Immunosuppressant Agents as Add-On Therapy Failed to Improve the Outcome of Immunoglobulin A Nephropathy with Crescent Score C1.

Background The renoprotective benefits of adding immunosuppressant therapy to corticosteroid (CS) treatment for immunoglobulin A nephropathy (IgAN) patients with less than 25% crescent formation (C1) remains uncertain, warranting further research. Methods A retrospective study was conducted on IgAN patients with crescent C1 lesions confirmed by renal biopsy at Xinqiao Hospital between May 1, 2017, and May 1, 2020. Patients were stratified into either the CS treatment group or the CS combined with an additional immunosuppressant therapy group. Follow-up assessments were conducted within 24 months. Propensity score analysis was used to match patients receiving CS and CS+immunosuppressant drug treatment in a 1:1 ratio. Primary outcomes included changes in estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR). Subgroup analyses were performed to evaluate the benefits of different populations. Composite endpoint outcomes comprised a 30% eGFR decrease, end-stage kidney disease (ESKD) necessitating dialysis or transplant, or kidney disease-related mortality. Adverse events were also compared between the two groups. Results: 296 IgAN patients with C1 lesions were included in the analysis. Baseline characteristics indicated that IgAN patients in the CS+immunosuppressant group exhibited poorer renal function and higher UACR levels. Propensity score analysis effectively minimized the influence of baseline clinical characteristics, including age, serum creatinine, initial eGFR, UACR, and 24-hour proteinuria. Both treatment groups demonstrated continuous eGFR improvement and significant UACR reduction during follow-up, especially at 6 months. However, no significant differences in eGFR and UACR reduction rates were observed between the two groups throughout the entire follow-up period, both before and after matching. Subgroup analysis revealed improved eGFR in both treatment groups, notably among patients with an initial eGFR below 90 ml/min/1.73 m2. Conversely, IgAN patients with C1 lesions and a cellular crescent ratio exceeding 50% treated with CS and immunosuppressant therapy experienced a significant improvement in renal function and a decline in urinary protein creatinine ratio. Composite endpoint outcomes did not significantly differ between the two groups, while the incidence of adverse events was comparable. Conclusion Our findings suggest that the addition of immunosuppressant therapy to corticosteroid monotherapy did not confer significant therapeutic advantages in patients with C1 lesions compared to CS monotherapy, although some specific patient populations appeared to derive modest benefits from this combined approach.

The Association of High Lipoprotein(a) Concentration and Risk of Ischaemic Stroke in Atrial Fibrillation Patients.

Background: Lipoprotein(a) [Lp(a)] is a well-established risk factor for ischaemic stroke (IS). It is unclear whether Lp(a) is associated with IS in patients with atrial fibrillation (AF). The aim of this study is to explore the association between the concentration of Lp(a) and the risk of IS in AF patients, hope to find the potential risk factor for the IS in AF patients. Methods: This study is a retrospective cohort study. The screened AF patients between January 2017 and July 2021 were matched at 1:1 by the propensity score matching (PSM) method in the Second Affiliated Hospital of Nanchang University. Associations between Lp(a) and ischaemic stroke were analysed using logistic regression models, stratified analysis and sensitivity analysis. Statistical analyses were conducted using IBM SPSS software. Results: The number of enrolled participates is 2258, which contains 1129 non-AF patients and 1129 AF patients. Among IS patients, the median Lp(a) concentration was higher than that of controls (17.03 vs. 15.36 mg/dL, P = 0.032). The Spearman rank-order correlation coefficients revealed significant positive relationships between IS and Lp(a) (P = 0.032). In addition, a significant increase in IS risk was associated with Lp(a) levels >30.00 mg/dL in unadjusted model [OR:1.263, 95% CI(1.046-1.523), P = 0.015], model 1 [OR:1.284, 95% CI(1.062,1.552), P = 0.010], model 2 [OR: 1.297, 95% CI(1.07,1.573). P = 0.008], and model 3 [OR: 1.290, 95% CI (1.064, 1.562). P = 0.009]. The stratified analysis indicated that this correlation was not affected by female sex [1.484 (1.117, 1.972), P = 0.006], age ≤ 60 [1.864 (1.067-3.254), P=0.029], hypertension [1.359 (1.074, 1.721), P = 0.011], or non-coronary heart disease (CHD) [1.388 (1.108, 1.738), P = 0.004]. Conclusion: High levels of Lp(a) were significantly related to IS in AF patients and may be a potential risk factor in the onset of an IS in AF patients.

