Objective To construct and evaluate a prognostic model for clear cell renal cell carcinoma(ccRCC)based on preoperative lipid ratios, cM0(i+)staging, and other clinical characteristics, so as to provide a precise tool for clinical prognosis assessment. Methods A retrospective analysis was conducted on the clinical data of 215 ccRCC patients treated in our hospital during May 2014 and May 2023. Lipid ratios were calculated using preoperative lipid data, and patients were divided into cM0(i+)stage or cM0 stage according to postoperative circulating tumor cells(CTCs)test results. The optimal lipid ratio and cutoff value were selected using receiver operating characteristic(ROC)curves and the X-tile method. Patients were subdivided into three groups based on the level of the low-density lipoprotein cholesterol to non-low-density lipoprotein cholesterol ratio(LNLR)and cM0(i+)staging:Group A [LNLR＞1.68 and diagnosed with cM0(i+)], Group B [LNLR＞1.68 or diagnosed with cM0(i+)], and Group C(LNLR ≤1.68 and diagnosed with cM0). Kaplan-Meier survival analysis was used to plot survival curves for patients in different groups. The log-rank test was employed to compare differences in recurrence-free survival(RFS)among the subgroups. Multivariate Cox regression analysis was conducted to identify the independent risk factors influencing RFS, and a nomogram prediction model was constructed based on these results. The predictive performance of the model was validated using ROC curves, calibration curves, and decision curves. Results ROC curves were plotted for lipid markers, and LNLR was identified as the most predictive for RFS. Its optimal cutoff point was 1. 68. Patients in Group A experienced a significantly shorter postoperative RFS. Multivariate Cox regression analysis identified preoperative LNLR, cM0(i+)staging, pathological grade, and stage as independent risk factors for RFS. A nomogram model was constructed based on these risk factors. The area under the ROC curve(AUC)for 1-, 3-, and 5-year RFS was 0.896(95% CI:0.8121-0.9627), 0.890(95%CI:0.7879-0.9641), and 0.870(95%CI:0.7697-0.9526), indicating good discriminatory ability and predictive performance. Calibration plots demonstrated good agreement between predicted and actual outcomes. Clinical decision curve analysis showed high clinical net benefit. Conclusion Preoperative LNLR level is an independent risk factor for RFS in ccRCC patients. The prognostic prediction model based on LNLR, cM0(i+)staging, patient pathological grade, and staging demonstrates good predictive performance for RFS and holds potential clinical application value.

Objective:To investigate the clinical characteristics, treatment status, and disease outcomes of Chinese patients with multifocal motor neuropathy (MMN).Methods:Inpatients with MMN who were admitted to Huashan Hospital, Shanghai Medical College, Fudan University between January 2014 and April 2024 were enrolled. Baseline information, clinical features, and treatment history were recorded. Disability and functional impairment were assessed using the Inflammatory Neuropathy Cause and Treatment (INCAT) scale.Results:A total of 39 MMN patients were included and classified according to the 2010 European Federation of Neurological Societies/Peripheral Nerve Society criteria: definite MMN (27 cases), probable MMN (3 cases), and possible MMN (9 cases). At onset, 29 cases (29/39, 74.4%) had unilateral upper limb involvement, 5 cases (5/39, 12.8%) had unilateral lower limb involvement, 1 case (1/39, 2.6%) had bilateral lower limb involvement, and 4 cases (4/39, 10.3%) had simultaneous upper and lower limb involvement. By the last follow-up, follow-up duration was 3.4 (5.4) years (range: 0-14.3 years), disease duration was 8.3 (5.9) years (range: 1.2-31.3 years); 27 patients (27/39, 69.2%) exhibited increased limb involvement compared to onset. Segmental conduction block was detected in 35 cases (35/39, 89.7%). Anti-GM1 IgM antibodies were positive in 14 cases (14/31, 45.2%), and cerebrospinal fluid protein-cell dissociation was observed in 6 cases (6/32, 18.8%). Among them, 38 patients were treated with intravenous immunoglobulin (IVIG) during the disease course. Among the 24 patients followed up for>1 year after IVIG initiation, long-term efficacy (≥1 year), medium-short-term efficacy (<1 year), and no efficacy were observed in 16.7% (4/24), 62.5% (15/24), and 20.8% (5/24) of cases, respectively. Patients with persistently positive anti-GM1 IgM antibodies tended to have medium-short-term relief. Cyclophosphamide was used in 7 cases, with long-term improvement in 1 case. One patient achieved sustained improvement after two courses of rituximab. No benefit was observed with plasma exchange, corticosteroids, or other immunosuppressants. The median INCAT score at disease onset was 1 (range: 0-4), while the median pre-immunotherapy INCAT score was 3 (range: 0-5), and at the last follow-up after treatment, the median INCAT score remained 3 (range: 0-5). A statistically significant increase in INCAT scores was observed from disease onset to pretreatment ( U=229.000, P<0.001). However, no statistically significant difference was found between pretreatment and posttreatment INCAT scores ( U=491.500, P=0.880). Conclusions:MMN is a slowly progressive immune-mediated peripheral neuropathy. Early diagnosis and treatment with IVIG are crucial. Evidence for the efficacy of cyclophosphamide and rituximab remains limited.

