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Yu-Hsiang Chiu,1,2 Chen-Chih Chu,1 Chun-Chi Lu,1 Feng-Cheng Liu,1 Shin-En Tang,3 Shi-Jye Chu,1 San-Yuan Kuo,1 Hsiang-Cheng Chen1 1Division of Rheumatology/Immunology/Allergies, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 2Department of Rheumatology and Clinical Immunology, University Medical Centre Utrecht, Utrecht, the Netherlands; 3Division of Thoracic Medicine, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, TaiwanCorrespondence: Hsiang-Cheng Chen, Division of Rheumatology/Immunology/Allergy, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, No. 325, Sec, 2, Cheng-Gong Road, Neihu 114, Taipei, Taiwan, R.O.C, Tel +886 2 87927135, Fax +886 2 87927136, Email hccheng@mail.ndmctsgh.edu.twObjective: Krebs von den Lungen-6 (KL-6) is expressed on regenerating type II pneumocytes and has been recognized as biomarkers in interstitial lung disease (ILD). We aim to identify the role of the serum KL-6 level in patients with newly diagnosed Sjögren syndrome (SS), as well as the correlation between the immunoassays.Methods: Patients with newly diagnosed SS and receiving HRCT for clinical reason during follow-up were included. Baseline KL-6 level was measured via enzyme-linked immunosorbent assay (ELISA) and latex particle-enhanced turbidimetric immunoassay (LETIA).Results: Of the 39 patients, 21 (53.85%) developed interstitial lung disease (ILD) by the conclusion of the follow-up period. The median time to diagnosis of ILD was 2.24 years (IQR 1.15– 4.34) in the ILD group. The median serum KL-6 level, measured using ELISA, was 1232 U/mL (IQR 937– 2242) and 764.5 U/mL (IQR 503.25– 1035.75) in the ILD group and the non-ILD group, respectively (p = 0.001). The median LETIA for serum KL-6 was 329 U/mL (IQR 235– 619) and 245 U/mL (IQR 215.25– 291) in the ILD group and the non-ILD group, respectively (p = 0.074).Conclusion: Serum KL-6 levels were higher in newly diagnosed SS patients with ILD diagnosis during follow-up. Thus, the serum KL-6 level can serve as a valuable biomarker to identify hidden ILD in patients with newly diagnosed SS patients. However, the immunoassay procedure may influence the efficacy of the prediction and its clinical association.Keywords: Sjögren syndrome, interstitial lung disease, KL-6

Chia-Chi Chu, Hirofumi HagaCampbelltown Hospital, Campbelltown, Sydney, NSW, AustraliaBackground: Osteoporosis is a debilitating disease that contributes to 1.5 million fractures per annum among women in the USA. The aim of this systemic review study was to determine the effects of oral bisphosphonates in preventing osteoporotic fractures in postmenopausal women.Methods: A literature search was performed of the MEDLINE®, Embase, and CENTRAL databases. Three types of oral bisphosphonates were identified for the study: alendronate, risedronate, and ibandronate. The chief outcome measure was the incidence of fractures in postmenopausal women.Results: Five randomized controlled studies were included in the meta-analysis. A total of 9,941 patients received oral bisphosphonate, while 5,956 patients received a placebo. The overall risk ratio for all fracture events was 0.73 (confidence interval: 0.66–0.81) There was no significant increased risk for upper gastrointestinal side effects in patients taking bisphosphonates (odds ratio: 1.00; confidence interval: 0.92–1.08).Conclusion: Oral bisphosphonates are associated with a statistically significant reduction in fracture risk in postmenopausal women. Adverse effects were similar for both placebo and oral bisphosphonates.Keywords: osteoporosis, fractures, alendronate, risedronate, ibandronate, fracture risk