Symptom networks analysis among people with Meniere's disease: Application for nursing care.

Objectives: This study aimed to explore and visualize the relationships among multiple symptoms in patients with Meniere's disease (MD) and aid clinical nurses in the design of accurate, individualized interventions. Methods: This study included 790 patients with MD at the Eye and ENT Hospital of Fudan University from October 2014 to December 2021. A self-designed symptom checklist was used to assess 15 MD-related symptoms and construct contemporaneous networks with all 15 symptoms in R software. Qgraph package and Fruchterman-Reingold layout were used for network visualization. Bootstrapping methods were performed to assess network accuracy and stability, and three centrality indices were adopted to describe relationships among symptoms. Results: Symptom networks showed good accuracy and stability. "Anxiety and nervousness"(98.2%), "aural fullness"(84.4%) and "tinnitus"(82.7%) were the common symptom in MD patients, while "tinnitus", "aural fullness" and "decline in word recognition", were more serious. MD patients with longer disease duration had higher prevalence and severity for all symptoms (P < 0.05). Symptom networks showed good accuracy and stability. "Decline in word recognition," "fatigue," and "anxiety and nervousness" were at the center of the symptom networks, which had the largest strength values and closeness. "Decline in word recognition," "headache," and "spatial discrimination and poor orientation" were the symptoms with the highest betweenness with the strongest bridging effect. The ≥1-year disease group exhibited higher centralities for "drop attack" and "anxiety and nervousness," and a lower centrality for "headache" compared with the <1-year disease group. Conclusions: The symptom networks of MD patients with varying disease durations were revealed. Clinicians and nurses must provide precision interventions tailored to modifying symptom severity and centrality. Nursing interventions should focus on word recognition issues and associated discomfort in MD patients with multiple symptoms.

Concomitant Near-Infrared Photothermy and Photoluminescence of Rod-Shaped Au52(PET)32 and Au66(PET)38 Synthesized Concurrently.

Gold nanoclusters exhibiting concomitant photothermy (PT) and photoluminescence (PL) under near-infrared (NIR) light irradiation are rarely reported, and some fundamental issues remain unresolved for such materials. Herein, we concurrently synthesized two novel rod-shaped Au nanoclusters, Au52(PET)32 and Au66(PET)38 (PET = 2-phenylethanethiol), and precisely revealed that their kernels were 4 × 4 × 6 and 5 × 4 × 6 face-centered cubic (fcc) structures, respectively, based on the numbers of Au layers in the [100], [010], and [001] directions. Following the structural growth mode from Au52(PET)32 to Au66(PET)38, we predicted six more novel nanoclusters. The concurrent synthesis provides rational comparison of the two nanoclusters on the stability, absorption, emission and photothermy, and reveals the aspect ratio-related properties. An interesting finding is that the two nanoclusters exhibit concomitant PT and PL under 785 nm light irradiation, and the PT and PL are in balance, which was explained by the qualitative evaluation of the radiative and non-radiative rates. The ligand effects on PT and PL were also investigated.

Is refractive error a factor affecting scoliosis?

