Preventing and treating neurotrophic keratopathy by a single intrastromal injection of AAV-mediated gene therapy.

PURPOSE: Neurotrophic keratopathy (NK) is a degenerative corneal condition resulting from corneal nerve injury. Current therapies, including the recombinant human nerve growth factor (rhNGF) therapy, requires continuous administration. This study aims to develop a novel and highly effective gene therapy strategy for the prevention and treatment of NK. METHODS: Adeno-associated virus (AAV) was transduced into corneal stromal cells by intrastromal injection. Three dimensional corneal wholemount imaging with co-immunostaining of ZO-1 and tubulin was utilized to assess the transduction of AAV.rh10. The efficacy of prevention and treatment of NK by a single intrastromal injection of AAV-Ngf was tested using capsaicin mouse model, herpes simplex keratitis (HSK) model, type Ⅱ diabetes model and alkali burn model. rhNGF eye drops served as the positive control. RESULTS: Intrastromal injection of AAV.rh10 efficiently transduced the subepithelial nerve plexus and retrogradely transported to the trigeminal ganglion (TG). A single injection of AAV.rh10-Ngf can significantly promote corneal nerve repair, accelerate corneal epithelial repair, reduce corneal stromal edema, and improve corneal sensitivity across the four NK models. The therapeutic effects were consistent with those achieved by continuous administration of rhNGF drops by 6 times daily. CONCLUSIONS: This proof-of-concept study demonstrates that AAV.rh10-Ngf gene therapy is a promising method for preventing and treating of NK. Our results underline the potential for developing clinical trials to further explore the safety and efficacy of such gene therapy.

Efficacy of orthokeratology lens with the modified small treatment zone on myopia progression and visual quality: a randomized clinical trial.

BACKGROUND: To evaluate the long-term effectiveness of orthokeratology (ortho-K) lenses with small treatment zone (STZ) or conventional treatment zone (CTZ) in controlling axial elongation in children with myopia as well as the impact on visual quality. We also sought to determine the effect of retinal visual signal quality on axial elongation. METHODS: This is a prospective randomized controlled study. A total of 140 participants (age ranging from 8 to 12 years) were randomly assigned to wear either STZ or CTZ ortho-K lenses. STZ ortho-K lenses design was achieved by changing the depth of reverse zone and the sagitta height of the optical zone. Using the IOL-Master 500, axial length (AL) was measured at baseline and after 6, 12 and 18 months of ortho-K treatment. Spherical aberration (SA) and corneal topographic parameters were obtained by the Pentacam anterior segment analyzer at baseline and the 1-month follow-up visit, and optical qualities were assessed by optical quality analysis system-II (OQAS-II) at baseline and after 1 month of lens wearing. Optical quality parameters mainly included the modulation transfer function (MTF) cutoff, Strehl ratio (SR), objective scattering index (OSI), and predicted visual acuity (PVA). RESULTS: A total of 131 participants completed the study, including 68 in the STZ group and 63 in the CTZ group. The STZ group had significantly reduced AL elongation compared to the CTZ group after treatment (12 months: 0.07 ± 0.11 mm vs. 0.14 ± 0.12 mm, P = 0.002; 18 months: 0.17 ± 0.15 mm vs. 0.26 ± 0.16 mm, P = 0.002). The topography in the STZ group showed a smaller treatment zone (TZ) diameter (2.50 ± 0.23 mm vs. 2.77 ± 0.18 mm, P < 0.001), a wider defocus ring width (2.45 ± 0.28 mm vs. 2.30 ± 0.30 mm, P = 0.006), and larger values of total amount of defocus (119.38 ± 63.71 D·mm2 vs. 91.40 ± 40.83 D·mm2, P = 0.003) and total SA (0.37 ± 0.25 µm vs. 0.25 ± 0.29 µm, P = 0.015), compared with the CTZ group. Objective visual quality decreased in both groups (P < 0.001). This was evidenced by a greater decrease in MTF cutoff (- 14.24 ± 10.48 vs. - 10.74 ± 9.46, P = 0.047) and SR values (- 0.09 ± 0.07 vs. - 0.06 ± 0.07, P = 0.026), and an increase in OSI value (0.84 ± 0.72 vs. 0.58 ± 0.53, P = 0.019). PVA9% decreased significantly in the STZ group but not the CTZ group. A statistically significant negative correlation was found between the changes in total SA and MTF cutoff values (r = - 0.202, P = 0.025). AL changes were associated with sex, change of MTF cutoff value, increment of total SA and TZ area. CONCLUSIONS: Compared with CTZ ortho-K lenses, STZ ortho-K lenses significantly inhibited axial elongation in children with myopia while moderately reducing their objective visual quality. Axial elongation was affected by retinal visual quality, and it may be a possible mechanism for ortho-K slowing myopia progression. Trial registration This trial is registered at Chinese Clinical Trial Registry on November 5, 2019 with trial registration number: ChiCTR1900027218. https://www.chictr.org.cn/showproj.html?proj=45380.