The phase changes and quantity-quality transfer of 17 batches of Ostreae Concha(Ostrea rivularis) during the raw material-calcined decoction pieces-standard decoction process were analyzed. The content of calcium carbonate(CaCO_3), the main component, was determined by chemical titration, and the extract yield and transfer rate were calculated. The CaCO_3 content in the raw material, calcined decoction pieces, and standard decoction was 94.39%-98.80%, 95.03%-99.22%, and 84.58%-90.47%, respectively. The process of raw material to calcined decoction pieces showed the yield range of 96.85% to 98.55% and the CaCO_3 transfer rate range of 96.92% to 99.27%. The process of calcined decoction pieces to standard decoction showed the extract yield range of 2.86% to 5.48% and the CaCO_3 transfer rate range of 2.59% to 5.13%. The results of X-ray fluorescence(XRF) assay showed that the raw material, calcined decoction pieces, and standard decoction mainly contained Ca, Na, Mg, Si, Br, Cl, Al, Fe, Cr, Mn, and K. The chemometric results showed an increase in the relative content of Cr, Fe, and Si from raw material to calcined decoction pieces and an increase in the relative content of Mg, Al, Br, K, Cl, and Na from calcined decoction pieces to standard decoction. X-ray diffraction(XRD) was employed to establish XRD characteristic patterns of the raw material, calcined decoction pieces, and standard decoction. The XRD results showed that the main phase of all three was calcite, and no transformation of crystalline form or generation of new phase was observed. Fourier transform infrared spectroscopy(FTIR) was employed to establish the FTIR characteristic spectra of the raw material, calcined decoction pieces, and standard decoction. The FTIR results showed that the raw material had internal vibrations of O-H, C-H, C=O, C-O, and CO■ groups. Due to the loss of organic matter components after calcination, no information about the vibrations of C-H, C=O, and C-O groups was observed in the spectra of calcined decoction pieces and standard decoction. In summary, this study elucidated the quantity-quality transfer and phase changes in the raw material-calcined decoction pieces-standard decoction process by determining the CaCO_3 content, calculating the extract yield and transfer rate, and comparing the element changes, FTIR characteristic spectra, and XRD characteristic pattern. The results were reasonable and reliable, laying a foundation for the subsequent process research and quality control of the formula granules of calcined Ostreae Concha(O. rivularis Gould), and providing ideas and methods for the quality control of the whole process of raw material-decoction pieces-standard decoction-formula granules of Ostreae Concha and other testacean traditional Chinese medicine.