BACKGROUND: Scoliosis is one of the most common surgical disorders of the pediatric spine. Refractive errors are commonly associated with vision impairment worldwide. However, it is currently unclear whether refractive error correlates directly with the development of scoliosis. METHODS: A cross-sectional study was performed in 2023, and a stratified cluster sampling technique was employed among school-aged students in Nantong City, China. Univariate and multivariate logistic regression analyses were used to investigate specific correlations between scoliosis and related parameters; various types of refractive errors were also included in the study. RESULTS: The prevalence of scoliosis among school-aged students was 2.2% in Nantong city. Multiple logistic regression analyses showed that myopia, hyperopia, astigmatism, and anisometropia were not correlated with the development of scoliosis (all, p≥0.05). Lower body mass index (BMI) [adjusted odds ratio (aOR) = 0.92; 95% confidence interval (CI): 0.88-0.95; p<0.001], living in rural areas (aOR = 1.40; 95% CI: 1.05-1.86; p = 0.020), and older age (aOR = 1.32; 95% CI: 1.25-1.38; p<0.001) had significantly higher risks of scoliosis. CONCLUSIONS: Refractive errors did not correlate with the development of scoliosis. However, BMI, living in rural areas and older age did correlate with the development of scoliosis.

Intercalated and Surface-Adsorbed Phosphate Anions in NiFe Layered Double-Hydroxide Catalysts Synergistically Enhancing Oxygen Evolution Reaction Activity.

The oxygen evolution reaction (OER), a crucial semireaction in water electrolysis and rechargeable metal-air batteries, is vital for carbon neutrality. Hindered by a slow proton-coupled electron transfer, an efficient catalyst activating the formation of an O-H bond is essential. Here, we proposed a straightforward one-step hydrothermal procedure for fabricating PO43--modified NiFe layered double-hydroxide (NiFe LDH) catalysts and investigated the role of PO43- anions in enhancing OER. Phosphate amounts can efficiently regulate LDH morphology, crystallinity, composition, and electronic configuration. The optimized sample showed a low overpotential of 267 mV at 10 mA cm-2. Density functional theory calculations revealed that intercalated and surface-adsorbed PO43- anions in NiFe LDH reduced the Gibbs free energy in the rate-determining step of *OOH formation, balancing oxygen-containing intermediate adsorption/dissociation and promoting the OER. Intercalated phosphate ions accelerated precatalyst dehydrogenation kinetics, leading to a rapid reconstruction into active NiFe oxyhydroxide species. Surface-adsorbed PO43- interacted favorably with adsorbed *OOH on the active Ni sites, stabilizing *OOH. Overall, the synergistic effects of intercalated and surface-adsorbed PO43- anions significantly contributed to enhanced OER activity. Achieving optimal catalytic activity requires a delicate equilibrium between thermodynamic and kinetic factors by meticulously regulating the quantity of introduced PO43- ions. This endeavor will facilitate a deeper comprehension of the influence of anions in electrocatalysis for OER.

Tumor biomarkers for diagnosis, prognosis and targeted therapy.

Tumor biomarkers, the substances which are produced by tumors or the body's responses to tumors during tumorigenesis and progression, have been demonstrated to possess critical and encouraging value in screening and early diagnosis, prognosis prediction, recurrence detection, and therapeutic efficacy monitoring of cancers. Over the past decades, continuous progress has been made in exploring and discovering novel, sensitive, specific, and accurate tumor biomarkers, which has significantly promoted personalized medicine and improved the outcomes of cancer patients, especially advances in molecular biology technologies developed for the detection of tumor biomarkers. Herein, we summarize the discovery and development of tumor biomarkers, including the history of tumor biomarkers, the conventional and innovative technologies used for biomarker discovery and detection, the classification of tumor biomarkers based on tissue origins, and the application of tumor biomarkers in clinical cancer management. In particular, we highlight the recent advancements in biomarker-based anticancer-targeted therapies which are emerging as breakthroughs and promising cancer therapeutic strategies. We also discuss limitations and challenges that need to be addressed and provide insights and perspectives to turn challenges into opportunities in this field. Collectively, the discovery and application of multiple tumor biomarkers emphasized in this review may provide guidance on improved precision medicine, broaden horizons in future research directions, and expedite the clinical classification of cancer patients according to their molecular biomarkers rather than organs of origin.

Probing Glycerolipid Metabolism using a Caged Clickable Glycerol-3-Phosphate Probe.