[Niche and interspecific association of main woody plants in Cunninghamia lanceolata plantation community in Jianfengling, China]. / 尖峰岭杉木人工林群落主要木本植物的生态位和种间联结.

Studies on niche and interspecific association can reveal plant interspecific relationship in the community, and provide theoretical support for promoting the transformation and development of plantation to natural forest. Based on Cunninghamia lanceolata investigation data of permanent plots of plantation in Jianfengling area of Hainan Tropical Rainforest National Park, we analyzed niche and interspecific association of the top 20 woody species in the community according to their importance values. The results showed that there were 163 species of woody species belonging to 101 genera and 55 families in the C. lanceolata plantation community, with complex species composition. As a constructive species, C. lanceolata had the highest importance value and niche breadth, and thus was the absolute dominant species in the community. It had a large niche overlap and niche similarity with many other species, among which the highest was observed in Adinandra hainanensis. The average niche overlap and niche similarity of the community were 0.54 and 0.49, respectively. The change trends of those two niche indicators were basically the same, indicating that some species were similar in resource demands. The overall association of main woody species was significantly positive. The χ2 test, association coefficient, Pearson correlation coefficient, and Spearman rank correlation coefficient suggested that the amounts of pairs with positive association were more than that with negative ones. The proportion of significant association species pairs was relatively low, indicating that the community stability was strong, species could coexist stably, and most species did not form close ties. On the whole, C. lanceolata had inhibited the regeneration of original tree species, and A. hainanensis, Garcinia oblongifolia, and Heptapleurum heptaphyllum could be used in natural transformation and restoration of C. lanceolata plantation in the Hainan Tropical Rainforest National Park.

[Growth characteristic of statolith of Todarodes pacificus in the East China Sea in the La Niña year]. / 拉尼娜发生期东海太平洋褶柔鱼耳石生长特征.

To investigate the differences on morphological growth patterns of statolith of Todarodes pacificus in the East China Sea during La Niña and normal years, we analyzed the samples of T. pacificus collected in the East China Sea by Chinese light purse seine fishery fleets from February to April in 2020 (a normal year) and 2021 (a La Niña year). The results showed that total statolith length (TSL), lateral dome length (LDL), wing length (WL), and maximum width (MW) could be used as characterization parameters to representing the morphological growth of statolith. The characterization parameters of statolith in T. pacificus differed significantly between different climate years and between different genders. The values of those characterization parameters of statolith were greater in normal year than those in La Niña year, which in both years were larger in females, except for TSL in males in La Niña year. The statolith growth of males were faster than that of females in different climate years. TSL, LDL, and WL increased faster in normal year, while MW increased faster in La Niña year. The relative size of statolith gradually slowed down with the growth of individuals.

Michael Acceptor Pyrrolidone Derivatives and Their Activity against Diffuse Large B-cell Lymphoma.

