Relationship between left atrial isolated surface area and early-term recurrence in patients with persistent atrial fibrillation after cryoballoon ablation.

OBJECTIVE: To investigate the effect of pulmonary vein antrum enlargement combined with left atrial roof cryoballoon ablation in patients with persistent atrial fibrillation (PeAF) by analyzing the relationship between left atrial isolation area surface area (ISA) and early postoperative recurrence. METHODS: 93 patients with PeAF were classified into recurrence and non-recurrence groups according to the results of the 1-year follow-up. Three-dimensional electroanatomical labeling map was constructed and merged with that of the left atrial pulmonary vein CTA, and the ISA and the left atrial surface area (LASA) were measured and analyzed to determine the relationship between ISA/LASA in relation to early postoperative recurrence. RESULTS: 93 patients were included and followed up for 1 year with AF-free recurrence rate of 75.3%. The ISA of the recurrence group was lower than that of the non-recurrence group. Left atrial internal diameter (LAD), left common pulmonary vein, the ISA, the ISA/LASA and early-term recurrence had statistical significance in both groups. The factors that significantly predicted early-term recurrence were left common pulmonary vein and the ISA/LASA. ISA/LASA (HR 0, 95% CI 0-0.005, P = 0.008) and left common pulmonary vein trunk (HR 7.754, 95% CI 2.256-25.651, P = 0.001) were the independent risk factors for early recurrence. ROC curve analysis showed that ISA/LASA predicted the best early recurrence after operation with a cut-off value of 15.2%. CONCLUSION: A greater ISA/LASA reduces early recurrence after cryoablation in patients with PeAF. An ISA/LASA of 15.2% may be the best cut-off value for predicting early recurrence after cryoablation for PeAF.

Breathable Wearable Smartsensors Deriving from Interface Self-Assembled Film for Tracking l-Cysteine.

The advent of wearable sensors heralds a transformation in the continuous, noninvasive analysis of biomarkers critical for disease diagnosis and fitness management. Yet, their advancement is hindered by the functional challenges affiliated with their active sensing analysis layer. Predominantly due to suboptimal intrinsic material properties and inconsistent dispersion leading to aggregation, thus compromising sensor repeatability and performance. Herein, an innovative approach to the functionalization of wearable electrochemical sensors was introduced, specifically addressing these limitations. The method involves a proton-induced self-assembly technique at the organic-water (O/W) interface, facilitating the generation of biomarker-responsive films. This research offers flexible, breathable sensor capable of real-time precision tracking l-cysteine (l-Cys) precision tracking. Utilizing an activation mechanism for Prussian blue nanoparticles by hydrogen peroxide, the catalytic core exhibits a specific response to l-Cys. The implications of this study refine the fabrication of film-based analysis electrodes for wearable sensing applications and the broader utilization of two-dimensional materials in functional-specific response films. Findings illuminate the feasibility of this novel strategy for precise biomarker tracking and extend to pave the way for constructing high-performance electrocatalytic analytical interfaces.

Acral persistent papular mucinosis: a rare child case report and literature review.

Background: Acral persistent papular mucinosis (APPM) is a rare idiopathic subtype of localized lichen myxedematosus. To date, there have been less than 41 APPM cases reported worldwide, however, almost all patients were older than 18 years of age. A 7-year-old child was first reported in this paper. Case Description: A 7-year-old boy was admitted to our hospital with a solitary skin-colored papule on the radial side of the middle segment of his right index finger. The patient wanted to know the exact diagnosis and remove it because the flexion movement of the middle segment had been affected. Thus, a surgery was performed. Histopathological examination of a biopsy specimen obtained from the papule on the radial side of the middle segment of his right index finger showed a focal and well-circumscribed deposit of mucin in the papillary and middermis. The deposit never extended deeply into the reticular dermis. Mucin spared a subepidermal area in the papillary dermis. Alcian blue stains can highlight the mucin. The papule was histologically diagnosed as an APPM and excised surgically. The wound gradually healed after the operation, and no obvious recurrence, scar or other discomfort was observed during follow-up so far. Conclusions: To the best of our knowledge, this is the rare case of a child APPM presenting as a solitary papule affecting the flexion movement of the middle segment. Since it is a rare disease, we report this case to contribute to future research on the diagnosis and pathogenesis of APPM.

