Objective:To investigate the predictive value of serum signal lymphocyte activation molecule family member 8(SLAMF8)levels for post-stroke cognitive impairment(PSCI).Methods:The GSE122063 dataset was selected from the Gene Expression Omnibus(GEO), and key genes associated with vascular dementia were identified using STRING network and Cytoscape software.This prospective cohort study involved 123 patients with acute cerebral infarction(ACI)who were admitted to the Department of Neurology at Jiangsu University Affiliated Hospital from January to December 2023.Patients were followed up for six months and categorized into PSCI and post-stroke non-cognitive impairment(PSNCI)groups based on the occurrence of PSCI.General data from both groups at baseline, as well as the Mini-Mental State Examination(MMSE)and Montreal Cognitive Assessment Scale(MoCA)scores at the six-month follow-up, were collected.Baseline serum levels of SLAMF8 and stabilin-1(STAB1), along with serum levels of interleukin-1β(IL-1β)and interleukin-6(IL-6)at the six-month follow-up, were measured.Pearson correlation analysis was used to assess the correlation between variables, while logistic regression analysis was employed to determine baseline factors influencing the occurrence of PSCI.Receiver Operating Characteristic(ROC)curves were plotted to analyze the predictive value of variables for PSCI occurrence.Results:The Cytoscape software identified SLAMF8 and STAB1 as key genes associated with vascular dementia, utilizing maximum neighborhood component density(DNMC)and eccentricity algorithms on the GSE122063 dataset.In the cohort study, patients in the PSCI group exhibited higher baseline NIHSS scores and serum SLAMF8 levels compared to the PSNCI group( t=3.033, 5.422; P<0.01). Additionally, they demonstrated significantly lower MMSE and MoCA scores( t=16.340, 18.634; P<0.001)and higher serum levels of IL-1β and IL-6( t=2.633, 2.632; P<0.05)at the 6-month follow-up.No significant difference was observed in baseline STAB1 levels between the two groups( t=1.280, P>0.05). In the PSCI group, there was no significant correlation between baseline serum SLAMF8 levels and admission NIHSS scores( r=0.257, P=0.082); however, SLAMF8 showed a negative correlation with both MMSE scores( r=-0.711, P<0.001)and MoCA scores( r=-0.686, P<0.001)at the 6-month follow-up.Logistic regression analysis indicated that baseline serum SLAMF8 levels( OR=1.142, P=0.001)and NIHSS scores( OR=1.094, P=0.007)were risk factors for the development of PSCI in patients with acute cerebral infarction(ACI). ROC curve analysis revealed that the area under the ROC curve(AUC)for baseline serum SLAMF8 levels in predicting PSCI occurrence in ACI patients was 0.776, while the AUC for the combined prediction using both SLAMF8 and NIHSS scores was 0.796.Furthermore, baseline serum SLAMF8 levels were positively correlated with serum IL-1β levels( r=0.652, P<0.001)and IL-6 levels( r=0.710, P<0.001)at the 6-month follow-up. Conclusions:The serum SLAMF8 level, exhibiting early high expression in ACI patients, may serve as a potential biological marker for predicting the occurrence of PSCI.