In this study, we present the probe SATE-G3P-N3 as a novel tool for metabolic labeling of glycerolipids (GLs) to investigate lipid metabolism in yeast cells. By introducing a clickable azide handle onto the glycerol backbone, this probe enables general labeling of glycerolipids. Additionally, this probe contains a caged phosphate moiety at the glycerol sn-3 position to not only facilitate probe uptake by masking negative charge but also to bypass the phosphorylation step crucial for initiating phospholipid synthesis, thereby enhancing phospholipid labeling. The metabolic labeling activity of the probe was thoroughly assessed through cellular fluorescence microscopy, mass spectrometry (MS), and thin-layer chromatography (TLC) experiments. Fluorescence microscopy analysis demonstrated successful incorporation of the probe into yeast cells, with labeling predominantly localized at the plasma membrane. LCMS analysis confirmed metabolic labeling of various phospholipid species (PC, PS, PA, PI, and PG) and neutral lipids (MAG, DAG, and TAG), and GL labeling was corroborated by TLC. These results showcased the potential of the SATE-G3P-N3 probe in studying GL metabolism, offering a versatile and valuable approach to explore the intricate dynamics of lipids in yeast cells.

Association between low-density lipoprotein cholesterol levels and serum uric acid to serum creatinine ratio in Chinese male gout patients.

This study aimed to evaluate the association between low-density lipoprotein cholesterol (LDL-C) and serum uric acid to serum creatinine (SUA/SCr) ratio in male gout patients at different BMIs. This real-world study included 956 male gout patients aged 18-83 years. We retrospectively analyzed the medical records of Chinese male gout patients from 2017 to 2019. The correlation between LDL-C and SUA/SCr was tested after adjusting for confounding factors. We found a nonlinear relationship between LDL-C and SUA/SCr in the whole study population. Stratification analysis showed that there was actually a nonlinear relationship between LDL-C and SUA/SCr in men with a BMI of 24-28, the inflection point of LDL-C was 1.8 mmol/L, when LDL-C was greater than 1.8 mmol/L, there was a positive correlation between LDL-C levels and SUA/SCr (ß = 0.67, 95% CI 0.35-0.98, P < 0.001). Moreover, LDL-C showed a significant positive correlation with SUA/SCr with a BMI of 28 or greater (ß = 0.30, 95% CI 0.05-0.55, P = 0.019). However, no association was found between LDL-C and SUA/SCr with a BMI of less than 24 (ß = 0.42, 95% CI - 0.03-0.86, P = 0.070). LDL-C levels were associated with SUA/SCr in Chinese male gout patients, but this correlation appeared inconsistent among different BMIs. Our findings suggest that LDL-C levels may be more noteworthy in overweight and/or obese male gout patients.

New Directions for Advanced Targeting Strategies of EGFR Signaling in Cancer.

Epidermal growth factor (EGF)-EGF receptor (EGFR) signaling studies paved the way for a basic understanding of growth factor and oncogene signaling pathways and the development of tyrosine kinase inhibitors (TKIs). Due to resistance mutations and the activation of alternative pathways when cancer cells escape TKIs, highly diverse cell populations form in recurrent tumors through mechanisms that have not yet been fully elucidated. In this review, we summarize recent advances in EGFR basic research on signaling networks and intracellular trafficking that may clarify the novel mechanisms of inhibitor resistance, discuss recent clinical developments in EGFR-targeted cancer therapy, and offer novel strategies for cancer drug development.

Postoperative myopic shift and visual acuity rehabilitation in patients with bilateral congenital cataracts.

Background: This study aimed to explore the postoperative myopic shift and its relationship to visual acuity rehabilitation in patients with bilateral congenital cataracts (CCs). Methods: Bilateral CC patients who underwent cataract extraction and primary intraocular lens implantations before 6 years old were included and divided into five groups according to surgical ages (<2, 2-3, 3-4, 4-5, and 5-6 years). The postoperative myopic shift rates, spherical equivalents (SEs), and the best corrected visual acuity (BCVA) were measured and analyzed. Results: A total of 1,137 refractive measurements from 234 patients were included, with a mean follow-up period of 34 months. The postoperative mean SEs at each follow-up in the five groups were linearly fitted with a mean R2 = 0.93 ± 0.03, which showed a downtrend of SE with age (linear regression). Among patients with a follow-up of 4 years, the mean postoperative myopic shift rate was 0.84, 0.81, 0.68, 0.24, and 0.28 diopters per year (D/y) in the five age groups (from young to old), respectively. The BCVA of those with a surgical age of <2 years at the 4-year visit was 0.26 (LogMAR), and the mean postoperative myopic shift rate was 0.84 D/y. For patients with a surgical age of 2-6 years, a poorer BCVA at the 4-year visit was found in those with higher postoperative myopic shift rates (r = 0.974, p = 0.026, Pearson's correlation test). Conclusion: Performing cataract surgery for patients before 2 years old and decreasing the postoperative myopic shift rates for those with a surgical age of 2-6 years may benefit visual acuity rehabilitation.