Polyvinyl chloride and polybutylene adipate microplastics affect peanut and rhizobium symbiosis by interfering with multiple metabolic pathways.

Microplastics (MPs), widely presented in cultivated soil, have caused serious stresses on crop growth. However, the mechanism by which MPs affect legumes and rhizobia symbiosis is still unclear. Here, peanut seedlings were inoculated with Bradyrhizobium zhanjiangense CCBAU 51778 and were grown in vermiculite with 3 %/5 % (w/w) addition of PVC (polyvinyl chloride)-MPs/PBAT (polybutylene adipate)-MPs. PVC-MPs and PBAT-MPs separately decreased nodule number by 33-100 % and 2.62-80.91 %. Transcriptome analysis showed that PVC-MPs affected more DEGs (differentially expressed genes) than PBAT-MPs, indicating PVC-MPs were more devastating for the symbiosis than PBAT-MPs. Functional annotation revealed that PVC-MPs and PBAT-MPs enriched DEGs related to biosynthesis pathways such as flavonoid, isoflavonoid, and phenylpropanoid, in peanut. And when the dose increased from 3 % to 5 %, PVC-MPs mainly enriched the pathways of starch and sucrose metabolism, alanine, aspartate and glutamate metabolism, diterpenoid biosynthesis, etc.; PBAT-MPs enriched cysteine and methionine metabolism, photosynthesis, MAPK signaling, and other pathways. These significantly enriched pathways functioned in reducing nodule number and promoting peanut tolerance to MPs stresses. This study reveals the effect of PVC-MPs and PBAT-MPs on peanut and rhizobium symbiosis, and provides new perspectives for legume production and environmental safety.

EMCMDA: predicting miRNA-disease associations via efficient matrix completion.

Abundant researches have consistently illustrated the crucial role of microRNAs (miRNAs) in a wide array of essential biological processes. Furthermore, miRNAs have been validated as promising therapeutic targets for addressing complex diseases. Given the costly and time-consuming nature of traditional biological experimental validation methods, it is imperative to develop computational methods. In the work, we developed a novel approach named efficient matrix completion (EMCMDA) for predicting miRNA-disease associations. First, we calculated the similarities across multiple sources for miRNA/disease pairs and combined this information to create a holistic miRNA/disease similarity measure. Second, we utilized this biological information to create a heterogeneous network and established a target matrix derived from this network. Lastly, we framed the miRNA-disease association prediction issue as a low-rank matrix-complete issue that was addressed via minimizing matrix truncated schatten p-norm. Notably, we improved the conventional singular value contraction algorithm through using a weighted singular value contraction technique. This technique dynamically adjusts the degree of contraction based on the significance of each singular value, ensuring that the physical meaning of these singular values is fully considered. We evaluated the performance of EMCMDA by applying two distinct cross-validation experiments on two diverse databases, and the outcomes were statistically significant. In addition, we executed comprehensive case studies on two prevalent human diseases, namely lung cancer and breast cancer. Following prediction and multiple validations, it was evident that EMCMDA proficiently forecasts previously undisclosed disease-related miRNAs. These results underscore the robustness and efficacy of EMCMDA in miRNA-disease association prediction.

The orientation of CpG conjugation on aluminum oxyhydroxide nanoparticles determines the immunostimulatory effects of combination adjuvants.