Objective:To investigate the effect of hypericin (Hyp) on neurologic impairment, ferroptosis and cuproptosis in mice with acute cerebral infarction.Methods:Sixty 8-week old male C57BL/6 mice were randomly divided into sham-operated group, middle cerebral artery occlusion (MCAO) group, MCAO+Hyp low-dose treatment group (L-Hyp group), and MCAO+Hyp high-dose treatment group (H-Hyp group), with 15 mice in each group. Intraluminal filament MCAO models in the later 3 groups were established. Saline was given intraperitoneally into the sham-operated group and MCAO group, and Hyp was given intraperitoneally at 0.5 mg/kg or 1 mg/kg into the L-Hyp group and H-Hyp group 24 hours after modeling. Twenty-four hours after Hyp, neurologic function was assessed using Garcia score, grip strength test, and fatigue baton test; brain tissue edema was assessed by dry-wet weight method; neuronal necrosis, survival and apoptosis were detected by HE staining, Nissl staining and TUNEL, respectively; ferroptosis and oxidative stress were assessed using iron assay kit, and reactive oxygen species (ROS), malondialdehyde (MDA) and glutathione (GSH) assay kits; cuproptosis was assessed using copper assay kit and mitochondrial oxidative phosphorylation was evaluated by mitochondrial respiratory chain complex Ⅲ and Ⅳ activity detection kits; morphological changes in neuronal mitochondria after ferroptosis and cuproptosis were observed by electron microscopy; protein expressions of ferroptosis-associated solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4), cuproptosis-associated solute carrier family 31 member 1 (SLC31A1), and ferredoxin 1 (FDX1) were detected by Western blotting.Results:(1) Compared with the MCAO group, the L-Hyp group and H-Hyp group had decreased modified Garcia score and brain water content, increased grip strength and rod-turning time, decreased number of necrotic and apoptotic neurons, increased number of survived neurons, decreased Fe 2+, ROS and MDA levels, increased GSH level and mitochondrial respiratory control rate, and decreased copper content, with significant differences ( P<0.05); and the above changes in the H-Hyp group were more obvious than those in the L-Hyp group, with significant differences ( P<0.05). Compared with the MCAO group, neurons in the L-Hyp group and H-Hyp group had significantly improved status in mitochondrial shrinkage, vacuolation, reduced cristulation, increased membrane density, ruptured cell membrane, endoplasmic reticulum damage and chromatin disruption ( P<0.05); and the H-Hyp group had signficantly more obvious improvement than the L-Hyp group ( P<0.05). (2) Compared with the MCAO group (0.38±0.09, 0.28±0.05), the L-Hyp group and H-Hyp group had significantly increased protein expressions of SLC7A11 and GPX4 (0.83±0.11, 0.49±0.06; 1.27±0.08, 0.84±0.04; P<0.05); the H-Hyp group had significantly higher SLC7A11 and GPX4 expressions than the L-Hyp group ( P<0.05). Compared with the MCAO group (2.76±0.17, 0.67±0.07), the L-Hyp group and H-Hyp group had significantly decreased protein expressions of SLC31A1 and FDX1 (1.72±0.07, 0.51±0.05; 1.12±0.06, 0.34±0.05; P<0.05); the H-Hyp group had significantly lower SLC31A1 and FDX1 expressions than the L-Hyp group ( P<0.05). Conclusion:Hyp can ameliorate ferroptosis and cuproptosis by regulating the protein expressions of SLC7A11, GPX4, SLC31A1 and FDX1, to alleviate oxidative stress injury in MCAO mice, thereby promoting the recovery of neurological function.

Objective:To investigate the predictive value of serum signal lymphocyte activation molecule family member 8(SLAMF8)levels for post-stroke cognitive impairment(PSCI).Methods:The GSE122063 dataset was selected from the Gene Expression Omnibus(GEO), and key genes associated with vascular dementia were identified using STRING network and Cytoscape software.This prospective cohort study involved 123 patients with acute cerebral infarction(ACI)who were admitted to the Department of Neurology at Jiangsu University Affiliated Hospital from January to December 2023.Patients were followed up for six months and categorized into PSCI and post-stroke non-cognitive impairment(PSNCI)groups based on the occurrence of PSCI.General data from both groups at baseline, as well as the Mini-Mental State Examination(MMSE)and Montreal Cognitive Assessment Scale(MoCA)scores at the six-month