 4 and 8 weeks after the last MP injection, respectively, and then allocated to the 2-, 4- and 8-week model groups (n=24 each). Rats in the control group (n=12) were not given any treatment. Histopathological analysis was performed and the concentration of tartrate-resistant acid phosphatase (TRAP) in plasma was determined. The activation of osteoclasts in the femoral head was assessed by TRAP staining. The expression of TLR4, MyD88, TRAF6 and NF-κB p65 that are involved in TLR4 signaling, and MCP-1 production were detected by using real-time PCR (RT-PCR) and Western blotting. The results showed that the osteonecrosis in the femoral head was clearly observed and the concentration of TRAP in the plasma was increased in the model rats. The femoral head tissues in MP-treated rats were positive for TRAP and the intensity of TRAP staining was greater in MP-treated rats than in control rats. As compared with the control group, the mRNA expression of TLR4 signaling-related factors was enhanced significantly at 4 and 8 weeks, and the protein levels of these factors increased significantly with time. It was concluded that MP could induce the femoral head osteonecrosis in rats, which was associated with osteoclast activation via the TLR4 signaling pathway. These findings suggest that TLR4 signaling pathway plays a pivotal role in the pathogenesis of steroid-induced osteonecrosis.

Rapid development of double-hit mRNA antibody cocktail against orthopoxviruses.

The Orthopoxvirus genus, especially variola virus (VARV), monkeypox virus (MPXV), remains a significant public health threat worldwide. The development of therapeutic antibodies against orthopoxviruses is largely hampered by the high cost of antibody engineering and manufacturing processes. mRNA-encoded antibodies have emerged as a powerful and universal platform for rapid antibody production. Herein, by using the established lipid nanoparticle (LNP)-encapsulated mRNA platform, we constructed four mRNA combinations that encode monoclonal antibodies with broad neutralization activities against orthopoxviruses. In vivo characterization demonstrated that a single intravenous injection of each LNP-encapsulated mRNA antibody in mice resulted in the rapid production of neutralizing antibodies. More importantly, mRNA antibody treatments showed significant protection from weight loss and mortality in the vaccinia virus (VACV) lethal challenge mouse model, and a unique mRNA antibody cocktail, Mix2a, exhibited superior in vivo protection by targeting both intracellular mature virus (IMV)-form and extracellular enveloped virus (EEV)-form viruses. In summary, our results demonstrate the proof-of-concept production of orthopoxvirus antibodies via the LNP-mRNA platform, highlighting the great potential of tailored mRNA antibody combinations as a universal strategy to combat orthopoxvirus as well as other emerging viruses.

Comparison of isocentric C-arm 3-dimensional navigation and conventional fluoroscopy for C1 lateral mass and C2 pedicle screw placement for atlantoaxial instability.

STUDY DESIGN: A retrospective study. OBJECTIVE: The aim of the study was to compare the precision of C1 lateral mass and C2 pedicle (C1LM-C2P) screw fixation for atlantoaxial instability using the isocentric C-arm 3-dimensional (Iso-C 3D) navigation versus conventional fluoroscopy. SUMMARY OF BACKGROUND DATA: The Iso-C 3D navigation has been widely used in spinal surgeries in recent years. The advantages of this navigation system compared with conventional fluoroscopy in C1LM-C2P screw fixation for atlantoaxial instability are not known. METHODS: Twenty-four patients diagnosed with atlantoaxial instability were treated with C1LM-C2P screw fixation in this study. The navigation group included 12 patients and the other 12 patients were in the conventional fluoroscopy group. The clinical and radiographic results were recorded and compared between the 2 groups. Patients were followed up with clinical examination and radiographs at a mean of 10.8 months. RESULTS: There were no significant differences between groups in the mean age, gender, and causes of atlantoaxial instability. Operative time was 130 ± 5.4 minutes in the navigation group versus 145 ± 6.5 minutes in the conventional fluoroscopy group. The mean blood loss in the navigation group was 304.2 ± 47.9 mL relative to 462.5 ± 55.4 mL in the conventional fluoroscopy group. The radiation time was significantly reduced using 3D navigation (47.5 ± 1.5 s vs. 64.0 ± 3.0 s). 95.8% (46/48) of 3D navigated screws and 83.3% (40/48) of fluoroscopy screws had no pedicle perforation. Each patient showed evidence of solid fusion after 6 months on cervical plain radiographies. CONCLUSION: On comparing the 2 imaging techniques, it was found that using Iso-C 3D navigation can significantly improve the accuracy of screw placement and decrease intraoperative fluoroscopic time and blood loss. This study demonstrates that Iso-C 3D navigation is a safe and effective means of guiding C1LM-C2P screw fixation for atlantoaxial instability.