In subunit vaccines, aluminum salts (Alum) are commonly used as adjuvants, but with limited cellular immune responses. To overcome this limitation, CpG oligodeoxynucleotides (ODNs) have been used in combination with Alum. However, current combined usage of Alum and CpG is limited to linear mixtures, and the underlying interaction mechanism between CpG and Alum is not well understood. Thus, we propose to chemically conjugate Alum nanoparticles and CpG (with 5' or 3' end exposed) to design combination adjuvants. Our study demonstrates that compared to the 3'-end exposure, the 5'-end exposure of CpG in combination adjuvants (Al-CpG-5') enhances the activation of bone-marrow derived dendritic cells (BMDCs) and promotes Th1 and Th2 cytokine secretion. We used the SARS-CoV-2 receptor binding domain (RBD) and hepatitis B surface antigen (HBsAg) as model antigens to demonstrate that Al-CpG-5' enhanced antigen-specific antibody production and upregulated cytotoxic T lymphocyte markers. Additionally, Al-CpG-5' allows for coordinated adaptive immune responses even at lower doses of both CpG ODNs and HBsAg antigens, and enhances lymph node transport of antigens and activation of dendritic cells, promoting Tfh cell differentiation and B cell activation. Our novel Alum-CPG strategy points the way towards broadening the use of nanoadjuvants for both prophylactic and therapeutic vaccines.

A Rare Lipoma of Tongue in a 4-Year-Old Child: A Case Report With Literature Review.

Lipoma of the tongue is a rare benign tumor that accounts for approximately 1% to 5% of all oral cavity tumors while 0.3% of tumors are of the tongue. Notably, it is rarer in children. In this article, we report the case of a 4-year-old girl with lipomas of the tongue. The lipomas were found at age 1 year by her parents, located on the tip, ventro, and dorsum of the tongue, and presenting with a trend to increase gradually. At the time of presentation to the hospital at age 4 years, the articulatory function of the patient was partially affected, and surgical excision was performed. The surgery was uneventful, and no evidence of recurrence was noted at 3 month follow-up.

The absolute number of small and diminutive adenomas with high-grade dysplasia is substantially higher compared with large adenomas: a retrospective pooled study.

Introduction: The risk that a large polyp (≥10 mm) evolves into high-grade dysplasia (HGD) is relatively high compared with that of a small/diminutive polyp (<10 mm). Recently, the detection of small and diminutive polyps has been substantially improved with the advancement of endoscopy. However, further research is needed on the role of the incidence of HGD caused by the co-occurrence of small and diminutive polyps in the progression of HGD. In this study, we aim to investigate whether and how the small and diminutive polyps correlate with the incidence of HGD in the population. Methods: The pooled data were deeply analyzed from four published randomized controlled trials (RCTs) regarding colon polyp detection. All polyps detected were examined and confirmed by pathologists. The primary outcome was the composition ratio of the HGD polyps in each polyp size category. Results: Among a total of 3,179 patients with 2,730 polyps identified, there were 83 HGD polyps confirmed, and 68 patients had at least one polyp with HGD. The risk of development of HGD was lower for a single small and diminutive polyp than for one large polyp (2.18% vs. 22.22%, P < 0.0001). On the contrary, the composition ratio for HGD from small and diminutive polyps was significantly higher than that from the large ones (68.67% vs. 31.33%, P < 0.0001). The combined number of HGD presented a trend negatively correlated to size. Conclusions: Our data demonstrated that the absolute number of HGD significantly derives more from small and diminutive polyps than from the large ones, and the collective number of small and diminutive polyps per patient is indicative of his/her HGD exposure. These findings positively provide novel perspectives on the management of polyps and may further optimize the prevention of colorectal cancer. Systematic Review Registration: http://www.chictr.org.cn, identifier ChiCTR1900025235, ChiCTR1800017675, ChiCTR1800018058, and ChiCTR1900023086.

Severe cytokine release syndrome induced by immune checkpoint inhibitors in cancer patients - A case report and review of the literature.

Cytokine release syndrome (CRS) can be induced by immune checkpoint inhibitors (ICIs). Although the incidence of CRS is low, it is often underreported. Here, we report two severe CRS cases and summarize and review 51 patients with ICI-induced CRS to explore the possible contributing factors to the disease prognosis and provide assistance for therapy. Our analysis found that the population with ICI-induced CRS consists mainly of male patients with an average age of 61.74 years. The primary malignant tumor type was lung cancer, and the clinical stage of most patients was stage IV. Notably, patients who experience a longer time to CRS onset, higher IL-6 levels, and lower platelet counts may be more likely to develop severe CRS. Cardiovascular, respiratory, neurological, and coagulation toxicities are more common in higher-grade CRS and may serve as markers for patient experiencing ICU admission, oxygen supplementation, hypotension, high-dose vasopressors usage, and intubation.