follow-up, were collected.Baseline serum levels of SLAMF8 and stabilin-1(STAB1), along with serum levels of interleukin-1β(IL-1β)and interleukin-6(IL-6)at the six-month follow-up, were measured.Pearson correlation analysis was used to assess the correlation between variables, while logistic regression analysis was employed to determine baseline factors influencing the occurrence of PSCI.Receiver Operating Characteristic(ROC)curves were plotted to analyze the predictive value of variables for PSCI occurrence.Results:The Cytoscape software identified SLAMF8 and STAB1 as key genes associated with vascular dementia, utilizing maximum neighborhood component density(DNMC)and eccentricity algorithms on the GSE122063 dataset.In the cohort study, patients in the PSCI group exhibited higher baseline NIHSS scores and serum SLAMF8 levels compared to the PSNCI group( t=3.033, 5.422; P<0.01). Additionally, they demonstrated significantly lower MMSE and MoCA scores( t=16.340, 18.634; P<0.001)and higher serum levels of IL-1β and IL-6( t=2.633, 2.632; P<0.05)at the 6-month follow-up.No significant difference was observed in baseline STAB1 levels between the two groups( t=1.280, P>0.05). In the PSCI group, there was no significant correlation between baseline serum SLAMF8 levels and admission NIHSS scores( r=0.257, P=0.082); however, SLAMF8 showed a negative correlation with both MMSE scores( r=-0.711, P<0.001)and MoCA scores( r=-0.686, P<0.001)at the 6-month follow-up.Logistic regression analysis indicated that baseline serum SLAMF8 levels( OR=1.142, P=0.001)and NIHSS scores( OR=1.094, P=0.007)were risk factors for the development of PSCI in patients with acute cerebral infarction(ACI). ROC curve analysis revealed that the area under the ROC curve(AUC)for baseline serum SLAMF8 levels in predicting PSCI occurrence in ACI patients was 0.776, while the AUC for the combined prediction using both SLAMF8 and NIHSS scores was 0.796.Furthermore, baseline serum SLAMF8 levels were positively correlated with serum IL-1β levels( r=0.652, P<0.001)and IL-6 levels( r=0.710, P<0.001)at the 6-month follow-up. Conclusions:The serum SLAMF8 level, exhibiting early high expression in ACI patients, may serve as a potential biological marker for predicting the occurrence of PSCI.

Objective:To investigate the effect of hypericin (Hyp) on neurologic impairment, ferroptosis and cuproptosis in mice with acute cerebral infarction.Methods:Sixty 8-week old male C57BL/6 mice were randomly divided into sham-operated group, middle cerebral artery occlusion (MCAO) group, MCAO+Hyp low-dose treatment group (L-Hyp group), and MCAO+Hyp high-dose treatment group (H-Hyp group), with 15 mice in each group. Intraluminal filament MCAO models in the later 3 groups were established. Saline was given intraperitoneally into the sham-operated group and MCAO group, and Hyp was given intraperitoneally at 0.5 mg/kg or 1 mg/kg into the L-Hyp group and H-Hyp group 24 hours after modeling. Twenty-four hours after Hyp, neurologic function was assessed using Garcia score, grip strength test, and fatigue baton test; brain tissue edema was assessed by dry-wet weight method; neuronal necrosis, survival and apoptosis were detected by HE staining, Nissl staining and TUNEL, respectively; ferroptosis and oxidative stress were assessed using iron assay kit, and reactive oxygen species (ROS), malondialdehyde (MDA) and glutathione (GSH) assay kits; cuproptosis was assessed using copper assay kit and mitochondrial oxidative phosphorylation was evaluated by mitochondrial respiratory chain complex Ⅲ and Ⅳ activity detection kits; morphological changes in neuronal mitochondria after ferroptosis and cuproptosis were observed by electron microscopy; protein expressions of ferroptosis-associated solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4), cuproptosis-associated solute carrier family 31 member 1 (SLC31A1), and ferredoxin 1 (FDX1) were detected by Western blotting.Results:(1) Compared with the MCAO group, the L-Hyp group and H-Hyp group had decreased modified Garcia score and brain water content, increased grip strength and rod-turning time, decreased number of necrotic and apoptotic neurons, increased number of survived neurons, decreased Fe 2+, ROS and MDA levels, increased GSH level and mitochondrial respiratory control rate, and decreased copper content, with significant differences ( P<0.05); and the above changes in the H-Hyp group were more obvious than those in the L-Hyp group, with significant differences ( P<0.05). Compared with the MCAO group, neurons in the L-Hyp group and H-Hyp group had significantly improved status in mitochondrial shrinkage, vacuolation, reduced cristulation, increased membrane density, ruptured cell membrane, endoplasmic reticulum damage and chromatin disruption ( P<0.05); and the H-Hyp group had signficantly more obvious improvement than the L-Hyp group ( P<0.05). (2) Compared with the MCAO group (0.38±0.09, 0.28±0.05), the L-Hyp group and H-Hyp group had significantly increased protein expressions of SLC7A11 and GPX4 (0.83±0.11, 0.49±0.06; 1.27±0.08, 0.84±0.04; P<0.05); the H-Hyp group had significantly higher SLC7A11 and GPX4 expressions than the L-Hyp group ( P<0.05). Compared with the MCAO group (2.76±0.17, 0.67±0.07), the L-Hyp group and H-Hyp group had significantly decreased protein expressions of SLC31A1 and FDX1 (1.72±0.07, 0.51±0.05; 1.12±0.06, 0.34±0.05; P<0.05); the H-Hyp group had significantly lower SLC31A1 and FDX1 expressions than the L-Hyp group ( P<0.05). Conclusion:Hyp can ameliorate ferroptosis and cuproptosis by regulating the protein expressions of SLC7A11, GPX4, SLC31A1 and FDX1, to alleviate oxidative stress injury in MCAO mice, thereby promoting the recovery of neurological function.

Objective:To explore the effectiveness, safety and cost between urinary follicle stimulating hormone (uFSH) and recombinant follicle stimulating hormone (rFSH) in controlled ovarian stimulation (COS) in China.Methods:Data were collected from 16 reproductive centers in China covering oocytes collection time from May 1, 2015 to June 30, 2018. Eligible patients were over 18 years old, adopting COS with uFSH (uFSH group) or rFSH (rFSH group) as start gonadotropins (Gn), and using in vitro fertilization (IVF) and (or) intracytoplasmic sperm injection for fertilisation, excluding frozen embryo recovery cycle. Generalised estimating equation was used to address the violation of independency assumption between cycles due to multiple IVF cycles for one person and clustering nature of cycles carried out within one center. Controlling variables included age, body mass index, anti-Müllerian hormone level, cause of infertility, ovulation protocol, type of fertilisation, number of embryos transferred, number of days of Gn use.Results:Totally 102 061 cycles met eligibility criteria and were included in the analyses. In terms of effectiveness, after controlling relevant unbalanced baseline characteristics, compared with rFSH group, the high oocyte retrieval (>15 oocytes was considered high retrieval) rate of uFSH group significantly decreased in gonadotropin-releasing hormone agonist protocol ( OR=0.642, P<0.01) and in gonadotropin-releasing hormone antagonist protocol ( OR=0.556, P=0.001), but the clinical pregnancy rate per transfer cycle and the live birth rate per transfer cycle significantly increased ( OR=1.179, OR=1.169, both P<0.01) in both agonist and antagonist protocols. For safety, multiple analysis result demonstrated that in the agonist protocol, compared with rFSH group, the incidence of moderate to severe ovarian hyperstimulation syndrome of uFSH group significantly decreased ( OR=0.644, P=0.002). The differences in ectopic pregnancy rate and multiple pregnancy rate between the uFSH and rFSH groups were not significant ( P=0.890, P=0.470) in all patients. In terms of cost, compared with rFSH group, the uFSH group had lower total Gn costs for each patient ( P<0.01). Conclusion:For patients who underwent COS, uFSH has better safety, and economic profiles over rFSH in China.

Different polymorphs of drugs have different molecular arrangements or molecular forces. Raman spectroscopy can reflect the change of molecular polarizability and can be used for the detection of drug polymorphs. The technology has been recorded for the analysis of polymorphism in European Pharmacacopoeia, British Pharamacopoeia and Chinese pharmacopoeia. This review focuses on the application of Raman spectroscopy in the study of pharmaceutical polymorphism. The advances in Raman spectroscopy in the qualitative, quantitative and dynamic processes of drug polymorphism are summarized and analyzed systematically, aiming to provide reference for researchers in related fields.