Three new discovery effector proteins from Candidatus Liberibacter asiaticus psy62 inhibit plant defense through interaction with AtCAT3 and AtGAPA.

KEY MESSAGE: We identify three SDEs that inhibiting host defence from Candidatus Liberibacter asiaticus psy62, which is an important supplement to the pathogenesis of HLB. Candidatus Liberibacter asiaticus (CLas) is the main pathogen of citrus Huanglongbing (HLB). 38 new possible sec-dependent effectors (SDEs) of CLas psy62 were predicted by updated predictor SignalP 5.0, which 12 new SDEs were found using alkaline phosphate assay. Among them, SDE4310, SDE4435 and SDE4955 inhibited hypersensitivity reactions (HR) in Arabidopsis thaliana (Arabidopsis, At) and Nicotiana benthamiana leaves induced by pathogens, which lead to a decrease in cell death and reactive oxygen species (ROS) accumulation. And the expression levels of SDE4310, SDE4435, and SDE4955 genes elevated significantly in mild symptom citrus leaves. When SDE4310, SDE4435 and SDE4955 were overexpressed in Arabidopsis, HR pathway key genes pathogenesis-related 2 (PR2), PR5, nonexpressor of pathogenesis-related 1 (NPR1) and isochorismate synthase 1 (ICS1) expression significantly decreased and the growth of pathogen was greatly increased relative to control with Pst DC3000/AvrRps4 treatment. Our findings also indicated that SDE4310, SDE4435 and SDE4955 interacted with AtCAT3 (catalase 3) and AtGAPA (glyceraldehyde-3-phosphate dehydrogenase A). In conclusion, our results suggest that SDE4310, SDE4435 and SDE4955 are CLas psy62 effector proteins that may have redundant functions. They inhibit ROS burst and cell death by interacting with AtCAT3 and AtGAPA to negatively regulate host defense.

The small molecule CBR-5884 inhibits the Candida albicans phosphatidylserine synthase.

Systemic infections by Candida spp. are associated with high mortality rates, partly due to limitations in current antifungals, highlighting the need for novel drugs and drug targets. The fungal phosphatidylserine synthase, Cho1, from Candida albicans is a logical antifungal drug target due to its importance in virulence, absence in the host, and conservation among fungal pathogens. Inhibitors of Cho1 could serve as lead compounds for drug development, so we developed a target-based screen for inhibitors of purified Cho1. This enzyme condenses serine and cytidyldiphosphate-diacylglycerol (CDP-DAG) into phosphatidylserine (PS) and releases cytidylmonophosphate (CMP). Accordingly, we developed an in vitro nucleotidase-coupled malachite-green-based high throughput assay for purified C. albicans Cho1 that monitors CMP production as a proxy for PS synthesis. Over 7,300 molecules curated from repurposing chemical libraries were interrogated in primary and dose-responsivity assays using this platform. The screen had a promising average Z' score of ~0.8, and seven compounds were identified that inhibit Cho1. Three of these, ebselen, LOC14, and CBR-5884, exhibited antifungal effects against C. albicans cells, with fungicidal inhibition by ebselen and fungistatic inhibition by LOC14 and CBR-5884. Only CBR-5884 showed evidence of disrupting in vivo Cho1 function by inducing phenotypes consistent with the cho1∆∆ mutant, including a reduction of cellular PS levels. Kinetics curves and computational docking indicate that CBR-5884 competes with serine for binding to Cho1 with a Ki of 1,550 ± 245.6 nM. Thus, this compound has the potential for development into an antifungal compound. IMPORTANCE: Fungal phosphatidylserine synthase (Cho1) is a logical antifungal target due to its crucial role in the virulence and viability of various fungal pathogens, and since it is absent in humans, drugs targeted at Cho1 are less likely to cause toxicity in patients. Using fungal Cho1 as a model, there have been two unsuccessful attempts to discover inhibitors for Cho1 homologs in whole-cell screens prior to this study. The compounds identified in these attempts do not act directly on the protein, resulting in the absence of known Cho1 inhibitors. The significance of our research is that we developed a high-throughput target-based assay and identified the first Cho1 inhibitor, CBR-5884, which acts both on the purified protein and its function in the cell. This molecule acts as a competitive inhibitor with a Ki value of 1,550 ± 245.6 nM and, thus, has the potential for development into a new class of antifungals targeting PS synthase.

