Diagnosis of poorly differentiated adenocarcinoma of the stomach by confocal laser endomicroscopy: A case report.

BACKGROUND: In recent years, confocal laser endomicroscopy (CLE) has become a new endoscopic imaging technology at the microscopic level, which is extensively performed for real-time in vivo histological examination. CLE can be performed to distinguish benign from malignant lesions. In this study, we diagnosed using CLE an asymptomatic patient with poorly differentiated gastric adenocarcinoma. CASE SUMMARY: A 63-year-old woman was diagnosed with gastric mucosal lesions, which may be gastric cancer, in the small curvature of the stomach by gastroscopy. She consented to undergo CLE for morphological observation of the gastric mucosa. Through the combination of CLE diagnosis and postoperative pathology, the intraoperative CLE diagnosis was considered to be reliable. According to our experience, CLE can be performed as the first choice for the diagnosis of gastric cancer. CONCLUSION: CLE has several advantages over pathological diagnosis. We believe that CLE has great potential in the diagnosis of benign and malignant gastric lesions.

Mouse auditory cortex sub-fields receive neuronal projections from MGB subdivisions independently.

Mouse auditory cortex is composed of six sub-fields: primary auditory field (AI), secondary auditory field (AII), anterior auditory field (AAF), insular auditory field (IAF), ultrasonic field (UF) and dorsoposterior field (DP). Previous studies have examined thalamo-cortical connections in the mice auditory system and learned that AI, AAF, and IAF receive inputs from the ventral division of the medial geniculate body (MGB). However, the functional and thalamo-cortical connections between nonprimary auditory cortex (AII, UF, and DP) is unclear. In this study, we examined the locations of neurons projecting to these three cortical sub-fields in the MGB, and addressed the question whether these cortical sub-fields receive inputs from different subsets of MGB neurons or common. To examine the distributions of projecting neurons in the MGB, retrograde tracers were injected into the AII, UF, DP, after identifying these areas by the method of Optical Imaging. Our results indicated that neuron cells which in ventral part of dorsal MGB (MGd) and that of ventral MGB (MGv) projecting to UF and AII with less overlap. And DP only received neuron projecting from MGd. Interestingly, these three cortical areas received input from distinct part of MGd and MGv in an independent manner. Based on our foundings these three auditory cortical sub-fields in mice may independently process auditory information.

Influence of centroid acceleration acquisition and filtering class on head injury criterion evaluation.

BACKGROUND: Although the Head Injury Criteria (HIC) has been widely applied to assess head impact injuries, it faces two outstanding problems: 1) HIC is affected strongly by the cut-off frequency when processing acceleration signals. And these cut-off frequencies are experiential and lack unified guidelines; 2) If the head was impacted on a different part, should the corresponding HIC threshold be the same? If these problems are not resolved, it could potentially lead to a critical misinterpretation of the safety assessment. METHODS: Finite element method was used to reconstruct head impacts. The head model includes tissues like skull, brainstem, cerebrospinal fluid, etc. The head model was impacted in the frontal, occipital, parietal or lateral direction with different impact velocities. Acceleration signals of the head model were extracted directly from the skull and the head centroid node. To obtain a robust HIC, the filtering class of acceleration signals were analyzed carefully. Then, the relation between rigid body HIC and the centroid node HIC were studied systematically. RESULTS: When the filtering class of rigid body acceleration and centroid node acceleration reached the cut-off frequency, the corresponding derivative of HIC tended to change smoothly. Using these cut-off frequencies, robust HICs were obtained. The rigid body HIC far exceeded that of centroid node HIC, such as 8, 9, 14 and 31 times exceeded in the frontal, occipital, parietal and lateral impact conditions, respectively. Moreover, approximate linear relations were found between the rigid body HIC and the centroid node HIC in different impact directions, respectively. From these relations, the injury thresholds of rigid body HIC of various directions were given quantitatively. CONCLUSIONS: The rational filtering class like CFC 800 and CFC 700 were given for rigid body HIC and centroid node HIC, respectively. The rigid body HIC had a significant discrepancy from the centroid node HIC. Linear relations between the rigid body HIC and centroid node HIC were found, and their slopes changed with impact directions. From these relations, we can adjust the injury thresholds reasonably if the head receives different impacts. These findings can effectively enhance the applicability of HIC.