OBJECTIVE: This study aimed to design and evaluate the efficacy of pyrrolidone derivatives as potential therapeutic agents against diffuse large B-cell lymphoma (DLBCL), a common and heterogeneous malignancy of the adult lymphohematopoietic system. Given the limitations of current therapies, there is a pressing need to develop new and effective drugs for DLBCL treatment. METHODS: A series of pyrrolidone derivatives were synthesized, and their antitumor activities were assessed, particularly against DLBCL cell lines. Structure-activity relationship (SAR) analysis was conducted to identify key structural components essential for activity. The most promising compound, referred to as compound 7, was selected for further mechanistic studies. The expression levels of relevant mRNA and protein were detected by RT-qPCR and Western blotting, and the expression of mitochondrial membrane potential and ROS was detected using flow cytometry for further assessment of cell cycle arrest and apoptosis. RESULTS: The compound 7 exhibited good antitumor activity among the synthesized derivatives, specifically in DLBCL cell lines. SAR analysis highlighted the critical role of α, ß-unsaturated ketones in the antitumor efficacy of these compounds. Mechanistically, compound 7 was found to induce significant DNA damage, trigger an inflammatory response, cause mitochondrial dysfunction, and disrupt cell cycle progression, ultimately leading to apoptosis of DLBCL cells. CONCLUSION: The compound 7 has good antitumor activity and can induce multiple cellular mechanisms leading to cancer cell death. These findings warrant further investigation of the compound 7 as a potential therapeutic agent for DLBCL.

Individualized dosing parameters for tacrolimus in the presence of voriconazole: a real-world PopPK study.

Objectives: Significant increase in tacrolimus exposure was observed during co-administration with voriconazole, and no population pharmacokinetic model exists for tacrolimus in renal transplant recipients receiving voriconazole. To achieve target tacrolimus concentrations, an optimal dosage regimen is required. This study aims to develop individualized dosing parameters through population pharmacokinetic analysis and simulate tacrolimus concentrations under different dosage regimens. Methods: We conducted a retrospective study of renal transplant recipients who were hospitalized at the Second Xiangya Hospital of Central South University between January 2016 and March 2021. Subsequently, pharmacokinetic analysis and Monte Carlo simulation were employed for further analysis. Results: Nineteen eligible patients receiving tacrolimus and voriconazole co-therapy were included in the study. We collected 167 blood samples and developed a one-compartment model with first-order absorption and elimination to describe the pharmacokinetic properties of tacrolimus. The final typical values for tacrolimus elimination rate constant (Ka), apparent volume of distribution (V/F), and apparent oral clearance (CL/F) were 8.39 h-1, 2690 L, and 42.87 L/h, respectively. Key covariates in the final model included voriconazole concentration and serum creatinine. Patients with higher voriconazole concentration had lower tacrolimus CL/F and V/F. In addition, higher serum creatinine levels were associated with lower tacrolimus CL/F. Conclusion: Our findings suggest that clinicians can predict tacrolimus concentration and estimate optimal tacrolimus dosage based on voriconazole concentration and serum creatinine. The effect of voriconazole concentration on tacrolimus concentration was more significant than serum creatinine. These findings may inform clinical decision-making in the management of tacrolimus and voriconazole therapy in solid organ transplant recipients.

Open-field exploration immediately before the retention test impairs retrieval and spaced fear extinction of contextual fear memory.

According to the behavioral tagging theory, various stages of fear memory, such as contextual fear conditioning, memory retrieval, and fear extinction, can be facilitated by the exploration of a novel open field (OF). A critical time window of efficacy exists for this process. Novel exploration closely adjacent to weak learning may interfere with the setting of the learning tag, leading to a negative effect. In this mouse study, we consistently showed that exposure to a novel or familiar OF immediately prior to the retention test impaired the retrieval of long-term contextual fear memory. However, OF exposure had no effect on the retrieval of recent or remote cued fear memory or short-term contextual fear memory or the reconsolidation of contextual fear memory. In addition, OF exposure impaired spaced but not massed extinction of contextual fear memory. These results suggest that interfering stimulus may result in the transient forgetting of fear memory; however, temporary loss of fear may lead to retention failure of fear extinction. The results of this study are an important complement to the behavioral tagging theory and may provide new guidance for the treatment of post-traumatic stress disorder.

Heterotopic mesenteric ossification caused by trauma: A case report.

BACKGROUND: Heterotopic mesenteric ossification (HMO) is a clinically rare condition characterized by the formation of bone tissue in the mesentery. The worldwide reporting of such cases is limited to just over 70 instances in the medical literature. The etiology of HMO remains unclear, but the disease is possibly induced by mechanical trauma, ischemia, or intra-left lower quadrant abdominal infection, leading to the differentiation of mesenchymal stem cells into osteoblasts. Here, we present a rare case of HMO that occurred in a 34-year-old male, who presented with left lower quadrant abdominal pain. CASE SUMMARY: We report the case of a 34-year-old male patient who presented with left lower abdominal pain following trauma to the left lower abdomen. He subsequently underwent surgical treatment, and the postoperative pathological diagnosis was HMO. CONCLUSION: We believe that although there is limited literature and research on HMO, when patients with a history of trauma or surgery to the left lower abdomen present with corresponding imaging findings, clinicians should be vigilant in distinguishing this condition and promptly selecting appropriate diagnostic and therapeutic interventions.