BACKGROUND: Anti-'Mi(a)' is one of the most important irregular red blood cell antibodies found in Taiwan. The aim of this study was to investigate whether specific HLA-DRB1 alleles are associated with anti-'Mi(a)' production. STUDY DESIGN AND METHODS: A case-control retrospective study was performed on 68 patients showing presence of anti-'Mi(a)' and 219 unrelated control subjects from the Mackay Memorial Hospital. HLA-DRB1 genotyping was carried out using sequence-based typing method. Fisher's exact test using 2 x 2 contingency tables was used to analyze significance of the association between DRB1 polymorphisms and presence of anti-'Mi(a)' in patients. RESULTS: HLA-DRB1*0901 allele frequency in the anti-'Mi(a)' group (30%) was significantly higher than in the control group (16%) with an odds ratio of 2.27 (95% confidence interval, 1.44-3.55; p = 0.0005; p(c) = 0.016). CONCLUSION: HLA-DRB1*0901 is significantly more prevalent in the anti-'Mi(a)' patients group than in the control group. It is suggested that cells from DR9 individuals might present processed 'Mi(a)' antigen-allospecific peptides more effectively than cells from individuals carrying other DR phenotypes. Finally, it was predicted that two epitopes, derived from the MiIII glycophorin amino acid sequence, were likely to bind preferentially with the DR9 molecule. Further work will be necessary to determine if these epitopes are responsible for anti-'Mi(a)' alloimmunization. [ABSTRACT FROM AUTHOR]

Background: Lipopolysaccharide (LPS) may activate hypoxia-inducible factor (HIF)-1α, which up-regulates cytokine expression and the lethality of LPS-induced shock. We investigated the effect of propofol on HIF-1α expression and acute lung injury in LPS-treated mice.Methods: A series of both positive and negative control experiments were performed. We injected BALB/C mice with propofol or vehicle i.p. immediately and 12 h after an LPS challenge. After 24 h, we examined the lung wet/dry weight ratio, neutrophil infiltration, and HIF-1α mRNA expression and inflammatory cytokines in the lung tissue. Survival was determined for 48 h after LPS injection. In vitro, we determined the responses of A549 cells, with and without HIF-1α silenced, to treatment with LPS alone and LPS plus propofol.Results: Propofol prolonged survival and attenuated acute lung injury and decreased the expression of HIF-1α, interleukin (IL)-6, keratinocyte-derived chemokine, and tumour necrosis factor-alpha (TNF-α) in the lungs of endotoxaemic mice. In HIF-1α knockdown-A549 cells, LPS-induced TNF-α, IL-6, and the pro-apoptotic gene, BNIP3 expression and apoptosis were reduced. Propofol, but not an inhibitor of nuclear factor κB, reduced HIF-1α expression in LPS-stimulated A549 cells. Propofol also down-regulated, in A549 cells, the expression of IL-6, IL-8, and TNF-α, Bcl-2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3), and apoptosis.Conclusions: Propofol reduces apoptosis in LPS-stimulated lung epithelial cells by decreasing HIF-1α, BNIP3, and cytokine production. Using propofol to inhibit HIF-1α expression may protect against the acute lung injury caused by LPS-induced sepsis. [ABSTRACT FROM AUTHOR]

Enzymatic reactions are essential for most cellular reactions and ubiquitous in living organisms. In the present study, we explore the pivotal role of the reverse reaction in enzymatic reactions. It is a powerful noise-buffering motif. By SSA (stochastic simulation algorithm), a remarkable 32% reduction of product CV (coefficient of variation) was observed. To better understand the causes, we split the upstream noise. The product CV reduction is more than 35% for the noise inherited from the enzyme but merely 6%-21% for that from the substrate. It implies that the system applies different strategies to different upstream noises. We identified two leading causes responsible for noise attenuation. A cell is well designed to control its intracellular noise, and to acquire wisdom from nature is always enjoyable., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Che-Chi Shu reports financial support was provided by National Science and Technology Council. Other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: It is debatable whether the area of substantia nigra hyperechogenicity (SN+) in transcranial sonography (TCS) is related to Parkinson's disease (PD) severity. Iron deposition, which is associated with the formation of SN+, may have different effects on dopamine nerve function as PD progresses. However, little research has explored the association between the SN + area and disease severity of PD in stages., Methods: 612 PD patients with sufficient bone window were retrospectively included from a PD database, and disease severity was assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) scores. Based on the Hoehn and Yahr (H-Y) scale, we classified the patients into seven groups (H-Y stage 1, 1.5, 2, 2.5, 3, 4, and 5) and then analyzed the correlations between the SN + area and the UPDRS scores separately., Results: Our results indicated a U-shaped relationship between the initial-SN + area and disease severity in PD: In the H-Y stage 1 group, the initial-SN + area was negatively correlated with the UPDRS total score (r = - 0.456, p < 0.001) and UPDRS-III score (r = - 0.497, p < 0.001). No correlation was observed in the groups of H-Y stages 1.5, 2, and 2.5. In the groups of H-Y stage ≥ 3, the initial-SN + area was positively correlated with the UPDRS total score and UPDRS-III score, with strongest correlation in the H-Y stage 5 group (all p values < 0.05). Moreover, the larger SN + area and average SN + area showed a similar evolutionary trend of correlation with UPDRS total score and UPDRS-III score., Conclusions: Our study indicated a U-shaped correlation between the SN + area with the UPDRS total score and UPDRS-III score as H-Y stage progressed. The evolution of the correlation may reflect the evolution of underlying pathological mechanisms related to iron deposition in the substantia nigra., Competing Interests: Declarations Conflict of interest The authors have no relevant financial or non-financial interests to disclose. Ethical approval This study was approved by the Medical Ethics Committee of the Second Hospital of Soochow University. Informed consent Informed consent was obtained from all individual participants included in the study., (© 2024. Fondazione Società Italiana di Neurologia.)