Uncovering lupus nephritis-specific genes and the potential of TNFRSF17-targeted immunotherapy: a high-throughput sequencing study.

Introduction: Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE). This study aimed to identify LN specific-genes and potential therapeutic targets. Methods: We performed high-throughput transcriptome sequencing on peripheral blood mononuclear cells (PBMCs) from LN patients. Healthy individuals and SLE patients without LN were used as controls. To validate the sequencing results, qRT-PCR was performed for 5 upregulated and 5 downregulated genes. Furthermore, the effect of the TNFRSF17-targeting drug IBI379 on patient plasma cells and B cells was evaluated by flow cytometry. Results: Our analysis identified 1493 and 205 differential genes in the LN group compared to the control and SLE without LN groups respectively, with 70 genes common to both sets, marking them as LN-specific. These LN-specific genes were significantly enriched in the 'regulation of biological quality' GO term and the cell cycle pathway. Notably, several genes including TNFRSF17 were significantly overexpressed in the kidneys of both LN patients and NZB/W mice. TNFRSF17 levels correlated positively with urinary protein levels, and negatively with complement C3 and C4 levels in LN patients. The TNFRSF17-targeting drug IBI379 effectively induced apoptosis in patient plasma cells without significantly affecting B cells. Discussion: Our findings suggest that TNFRSF17 could serve as a potential therapeutic target for LN. Moreover, IBI379 is presented as a promising treatment option for LN.

Sodium butyrate restricts neutrophils migration and NETs formation through reducing macrophage-derived CXCL16 in calculous cholecystitis.

Background: Neutrophil extracellular traps (NETs) havebeen demonstrated to initiate gallstone formation. Cholecystitis is a common complication of gallstones. As short-chain fatty acids (SCFAs), Butyrate acid has anti-inflammatory effects and alleviates cholesterol gallstones. However, the role of Butyrate acid in NETs of calculous cholecystitis and the molecular mechanism remains unclear. The effect of Sodium butyrate on neutrophil migration and NETs formation involved in macrophages polarization and exosomalCXCL16 in calculous cholecystitis was explored in our study. Methods: The number of neutrophils and NETs, macrophages polarization and exosomal CXCL16 level were analyzed in clinic samples from patients. Exosomes were obtained and verified by gradient centrifugation, transmission electron microscopy, NanoSight analysis and Western blotting. Transwell, immunofluorescence and ELISA were used to detect neutrophil migration and NETs formation. Results: Our results demonstrated that a large number of neutrophils and NETs, as well as M1 macrophages and exosomal CXCL16, were found in the blood of gallstones patients, especially patients with acute calculous cholecystitis. Exosomal CXCL16 was upregulated in plasma of calculous cholecystitis patients or Lipopolysaccharide induced macrophages, and promoted neutrophil cell migration and NETs formation. Sodium butyrate reduced exosomal CXCL16 secretion through the inhibition of M1 macrophage polarization to suppress neutrophils migration and NETs formation. Conclusion: Our study suggested that Sodium butyrate may inhibit neutrophils migration and NETs formation to alleviate calculous cholecystitis by reducing exosomal CXCL16 secretion from macrophage and macrophage polarization. General significance: Our finding may provide a link between exosomes and neutrophils to serve as a potential therapeutic intervention in calculous cholecystitis.

Running Gait and Control of Quadruped Robot Based on SLIP Model.