Preventive and reparative potentials of heat-inactivated and viable commensal Bacillus pumilus SE5 in ameliorating the adverse impacts of high soybean meal in grouper (Epinephelus coioides).

Probiotic Bacillus pumilus SE5, heat-inactivated (HSE5) or active (ASE5), were supplemented to high soybean meal (HSM) (36 %) diet at whole term (0-56 days) and middle term (29-56 days) to investigate the preventing and repairing effects of B. pumilus SE5 in ameliorating the adverse effects of HSM in Epinephelus coioides. The results suggested that the HSM significantly decreased the weight gain rate (WGR), specific growth rate (SGR), and increased the feed conversion rate (FCR) at day 56 (P < 0.05), while HSE5 and ASE5 promoted the growth performance. The HSE5 and ASE5 showed preventive and reparative functions on the antioxidant capacity and serum immunity, with significantly increased the total antioxidant capacity (T-AOC), superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GSH-PX) activities, and reduced malondialdehyde (MDA) level, and increased acid phosphatase (ACP), alkaline phosphatase (AKP), immunoglobulin M (IgM) and complement 3 (C3). The HSM impaired the intestinal health (destroyed the intestinal structure, significantly increased the contents of serum D-lactic acid and diamine oxidase, and reduced the expressions of claudin-3 and occludin), while HSE5 and ASE5 improved them at whole term and middle term. The HSM impaired the intestinal microbiota and reduced its diversity, and the HSE5 or ASE5 improved the intestinal microbiota (especially at whole term). HSE5 and ASE5 improved the intestinal mRNA expressions of anti-inflammatory genes (il-10 and tgf-ß1) and reduced the expressions of pro-inflammatory genes (il-1ß, il-8, il-12), and promoted the expressions of humoral immune factor-related genes (cd4, igm, mhcII-α) and antimicrobial peptide genes (ß-defensin, epinecidin-1 and hepcidin-1), and decreased the expressions of NF-κB/MAPK signaling pathway-related genes (ikk-α, nf-κb, erk-1), and improved the expressions of MAPK signaling pathway-related gene p38-α (P < 0.05). In conclusion, the heat-inactivated and active B. pumilus SE5 effectively prevented and repaired the suppressive effects of soybean meal in E. coioides, which underscored the potential of B. pumilus SE5 as a nutritional intervention agent in HSM diet in aquaculture.

Platelets promote primary hepatocellular carcinoma metastasis through TGF-ß1-mediated cancer cell autophagy.

Previous research has revealed that platelets promote tumor metastasis by binding to circulating tumor cells (CTCs). However, the role of platelets in epithelial-mesenchymal transition (EMT) of cancer cells at the primary tumor site, the crucial initial step of tumor metastasis, remains to be elucidated. Here, we found that platelet releasate enhanced EMT and motility of hepatocellular carcinoma (HCC) cells via AMPK/mTOR-induced autophagy. RNA-seq indicated that platelet releasate altered TGF-ß signaling pathway of cancer cells. Inhibiting TGFBR or deleting platelet TGF-ß1 suppressed AMPK/mTOR pathway activation and autophagy induced by platelet releasate. Compared with Pf4cre-; Tgfb1fl/fl mice, HCC orthotopic models established on Pf4cre+; Tgfb1fl/fl mice showed reduced TGF-ß1 in primary tumors, which corresponded with decreased cancer cell EMT, autophagy, migration ability and tumor metastasis. Inhibition of autophagy via Atg5 knockdown in cancer cells negated EMT and metastasis induced by platelet-released TGF-ß1. Clinically, higher platelet count correlated with increased TGF-ß1, LC3 and N-cad expression in primary tumors of HCC patients, suggesting a link between platelets and HCC progression. Our study indicates that platelets promote cancer cell EMT in the primary tumor and HCC metastasis through TGF-ß1-induced HCC cell autophagy via the AMPK/mTOR pathway. These findings offer novel insights into the role of platelets in HCC metastasis and the potential therapeutic targets for HCC metastasis.