Potentiating the Immune Responses of HBsAg-VLP Vaccine Using a Polyphosphoester-Based Cationic Polymer Adjuvant.

Virus-like particle (VLP)-based vaccines are required to be associated with a suitable adjuvant to potentiate their immune responses. Herein, we report a novel, biodegradable, and biocompatible polyphosphoester-based amphiphilic cationic polymer, poly(ethylene glycol)-b-poly(aminoethyl ethylene phosphate) (PEG-PAEEP), as a Hepatitis B surface antigen (HBsAg)-VLP vaccine adjuvant. The polymer adjuvant effectively bound with HBsAg-VLP through electrostatic interactions to form a stable vaccine nanoformulation with a net positive surface charge. The nanoformulations exhibited enhanced cellular uptake by macrophages. HBsAg-VLP/PEG-PAEEP induced a significantly higher HBsAg-specific IgG titer in mice than HBsAg-VLP alone after second immunization, indicative of the antigen-dose sparing advantage of PEG-PAEEP. Furthermore, the nanoformulations exhibited a favorable biocompatibility and in vivo tolerability. This work presents the PEG-PAEEP copolymer as a promising vaccine adjuvant and as a potentially effective alternative to aluminum adjuvants.

Self-expanding metal stents versus decompression tubes as a bridge to surgery for patients with obstruction caused by colorectal cancer: a systematic review and meta-analysis.

BACKGROUND: Using self-expanding metal stents (SEMS) and decompression tubes (DT) as a bridge-to-surgery (BTS) treatment may avoid emergency operations for patients with colorectal cancer-caused obstructions. This study aimed to evaluate the efficacy and safety of the two approaches. METHODS: We systematically retrieved literature from January 1, 2000, to May 30, 2023, from the PubMed, Embase, Web of Science, SinoMed, Wanfang Data, Chinese National Knowledge Infrastructure, and Cochrane Central Register of Clinical Trials databases. Randomized controlled trials (RCTs) or cohort studies of SEMS versus DT as BTS in colorectal cancer obstruction were selected. Risks of bias were assessed for RCTs and cohort studies using the Cochrane Risk of Bias tool version 2 and Risk of Bias in Nonrandomized Studies of Interventions. Certainty of evidence was determined using the Graded Recommendation Assessment. Odds ratio (OR), mean difference (MD), and 95% confidence interval (95% CI) were used to analyze measurement data. RESULTS: We included eight RCTs and eighteen cohort studies involving 2,061 patients (SEMS, 1,044; DT, 1,017). Pooled RCT and cohort data indicated the SEMS group had a significantly higher clinical success rate than the DT group (OR = 1.99, 95% CI 1.04, 3.81, P = 0.04), but no significant difference regarding technical success (OR = 1.29, 95% CI 0.56, 2.96, P = 0.55). SEMS had a shorter postoperative length of hospital stays (MD = - 4.47, 95% CI - 6.26, - 2.69, P < 0.00001), a lower rates of operation-related abdominal pain (OR = 0.16, 95% CI 0.05, 0.50, P = 0.002), intraoperative bleeding (MD = - 37.67, 95% CI - 62.73, - 12.60, P = 0.003), stoma creation (OR = 0.41, 95% CI 0.23, 0.73, P = 0.002) and long-term tumor recurrence rate than DT (OR = 0.47, 95% CI 0.22, 0.99, P = 0.05). CONCLUSION: SEMS and DT are both safe as BTS to avoid emergency surgery for patients with colorectal cancer obstruction. SEMS is preferable because of higher clinical success rates, lower rates of operation-related abdominal pain, intraoperative bleeding, stoma creation, and long-term tumor recurrence, as well as a shorter postoperative length of hospital stays. Trial registration CRD42022365951 .