Legged robots have shown great adaptability to various environments. However, conventional walking gaits are insufficient to meet the motion requirements of robots. Therefore, achieving high-speed running for legged robots has become a significant research topic. In this paper, based on the Spring-Loaded Inverted Pendulum (SLIP) model and the optimized Double leg-Spring-Loaded Inverted Pendulum (D-SLIP) model, the running control strategies for the double flying phase Bound gait and the Rotatory gallop gait of quadruped robots are designed. First, the dynamics of the double flying phase Bound gait and Rotatory gallop gait are analyzed. Then, based on the "three-way" control idea of the SLIP model, the running control strategy for the double flying phase Bound gait is designed. Subsequently, the SLIP model is optimized to derive the D-SLIP model with two touchdown legs, and its dynamic characteristics are analyzed. And the D-SLIP model is applied to the running control strategy of the Rotatory gallop gait. Furthermore, joint simulation verification is conducted using Adams virtual prototyping and MATLAB/Simulink control systems for the designed control strategies. Finally, experimental verification is performed for the double flying phase Bound gait running control strategy. The experimental results demonstrate that the quadruped robot can achieve high-speed and stable running.

Multifaceted Characterization of Human Embryonic Stem Cell-Derived Mesenchymal Stem/Stromal Cells Revealed Amelioration of Acute Liver Injury in NOD-SCID Mice.

Human embryonic stem cells (hESCs) are advantaged sources for large-scale and homogeneous mesenchymal stem/stromal cells (MSCs) generation. However, due to the limitations in high-efficiency procedures for hESC-MSCs induction, the systematic and detailed information of mesengenesis and early MSC development are largely obscure. In this study, we took advantage of the well-established twist-related protein 1 (TWIST1)-overexpressing hESCs and two small molecular cocktails (CHIR99021, decitabine) for high-efficient MSC induction. To assess the multidimensional biological and transcriptomic characteristics, we turned to cellular and molecular methods, such as flow cytometry (FCM), quantitative reverse transcription-polymerase chain reaction (qRT-PCR), in vitro tri-lineage differentiation, cytokine secretion analysis, in vivo transplantation for acute liver injury (ALI) management, and bioinformatics analyses (eg, gene ontology-biological processes [GO-BP], Kyoto Encyclopedia of Genes and Genomes [KEGG], HeatMap, and principal component analysis [PCA]). By combining TWIST1 overexpression (denoted as T) and the indicated small molecular cocktails (denoted as S), hESCs high-efficiently differentiated into MSCs (denoted as TS-MSCs, induced by T and S combination) within 2 weeks. TS-MSCs satisfied the criteria for MSC definition and revealed comparable tri-lineage differentiation potential and ameliorative efficacy upon ALI mice. According to RNA-sequencing (SEQ) analysis, we originally illuminated the gradual variations in gene expression pattern and the concomitant biofunctions of the programmed hESC-MSCs. Overall, our data indicated the feasibility of high-efficient generation of hESC-MSCs by TWIST1 and cocktail-based programming. The generated hESC-MSCs revealed multifaceted in vivo and in vitro biofunctions as adult BM-MSCs, which collectively suggested promising prospects in ALI management in future.

Interactome profiling of Crimean-Congo hemorrhagic fever virus glycoproteins.

Crimean-Congo hemorrhagic fever virus (CCHFV) is a biosafety level-4 pathogen requiring urgent research and development efforts. The glycoproteins of CCHFV, Gn and Gc, are considered to play multiple roles in the viral life cycle by interactions with host cells; however, these interactions remain largely unclear to date. Here, we analyzed the cellular interactomes of CCHFV glycoproteins and identified 45 host proteins as high-confidence Gn/Gc interactors. These host molecules are involved in multiple cellular biological processes potentially associated with the physiological actions of the viral glycoproteins. Then, we elucidated the role of a representative cellular protein, HAX1. HAX1 interacts with Gn by its C-terminus, while its N-terminal region leads to mitochondrial localization. By the strong interaction, HAX1 sequestrates Gn to mitochondria, thus depriving Gn of its normal Golgi localization that is required for functional glycoprotein-mediated progeny virion packaging. Consistently, the inhibitory activity of HAX1 against viral packaging and hence propagation was further elucidated in the contexts of pseudotyped and authentic CCHFV infections in cellular and animal models. Together, the findings provide a systematic CCHFV Gn/Gc-cell protein-protein interaction map, but also unravel a HAX1/mitochondrion-associated host antiviral mechanism, which may facilitate further studies on CCHFV biology and therapeutic approaches.