Drugs, Chinese Herbal/isolation & purification* ; Calcium Carbonate/analysis* ; Quality Control

Objective:To investigate the clinical characteristics, treatment status, and disease outcomes of Chinese patients with multifocal motor neuropathy (MMN).Methods:Inpatients with MMN who were admitted to Huashan Hospital, Shanghai Medical College, Fudan University between January 2014 and April 2024 were enrolled. Baseline information, clinical features, and treatment history were recorded. Disability and functional impairment were assessed using the Inflammatory Neuropathy Cause and Treatment (INCAT) scale.Results:A total of 39 MMN patients were included and classified according to the 2010 European Federation of Neurological Societies/Peripheral Nerve Society criteria: definite MMN (27 cases), probable MMN (3 cases), and possible MMN (9 cases). At onset, 29 cases (29/39, 74.4%) had unilateral upper limb involvement, 5 cases (5/39, 12.8%) had unilateral lower limb involvement, 1 case (1/39, 2.6%) had bilateral lower limb involvement, and 4 cases (4/39, 10.3%) had simultaneous upper and lower limb involvement. By the last follow-up, follow-up duration was 3.4 (5.4) years (range: 0-14.3 years), disease duration was 8.3 (5.9) years (range: 1.2-31.3 years); 27 patients (27/39, 69.2%) exhibited increased limb involvement compared to onset. Segmental conduction block was detected in 35 cases (35/39, 89.7%). Anti-GM1 IgM antibodies were positive in 14 cases (14/31, 45.2%), and cerebrospinal fluid protein-cell dissociation was observed in 6 cases (6/32, 18.8%). Among them, 38 patients were treated with intravenous immunoglobulin (IVIG) during the disease course. Among the 24 patients followed up for>1 year after IVIG initiation, long-term efficacy (≥1 year), medium-short-term efficacy (<1 year), and no efficacy were observed in 16.7% (4/24), 62.5% (15/24), and 20.8% (5/24) of cases, respectively. Patients with persistently positive anti-GM1 IgM antibodies tended to have medium-short-term relief. Cyclophosphamide was used in 7 cases, with long-term improvement in 1 case. One patient achieved sustained improvement after two courses of rituximab. No benefit was observed with plasma exchange, corticosteroids, or other immunosuppressants. The median INCAT score at disease onset was 1 (range: 0-4), while the median pre-immunotherapy INCAT score was 3 (range: 0-5), and at the last follow-up after treatment, the median INCAT score remained 3 (range: 0-5). A statistically significant increase in INCAT scores was observed from disease onset to pretreatment ( U=229.000, P<0.001). However, no statistically significant difference was found between pretreatment and posttreatment INCAT scores ( U=491.500, P=0.880). Conclusions:MMN is a slowly progressive immune-mediated peripheral neuropathy. Early diagnosis and treatment with IVIG are crucial. Evidence for the efficacy of cyclophosphamide and rituximab remains limited.

Objective:To investigate the impact of circular RanGTPase activating protein 1 (circRANGAP1) on the biological behavior of trophoblast cells in preeclampsia and its potential mechanisms.Methods:Placental tissues were collected from preeclampsia patients and age- and gestational age- matched control pregnant women admitted to Shengjing Hospital of China Medical University from August 2020 to December 2022 (eight cases each in the early-onset preeclampsia group and early-onset control group, and 24 cases each in the late-onset preeclampsia group and late-onset control group). The expression levels of circRANGAP1 and eukaryotic translation initiation factor 4A3 (EIF4A3) mRNA in placental tissues were detected by real-time quantitative polymerase chain reaction (RT-qPCR), and EIF4A3 protein expression was assessed by Western blotting. In HTR-8/Svneo cells, the proliferation, migration, and invasion abilities were evaluated by cell counting assay, scratch assay, Transwell invasion assay, and the regulatory effect of EIF4A3 on circRANGAP1 was examined by RNA binding protein immunoprecipitation (RIP). Changes of circRANGAP1 expression in HTR-8/Svneo cells were detected by RT-qPCR after EIF4A3 knockdown. Statistical analysis was performed using independent sample t-test, non-parametric Chi-square test, or Pearson correlation analysis. Results:(1) There was no significant difference in circRANGAP1 expression between the early-onset preeclampsia group and the early-onset control group. However, circRANGAP1 expression