Excessive alcohol consumption is a significant pathogenic factor involved in the initiation of noninfectious gastric ulcers. Probiotics based on a specific strain can mitigate gastric damage. However, the protective effects of Pediococcus acidilactici (GKA4) and Lactobacillus brevis (GKL93) against alcohol-induced gastric mucosal damage remain unclear. Hence, the gastroprotective effects of these probiotic strains were investigated in BALB/c mice with gastric mucosa damage induced by absolute alcohol. The results revealed that preadministration of GKA4 and GKL93 increased the expression of antioxidative enzymes (SOD, catalase, GPx), anti-inflammatory cytokines (IL-4 and IL-10), and heat shock protein genes (HSP70 and HSP90) and decreased the expression of apoptosis-related genes (Bax, cytochrome c, and caspase-3), MDA, and pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α). Mechanistically, GKA4 and GKL93 increased the relative abundance of beneficial flora ( Coriobacteriia , Lachnospiraceae&#95;NK4A136&#95;group , Roseburia , f&#95;&#95;Oscillospiraceae unclassified , Ruminococcus , Adlercreutzia , and [Eubacterium]&#95;xylanophilum&#95;group ) that may promote antioxidant and anti-inflammatory effects via upregulation of the expression of proteins in the Nrf2/HO-1 pathway and downregulation of the expression of proteins in the NF-κB/iNOS/COX-2 signaling pathway, subsequently attenuating gastrointestinal permeability and ulcer symptoms. Furthermore, correlation analysis revealed that [Eubacterium]&#95;xylanophilum&#95;group and f&#95;Oscillospiraceae&#95;unclassified were two significant beneficial flora associated with ethanol-induced gastric ulcers after preadministration of GKA4 and GKL93. In summary, the gastroprotective effects of P. acidilactici GKA4 and L. brevis GKL93 against ethanol-induced gastric ulcers in mice include suppressing oxidative- and inflammatory-related pathways and modulation of the gut microbiota. This novel finding highlights the potential of these probiotics as functional materials in preventing alcohol-induced gastric mucosal damage.

Aims/introduction: This study aims to investigate the association between cross-sectional area (CSA) imaging findings of nerve ultrasound and conventional nerve conduction studies (NCS) for patients with distal symmetric sensorimotor polyneuropathy (DSPN) due to type 2 diabetes mellitus., Materials and Methods: We enrolled 103 patients with type 2 diabetes mellitus and collected their demographic data, modified Michigan Neuropathy Screening Instrument (mMNSI) score, NCS, and ultrasonography images of peripheral nerves. The relationship of ultrasound variables for individual nerves and the ultrasound pattern sum score (UPSS) to conventional NCS findings was investigated., Results: A higher grade of DSPN was associated with a notably higher CSA. Multivariate step-wise regression analysis revealed that the number of abnormal nerves was a positive independent variable for UPSS (β coefficient = 0.4205; P < 0.0001). Of the five nerves studied, abnormalities of the tibial nerve (P ≤ 0.0100) and ulnar nerve (P = 0.052) were the most significant variables., Conclusions: The tibial nerve exhibited the most substantial association with elevated UPSS. In addition, a strong correlation was observed between abnormal NCS findings and UPSS in patients with DSPN., (© 2024 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