[Construction of biofilm formation related mutants in Vibrio parahaemolyticus].

OBJECTIVE: To construct the mutants of biofilm related genes in Vibrio parahaemolyticus and confirm the mutants. METHODS: The homologous upstream and downstream flanking fragments of target gene were amplified by using PCR, and the fusion homologous fragment was amplified by using the two flanking fragments as template. Then the fusion homologous fragment was digested by restriction enzyme and cloned into suicide plasmid pDS132. The recombinant plasmid was transferred into Vibrio parahaemolyticus RIMD 2210633 through conjugation. The mutants were screened and identified by PCR and the phenotype of one mutant was analyzed in order to verify that the mutants were constructed successfully. RESULTS: Six recombinant plasmids carrying the fusion homologous fragments of genes vbfR, crp, hns, swrZ, swrT and cpsR respectively were constructed and identified by PCR. The amplification products of 1190, 1128, 1136, 953, 1242 and 1112 bp were obtained respectively. The six mutants (ΔvbfR, Δcrp, Δhns, ΔswrZ, ΔswrT and ΔcpsR) were constructed using recombinant plasmids. Verified by PCR, the size of amplification products of mutants (1190, 1128, 1136, 953, 1242 and 1112 bp respectively) was less (610, 739, 421, 542, 427 and 1367 bp respectively) than the corresponding positive control. Meanwhile, none of the products was amplified using the primers locating on the target gene. One mutant Δhns was selected to test the ability of biofilm formation. The result showed that the ability of biofilm formation of mutant Δhns was increased compared with the wild type. CONCLUSION: Six mutants of biofilm related genes in Vibrio parahaemolyticus were constructed and tested by molecular and phenotype experiment to confirm that the mutants were constructed successfully.

[Therapeutic efficacy and mechanisms of quercetin in a rat model of nonalcoholic fatty liver disease].

OBJECTIVE: To determine the efficacy of the plant-derived bioflavonoid, quercetin, for treating nonalcoholic fatty liver disease (NAFLD) by using a rat model, and to investigate the molecular mechanism underlying its therapeutic effects. METHODS: One-hundred Sprague-Dawley rats were randomly assigned into the normal control group (normal group), untreated NAFLD model control group (model group), 75 mg/kg/day quercetin treatment group (low-dose group), and 300 mg/kg/day quercetin treatment group (high-dose group). The NAFLD rat model was established by providing four weeks of a high-fat diet; the normal group received normal rat chow diet. The quercetin treatments were administered for eight weeks after model establishment and control groups received simultaneous gavages of isotonic saline, with continuation of the respective diets. At the end of the eight weeks (experimental week 12), the rats were sacrificed for liver and serum collection. Intergroup differences in liver index, fasting blood glucose (FBG), triglycerides (TG), interleukin (IL)-18, IL-10, malondialdehyde (MDA), and histopathological features were assessed by independent samples t-test (normal vs. model), one-way ANOVA (model vs. treatments), and least significant difference t-test (pairwise comparisons); correlations were assessed by Pearson's correlation coefficient. RESULTS: Compared with the normal group, the model group showed significantly higher liver index (t=-2.327), FBG (t=-3.482), TG (t=-0.302), and serum IL-18 (t=-2.704) (all P less than 0.05), but significantly lower IL-10 (t=2.622, P less than 0.05); the MDA level was also higher in the model group, but the difference was not significant (t=-1.083, P less than 0.05). Livers from the model group showed obvious histological features of inflammation (lymphocyte and neutrophil infiltration) and steatosis (cytoplasmic lipid droplets). Inflammation was positively correlated with IL-18 (P less than 0.05), but negatively correlated with IL-10 (P less than 0.05), while steatosis was negatively correlated with IL-10 (P less than 0.05). Compared to the model group, quercetin treatment (both low- and high-dose) led to significant decreases in the liver index, FBG and IL-18 (all, P less than 0.01), and significant increase in IL-10 (P less than 0.05); however, the changes in liver index, FBG and IL-10 were not significantly different between the low- and high-dose treatment groups, but the high-dose of quercetin did induce a significantly greater decrease in IL-18 than the low-dose (P less than 0.05). CONCLUSION: NAFLD rats have higher serum levels of IL-18 but lower levels of IL-10 than their healthy counterparts, and these differential cytokine expressions may be related to liver inflammation and steatosis. Quercetin treatment may help to delay the progression of NAFLD, possibly by adjusting the balance of inflammatory cytokines.