was higher in the late-onset preeclampsia group compared to the late-onset control group [(3.764±3.297) vs. (0.960±0.720), t=4.07, P<0.001]. In late-onset preeclampsia patients, circRANGAP1 expression was positively correlated with both systolic and diastolic blood pressure (systolic: r=0.639, P<0.01; diastolic: r=0.800, P<0.001). There was no significant difference in EIF4A3 mRNA and protein expression between the early-onset preeclampsia group and the early-onset control group, but EIF4A3 mRNA and protein expression were higher in the late-onset preeclampsia group compared to the late-onset control group [mRNA: (2.963±3.081) vs. (1.149±0.667), t=2.30, P=0.028; protein: (2.504±1.008) vs. (0.258±0.180), t=4.39, P=0.005]. (2) After small interfering (si) RNA knockdown, there was no significant difference in mRANGAP1 expression, but circRANGAP1 expression decreased [(1.000±0.004), (0.465±0.031), and (0.621±0.030)], with si-1 showing the highest knockdown efficiency ( t=23.59, P=0.002). Specific knockdown of circRANGAP1 resulted in increased proliferation [(1.297±0.058) vs. (1.456±0.030), t=－5.97, P<0.001], invasion [(94.400± 6.504) vs. (219.000±19.870), t=－13.32, P<0.001], and migration [(25.493±3.498)% vs. (58.456±3.277)%, t=－15.38, P<0.001] abilities of trophoblast cells. (3) There are six binding sites for EIF4A3 in the upstream region of circRANGAP1 pre-mRNA. EIF4A3 can bind through regions a and b, but not region c. After siRNA knockdown, EIF4A3 expression decreased [(1.003±0.101), (0.276±0.060), (0.398±0.074), and (0.184±0.017)], with si-3 showing the highest knockdown efficiency. After EIF4A3 knockdown, circRANGAP1 expression in trophoblast cells decreased [(1.004±0.118) vs. (0.480±0.039), t=5.96, P=0.027]. Conclusion:circRANGAP1, regulated by EIF4A3, inhibits the proliferation, migration, and invasion abilities of trophoblast cells, thereby participating in the pathogenesis of preeclampsia.

ObjectiveIn recent years, the negative impact of microgravity on astronauts’ nervous systems has received widespread attention. The repetitive transcranial magnetic stimulation (rTMS) technology has shown significant positive effects in the treatment of neurological and psychiatric disorders. The potential benefits of combined frequency stimulation (CFS) which combines different frequency stimulation patterns in ameliorating neurological dysfunctions induced by the microgravity environment, still require in-depth investigation. Exploring the therapeutic effects and electrophysiological mechanisms of CFS in improving various neurological disorders caused by microgravity holds significant importance for neuroscience and the clinical application of magnetic stimulation. MethodsThis study employed 40 C57BL/6 mice, randomly divided into 5 groups: sham group, hindlimb unloading (HU) group, 10 Hz group, 20 Hz group, and combined frequency stimulation (10 Hz+20 Hz, CFS) group. Mice in all groups except the sham group received 14 d of simulated microgravity conditions along with 14 d of repetitive transcranial magnetic stimulation. The effects of CFS on negative emotions and spatial cognitive abilities were assessed through sucrose preference tests and water maze experiments. Finally, patch-clamp techniques were used to record action potentials, resting membrane potentials, and ion channel dynamics of granule neurons in the hippocampal dentate gyrus (DG) region. ResultsCompared to the single-frequency stimulation group, behavioral results indicated that the combined frequency stimulation (10 Hz+20 Hz) significantly improved cognitive impairments and negative emotions in simulated microgravity mice. Electrophysiological experiments revealed a decrease in excitability of granule neurons in the hippocampal DG region after HU manipulation, whereas the combined frequency stimulation notably enhanced neuronal excitability and improved the dynamic characteristics of voltage-gated Na⁺ and K⁺ channels. ConclusionThe repetitive transcranial magnetic stimulation with combined frequencies (10 Hz+20 Hz) effectively ameliorates cognitive impairments and negative emotions in simulated microgravity mice. This improvement is likely attributed to the influence of combined frequency stimulation on neuronal excitability and the dynamic characteristics of Na⁺ and K⁺ channels. Consequently, this study holds the promise to provide a theoretical basis for alleviating cognitive and emotional disorders induced by microgravity environments.

