Objective:To construct a nomogram based on preoperative MRI imaging features for the prediction of muscle-invasive upper urinary tract urothelial carcinoma（UTUC）and evaluate its performance.Methods:This retrospective cohort study analyzed the clinical data of 99 UTUC patients treated at the First Affiliated Hospital of Nanjing Medical University from April 2018 to May 2024. Among them，69（69.7%）were male and 30（30.3%）were female，with a median age of 67.0 years. All patients underwent preoperative MRI and radical nephroureterectomy. According to postoperative pathology，tumors staged ≥ T 2 were assigned to the muscle-invasive group，and those staged ≤ T 1 were assigned to the non-muscle-invasive group. Baseline data，pathological information，and imaging characteristics were collected and compared between the two groups. Logistic regression analysis was performed to identify risk factors for muscle-invasive UTUC，and a nomogram was constructed. The diagnostic performance of the model was assessed using receiver operating characteristic（ROC）curves，calibration curves，and decision curve analysis（DCA）. Results:Among the 99 patients，70（70.7%）were diagnosed with muscle-invasive UTUC，and 29（29.3%）with non-muscle-invasive UTUC. The muscle-invasive group had significantly larger tumor size［4.5（2.8，7.0）cm vs. 3.0（2.3，4.5）cm， P = 0.029］，a higher incidence of multifocal tumors［37.1%（26/70）vs. 3.5%（1/29）， P < 0.001］，patchy tumors［30.0%（21/70）vs. 6.9%（2/29）， P = 0.019］，spiculated tumor margins［52.9%（37/70）vs. 17.2%（5/29）， P = 0.001］，tumor compression on renal parenchyma or periureteral/peripelvic fat［68.6%（48/70）vs. 10.3%（3/29）， P < 0.001］，high-grade pathology［92.9%（65/70）vs. 75.9%（22/29）， P = 0.043］，lymph node metastasis［28.6%（20/70）vs. 0， P = 0.001］，and lymphovascular invasion［42.9%（30/70）vs. 10.3%（3/29）， P=0.002］. The apparent diffusion coefficient（ADC）values［0.9（0.8，1.1）× 10 -3 mm2/s vs. 1.1（1.0，1.4）× 10 -3 mm2/s， P < 0.001］and normalized ADC（NADC）values［0.8（0.7，1.0）vs. 0.9（0.8，1.1）， P = 0.002］were significantly lower in the muscle-invasive group. Univariate logistic regression identified multifocality，patchy tumor patterns，spiculated tumor margins，tumor compression on renal parenchyma or periureteral/peripelvic fat，and low NADC values as risk factors for muscle-invasive UTUC（all P < 0.05）. Multivariate analysis revealed multifocality（ OR = 17.903，95% CI 1.650 - 194.253， P = 0.018），tumor compression on renal parenchyma or perirenal / ureteral fat（ OR = 14.690，95% CI 3.069 - 70.323， P < 0.001），and low NADC value（ OR = 0.016，95% CI 0.001 - 0.471， P = 0.017）as independent risk factors. A nomogram was constructed based on these factors. The area under the ROC curve（AUC）of the model was 0.898（95% CI 0.838 - 0.957），with an optimal cutoff value of 0.639. The model showed an accuracy of 83.8%，sensitivity of 81.4%，and specificity of 89.7%. Calibration curves indicated good calibration，and DCA showed that the model provided substantial clinical net benefit. Conclusions:This study constructed a nomogram based on preoperative MRI features，including tumor multifocality，compression on renal parenchyma or periureteral/peripelvic fat and NADC value，which demonstrates good predictive performances for muscle-invasive UTUC.