[Effects of quercetin on serum levels of resistin and IL-18 and on insulin resistance in nonalcoholic fatty liver disease rats].

OBJECTIVE: To investigate the effects of quercetin on serum levels of resistin and interleukin (IL)-18 and incidence of insulin resistance (IR) in nonalcoholic fatty liver disease (NAFLD) using a rat model. METHODS: NAFLD was induced in Sprague-Dawley rats by administering a high-fat diet for four weeks. The model rats were then treated with quercetin (oral gavage administration; low dose group: 75 mg/kg/day, high dose group: 300 mg/kg/day) for eight weeks. Untreated model rats served as controls. Serum levels of resistin, triglyceride (TG), IL-18, fasting plasma glucose (FPG), fasting insulin (FINS), and malondialdehyde (MDA) were measured by standard biochemical assays before and after the quercetin administration. In addition, the insulin resistance index (HOMA-IR) was calculated and pathological changes in liver were observed by histological analysis. RESULTS: Compared to the untreated model rats, the quercetin treated model rats showed significantly lower serum resistin (5.98 vs. 2.70), serum IL-18 (10.93 vs. 8.21), FPG (7.45 vs. 4.99), FINS (12.69 vs. 8.59), and HOMA-IR (4.22 vs. 1.87) (all P less than 0.01). Compared to the untreated model group, the high dose group showed significantly lower TG (t = 4.70) and MDA (t = 5.14) (both P less than 0.01). Serum levels of resistin and IL-18, and levels of TG, FPG and FINS were found to be positively correlated with HOMA-IR and the degree of liver disease (r more than 0, all P less than 0.05). The degree of degeneration was decreased in accordance with the dosages of quercetin, as compared to the untreated model group (U = 4.41 and 2.19, both P less than 0.05), and the pathological degree was less extensive in the high dose group than in the low dose group (U = 2.44, P less than 0.01). CONCLUSION: Quercetin treatment reduces levels of inflammatory cytokines and improves lipid peroxidation and IR in NAFLD rats, and its beneficial effects appear to increase with higher dosage.

Functional near-infrared spectroscopy in elderly patients with four types of dementia.

BACKGROUND: Functional near-infrared spectroscopy (fNIRS) is commonly used to study human brain function by measuring the hemodynamic signals originating from cortical activation and provides a new noninvasive detection method for identifying dementia. AIM: To investigate the fNIRS imaging technique and its clinical application in differential diagnosis of subtype dementias including frontotemporal lobe dementia, Lewy body dementia, Parkinson's disease dementia (PDD) and Alzheimer's disease (AD). METHODS: Four patients with different types of dementia were examined with fNIRS during two tasks and a resting state. We adopted the verbal fluency task, working memory task and resting state task. Each patient was compared on the same task. We conducted and analyzed the fNIRS data using a general linear model and Pearson's correlation analysis. RESULTS: Compared with other types of dementias, fNIRS showed the left frontotemporal and prefrontal lobes to be poorly activated during the verbal fluency task in frontotemporal dementia. In Lewy body dementia, severe asymmetry of prefrontal lobes appeared during both verbal fluency and working memory tasks, and the patient had low functional connectivity during a resting state. In PDD, the patient's prefrontal cortex showed lower excitability than the temporal lobe during the verbal fluency task, while the prefrontal cortex showed higher excitability during the working memory task. The patient with AD showed poor prefrontal and temporal activation during the working memory task, and more activation of frontopolar instead of the dorsolateral prefrontal cortex. CONCLUSION: Different hemodynamic characteristics of four types of dementia (as seen by fNIRS imaging) provides evidence that fNIRS can serve as a potential tool for the diagnosis between dementia subtypes.