A novel training program: laparoscopic versus robotic-assisted low anterior resection for rectal cancer can be trained simultaneously.

Background: Current expectations are that surgeons should be technically proficient in minimally invasive low anterior resection (LAR)-both laparoscopic and robotic-assisted surgery. However, methods to effectively train surgeons for both approaches are under-explored. We aimed to compare two different training programs for minimally invasive LAR, focusing on the learning curve and perioperative outcomes of two trainee surgeons. Methods: We reviewed 272 consecutive patients undergoing laparoscopic or robotic LAR by surgeons A and B, who were novices in conducting minimally invasive colorectal surgery. Surgeon A was trained by first operating on 80 cases by laparoscopy and then 56 cases by robotic-assisted surgery. Surgeon B was trained by simultaneously performing 80 cases by laparoscopy and 56 by robotic-assisted surgery. The cumulative sum (CUSUM) method was used to evaluate the learning curves of operative time and surgical failure. Results: For laparoscopic surgery, the CUSUM plots showed a longer learning process for surgeon A than surgeon B (47 vs. 32 cases) for operative time, but a similar trend in surgical failure (23 vs. 19 cases). For robotic surgery, the plots of the two surgeons showed similar trends for both operative times (23 vs. 25 cases) and surgical failure (17 vs. 19 cases). Therefore, the learning curves of surgeons A and B were respectively divided into two phases at the 47th and 32nd cases for laparoscopic surgery and at the 23rd and 25th cases for robotic surgery. The clinicopathological outcomes of the two surgeons were similar in each phase of the learning curve for each surgery. Conclusions: For surgeons with rich experience in open colorectal resections, simultaneous training for laparoscopic and robotic-assisted LAR of rectal cancer is safe, effective, and associated with accelerated learning curves.

An evaluation of the clinical efficacy of the application of 28mm cryoballoon for linear ablation of left atrial apex combined with enlarged pulmonary vein vestibule ablation for persistent atrial fibrillation.

OBJECTIVE: to retrospectively investigate the efficacy and safety of the application of 28 mm cryoballoon for pulmonary vein electrical isolation (PVI) combined with top left atrial linear ablation and pulmonary vein vestibular expansion ablation for persistent atrial fibrillation. METHODS: From July 2016 to December 2020, 413 patients diagnosed with persistent atrial fibrillation were evaluated, including 230 (55.7%) in the PVI group (PVI only) and 183 (44.3%) in the PVIPLUS group (PVI plus ablation of the left atrial apex and pulmonary vein vestibule). The safety and efficacy of the two groups were retrospectively analyzed. RESULTS: The AF/AT/AFL-free survival rates at 6, 12, 18, 24 and 30 months after procedure was 86.6%, 72.6%, 70.0%, 61.1% and 56.3% in the PVI group and 94.5%, 87.0%, 84.1%, 75.0% and 67.9% in the PVIPLUS group, respectively. At 30 months after procedure, the AF/AT/AFL-free survival rate was significantly higher in the PVIPLUS group than in the PVI group (P = 0.036; HR:0.63; 95% CI:0.42 to 0.95). CONCLUSION: The application of 28-mm cryoballoon for pulmonary vein electrical isolation combined with linear ablation of the left atrial apex and expanded ablation of the pulmonary vein vestibule improves the outcome of persistent atrial fibrillation.

Nitrogen fertilization rates mediate rhizosphere soil carbon emissions of continuous peanut monoculture by altering cellulose-specific microbess.