Cause of death during nasopharyngeal carcinoma survivorship: a population-based analysis.

Background: Recently, the survival rate of nasopharyngeal carcinoma (NPC) patients has improved greatly due to developments in NPC treatments. But cause-specific mortality in NPC patients remains unclear. This study aims to investigate the common causes of death in NPC patients. Methods: Eligible patients with NPC were included from the Surveillance, Epidemiology, and End Results (SEER) database. Standardized mortality ratios(SMRs) were calculated to compare death rates in NPC patients with those in the general population. Results: A total of 3475 patients with NPC were included, of whom 1696 patients died during the follow-up period. 52.83% of deaths were caused by NPC, followed by other cancers (28.13%) and non-cancer causes (18.46%). The proportion of patients who died of NPC decreased over survival time. Moreover, non-cancer causes of death increase from 12.94% to 51.22% over time after 10 years of diagnosis. Heart diseases was the most common non-cancer cause of death in NPC patients. Conclusions: Although NPC remains the leading cause of death after NPC diagnosis, other non-NPC causes of death represent an increased number of death in NPC patients. These findings support the involvement of multidisciplinary care for follow-up strategy in NPC patients.

A comparative study of the predictive value of four models for death in patients with severe burns.

OBJECTIVE: To assess the prognostic value of the Ryan score, Belgian Outcome of Burn Injury (BOBI) score,revised Baux (rBaux) score, and a new model (a Logit(P)-based scoring method created in 2020) for predicting mortality risk in patients with extremely severe burns and to conduct a comparative analysis. METHODS: A retrospective analysis was conducted on 599 burn patients who met the inclusion criteria and were admitted to the burn unit of the First Affiliated Hospital of Nanchang University from 2017 to 2022. Relevant information was collected, and receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were plotted for each of the four models in assessing mortality in these burn patients using both age-stratified and unstratified forms. The ROC curve section was further compared with the area under the curve (AUC), optimal cutoff value, as well as its sensitivity and specificity. Additionally, the quality of the AUC was assessed using the Delong test. RESULT: Among the patients who met the inclusion criteria, 532 were in the survival group and 67 in the death group. Irrespective of age stratification, the novel model exhibited superior performance with an AUC of 0.868 (95% CI: 0.838-0.894) among all four models predicting mortality risk in included patients, and also demonstrated better AUC quality than other models; the calibration curves showed that the accuracy of all four models was good; the DCA curves showed that the clinical utility of the novel model and rBuax score were better. In the comparison of four scoring models across different age groups, the new model demonstrated the largest AUC in both 0-19 years (0.954, 95% CI 0.914-0.979) and 20-59 years groups (0.838, 95% CI 0.793-0.877), while rBuax score exhibited the highest AUC in ≥ 60 years group (0.708, 95% CI of 0.602-0.800). The calibration curves showed that the four models exhibited greater accuracy within the age range of 20-59 years, while the DCA curves indicated that both the novel model and rBuax score scale displayed better prediction in both the 20-59 and ≥ 60 years groups. CONCLUSIONS: All four models demonstrate accurate and effective prognostication for patients with severe burns. Both the novel model and rBaux score exhibit enhanced prediction utility. In terms of the model itself alone, the new model is not simpler than, for example, the rBaux score, and whether it can be applied clinicallyinvolves further study.

Proliferative glomerulonephritis with monoclonal IgG Lambda deposits caused by plasmablastic lymphoma: a case report.