The effects of childhood maltreatment on adolescent non-suicidal self-injury behavior: mediating role of impulsivity.

Background: Non-suicidal self-injury (NSSI) severely challenges mental health in adolescents. Childhood maltreatment experience acts as high-risk factor for adolescents to engage in NSSI behaviors. On the other hand, impulsivity or loss of control sets the threshold for NSSI execution. Here we examined the effects of childhood maltreatment on adolescent NSSI-related clinical outcomes and the potential role of impulsivity. Methods: We assessed the clinical data of 160 hospitalized NSSI adolescents and recruited 64 age-matched healthy subjects as a control group. The clinical symptoms of NSSI are expressed by the NSSI frequency, depression, and anxiety measured by the Ottawa Self-Injury Inventory, the Beck Depression Inventory, and the Beck Anxiety Inventory. Childhood maltreatment and impulsivity were assessed with Childhood Trauma Questionnaire and Barratt Impulsiveness Scale. Results: The results showed that when compared to HC group, NSSI group is more likely to experience childhood maltreatment. Notably, NSSI group with Childhood maltreatment accompanies higher trait impulsivity and exacerbated clinical outcomes, such as NSSI frequency, depression and anxiety symptoms. Mediation analyses indicated that the association between childhood maltreatment and NSSI-related clinical outcomes was partially explained by impulsivity. Conclusion: We found that NSSI adolescents have a higher proportion of childhood maltreatment. Impulsivity plays a mediating role between childhood maltreatment and NSSI behaviors.

Orbitofrontal cortex-hippocampus potentiation mediates relief for depression: A randomized double-blind trial and TMS-EEG study.

It has been 15 years since repetitive transcranial magnetic stimulation (rTMS) targeting the dorsolateral prefrontal cortex (DLPFC) was approved by the FDA for clinical depression treatment. Yet, the underlying mechanisms for rTMS-induced depression relief are not fully elucidated. This study analyzes TMS-electroencephalogram (EEG) data from 64 healthy control (HC) subjects and 53 patients with major depressive disorder (MDD) before and after rTMS treatment. Prior to treatment, patients with MDD have lower activity in the DLPFC, the hippocampus (HPC), the orbitofrontal cortex (OFC), and DLPFC-OFC connectivity compared with HCs. Following active rTMS treatment, patients with MDD show a significant increase in the DLPFC, HPC, and OFC. Notably, the increase in HPC activity is specifically associated with amelioration of depressive symptoms but not anxiety or sleep quality. The orbitofrontal-hippocampal pathway plays a crucial role in mediating depression relief following rTMS treatment. These findings suggest potential alternative targets for brain stimulation therapy against depression (chictr.org.cn: ChiCTR2100052007).

Inhalable vaccine of bacterial culture supernatant extract mediates protection against fatal pulmonary anthrax.

Pulmonary anthrax is the most fatal clinical form of anthrax and currently available injectable vaccines do not provide adequate protection against it. Hence, next-generation vaccines that effectively induce immunity against pulmonary anthrax are urgently needed. In the present study, we prepared an attenuated and low protease activity Bacillus anthracis strain A16R-5.1 by deleting five of its extracellular protease activity-associated genes and its lef gene through the CRISPR-Cas9 genome editing system. This mutant strain was then used to formulate a lethal toxin (LeTx)-free culture supernatant extract (CSE) anthrax vaccine, of which half was protective antigen (PA). We generated liquid, powder, and powder reconstituted formulations that could be delivered by aerosolized intratracheal inoculation. All of them induced strong humoral, cellular, and mucosal immune responses. The vaccines also produced LeTx neutralizing antibodies and conferred full protection against the lethal aerosol challenges of B. anthracis Pasteur II spores in mice. Compared to the recombinant PA vaccine, the CSE anthrax vaccine with equal PA content provided superior immunoprotection against pulmonary anthrax. The preceding results suggest that the CSE anthrax vaccine developed herein is suitable and scalable for use in inhalational immunization against pulmonary anthrax.