Clinical Features and Risk Factors for Baker's Cyst in Patients with Rheumatoid Arthritis.

OBJECTIVES: Baker's cyst (BC) is a complex complication of rheumatoid arthritis (RA), with a poor prognosis. This paper aimed to analyze the clinical features and risk factors for BC in patients with RA to assist clinicians in early warning and appropriate action. METHODS: The Clinical features of hospitalized RA patients with knee affected were analyzed retrospectively. The R software was used for the statistical analysis, while logistic regression analyses were used to determine independent risk factors. RESULTS: A total of 367 RA patients with knee affected were studied, and BC was diagnosis in 15.3% of them. The BC group exhibited a higher proportion of knee-only affected than the non-BC group (p < 0.05), while the attributes linked to disease activity exhibited no disparity. Logistic regression analyses selected two independent risk factors for BC: knee-only affected and anemia. 26.8% of patients with BC developed rupture, exhibiting a higher proportion of knee-only affected (p < 0.05), compared to those unruptured. CONCLUSIONS: The occurrence and rupture of BC in RA patients were significantly related to local inflammation, but not to systemic one. Incorporating local treatment may be a more advantageous option compared to solely relying on systemic therapy.

Nursing management of intracranial hypertension in adults with severe brain injury in a neurosurgery intensive care unit: a best practice implementation project.

INTRODUCTION: The nursing management of intracranial hypertension in adult patients with severe brain injury is crucial for maintaining the stability of intracranial pressure, which ultimately improves patient outcomes. OBJECTIVES: This project aimed to implement evidence-based practices for the nursing management of intracranial hypertension in adult patients with severe brain injury. METHODS: This evidence implementation project was conducted in a neurosurgery intensive care unit in a large tertiary hospital in Guangzhou, China. The project was guided by the JBI Evidence Implementation Framework, which is an audit and feedback model with seven stages. The Ottawa Model of Research Use was used to identify barriers and facilitators to best practices and to develop improvement strategies. RESULTS: Thirty-three nurses and 50 patients with severe brain injury participated in the baseline and follow-up audits. After project implementation, follow-up audits revealed significantly improved compliance with best practices compared with baseline. Nurses' awareness of best practices increased (41% to 96%); nursing assessment, monitoring, and interventions related to intracranial hypertension rose significantly (from 82%, 75%, and 59% to 98%, 84%, and 87%, respectively); and patients' optic nerve sheath diameter was notably lower (6.002±0.677 mm to 5.698±0.730 mm). CONCLUSIONS: The systematic integration of consistent training and education, together with the refinement of care processes and the creation of relevant tools, led to a significant improvement in awareness and adherence to best practices. Further testing of this program in more hospitals is needed. SPANISH ABSTRACT: http://links.lww.com/IJEBH/A243.

Improving Hand Gesture Recognition Robustness to Dynamic Posture Variations by Multimodal Deep Feature Fusion.

Surface electromyography (sEMG), a human-machine interface for gesture recognition, has shown promising potential for decoding motor intentions, but a variety of nonideal factors restrict its practical application in assistive robots. In this paper, we summarized the current mainstream gesture recognition strategies and proposed a gesture recognition method based on multimodal canonical correlation analysis feature fusion classification (MCAFC) for a nonideal condition that occurs in daily life, i.e., posture variations. The deep features of the sEMG and acceleration signals were first extracted via convolutional neural networks. A canonical correlation analysis was subsequently performed to associate the deep features of the two modalities. The transformed features were utilized as inputs to a linear discriminant analysis classifier to recognize the corresponding gestures. Both offline and real-time experiments were conducted on eight non-disabled subjects. The experimental results indicated that MCAFC achieved an average classification accuracy, average motion completion rate, and average motion completion time of 93.44%, 94.05%, and 1.38 s, respectively, with multiple dynamic postures, indicating significantly better performance than that of comparable methods. The results demonstrate the feasibility and superiority of the proposed multimodal signal feature fusion method for gesture recognition with posture variations, providing a new scheme for myoelectric control.

Deciphering the mitochondria-inflammation axis: Insights and therapeutic strategies for heart failure.