Introduction: Crops influence both soil microbial communities and soil organic carbon (SOC) cycling through rhizosphere processes, yet their responses to nitrogen (N) fertilization have not been well investigated under continuous monoculture. Methods: In this study, rhizosphere soil microbial communities from a 5-year continuous mono-cropped peanut land were examined using Illumina HighSeq sequencing, with an N fertilization gradient that included 0 (N0), 60 (N60), 120 (N120) and 180 (N180) kg hm-2. Soil respiration rate (R s) and its temperature sensitivity (Q 10) were determined, with soil carbon-acquiring enzyme activities assayed. Results and discussion: The obtained results showed that with N fertilization, soil mineral N (Nmin) was highly increased and the soil C/N ratio was decreased; yields were unchanged, but root biomass was stimulated only at N120. The activities of ß-1,4-glucosidase and polyphenol oxidase were reduced across application rates, but that of ß-1,4-cellobiohydrolase was increased only at N120. Bacterial alpha diversity was unchanged, but fungal richness and diversity were increased at N60 and N120. For bacterial groups, the relative abundance of Acidobacteria was reduced, while those of Alphaproteobacteria and Gammaproteobacteria were increased at N60 and N120. For fungal members, the pathogenic Sordariomycetes was inhibited, but the saprotrophic Agaricomycetes was promoted, regardless of N fertilization rates. RDA identified different factors driving the variations in bacterial (root biomass) and fungal (Nmin) community composition. N fertilization increased R s slightly at N60 and significantly at N120, mainly through the promotion of cellulose-related microbes, and decreased R s slightly at N180, likely due to carbon limitation. N fertilization reduced microbial biomass carbon (MBC) at N60, N120 and N180, decreased SOC at N120 and N180, and suppressed dissolved organic carbon (DOC) at N180. In addition, the unchanged Q 10 may be a joint result of several mechanisms that counteracted each other. These results are of critical importance for assessing the sustainability of continuously monocultured ecosystems, especially when confronting global climate change.

Early versus late drain removal in patients after pancreatoduodenectomy: A systematic review and meta-analysis.

Whether early or late drain removal (EDR/LDR) is better for patients after pancreatic resection remains controversial. We aim to systematically evaluate the safety and efficacy of early or late drain removal in patients who undergo pancreatic resection. We searched seven databases from January 1, 2000, through September 2021, and included randomized controlled trials (RCTs) or observational studies comparing EDR vs. LDR in patients after pancreatic resection. We separately pooled effect estimates across RCTs and observational studies. Finally, we included 4 RCTs with 711 patients and 8 nonRCTs with 7207 patients. Based on the pooled RCT data, compared to LDR, EDR reduced hospital length of stay (LOS) (RR: -2.59, 95% CI: -4.13 to -1.06) and hospital cost (RR: -1022.27, 95% CI: -1990.39 to -54.19). Based on the pooled nonRCT data, EDR may reduce the incidence of all complications (OR: 0.45, 95% CI: 0.32 to 0.63), pancreatic fistula (OR: 0.26, 95% CI: 0.15 to 0.45), wound infection (RR: 0.59, 95% CI: 0.06 to 5.45)), reoperation (OR: 0.62, 95% CI: 0.40 to 0.96) and hospital readmission (OR: 0.57, 95% CI: 0.47 to 0.69). There was an uncertain effect on mortality (OR from pooled nonRCTs: 1.02, 95% CI: 0.41 to 2.53) and delayed gastric emptying (RR from pooled RCTs: 0.76, 95% CI: 0.41 to 1.41). The findings of this meta-analysis suggest that early drain removal is associated with lower hospital cost, is safe and may reduce the incidence of complications compared to late drain removal in patients after pancreaticoduodenectomy.

Remimazolam besylate for the sedation of postoperative patients undergoing invasive mechanical ventilation in the ICU: a prospective dose‒response study.