INTRODUCTION: As a very rare form of B-cell lymphoma, plasmablastic lymphoma (PBL) typically occurs in patients with underlying immunosuppression, including human immunodeficiency virus (HIV), organ transplantation, and autoimmune diseases. For HIV-positive patients, PBL normally originates in the gastrointestinal tract, especially from the oral cavity in most cases. It is extremely rare to find abdominal cavity involvement in PBL, and there has been no previously reported instance of proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) attributed to monoclonal IgG (MIgG) lambda secreted by PBL. CASE PRESENTATION: We report the case of an HIV-negative female with nephrotic syndrome, renal insufficiency, and multiple swollen lymph nodes. Ascitic fluid cytology revealed a high level of plasmablast-like lymphocytes with the restriction of lambda light chains. Besides, the renal biopsy revealed PGNMID, which could presumably be secondary to MIgG-lambda-secreting by PBL. MIgG-lambda-restricted expression was discovered earlier in the kidney tissue than in the blood. CONCLUSION: The diagnostic landscape for PBL is notoriously intricate, necessitating a multifaceted and nuanced approach to mitigate the risks of erroneous identification.

Exploring the challenge of early gastric cancer diagnostic AI system face in multiple centers and its potential solutions.

BACKGROUND: Artificial intelligence (AI) performed variously among test sets with different diversity due to sample selection bias, which can be stumbling block for AI applications. We previously tested AI named ENDOANGEL, diagnosing early gastric cancer (EGC) on single-center videos in man-machine competition. We aimed to re-test ENDOANGEL on multi-center videos to explore challenges applying AI in multiple centers, then upgrade ENDOANGEL and explore solutions to the challenge. METHODS: ENDOANGEL was re-tested on multi-center videos retrospectively collected from 12 institutions and compared with performance in previously reported single-center videos. We then upgraded ENDOANGEL to ENDOANGEL-2022 with more training samples and novel algorithms and conducted competition between ENDOANGEL-2022 and endoscopists. ENDOANGEL-2022 was then tested on single-center videos and compared with performance in multi-center videos; the two AI systems were also compared with each other and endoscopists. RESULTS: Forty-six EGCs and 54 non-cancers were included in multi-center video cohort. On diagnosing EGCs, compared with single-center videos, ENDOANGEL showed stable sensitivity (97.83% vs. 100.00%) while sharply decreased specificity (61.11% vs. 82.54%); ENDOANGEL-2022 showed similar tendency while achieving significantly higher specificity (79.63%, p < 0.01) making fewer mistakes on typical lesions than ENDOANGEL. On detecting gastric neoplasms, both AI showed stable sensitivity while sharply decreased specificity. Nevertheless, both AI outperformed endoscopists in the two competitions. CONCLUSIONS: Great increase of false positives is a prominent challenge for applying EGC diagnostic AI in multiple centers due to high heterogeneity of negative cases. Optimizing AI by adding samples and using novel algorithms is promising to overcome this challenge.

Setting 6-Minute Minimal Examination Time Improves the Detection of Focal Upper Gastrointestinal Tract Lesions During Endoscopy: A Multicenter Prospective Study.

INTRODUCTION: Positive correlation between examination time and neoplasm detection using esophagogastroduodenoscopy (EGD) has been described by observational studies, but the effect of setting minimal examination time still requires investigation. METHODS: This prospective, 2-stage, interventional study was conducted in 7 tertiary hospitals in China, enrolling consecutive patients undergoing intravenously sedated diagnostic EGDs. In stage I, the baseline examination time was collected without informing the endoscopists. In stage II, the minimal examination time was set for the same endoscopist according to the median examination time of normal EGDs in stage I. The primary outcome was the focal lesion detection rate (FDR), defined as the proportion of subjects with at least one focal lesion among all subjects. RESULTS: A total of 847 and 1,079 EGDs performed by 21 endoscopists were included in stages I and II, respectively. In stage II, the minimal examination time was set as 6 minutes, and the median time for normal EGD increased from 5.8 to 6.3 minutes ( P < 0.001). Between the 2 stages, the FDR was significantly improved (33.6% vs 39.3%, P = 0.011), and the effect of the intervention was significant (odds ratio, 1.25; 95% confidence interval, 1.03-1.52; P = 0.022) even after adjusting for subjects' age, smoking status, endoscopists' baseline examination time, and working experience. The detection rate of high-risk lesions (neoplastic lesions and advanced atrophic gastritis) was also significantly higher in stage II (3.3% vs 5.4%, P = 0.029). In the endoscopist-level analysis, all practitioners reached a median examination time of 6 minutes, and the coefficients of variation of FDR (36.9%-26.2%) and examination time (19.6%-6.9%) decreased in stage II. DISCUSSION: Setting a 6-minute minimal examination time significantly improved the detection of focal lesions during EGDs and has the potential to be implemented for quality improvement.