Objective To study the expression and clinical significance of neural Wiskott-Alrdich syndrome protein(N-WASP)in pla-centas with preeclampsia.Methods This study included a total of 65 pregnant women:15 in the early-onset preeclampsia group,15 in the early-onset control group,15 in the late-onset preeclampsia group,and 20 in the late-onset control group.Real-time fluorescence quan-titative PCR(RT-qPCR)was used to detect the relative expression of N-WASP mRNA in placental tissues.Western blotting and immu-nohistochemistry were used to detect the expression and position of N-WASP protein in placental tissues from each group.Results RT-qPCR revealed significantly lower N-WASP mRNA expression levels in the placental tissue of the early-onset preeclampsia group compared to those in the early-onset control group(0.50±0.19 vs.0.93±0.73,P＜0.05).The N-WASP mRNA expression levels in late-onset preeclampsia placenta were significantly lower than those in the late-onset control group(0.83±0.34 vs.1.15±0.34,P＜0.05).Western blotting revealed significantly lower N-WASP protein expression in the placental tissue of early-onset preeclampsia compared to that in the early-onset control group(0.35±0.17 vs.0.72±0.21,P＜0.05).The N-WASP protein expression in late-onset preeclampsia placenta was significantly lower than that in the late-onset control group(0.39±0.16 vs.0.76±0.20,P＜0.05).The N-WASP mRNA expression in the placenta negatively correlated with the occurrence of early-onset(r =-0.37,P = 0.042)and late-onset preeclampsia(r =-0.39,P = 0.019).Immunohistochemistry revealed that N-WASP protein was localized in the cytoplasm of syncytiotrophoblasts,cytotrophoblasts,villous stromal cells,and vascular endothelial cells.Conclusion The low expression of N-WASP may be closely associated with preeclampsia.

ObjectiveTo investigate the effect of shikosin （SHI） on psoriasis （PSO） and explore the underlying mechanism via the cyclic guanosine monophosphate-adenosine monophosphate synthase （cGAS）/stimulator of interferon genes （STING） signaling pathway. MethodHaCaT cells were classified into normal culture（Control）， a mixture of five proinflammatory cytokines（M5）， low-， medium-， and high-dose SHI （L-SHI， M-SHI， and H-SHI， respectively）， and SHI+ADU-S100 groups. The cells in the M5 group were stimulated with 10 μg·L^-1 interleukin （IL）-1α， IL-17， IL-22， tumor necrosis factor （TNF）-α， and oncostatin M （OSM） for 48 h. The cells in the L-SHI， M-SHI， and H-SHI groups were treated with 0.1， 1， 10 μmol·L^-1 SHI， respectively， on the basis of the treatment in the M5 group. The cells in the SHI+ADU-S100 group were treated with 10 μmol·L^-1 STING activator ADU-S100 on the basis of the treatment in the H-SHI group. The methyl thiazolyl tetrazolium （MTT） assay and colony formation assay were employed to examine the effect of SHI on the proliferation of HaCaT cells. The wound healing assay was employed to examine the effect of SHI on the migration of HaCaT cells. Flow cytometry was employed to detect the effect of SHI on the apoptosis of HaCaT cells. Enzyme-linked immunosorbent assay was employed to measure the levels of IL-1β， IL-6， IL-15， IL-23， and interferon-γ （IFN-γ） in HaCaT cells. Western blot was employed to determine the protein levels of cGAS and STING in HaCaT cells. ResultCompared with Control group， the M5 group showed decreased survival rate， colony formation， and would healing rate of HaCaT cells， increased apoptosis rate， elevated levels of IL-1β， IL-6， IL-15， IL-23， and IFN-γ， and up-regulated protein levels of cGAS and STING （P<0.01）. Compared with the M5 group， the L-SHI， M-SHI， and H-SHI groups showed increased survival rate， cell colony formation， and wound healing rate， decreased apoptosis rate， lowered levels of IL-1β， IL-6， IL-15， IL-23， and IFN-γ， and down-regulated protein levels of cGAS and STING （P<0.01）. Compared with the H-SHI group， the SHI+ADU-S100 group showed decreased survival rate， cell colony formation， and wound healing rate， increased apoptosis rate， risen levels of IL-1β， IL-6， IL-15， IL-23， and IFN-γ， and up-regulated protein levels of cGAS and STING （P<0.01）. ConclusionSHI can inhibit the inflammation in the cell model of PSO by inhibiting the cGAS/STING signaling pathway.