This single-center study aimed to determine the effective dose and safety of remimazolam besylate for the sedation of postoperative patients undergoing invasive mechanical ventilation in the intensive care unit (ICU). Mechanically ventilated patients admitted to the ICU after surgery were included. The Narcotrend index (NTI) was used to assess the depth of sedation, and the Richmond Agitation-Sedation Scale (RASS) score was also recorded. Remimazolam besylate was administered initially at a loading dose of 0.02 mg/kg, followed by a gradual increase of 0.005 mg/kg each time until the targeted depth of sedation was achieved (NTI 65-94). A maintenance dose of remimazolam besylate was administered starting at 0.2 mg/kg/h, followed by increments or subtractions of 0.05 mg/kg/h each time until a satisfactory depth of sedation was achieved and maintained for at least 30 min. The demographic data, anesthesia, surgery types, hemodynamics and respiratory parameters were recorded. Adverse events and adverse drug reactions were monitored for safety. Twenty-three patients were eventually included in this study covering a period of 1 year. A satisfactory depth of sedation was achieved by a single intravenous infusion of remimazolam besylate at a loading dose of 0.02-0.05 mg/kg followed by a maintenance dose of 0.20-0.35 mg/kg/h. There were no significant changes in hemodynamic and respiratory parameters within 10 min after the administration of remimazolam besylate. In addition, a significant correlation was observed between the NTI and the RASS score for assessing sedation (r = 0.721, P < 0.001). The NTI showed a predictive probability for a RASS score of 0.817. Remimazolam besylate was effective for mild/moderate sedation of invasively mechanically ventilated postoperative patients in the ICU while maintaining excellent respiratory and hemodynamic stability. The NTI can be used as a good tool for the objective evaluation of the depth of sedation and agitation.

Effects of spleen nerve denervation on depression-like phenotype, systemic inflammation, and abnormal composition of gut microbiota in mice after administration of lipopolysaccharide: A role of brain-spleen axis.

BACKGROUND: Accumulating evidence suggests the role of brain-spleen axis as well as brain-gut-microbiota axis in inflammation-related depression. The spleen mediates anti-inflammatory effects of the vagus nerve which plays a role in depression. However, the role of spleen nerve in inflammation-related depression remains unclear. METHODS: The effects of the splenic nerve denervation (SND) in the depression-like phenotype, systemic inflammation, and abnormal composition of gut microbiota in adult mice after administration of lipopolysaccharide (LPS) were examined. RESULTS: LPS (0.5 mg/kg) caused depression-like phenotype, systemic inflammation, splenomegaly, increased expression of Iba1 (ionized calcium-binding adapter molecule 1) and decreased expression of postsynaptic density protein-95 (PSD-95) in the hippocampus in the sham-operated mice. In contrast, LPS did not produce depression-like phenotype, and abnormal expressions of Iba1 and PSD-95 in the hippocampus in the SND-operated mice. Furthermore, SND significantly blocked LPS-induced increased plasma levels of pro-inflammatory cytokine interleukin-6 although SND did not affect LPS-induced splenomegaly and increased plasma levels of tumor necrosis factor-α in mice. There were significant changes in several microbiota among the four groups. Interestingly, there were correlations between the relative abundance of several microbiota and Iba1 (or PSD-95) expression in the hippocampus. In addition, expression of Iba1 in the hippocampus was correlated with the relative abundance of several microbiota. LIMITATIONS: Detailed mechanisms are unclear. CONCLUSIONS: These results suggest that the splenic nerve plays a role in inflammation-related depression, microglial activation in the hippocampus, and that gut microbiota may regulate microglial function in the brain via gut-microbiota-brain axis.

Effects of (R)-ketamine on reduced bone mineral density in ovariectomized mice: A role of gut microbiota.

Depression is a high risk for osteoporosis, suggesting an association between depression and low bone mineral density (BMD). We reported that the novel antidepressant (R)-ketamine could ameliorate the reduced BMD in the ovariectomized (OVX) mice which is an animal model of postmenopausal osteoporosis. Given the role of gut microbiota in depression and bone homeostasis, we examined whether gut microbiota plays a role in the beneficial effects of (R)-ketamine in the reduced BMD of OVX mice. OVX or sham was operated for female mice. Subsequently, saline (10 ml/kg/day, twice weekly) or (R)-ketamine (10 mg/kg/day, twice weekly) was administered intraperitoneally into OVX or sham mice for the six weeks. The reduction of cortical BMD and total BMD in the OVX mice was significantly ameliorated after subsequent repeated intermittent administration of (R)-ketamine. Furthermore, there were significant changes in the α- and ß-diversity between OVX + saline group and OVX + (R)-ketamine group. There were correlations between several OTUs and cortical (or total) BMD. There were also positive correlations between the genera Turicibacter and cortical (or total) BMD. Moreover, there were correlations between several metabolites in blood and cortical (or total) BMD. These data suggest that (R)-ketamine may ameliorate the reduced cortical BMD and total BMD in OVX mice through anti-inflammatory actions via gut microbiota. Therefore, it is likely that (R)-ketamine would be a therapeutic drug for depressed patients with low BMD or patients with osteoporosis.