A network causal relationship between type-1 diabetes mellitus, 25-hydroxyvitamin D level and systemic lupus erythematosus: Mendelian randomization study.

BACKGROUND: Observational studies have suggested a relationship between type-1 diabetes mellitus (T1DM) and systemic lupus erythematosus (SLE). In both autoimmunities, 25-hydroxyvitamin D (25-OHD) deficiency is common. However, the causality between T1DM, 25-OHD level and SLE remains largely unknown. METHODS: Independent genetic variants associated with T1DM, 25-OHD level, and SLE from the largest genome-wide association studies were used to conduct two-sample bidirectional Mendelian randomization (BIMR) and two-step Mendelian randomization (MR) analysis to estimate causal relationship between T1DM, 25-OHD level and SLE, and further multivariable Mendelian randomization (MVMR) was used to verify direct causality of T1DM and 25-OHD level on SLE. A series of sensitivity analysis as validation of primary MR results were performed. RESULTS: Consistent with the results of BIMR, there was strong evidence for a direct causal effect of T1DM on the risk of SLE (ORMVMR-IVW = 1.249, 95% CI = 1.148-1.360, PMVMR-IVW = 1.25×10-5), and 25-OHD level was negatively associated with the risk of SLE (ORMVMR-IVW = 0.305, 95% CI = 0.109-0.857, PMVMR-IVW = 0.031). We also observed a negative causal effect of T1DM on 25-OHD level (ORBIMR-IVW = 0.995, 95% CI = 0.991-0.999, PBIMR-IVW = 0.030) while the causal effect of 25-OHD level on the risk of T1DM did not exist (PBIMR-IVW = 0.106). In BIMR analysis, there was no evidence for causal effects of SLE on the risk of T1DM and 25-OHD level (PBIMR-IVW > 0.05, respectively). CONCLUSION: Our MR analysis suggested that there was a network causal relationship between T1DM, 25-OHD level and SLE. T1DM and 25-OHD level both have causal associations with the risk of SLE, and 25-OHD level could be a mediator in the causality of T1DM and SLE.

Oral administration of the herbal oligonucleotide XKC-sRNA-h3 prevents angiotensin II-induced hypertension in mice.

Hypertension has become a growing public health concern worldwide. In fact, hypertension is commonly associated with increased morbidity and mortality. Currently, oligonucleotide drugs have proven to be promising therapeutic agents for various diseases. In the present study, we aimed to demonstrate that a herbal small RNA (sRNA), XKC-sRNA-h3 (B55710460, F221. I000082.B11), exhibits potent antihypertensive effects by targeting angiotensin-converting enzyme (ACE) in mice. When compared with captopril, oral administration of the sphingosine (d18:1)-XKC-sRNA-h3 bencaosome more effectively prevented angiotensin II-induced hypertensive cardiac damage and alleviated kidney injury in mice. Such findings indicated that XKC-sRNA-h3 may be a novel orally available ACE inhibitor type oligonucleotide drug for hypertension.