The controlled synthesis of Ag/Au nanocomposite particles has remained a significant challenge in nanomaterial research. This study presents the synthesis, characterization, and surface-enhanced Raman scattering (SERS) performance of silver (Ag) and gold (Au) nanostar composites. The structural and plasmonic properties of these nanocomposites were optimized by varying the molar ratios of silver nanostars (AgNSs) and gold nanostars (AuNSs). By synthesizing composite nanostars with differing AgNS/AuNS ratios, we systematically compared their optical and spectroscopic behaviors. The results demonstrated that Ag/Au nanostar composites function as highly effective SERS substrates for the detection of rhodamine 6G (R6G), with solutions tested at concentrations from 10 -15 to 10 -6 M. Compared to individual AgNS or AuNS substrates, the Ag/Au nanocomposites exhibited significantly enhanced SERS signals, with superior consistency and sensitivity. Notably, the nanostar composite with a 75 : 25 Ag/Au ratio showed the highest SERS performance, achieving an enhancement factor of 8.9 × 10 6 and a detection limit of 10 -15 M for R6G. Additionally, this composite demonstrated excellent long-term stability, maintaining performance until ten weeks of storage. To our knowledge, this represents the highest sensitivity reported for R6G detection using label-free SERS. The study further provides a detailed analysis of the composition-dependent SERS activity, underscoring the potential of Ag/Au nanocomposites as advanced SERS substrates for applications in chemical and biological sensing, as well as environmental monitoring.

Eye movements (EM) during naming alphabetic versus logographic stimuli in children with and without developmental dyslexia (DD) were examined for each stimulus separately to identify conspicuous characteristics that influence naming performance. 40 children (group DD = 18; control group C = 22) were taught Chinese characters. EM were recorded during naming alphabetic words, pictures and Chinese characters. Main variables were articulation latencies, numbers and durations of fixations, secondary variables were fixation locations and error rates. Group DD showed significantly longer latencies and more fixations while reading words, but only insignificantly more fixations while naming pictures and Chinese characters. However, their error rate was significantly higher during naming Chinese characters but correlated neither with severity of phonological deficit nor with visual complexity. Their first fixation was significantly more often on the center of characters, in group C on the left. In both groups, EM variables were influenced by conspicuous features of characters, such as visual complexity, composition and structure. EM variables and scanning behavior while naming Chinese characters indicate holistic processing in the visuo-spatial pathway and were affected by conspicuous features of characters. The higher error rate in group DD could be determined by several factors, without a major role of the phonological deficit., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Numerous studies have demonstrated that hospice palliative care interventions for cancer patients can reduce health care utilzation. In Taiwan, 20-25% of patients who require mechanical ventilation are using prolonged mechanical ventilation (PMV); however, only a limited number of studies have addressed the effectiveness of hospice palliative care for these patients. This study investigated the impact of hospice palliative care utilization on medical utilization among subjects using PMV., Methods: By using the health insurance database of a nationwide population-based study, we identified subjects who had been on mechanical ventilation for > 21 d, were age ≥18 y between 2009 and 2017, and had received hospice palliative care. The control group was formed through 1:1 matching by using propensity scoring after excluding patients who had participated in palliative care for <15 d or for >181 d. Furthermore, we used a conditional logistic regression analysis to investigate the incidence of ICU admission, emergency department presentation, and cardiopulmonary resuscitation within 14 d before death., Results: A total of 186,533 new subjects receiving PMV age ≥ 18 y were admitted between 2009 and 2017. In addition, the number of subjects receiving palliative care increased annually, rising from 0.6% in 2009 to 41.33% in 2017. The emergency department visits (odds ratio [OR] 0.68, 95% CI 0.63-0.74), ICU admission (OR 0.59, 95% CI 0.53-0.66), cardiopulmonary resuscitation (OR 0.40, 95% CI 0.35-0.46), and total hospitalization cost ($1,319.91 ± $1,821.66 versus $1,544.37 ± $2,309.27 [$USD], P < .001) were significant lower in the palliative care group., Conclusions: Subjects undergoing PMV while receiving hospice palliative care experienced significant reductions in total hospitalization costs, ICU admissions, cardiopulmonary resuscitation, and medical expenses within 14 d before death., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2024 by Daedalus Enterprises.)