Heart failure (HF) is a clinical syndrome resulting from left ventricular systolic and diastolic dysfunction, leading to significant morbidity and mortality worldwide. Despite improvements in medical treatment, the prognosis of HF patients remains unsatisfactory, with high rehospitalization rates and substantial economic burdens. The heart, a high-energy-consuming organ, relies heavily on ATP production through oxidative phosphorylation in mitochondria. Mitochondrial dysfunction, characterized by impaired energy production, oxidative stress, and disrupted calcium homeostasis, plays a crucial role in HF pathogenesis. Additionally, inflammation contributes significantly to HF progression, with elevated levels of circulating inflammatory cytokines observed in patients. The interplay between mitochondrial dysfunction and inflammation involves shared risk factors, signaling pathways, and potential therapeutic targets. This review comprehensively explores the mechanisms linking mitochondrial dysfunction and inflammation in HF, including the roles of mitochondrial reactive oxygen species (ROS), calcium dysregulation, and mitochondrial DNA (mtDNA) release in triggering inflammatory responses. Understanding these complex interactions offers insights into novel therapeutic approaches for improving mitochondrial function and relieving oxidative stress and inflammation. Targeted interventions that address the mitochondria-inflammation axis hold promise for enhancing cardiac function and outcomes in HF patients.

Transcriptome sequencing of garlic reveals key genes related to the heat stress response.

With global warming, heat stress has become an important factor that seriously affects crop yield and quality. Therefore, understanding plant responses to heat stress is important for agricultural practice, but the molecular mechanism of high-temperature tolerance in garlic remains unclear. In this study, 'Xusuan No. 6' was used as the experimental material. After heat stress for 0 (CK), 2 and 24 h, transcriptome sequencing was used to screen metabolic pathways and differentially expressed genes (DEGs) closely related to heat stress and was further verified by quantitative real-time polymerase chain reaction (qRT-PCR). A total of 86,110 unigenes obtained from the raw transcriptome sequencing data were spliced. After 2 h of heat treatment, the expression levels of 8898 genes increased, and 3829 genes were decreased in leaves. After 24 h, the expression levels of 7167 genes were upregulated, and 3176 genes were downregulated. Gene Ontology enrichment analysis showed that DEGs were mainly enriched in seven categories: cellular processes, metabolic processes, binging, catalytic activity, cellular anatomical entity and protein-containing complex response to stimulus. Kyoto Encyclopedia of Genes and Genomes pathway enrichment showed that DEGs are involved in protein processing in the endoplasmic reticulum, plant hormone signal transduction, phenylpropanoid biosynthesis, and photosynthetic antenna proteins. Six genes were selected and further verified by qRT-PCR. In this study, the full-length transcriptome of garlic was constructed, and the regulatory genes related to the heat resistance of garlic were studied. Taken together, these findings can provide a theoretical basis for the cloning of heat resistance genes in garlic and for the analysis of heat resistance mechanisms.

Penetrative Ionic Organic Molecular Cage Nanozyme for the Targeted Treatment of Keratomycosis.

Keratomycosis, caused by pathogenic fungi, is an intractable blinding eye disease. Corneal penetration is an essential requirement for conventional antifungal medications to address keratomycosis. Due to the distinctive anatomical and physiological structure of the cornea, the therapeutic efficacy is hampered by the inadequate penetration capacity. Despite the emergence of diverse antifungal drug delivery systems and advanced antifungal nanomaterials, it has remained challenging to achieve corneal penetration over the past decade. This study fabricates a penetrative ionic organic molecular cage-based nanozyme (OMCzyme) for treating keratomycosis. The synthesis of OMCzyme involved two steps. Initially, the ionic OMC is synthesized by a [2+3] cycloimination reaction of triformylphloroglucinol and 2,3-diaminopropionic acid. Subsequently, OMCzyme is fabricated by coordination of Fe2⁺ with carboxyl anions and phenolic hydroxyls in the organic cage, and further deposition of silver nanoparticles on the surface of OMC-Fe complex. The as-prepared OMCzyme demonstrates excellent water dispersion, peroxidase-like activity, in vitro and in vivo biocompatibility, and corneal penetration. Notably, the nanozyme displays targeted antifungal activity, effectively combating Fusarium solani with negligible cytotoxicity toward human corneal epithelial cells. The hybrid mimic is further demonstrated to be effective in treating keratomycosis in mice, indicating the potential of OMCzyme for curing fungal infectious diseases.