Efficacy and Safety of CMAB008 Compared with Innovator Infliximab in Patients with Moderate-to-Severe Rheumatoid Arthritis Receiving Concomitant Methotrexate: A Randomized, Double-blind, Multi-center, Phase III Non-inferiority Study.

OBJECTIVES: The aim of this work is to verify the non-inferior efficacy and safety of CMAB008 compared with innovator infliximab in rheumatoid arthritis patients combined with methotrexate. METHODS: We conducted a randomized, double-blinded, parallel, positive control design, multicenter study, with a stable dose of methotrexate. Patients were enrolled randomly with a ratio of 1:1 to receive intravenously CMAB008 3 mg/kg or innovator infliximab 3 mg/kg at weeks 0, 2, 6, 14, 22 and 30. The primary efficacy endpoint was American College of Rheumatology 20% improvement criteria (ACR20) response rate at week 30. The non-inferiority was established if the lower limit of the one-sided 97.5% confidence interval (CI) for the difference was more than - 15% and the equivalence was established if the two-sided 95% CI was within ± 15% in an exploratory equivalence analysis. The secondary endpoints included other efficacy assessment parameters, as well as immunogenicity, safety, and pharmacokinetics. RESULTS: In the full analysis population (FAS), 110 (57.6%) of 191 patients in the CMAB008 group and 120 (62.2%) of 193 patients in the innovator infliximab group reached the primary outcome of ACR20 at week 30. The differences of the rates were - 4.6% and the lower limit of one-sided 97.5% confidence interval was - 14.29%, not less than the lower limit of the non-inferiority margin (- 15%); so CMAB008 was non-inferior to innovator infliximab. Further, CMAB008 was equivalent to innovator infliximab both in FAS (difference - 4.6%, 95% CI - 14.29% to 5.12%) and PPS (difference - 3.3%, 95% CI - 13.18% to 6.62%). The efficacy, safety, immunogenicity, and pharmacokinetics are highly similar between CMAB008 and innovator infliximab. CONCLUSIONS: Non-inferior efficacy of CMAB008 to innovator infliximab is illustrated with similar early and lasting therapeutic effects, and the equivalence is further demonstrated. CMAB008 is well tolerated and has semblable safety compared with the innovator infliximab. TRIAL REGISTRATION NUMBER: NCT03478111.

A sustainable revival process for defective LiFePO4 cathodes through the synergy of defect-targeted healing and in-situ construction of 3D-interconnected porous carbon networks.

The reutilization of spent cathode materials plays a key role in the sustainable development of Li-ion battery technology. However, current recycling approaches generally based on hydro-/pyrometallurgy fail to cater to Co-free cathodes (e.g., LiFePO4, or LFP) owing to high consumption and secondary contamination. Here, a sustainable process is proposed for the revival of defective LFP cathodes through the synergy of defect-targeted healing and surface modification. Li deficiency and Fe oxidation of cathodes are precisely repaired by solution-based relithiation; meanwhile, 3D-interconnected porous carbon networks (3dC) are in-situ constructed with the intervention of salt template during annealing, which enhances the rate performance and electronic/ionic conductivity, by providing more convenient migration channels for Li ions and controlling carbon hybridization. Nitrogen is also doped via induction of urea to fabricate advanced nanohybrid rLFP@3dC-N. New cells using rLFP@3dC-N as cathode exhibit a reversible capacity of up to 169.74 and 141.79 mAh g-1 at 0.1 and 1C, respectively, with an excellent retention rate of over 95.7% at 1C after 200 cycles. Impressively, a high capacity of 107.18 mAh g-1 is retained at 5C. This novel concepts for Li replenishment and the construction of ion-transfer channels as well as conductive networks facilitate the regeneration of spent LFP and the optimization of its high-rate performance.

Efficacy and safety of tofacitinib in Chinese patients with active psoriatic arthritis: a phase 3, randomised, double-blind, placebo-controlled study.