Mesenchymal Stem Cell-Derived Exosomes Attenuate Murine Cytomegalovirus-Infected Pneumonia via NF-κB/NLRP3 Signaling Pathway.

Reactivation and infection with cytomegalovirus (CMV) are frequently observed in recipients of solid organ transplants, bone marrow transplants, and individuals with HIV infection. This presents an increasing risk of allograft rejection, opportunistic infection, graft failure, and patient mortality. Among immunocompromised hosts, interstitial pneumonia is the most critical clinical manifestation of CMV infection. Recent studies have demonstrated the potential therapeutic benefits of exosomes derived from mesenchymal stem cells (MSC-exos) in preclinical models of acute lung injury, including pneumonia, ARDS, and sepsis. However, the role of MSC-exos in the pathogenesis of infectious viral diseases, such as CMV pneumonia, remains unclear. In a mouse model of murine CMV-induced pneumonia, we observed that intravenous administration of mouse MSC (mMSC)-exos reduced lung damage, decreased the hyperinflammatory response, and shifted macrophage polarization from the M1 to the M2 phenotype. Treatment with mMSC-exos also significantly reduced the infiltration of inflammatory cells and pulmonary fibrosis. Furthermore, in vitro studies revealed that mMSC-exos reversed the hyperinflammatory phenotype of bone marrow-derived macrophages infected with murine CMV. Mechanistically, mMSC-exos treatment decreased activation of the NF-κB/NLRP3 signaling pathway both in vivo and in vitro. In summary, our findings indicate that mMSC-exo treatment is effective in severe CMV pneumonia by reducing lung inflammation and fibrosis through the NF-κB/NLRP3 signaling pathway, thus providing promising therapeutic potential for clinical CMV infection.

Atomically Precise Nanometer-Sized Pt Catalysts with an Additional Photothermy Functionality.

Atomically precise ~1-nm Pt nanoparticles (nanoclusters, NCs) with ambient stability are important in fundamental research and exhibit diverse practical applications (catalysis, biomedicine, etc.). However, synthesizing such materials is challenging. Herein, by employing the mixture ligand protecting strategy, we successfully synthesized the largest organic-ligand-protected (~1-nm) Pt23 NCs precisely characterized with mass spectrometry and single-crystal X-ray diffraction analyses. Interestingly, natural population analysis and Bader charge calculation indicate an alternate, varying charge -layer distribution in the sandwich-like Pt23 NC kernel. Pt23 NCs can catalyze the oxygen reduction reaction under acidic conditions without requiring calcination and other treatments, and the resulting specific and mass activities without further treatment are sevenfold and eightfold higher than those observed for commercial Pt/C catalysts, respectively. Density functional theory and d-band center calculations interpret the high activity. Furthermore, Pt23 NCs exhibit a photothermal conversion efficiency of 68.4 % under 532-nm laser irradiation and can be used at least for six cycles, thus demonstrating great potential for practical applications.