Factors affecting the effectiveness and safety of polymyxin B in the treatment of Gram-negative bacterial infections: A meta-analysis of 96 articles.

PURPOSE: Polymyxin B, with its unique structure and mechanism of action, has emerged as a key therapeutic agent against Gram-negative bacteria. The study aims to explore potential factors to influence its effectiveness and safety. METHODS: A model-based meta-analysis of 96 articles was conducted, focusing on factors like dosage, bacterial species, and combined antibiotic therapy. The analysis evaluated mortality rates and incidence rate of renal dysfunction, also employing parametric survival models to assess 30-d survival rates. RESULTS: In the study involving 96 articles and 9716 patients, polymyxin B's daily dose showed minimal effect on overall mortality, with high-dose group mortality at 33.57% (95% confidence intervals [CI]: 29.15-38.00) compared to the low-dose group at 35.44% (95% CI: 28.99-41.88), P = 0.64. Mortality significantly varied by bacterial species, with Pseudomonas aeruginosa infections at 58.50% (95% CI: 55.42-63.58). Monotherapy exhibited the highest mortality at 40.25% (95% CI: 34.75-45.76), P < 0.01. Renal dysfunction was more common in high-dose patients at 29.75% (95% CI: 28.52-30.98), with no significant difference across antibiotic regimens, P = 0.54. The 30-d overall survival rate for monotherapy therapy was 63.6% (95% CI: 59.3-67.5) and 70.2% (95% CI: 64.4-76.2) for association therapy with ß-lactam drugs. CONCLUSIONS: The dosage of polymyxin B does not significantly change death rates, but its effectiveness varies based on the bacterial infection. Certain bacteria like P. aeruginosa are associated with higher mortality. Combining polymyxin B with other antibiotics, especially ß-lactam drugs, improves survival rates. Side effects depend on the dose, with lower doses being safer. These findings emphasize the importance of customizing treatment to balance effectiveness and safety.

Type one autoimmune pancreatitis based on clinical diagnosis: A case report.

BACKGROUND: Autoimmune pancreatitis (AIP) is a rare form of autoimmune-mediated pancreatitis, which is easily misdiagnosed as pancreatic cancer and thus treated surgically. We studied the diagnosis and treatment of a patient with type 1 AIP recently admitted to our hospital, and reviewed the literature to provide a reference for clinical diagnosis of AIP. CASE SUMMARY: The chief complaint was yellowing of the body, eyes and urine for 21 d. The patient's clinical presentation was obstructive jaundice and imaging suggested pancreatic swelling. It was difficult to distinguish between inflammation and tumor. Serum immunoglobulin G4 (IgG4) was markedly elevated. IgG4 is an important serological marker for type 1 AIP. The patient was diagnosed with AIP, IgG4-related cholangitis, acute cholecystitis and hepatic impairment. After applying hormonal therapy, the patient's symptoms improved significantly. At the same time, imaging suggested that pancreatic swelling subsided, and liver function and other biochemical indicators decreased. The treatment was effective. CONCLUSION: In patients with pancreatic swelling, the possibility of AIP should be considered.

Balance recovery for lower limb exoskeleton in standing posture based on orbit energy analysis.

Introduction: The need for effective balance control in lower limb rehabilitation exoskeletons is critical for ensuring stability and safety during rehabilitation training. Current research into specialized balance recovery strategies is limited, highlighting a gap in biomechanics-inspired control methods. Methods: We introduce a new metric called "Orbit Energy" (OE), which assesses the balance state of the human-exoskeleton system based on the dynamics of the overall center of mass. Our control framework utilizes OE to choose appropriate balance recovery strategies, including torque controls at the ankle and hip joints. Results: The efficacy of our control algorithm was confirmed through Matlab Simulink simulations, which analyzed the recovery of balance under various disturbance forces and conditions. Further validation came from physical experiments with human subjects wearing the exoskeleton, where a significant reduction in muscle activation was observed during balance maintenance under external disturbances. Discussion: Our findings underscore the potential of biomechanics-inspired metrics like OE in enhancing exoskeleton functionality for rehabilitation purposes. The introduction of such metrics could lead to more targeted and effective balance recovery strategies, ultimately improving the safety and stability of exoskeleton use in rehabilitation settings.