Transverse myelitis in systemic lupus erythematosus: A case report and systematic literature review.

OBJECTIVE: Acute transverse myelitis (TM) is a rare complication secondary to systemic lupus erythematosus (SLE) that can cause patients' extensive and severe neuropsychiatric disorders. Due to the rarity of the onset of acute TM, there is still no standard treatment protocol. This study was to summarize the clinical features of SLE-TM through a case report and systematic review. METHODS: We report a case of acute TM with the initial symptoms of headache and fever on admission to hospital, with lesions in medulla oblongata, cervical medulla, and thoracic medulla. Furthermore, all cases of SLE combined with acute TM from January 1975 to February 2022 were concluded and reviewed to compare the disease's current treatment strategies and prognosis. RESULTS: Patients with SLE-TM are mainly female (97.65%), with an average age of 36.89, a TM incidence of 24.51% and a longitudinal myelitis (LM) incidence of 67.76%. In addition, 68.63% of patients present an increased albumin, and only 16.50% of patients could recover. 32.35% of patients showed positive anti-cardiolipin antibody. Moreover, the patients who could recover are generally younger than those in the improved and paraparesis groups. After classifying the statistical results twice according to magnetic resonance imaging results and prognosis respectively, the erythrocyte sedimentation rate (ESR) in LM group was significantly higher than that in the other two groups. The positive rate of anti-DNA and anti-cardiolipin antibody (ANCL) in TM group was significantly higher than that of the other groups. According to the prognostic grouping, ESR in the recovery group was significantly higher than those in the other two groups. The positive ANCL in the poor prognosis group was slightly higher than that in the other two groups. CONCLUSION: We offer a novel insight for this rare disease and hope to bring some inspiration the basic research for SLE-TM.

Nuclear factor of activated T cells 4 in the prefrontal cortex is required for prophylactic actions of (R)-ketamine.

(R, S)-ketamine has prophylactic antidepressant-like effects in rodents; however, the precise molecular mechanisms underlying its action remain unknown. Using RNA-sequencing analysis, we searched novel molecular target(s) that contribute to the prophylactic effects of (R)-ketamine, a more potent enantiomer of (R, S)-ketamine. Pretreatment with (R)-ketamine (10 mg/kg, 6 days before) significantly ameliorated body weight loss, splenomegaly, and increased immobility time of forced swimming test in lipopolysaccharide (LPS: 1.0 mg/kg)-treated mice. RNA-sequencing analysis of prefrontal cortex (PFC) and subsequent IPA (Ingenuity Pathway Analysis) revealed that the nuclear factor of activated T cells 4 (NFATc4) signaling might contribute to sustained prophylactic effects of (R)-ketamine. Quantitative RT-PCR confirmed that (R)-ketamine significantly attenuated the increased gene expression of NFATc4 signaling (Nfatc4, Cd4, Cd79b, H2-ab1, H2-aa) in the PFC of LPS-treated mice. Furthermore, pretreatment with NFAT inhibitors (i.e., NFAT inhibitor and cyclosporin A) showed prophylactic effects in the LPS-treated mice. Similar to (R)-ketamine, gene knockdown of Nfatc4 gene by bilateral injection of adeno-associated virus (AAV) into the mPFC could elicit prophylactic effects in the LPS-treated mice. In conclusion, our data implicate a novel NFATc4 signaling pathway in the PFC underlying the prophylactic effects of (R)-ketamine for inflammation-related depression.