Objective:To investigate the clinical value of multiparameteric quantitative ultrasound combined with a non-invasive prediction model for assessing high-risk steatohepatitis.Methods:One hundred and ninety-four cases with metabolic-associated fatty liver disease (MAFLD) who underwent liver biopsy in Huashan Hospital, Fudan University, from June 2021 to September 2022 were selected. Shear wave elastography (SWE), shear wave dispersion (SWD) imaging, and attenuation imaging (ATI) examinations were conducted in all patients before biopsy. High-risk steatohepatitis was defined as a total activity score of ≥4 in patients with steatohepatitis, hepatocellular ballooning, and liver lobular inflammation based on pathological hepatic steatosis, inflammatory activity, and fibrosis scoring system (SAF), and fibrosis stage≥F2. Binary logistic regression analysis was used to identify the factors influencing high-risk steatohepatitis. A predictive model for diagnosing high-risk steatohepatitis was constructed using R language. The DeLong test was used to compare the area under the curve between groups. Measurement data was compared between groups using the t-test or rank-sum test, and count data were compared between groups using the χ2 test. Results:There were 46 cases (23.7%) with high-risk steatohepatitis. The quantitative ultrasound parameters included elastic modulus ( OR=2.958, 95% CI: 1.889-4.883, P<0.001), dispersion coefficient ( OR=1.786, 95% CI: 1.424-2.292, P<0.001) and attenuation coefficient ( OR=42.642, 95% CI: 3.463-640.451, P=0.004). Serological indexes of fasting blood glucose ( OR=1.196, 95% CI: 1.048-1.392, P=0.011), alanine aminotransferase ( OR=1.012, 95% CI: 1.006-1.019, P<0.001), aspartate aminotransferase ( OR=1.027, 95% CI: 1.014-1.042, P<0.001), γ-glutamyl transferase ( OR=1.008, 95% CI: 1.001-1.017, P=0.041) and HDL cholesterol ( OR=0.087, 95% CI: 0.016-0.404, P=0.003) were the factors influencing its progression. The AUCs of elastic modulus, dispersion coefficient, attenuation coefficient, multiparametric ultrasound model, serological index model, and ultrasound combined with serology model for the diagnosis of high-risk steatohepatitis were 0.764, 0.758, 0.634, 0.786, 0.773 and 0.825, respectively. The results of the DeLong test showed that the ultrasound combined with the serological model was significantly better than the serological index model and the elastic modulus, dispersion coefficient, and attenuation coefficient alone ( P=0.024, 0.027, 0.038 and <0.001). Conclusion:The combination of multiparametric quantitative ultrasound is helpful for the non-invasive diagnosis of high-risk steatohepatitis and possesses great clinical significance.

OBJECTIVE To quantitatively and qualitatively analyze the progress of potentially inappropriate medication （PIM） research by means of bibliometrics， and to predict the hotspots and trends of PIM， so as to provide reference for PIM research in China. METHODS The research literature related to PIM were searched from Web of Science core database， and the publication trend of the literature was analyzed on the bibliometric online analysis platform and CiteSpace 5.8.R3 software. The research results were visualized and analyzed， and the research hotspots of PIM were summarized through gCLUTO. RESULTS About PIM research， the annual number of the literature issued from 2012 to 2021 showed a continuous growth trend totally； the United States had the largest number of literature （241 pieces）； the University of Sydney in Australia was the research institution with the largest number of literature （59 pieces）； O’Mahony D from University College Cork， Ireland， published the most literature （23 pieces）； the research of PIM involved 57 disciplines， among which there was the largest number of literature about gerontology （384 pieces）； International Journal of Clinical Pharmacy was the journal with the largest number of literature （61 pieces）； Journal of the American Geriatrics Society was cited most frequently （1 197 times）. The hotspots of PIM research mainly focused on seven aspects： the standard of PIM， the safety and economy research of PIM， the risk factors research of PIM， the PIM research of chronic patients， the PIM research of antipsychotics， the research of pharmacists’ participation in PIM management， and the PIM research about palliative care of tumor patients. CONCLUSIONS The heat of research on PIM has been on the rise， and there is little cooperation between countries and institutions， and more cooperation is needed. In the future， the focus of Chinese pharmacists’ research on PIM may be on the deep localization of PIM standards， PIM intervention and precise medication guidance， and PIM management of specific diseases and drugs.