Aims: This study aimed to identify metabolic markers for diabetic peripheral neuropathic pain (DPNP) in patients with type 2 diabetes mellitus (T2DM)., Materials and Methods: Blood metabolite levels in the amino acid, biogenic amine, sphingomyelin, phosphatidylcholine (PC), carnitines, and hexose classes were analyzed in nondiabetic control (n = 27), T2DM without DPNP (n = 58), and T2DM with DPNP (n = 29) using liquid chromatography tandem mass spectrometry. Variable importance projection (VIP) evaluation by partial least squares discriminant analysis was performed on clinical parameters and metabolites., Results: Sixteen variables with VIP > 1.0 (P < 0.05) were identified across all patient groups, and 5 variables were identified to discriminate between the two T2DM groups. DPNP patients showed elevated fasting blood glucose, glutamate, PC aa C36:1, lysoPC a C18:1, and lysoPC a C18:2, while low-density lipoprotein cholesterol, phenylalanine, and tryptophan were reduced. Glutamate, lysoPC a C18:1, and lysoPC a C18:2 discriminated T2DM with DPNP from those without DPNP with an AUC of 0.671. The AUC was improved to 0.765 when ratios of metabolite pairs were considered., Interpretation: Blood metabolites include glutamate, and phospholipid-related metabolites implicated in neuropathic pain may have the potential as biomarkers for DPNP. Further investigation is required to understand the mechanism of action of these altered metabolites in DPNP., (© 2024 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Objectives: To establish the pharmacokinetic model of linezolid in neonates, and to optimize the administration regimen., Methods: A prospective study was conducted among 64 neonates with sepsis who received linezolid as anti-infective therapy, and liquid chromatography-tandem mass spectrometry was used to measure the plasma concentration of the drug. Clinical data were collected, and nonlinear mixed effects modeling was used to establish a population pharmacokinetic (PPK) model. Monte Carlo simulation and evaluation was performed for the optimal administration regimen of children with different features., Results: The pharmacokinetic properties of linezolid in neonates could be described by a single-compartment model with primary elimination, and the population typical values for apparent volume of distribution and clearance rate were 0.79 L and 0.34 L/h, respectively. The results of goodness of fit, visualization verification, and the Bootstrap method showed that the model was robust with reliable results of parameter estimation and prediction. Monte Carlo simulation results showed that the optimal administration regimen for linezolid in neonates was as follows: 6 mg/kg, q8h, at 28 weeks of gestational age (GA); 8 mg/kg, q8h, at 32 weeks of GA; 9 mg/kg, q8h, at 34-37 weeks of GA; 11 mg/kg, q8h, at 40 weeks of GA., Conclusions: The PPK model established in this study can provide a reference for individual administration of linezolid in neonates. GA and body weight at the time of administration are significant influencing factors for the clearance rate of linezolid in neonates.

Background: Phthalates, ubiquitous in plastics and softening agents, are pervasive in our daily environment. Growing concerns have emerged regarding their potential impact on renal health, particularly due to their propensity to induce oxidative stress. However, the relationship between phthalate exposure and urolithiasis remains poorly understood. This research seeks to explore the connection between phthalate exposure, oxidative stress, and the risk of urolithiasis., Methods: A case-control study involving 285 patients diagnosed with calcium urolithiasis and 594 healthy controls was conducted. Participants completed structured questionnaires and provided urine samples for measuring 10 phthalate metabolites, biomarkers of oxidative stress (malondialdehyde [MDA]) and early renal injury (N-acetyl-beta-D-glucosaminidase [NAG] and albumin/creatinine ratio [ACR]). For subsequent analyses, we utilized distinct categories: the sum of high-molecular-weight phthalate metabolites (∑HMWm), the sum of low-molecular-weight phthalate metabolites (∑LMWm), and the daily intake of di-2-ethylhexyl phthalate (DEHP)(DI&#95;DEHP&#95;5)., Results: Stone patients exhibited significantly elevated urinary biomarkers of oxidative stress (MDA) and early renal injury (NAG and ACR), along with higher levels of 9 out of 10 assessed phthalate metabolites compared to normal controls. Within the study population, significant positive associations were found between almost all individual phthalate metabolites and urinary biomarkers of oxidative stress (MDA) as well as early renal injury (NAG and ACR). Logistic regression further confirmed that elevated phthalate levels, including ∑HMWm, ∑LMWm, and DI&#95;DEHP&#95;5, were uniformly associated with an increased risk of oxidative stress, early renal injury, and urolithiasis after adjusting for confounding factors., Conclusions: Our study uncovers a novel association between phthalate exposure and the risk of urolithiasis, underscoring the heightened risk of kidney injury posed by such exposure. Considering the widespread presence of phthalates, regulatory measures and public health interventions are crucial to mitigate phthalate-related nephrotoxicity, while further large-scale longitudinal research is imperative to validate our initial findings and elucidate the underlying mechanisms., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Particulate matter (PM) with an aerodynamic diameter of ≤2.5 μm (PM2.5) significantly contributes to various disease-related respiratory inflammations. Armillaria mellea , recognized for its medicinal properties, could alleviate these respiratory ailments. However, its efficacy against PM2.5-induced inflammation remains elusive. In this study, we investigated whether A. mellea mycelia could mitigate PM2.5-induced respiratory inflammation and assessed the underlying mechanisms. Our results showed that A. mellea mycelia significantly reduced PM2.5-induced nitric oxide (NO) production and nuclear factor (NF)-κB activation in macrophages. Furthermore, A. mellea mycelia suppressed the expression of inflammatory mediators, indicating their potent antioxidant and anti-inflammatory properties. In murine models, A. mellea mycelia mitigated PM2.5-induced lung inflammation and cytokine secretion, restoring lung inflammatory status. Our results highlight the potential of A. mellea mycelia to treat PM2.5-induced respiratory inflammation. The antioxidant and anti-inflammatory effects of A. mellea mycelia demonstrated in vitro and in vivo hold promising potential for developing respiratory health improvement interventions upon PM2.5 exposure.