OBJECTIVES: Efficacy and safety of tofacitinib, an oral Janus kinase inhibitor, were evaluated in a 6-month, double-blind, phase 3 study in Chinese patients with active (polyarthritic) psoriatic arthritis (PsA) and inadequate response to ≥1 conventional synthetic disease-modifying antirheumatic drug. METHODS: Patients were randomised (2:1) to tofacitinib 5 mg twice daily (N=136) or placebo (N=68); switched to tofacitinib 5 mg twice daily after month (M)3 (blinded). PRIMARY ENDPOINT: American College of Rheumatology (ACR50) response at M3. Secondary endpoints (through M6) included: ACR20/50/70 response; change from baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI); ≥75% improvement in Psoriasis Area and Severity Index (PASI75) response, and enthesitis and dactylitis resolution. Safety was assessed throughout. RESULTS: The primary endpoint was met (tofacitinib 5 mg twice daily, 38.2%; placebo, 5.9%; p<0.0001). M3 ACR20/ACR70/PASI75 responses, and enthesitis and dactylitis resolution rates, were higher and HAQ-DI reduction was greater for tofacitinib 5 mg twice daily versus placebo. Incidence of adverse events (AEs)/serious AEs (M0-3): 68.4%/0%, tofacitinib 5 mg twice daily; 75.0%/4.4%, placebo. One death was reported with placebo→tofacitinib 5 mg twice daily (due to accident). One serious infection, non-serious herpes zoster, and lung cancer case each were reported with tofacitinib 5 mg twice daily; four serious infections and one non-serious herpes zoster case were reported with placebo→tofacitinib 5 mg twice daily (M0-6). No non-melanoma skin cancer, major adverse cardiovascular or thromboembolism events were reported. CONCLUSION: In Chinese patients with PsA, tofacitinib efficacy was greater than placebo (primary and secondary endpoints). Tofacitinib was well tolerated; safety outcomes were consistent with the established safety profile in PsA and other indications. TRIAL REGISTRATION NUMBER: NCT03486457.

Clinical value of the prognostic nutritional index and red blood cell distribution width-to-albumin ratio for the prediction of severity of and mortality associated with Stevens-Johnson syndrome/toxic epidermal necrolysis.

The prognostic nutritional index (PNI) and red blood cell distribution width-to-albumin ratio (RAR) are considered to be related to the prognosis of disease severity. However, the role of these biomarkers in predicting Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) severity and mortality is unclear. The aim of the current study was to investigate the association of PNI and RAR with severity and mortality in individuals with SJS/TEN. Clinical data were retrospectively collected from 74 individuals with SJS/TEN and 74 healthy individuals, who were matched for age and sex during the same period. PNI, RAR, and other indicators were compared between individuals with SJS/TEN and healthy controls. The association of PNI and RAR with SJS/TEN severity was assessed using Spearman or Pearson correlation analyses. Individuals with SJS/TEN were categorized into two groups, either survivors or nonsurvivors. The correlation between PNI, RAR, and SJS/TEN mortality was analyzed using univariate and multivariate logistic regression. The predictive value of the previously mentioned indicators on the mortality of patients with SJS/TEN was assessed using receiver operating characteristic curve analysis. The RAR level of patients with SJS/TEN was greater than that of the control group (p < 0.05), whereas PNI was lower. In compliance with correlation analysis, RAR was positively correlated with SCORTEN (Score of Toxic Epidermal Necrolysis) and ABCD-10 (age, bicarbonate, cancer, dialysis, 10% body surface area) (p < 0.05), and PNI was negatively correlated (p < 0.05). RAR is a risk factor for death in patients with SJS/TEN, but an elevated PNI level is a protective factor for mortality. The best cutoff values of PNI and RAR for predicting death in patients with SJS/TEN were 31.375 (sensitivity, 84.7%; specificity, 80%) and 0.486 (sensitivity, 73.3%; specificity, 84.7%). These results underscore the potential clinical value of PNI and RAR as appropriate and meaningful biomarkers to assess the severity of SJS/TEN and the mortality associated with it.