Objective To explore the effect of intraoperative parathyroid hormone (IOPTH) examination on parathyroidectomy for primary hyperparathyroidism.Methods The clinical data of 41 PHPT patients who received IOPTH monitoring (IOPTH group) from Jan.2009 to Dec.2014 were retrospectively analyzed.The clinical manifestation,examination and changes of parathyroid hormone and calcium before and after operation were collected.Results There were 12 males and 29 females.36 cases had parathyroid adenoma,and 5 cases were parathyroid carcinoma.23 cases were positive in 24 cases of 99Icm-MIBI parathyroid adenoma radionuclide examination,and 2 cases were positive in 3 cases of parathyroid carcinoma radionuclide 99Tcm-MIBI inspection (P＝ 0.213).10 mins after tumor resection,PTH in all cases decreased by 50％ or more than that before tumor resection except for one case of parathyroid carcinoma.23 cases appeared hypocalcemia in 36 cases of parathyroid adenoma after surgery and 2 cases appeared hypocalcemia in 5 cases of parathyroid cancer patients (P＝0.361).No postoperative hoarseness,cough,bleeding occoured.Patients were followed up from 6 to 72 months.Hypocalcemia symptoms recovered 2 weeks to 3 months after surgery.No permanent hypoparathyroidism occured.One case of parathyroid carcinoma died of hypercalcemia 5 months after surgery.The remaining 40 cases survived without recurrence or death.Conclusions Intraoperative PTH monitoring can help doctors analyze whether all the hyperthyroidism glands have been removed,which can help to avoid miss diagnosis of multiple gland disease and unnecessary bilateral neck exploration.This method is highly accurate so it is recommended for routine use in PHPT surgery.

Objective To study the pharmacokinetics difference of levofloxacin polymorphs in rats, evaluate the advantageous medical polymorph,and explore the effects of different polymorphs on clinical medicine. Methods Four crystal forms of levofloxacin were administered intragastrically to rats,and high performance liquid chromatography( HPLC)was used to measure the contents of levofloxacin in rat plasma. The pharmacokinetic parameters were calculated and compared Results After a single oral dose,the peak plasma concentration(Cmax)of crystal forms ofⅠ,Ⅱ,ⅢandⅣof levofloxacin was 6. 984,9. 692,9. 405,6.424 mg·L-1;the time to peak(tmax)was 0.6,0.9,1.0,1.0 h;the half-life(t1/2)was 4.207,2.97,4.857,1.695 h;theareaunderthecurve(AUC0→12h)was31.478,42.385,32.406,31.636mg·h·L-1. Conclusion Thereisnostatistically significant difference in pharmacokinetic parameters. However,compared with other crystal forms,plasma concentration of crystal form II is higher and maintained longer. Therefore,crystal form II of levofloxacin is an advantageous polymorph for medicine.

Objective　To evaluate the safety and efficacy of antegrade selective cerebral perfusion (ASCP) during aortic arch surgery as a means of extending the safe period of systemic circulatory arrest using multimodality neuromonitoring to objectively quantify the physiologic responses. Methods　In twenty-two patients (all less than age 60) scheduled for repair of an aortic arch aneurysm, preoperative verification of effective collateral perfusion through both the carotid and vertebrobasilar arterial systems was documented with transcranial Doppler ultrasonography (TCD). During cardiopulmonary bypass, the sole arterial inflow from the pump was via the right subclavian artery. The magnitude of ASCP was quantified by TCD using peak middle cerebral artery velocity, while flow adequacy was measured by continuous regional cerebrovenous oxygen saturation (rSO2) using dual-wavelength spatially resolved near-infrared spectroscopy. Results　All patients experienced an uneventful recovery. Flow in the middle cerebral artery became undetectable at ASCP < 5*!ml*kg-1*min-1, so adjustments from a 15-20*!ml*kg-1*min-1 baseline were used to maintain rSO2 above 50%. Furthermore, ASCP flow was highly correlated (P<0.01) with both peak middle cerebral artery velocity and rSO2 (r=0.86 and 0.96, respectively). Conclusion　Neuromonitoring guided ASCP may be expected to extend the safe period and is at least partly responsible for the absence of neurologic complications in this patient cohort.