Background: Multilevel anterior cervical discectomy and fusion inevitably yields a higher chance of pseudarthrosis or require more reoperations than single-level procedures. Therefore, multilevel cervical disc arthroplasty (CDA) could be an alternative surgery for cervical spondylosis, as it (particularly 3- and 4-level CDA) could preserve more functional motility than single-level disc diseases. This study aimed to investigate the clinical and radiological outcomes of 4-level CDA, a relatively infrequently indicated surgery., Methods: The medical records of consecutive patients who underwent 4-level CDA were retrospectively reviewed. These highly selected patients typically had multilevel disc herniations with mild spondylosis. The inclusion criteria were symptomatic cervical spondylotic myelopathy, radiculopathy, or both, that were medically refractory. The clinical outcomes were assessed. The radiographic outcomes, including global and individual segmental range of motion (ROM) at C3-7, and any complications were also analyzed., Results: Data from a total of 20 patients (mean age: 56 ± 8 years) with an average follow-up of 34 ± 20 months were analyzed. All patients reported improved clinical outcomes compared with that of preoperation, and the ROMs at C3-7 were not only preserved but also trended toward an increase (35 ± 8 vs 37 ± 10 degrees, pre- vs postoperation, P = 0.271) after the 4-level CDA. However, global cervical alignment remained unchanged. There was one permanent C5 radiculopathy, but no other neurological deteriorations or any reoperations occurred., Conclusion: For these rare but unique indications, 4-level CDA yielded clinical improvement and preserved segmental motility with low rates of complications. Four-level CDA is a safe and effective surgery, maintaining the ROM in patients with primarily disc herniations and mild spondylosis., Clinical Relevance: For patients with mild spondylosis, whose degeneration at the cervical spine is not so severe, CDA is more suitable., Competing Interests: Declaration of Conflicting Interests : The authors report no conflicts of interest in this work., (This manuscript is generously published free of charge by ISASS, the International Society for the Advancement of Spine Surgery. Copyright © 2024 ISASS. To see more or order reprints or permissions, see http://ijssurgery.com.)

Background The protracted battle against coronavirus disease 2019 (COVID-19) has had a profound impact on various facets of society. The epidemiology of several diseases underwent alterations following the implementation of social restrictive strategies and non-pharmaceutical interventions (NPI). Methods In response to these changes, we conducted a retrospective nationwide surveillance study to investigate the prevalence of sexually transmitted infections during the pandemic. Weekly incidences of gonorrhea, syphilis, human immunodeficiency virus (HIV), and enterovirus were extracted from the national surveillance database. Results Over the period from 2015 to 2022, a sustained increase in gonorrhea notifications was evident (linear trend with a rising slope of 0.24 and an R-squared value of 0.62). When comparing the pre-pandemic period (2017-2019) with the pandemic period (2020-2022), a significant surge in gonorrhea notifications was observed (85 notifications per week pre-pandemic vs 143 notifications during the pandemic, representing a 68% increase, P Conclusions Our study highlights a significant rise in gonorrhea notifications during the pandemic. Despite disruptions to gonorrhea testing and medical services, and the implementation of NPI, there was no significant decrease in the incidence of gonorrhea in Taiwan. Gonorrhea emerged as a critical public health concern during the pandemic.