68 Ga-DOTATATE and 68 Ga-FAPI Imaging in Neuroendocrine Neoplasms of Different Grades.

ABSTRACT: We report findings from 68 Ga-DOTATATE and 68 Ga-FAPI PET/CT in a 43-year-old woman with neuroendocrine neoplasms. DOTATATE and FAPI uptake differed in different lesions. These results suggest a potential value for dual-tracer imaging in the evaluation of neuroendocrine neoplasms that have different grades.

Simplified S1 vertebral bone quality score independently predicts proximal junctional kyphosis after surgery for degenerative lumbar scoliosis.

OBJECTIVE: Our study aimed to assess the effectiveness of the simplified S1 vertebral bone quality (VBQ) score in predicting the incidence of proximal junctional kyphosis (PJK) after surgery for degenerative lumbar scoliosis (DLS). METHODS: We reviewed 122 patients with DLS who underwent posterior lumbar decompression and long-segment fusion surgery in our hospital from January 2016 to December 2020. The patients were classified into PJK group and non-PJK group. S1 VBQ scores are determined by signal intensity measurements taken from the mid-sagittal plane of T1-weighted non-contrast MRI. Logistic regression analysis was used to identify factors associated with PJK. Receiver-operating characteristic curve (ROC) analysis was used to evaluate the value of S1 VBQ score in predicting pedicle PJK after DLS. RESULTS: 122 DLS patients (90 females and 32 males) met the inclusion criteria. In addition, 27 patients (22.13%) had PJK at the time of last follow-up. VBQ was higher in PJK patients than non-PJK patients (3.58 ± 0.67 vs. 3.08 ± 0.54, p < 0.001). Preoperatively, patients in the PJK group had a greater TLK than those in the non-PJK group (20.00 ± 6.22 vs. 16.86 ± 5.38, p = 0.011). After surgery, patients in the PJK group had greater TLK (p < 0.001) and PJA (p < 0.001) compared with the non-PJK group. At final FU, patients in the PJK group had greater TK (p = 0.002), TLK (p < 0.001), SVA (p < 0.001), and PJA (p < 0.001) than patients in the non-PJK group (Table 4). In multivariate logistic regression analysis, higher VBQ score (OR 4.565, 95% CI 1.43-14.568, p = 0.010), advanced age (OR 1.119, 95% CI 1.021-1.227, p = 0.016), and larger TLK (OR 1.191, 95% CI 1.041-1.362, p = 0.011) were significant predictors of postoperative PJK in patients with DLS (Table 6). A statistically significant positive correlation existed between VBQ score and PJA change (r = 0.370, p < 0.001). We created ROC curves for VBQ scores as predictors of PJK with a diagnostic accuracy of 72.1% (95% CI 60.15-82.9%.The ideal limit for the VBQ score was 3.205 (sensitivity: 77.8%, specificity: 81.4%). CONCLUSION: To the best of our knowledge, this is the first study to evaluate the effectiveness of the S1 VBQ score in predicting postoperative PJK in DLS. Our study included major risk factors and found that S1 VBQ score was a significant predictor of PJK in patients undergoing DLS surgery. The higher the S1 VBQ score, the higher the probability of PJK.

Changes of soil nutrients and organic carbon fractions in Caragana korshinskii forests with different restoration years in mountainous areas of southern Ningxia, China.

Vegetation restoration can effectively enhance soil quality and soil organic carbon (SOC) sequestration. In this study, the distribution characteristics of soil nutrients and SOC along soil profile (0-100 cm), and their responses to restoration years (16, 28, 38 years) were studied in Caragana korshinskii plantations in the southern mountainous area of Ningxia, compared with cropland and natural grassland. The results showed that: 1) the contents of SOC, soil total nitrogen (TN), total phosphorus (TP), particulate organic carbon (POC), mineral-associated organic carbon (MAOC) and the proportion of particulate organic carbon to total organic carbon (POC/SOC) all decreased with increasing soil depth. The ratio of mineral-associated organic carbon to total organic carbon (MAOC/SOC) exhibited an opposite trend. 2) The contents of SOC, TN, TP, C:P, N:P, POC and MAOC gra-dually decreased as the restoration years increased. However, the C:N ratio showed no significant change. The POC/SOC ratio initially increased and then decreased, while the MAOC/SOC ratio decreased initially and then increased. 3) In three different types of vegetation, POC, MAOC, and SOC showed a highly significant positive linear correlation, with the increase in SOC mainly depended on the increase in MAOC. The SOC, TN, TP, POC and MAOC contents in natural grassland and C. korshinskii plantations were significantly higher than those in cropland. In conclusion, soil nutrients and POC and MAOC contents of C. korshinskii plantations gradually decreased with the increases in restoration years. However, when compared with cropland, natural grassland and C. korshinskii plantations demonstrated a greater capacity to maintain and enhance soil nutrient and carbon storage.