Colorectal cancer (CRC) is a common cancer worldwide with an increasing annual incidence. Cancer stem cells (CSCs) play important roles in the occurrence, development, recurrence, and metastasis of CRC. The molecular mechanism regulating the development of colorectal CSCs remains unclear. The discovery of human induced pluripotent stem cells (hiPSCs) through somatic cell reprogramming has revolutionized the fields of stem cell biology and translational medicine. In the present study, we converted hiPSCs into cancer stem-like cells by culture with conditioned medium (CM) from CRC cells. These transformed cells, termed hiPSC-CSCs, displayed cancer stem-like properties, including a spheroid morphology and the expression of both pluripotency and CSC markers. HiPSC-CSCs showed tumorigenic and metastatic abilities in mouse models. The epithelial-mesenchymal transition phenotype was observed in hiPSC-CSCs, which promoted their migration and angiogenesis. Interestingly, upregulation of C-MYC was observed during the differentiation of hiPSC-CSCs. Mechanistically, CREB binding protein (CBP) bound to the C-MYC promoter, while histone deacetylase 1 and 3 (HDAC1/3) dissociated from the promoter, ultimately leading to an increase in histone acetylation and C-MYC transcriptional activation during the differentiation of hiPSC-CSCs. Pharmacological treatment with a CBP inhibitor or abrogation of CBP expression with a CRISPR/Cas9-based strategy reduced the stemness of hiPSC-CSCs. This study demonstrates for the first time that colorectal CSCs can be generated from hiPSCs. The upregulation of C-MYC via histone acetylation plays a crucial role during the conversion process. Inhibition of CBP is a potential strategy for attenuating the stemness of colorectal CSCs., Competing Interests: Competing interests The authors declare no competing interests. Ethics approval and consent to participate The authors declare that all methods were performed in accordance with the relevant guidelines and regulations. The procedures for collecting human blood samples were approved by the Institutional Review Board of the National Taiwan University Hospital. Signed informed consent was obtained from all participants. Additionally, the authors have obtained written informed consent for publication of the images., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Postpartum depression is a major psychiatric disorder associated with maternal suicide and child developmental disturbances. In this study, we aimed to investigate whether general anesthesia for cesarean delivery is associated with a higher rate of new-onset depression after delivery than neuraxial anesthesia., Methods: This is a nationwide retrospective cohort study using data retrieved from the National Health Insurance Research Database between 2014 and 2018. Women who had cesarean delivery under general or neuraxial anesthesia were enrolled. After 1:4 propensity score matching, there were 4544 and 18,176 women under the general and neuraxial anesthesia groups, respectively. The primary outcome was new-onset depression diagnosed after delivery in a time-to-event analysis setting., Results: After propensity-score matching, the rate of new-onset depression diagnosed within 1 year was 1.10 % (50/4488) and 0.86 % (157/18176) after cesarean delivery under general and neuraxial anesthesia, respectively. For depression diagnosed within 90 days of delivery, significant difference between the two groups was noted (0.51 % vs. 0.30 %, P = 0.031). In the time-to-event analysis with Cox regression model, women who delivered under general anesthesia were associated with significantly higher risk of postpartum depression within 90 days (Hazard ratio [HR], 1.71; 95 % CI, 1.05-2.79) compared with those under neuraxial anesthesia., Limitations: The observational design only allows asserting association, rather than establishing causality between exposure and outcomes., Conclusions: Women who underwent cesarean delivery under general anesthesia had a higher risk of subsequent depression within 90 days than those under neuraxial anesthesia. Early screening for depressive disorders might facilitate timely management., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Osteoarthritis (OA) is a degenerative joint disease primarily affecting the elderly. It is characterized by the progressive decline of joint cartilage and alterations in the underlying bone. Several probiotic strains have exhibited immunomodulatory and anti-inflammatory properties. Here, we examined the functions of live and dead Clostridium butyricum GKB7 (GKB7-L and GKB7-D) in a preclinical anterior cruciate ligament transection (ACLT)-enhanced OA procedure. Oral administration of GKB7-L and GKB7-D ameliorated ACLT-induced bone pain as assessed by weight-bearing behavioral testing but did not affect body weight. Micro-computed tomography (CT) results showed that GKB7-L and GKB7-D diminished ACLT-induced bone destruction and loss. GKB7-L and GKB7-D-enriched therapies also reduced ACLT-induced production of the pro-inflammatory cytokines interleukin (IL)-1β and tumor necrosis factor (TNF)-α, as well as the chondrolytic factor matrix metalloproteinase (MMP)-3, leading to inhibition of aggrecan and collagen type II degradation and thereby blocking cartilage breakdown. We therefore suggest that oral supplementation with GKB7-L or GKB7-D can be beneficial in the prevention and treatment of OA., (© 2024 Wiley Periodicals LLC.)

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide, affecting >30% of the global population. Metabolic dysregulation, particularly insulin resistance and its subsequent manifestation as type 2 diabetes mellitus, serves as the fundamental pathogenesis of metabolic liver disease. Clinical evidence of the recent nomenclature evolution is accumulating. The interaction and impacts are bidirectional between MASLD and diabetes in terms of disease course, risk, and prognosis. Therefore, there is an urgent need to highlight the multifaceted links between MASLD and diabetes for both hepatologists and diabetologists. The surveillance strategy, risk stratification of management, and current therapeutic achievements of metabolic liver disease remain the major pillars in a clinical care setting. Therefore, the Taiwan Association for the Study of the Liver (TASL), Taiwanese Association of Diabetes Educators, and Diabetes Association of the Republic of China (Taiwan) collaboratively completed the first guidance in patients with diabetes and MASLD, which provides practical recommendations for patient care., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

Cervical synovial cyst (CSC) is a rare condition that often leads patients to seek medical attention due to cervical stenosis symptoms. There's ongoing debate about the best management strategy. To address this, a review of literature from the past 20 years (2003-2023) was conducted using keywords like "cervical synovial cyst," "cervical ganglion cyst," and "cervical juxtafacet cyst." Data on patient demographics, imaging characteristics, treatment methods, and clinical outcomes were collected. A total of 79 patients were diagnosed with CSCs, averaging 62.3 years old, with a slight male predominance (45 males, 34 females). Most cysts were located at the C1-2 and C7-T1 joints, with myelopathy being the most common symptom. Subaxial CSCs had a higher incidence of radiculopathy compared to axial CSCs. Most cases were treated surgically, with decompression performed with or without fusion. Patients generally reported symptom improvement regardless of the surgical method. Overall, surgical intervention effectively improved neurological symptoms associated with CSCs., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

In response to the growing demand for immune-related products, this study evaluated the safety and immune-modulating potential of three newly discovered Lactiplantibacillus plantarum strains (GKM3, GKK1, and GKD7) through toxicity tests and whole-genome sequencing. Safety evaluations, including the analysis of antimicrobial resistance genes, virulence factors, plasmids, and prophages, classified these strains as safe for human consumption. Acute oral toxicity tests further supported their safety. To evaluate their immune-modulating potential, dendritic cells were exposed to these strains, and the secretion of key cytokines (IFN-β and IL-12) was measured. Among the strains, GKK1 exhibited the highest enhancement of IFN-β and IL-12 production, suggesting its potential as an immune-stimulating probiotic. Bioinformatics analysis revealed potential metabolic pathways and secondary metabolites, including predicted bacteriocins, associated with immune modulation. The presence of a nitrate reductase region in the GKK1 strain indicated its ability to produce nitric oxide, a critical molecule involved in immune regulation and host defense. The presence of glucorhamnan-related gene clusters in GKK1 also suggested immune-enhancing effects. Nitrate reductase expression was confirmed using qPCR, with the highest levels detected in GKK1. Moreover, this study is the first to show an anti-inflammatory effect of plantaricin A, linked to its presence in strain GKM3 and its potential therapeutic applications due to sequence similarity to known anti-inflammatory peptides. Overall, these three L. plantarum strains demonstrated a safe profile and GKK1 showed potential as an immunity-enhancing probiotic. However, additional investigation is required to confirm the involvement of specific metabolic pathways, secondary metabolites, and bacteriocins in immune responses.