Development and validation of a nomogram to predict the risk of residual low back pain after tubular microdiskectomy of lumbar disk herniation.

OBJECTIVE: Tubular microdiskectomy (tMD) is one of the most commonly used for treating lumbar disk herniation. However, there still patients still complain of persistent postoperative residual low back pain (rLBP) postoperatively. This study attempts to develop a nomogram to predict the risk of rLBP after tMD. METHODS: The patients were divided into non-rLBP (LBP VAS score < 2) and rLBP (LBP VAS score ≥ 2) group. The correlation between rLBP and these factors were analyzed by multivariate logistic analysis. Then, a nomogram prediction model of rLBP was developed based on the risk factors screened by multivariate analysis. The samples in the model are randomly divided into training and validation sets in a 7:3 ratio. The Receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to evaluate the diskrimination, calibration and clinical value of the model, respectively. RESULTS: A total of 14.3% (47/329) of patients have persistent rLBP. The multivariate analysis suggests that higher preoperative LBP visual analog scale (VAS) score, lower facet orientation (FO), grade 2-3 facet joint degeneration (FJD) and moderate-severe multifidus fat atrophy (MFA) are risk factors for postoperative rLBP. In the training and validation sets, the ROC curves, calibration curves, and DCAs suggested the good diskrimination, predictive accuracy between the predicted probability and actual probability, and clinical value of the model, respectively. CONCLUSION: This nomogram including preoperative LBP VAS score, FO, FJD and MFA can serve a promising prediction model, which will provide a reference for clinicians to predict the rLBP after tMD.

Cancer drug indication approvals in China and the United States: a comparison of approval times and clinical benefit, 2001-2020.

Background: Perceived delays in cancer drug approvals have been a major concern for policymakers in China. Policies have been implemented to accelerate the launch of new cancer drugs and indications. This study aimed to assess similarities and differences between China and the United States in the approvals, timing, and clinical benefit evidence of cancer drug indications between 2001 and 2020. Methods: This study retrospectively identified all cancer drugs and indications approved in both China and the United States from January 1st, 2001 to December 31, 2020, and described differences in approval times as well as in submission and review times. Information on the availability of overall survival benefit evidence by December 31, 2020, was collected. Univariate and multiple logistic regression analyses were used to assess whether evidence of benefit and other factors affected the propensity and timing of approvals of cancer drug indications in China. Findings: Between 2001 and 2020, 229 indications corresponding to 145 cancer drugs approved in the United States were identified. Of those, 80 indications (34.9%) were also approved in China by the end of 2020. Cancer drug indications were approved in China at a median of 1273.5 days after approval in the United States. The median submission and review time differences for cancer drug indications in China were 1198.0 days and 180.0 days respectively. Submission time differences accounted for most of the approval time differences (p < 0.001). Indications supported by overall survival benefit evidence had shorter median review time differences (145.0 days) than those without such evidence (235.0 days, p = 0.008). Indications with overall survival benefit evidence were 3.94 times more likely to be approved in China compared to those without such evidence (p = 0.001), controlling for approval year, cancer type, and the prevalence of cancer by site. Interpretation: FDA-approved cancer drug indications demonstrating a survival benefit were more likely to receive approvals in China with shorter regulatory review times compared to indications without such evidence. Given that manufacturer submission times were the main driver of cancer drug approval times in China, factors influencing submission timing should be explored. Funding: No funding.