Objective:To construct a nomogram based on preoperative MRI imaging features for the prediction of muscle-invasive upper urinary tract urothelial carcinoma（UTUC）and evaluate its performance.Methods:This retrospective cohort study analyzed the clinical data of 99 UTUC patients treated at the First Affiliated Hospital of Nanjing Medical University from April 2018 to May 2024. Among them，69（69.7%）were male and 30（30.3%）were female，with a median age of 67.0 years. All patients underwent preoperative MRI and radical nephroureterectomy. According to postoperative pathology，tumors staged ≥ T 2 were assigned to the muscle-invasive group，and those staged ≤ T 1 were assigned to the non-muscle-invasive group. Baseline data，pathological information，and imaging characteristics were collected and compared between the two groups. Logistic regression analysis was performed to identify risk factors for muscle-invasive UTUC，and a nomogram was constructed. The diagnostic performance of the model was assessed using receiver operating characteristic（ROC）curves，calibration curves，and decision curve analysis（DCA）. Results:Among the 99 patients，70（70.7%）were diagnosed with muscle-invasive UTUC，and 29（29.3%）with non-muscle-invasive UTUC. The muscle-invasive group had significantly larger tumor size［4.5（2.8，7.0）cm vs. 3.0（2.3，4.5）cm， P = 0.029］，a higher incidence of multifocal tumors［37.1%（26/70）vs. 3.5%（1/29）， P < 0.001］，patchy tumors［30.0%（21/70）vs. 6.9%（2/29）， P = 0.019］，spiculated tumor margins［52.9%（37/70）vs. 17.2%（5/29）， P = 0.001］，tumor compression on renal parenchyma or periureteral/peripelvic fat［68.6%（48/70）vs. 10.3%（3/29）， P < 0.001］，high-grade pathology［92.9%（65/70）vs. 75.9%（22/29）， P = 0.043］，lymph node metastasis［28.6%（20/70）vs. 0， P = 0.001］，and lymphovascular invasion［42.9%（30/70）vs. 10.3%（3/29）， P=0.002］. The apparent diffusion coefficient（ADC）values［0.9（0.8，1.1）× 10 -3 mm2/s vs. 1.1（1.0，1.4）× 10 -3 mm2/s， P < 0.001］and normalized ADC（NADC）values［0.8（0.7，1.0）vs. 0.9（0.8，1.1）， P = 0.002］were significantly lower in the muscle-invasive group. Univariate logistic regression identified multifocality，patchy tumor patterns，spiculated tumor margins，tumor compression on renal parenchyma or periureteral/peripelvic fat，and low NADC values as risk factors for muscle-invasive UTUC（all P < 0.05）. Multivariate analysis revealed multifocality（ OR = 17.903，95% CI 1.650 - 194.253， P = 0.018），tumor compression on renal parenchyma or perirenal / ureteral fat（ OR = 14.690，95% CI 3.069 - 70.323， P < 0.001），and low NADC value（ OR = 0.016，95% CI 0.001 - 0.471， P = 0.017）as independent risk factors. A nomogram was constructed based on these factors. The area under the ROC curve（AUC）of the model was 0.898（95% CI 0.838 - 0.957），with an optimal cutoff value of 0.639. The model showed an accuracy of 83.8%，sensitivity of 81.4%，and specificity of 89.7%. Calibration curves indicated good calibration，and DCA showed that the model provided substantial clinical net benefit. Conclusions:This study constructed a nomogram based on preoperative MRI features，including tumor multifocality，compression on renal parenchyma or periureteral/peripelvic fat and NADC value，which demonstrates good predictive performances for muscle-invasive UTUC.

Abstract Glutamate receptors are widely distributed in the central nervous system(CNS) and participate in the delivery of excitatory neurotransmitters, including ionotropic glutamate receptors and metabotropic glutamate receptors. Metabotropic glutamate receptors(mGluRs) regulate neuronal excitability and synaptic plasticity, and are classified into group Ⅰ, Ⅱ and Ⅲ. The roles of group Ⅰ mGluRs in psychiatric and neurodegenerative diseases have been extensively studied, especially in the pathological progression of acute brain injury. Several studies have shown that group Ⅰ mGluRs can be involved in eliminating inflammatory damage, suppressing cell apoptosis, regulating neural network disorders, and promoting brain function recovery after acute brain injury. Therefore, group Ⅰ mGluRs have the potential to be effective targets for the treatment of acute brain injury. This paper reviews the distribution and function of group Ⅰ mGluRs in CNS, the pathological role in acute brain injury, and explore the potential of the development of drugs targeting group Ⅰ mGluRs.

Abstract: Integrated stress response is an adaptive response produced by eukaryotic cells after intracellular and extracellular stimulation. The activation of integrated stress response inhibits the translation of most proteins, yet it can promote the translation of certain proteins to cope with complex cellular microenvironment changes. A large number of studies have found that in a variety of nervous system diseases, the integrated stress response can be activated by stress signals of disease-related cells and participates in the occurrence and progression of diseases through processes such as learning and memory consolidation, myelin regeneration and synaptic plasticity. This article summarizes the role, mechanism and possible drug targets of integrated stress response in central nervous system diseases and discusses the potential of pharmacological methods to regulate integrated stress response in the treatment of central nervous system diseases, in order to provide reference for pathological research on and drug development for central nervous system diseases.

Objective:To document any improvement in the breathing control of stroke survivors with dysarthria after practicing Liuzijue qigong.Methods:A total of 157 stroke survivors with dysarthria and abnormal respiration control were randomly divided into an observation group and a control group. Both groups were given traditional breathing training and basic articulation training (including articulatory organ training and speech training). The observation group also received training in Liuzijue qigong. It requires inhaling through the nose and exhaling through the mouth while producing the speech sounds xu, he, hu, si, chui and xi. The training lasted two weeks. Both groups were then evaluated using the modified Frenchay dysarthria assessment. Maximum phonation time, maximum counting ability and volume were also recorded as secondary indexes.Results:After the 2-week intervention, significant improvement was observed in the average scores on all of the indexes, with all of the observation group′s average scores except for volume significantly better than those of the control group. The average volume scores were significantly improved, but not significantly different.Conclusion:Supplementing basic articulation training with Liuzijue qigong can improve respiratory function and the speaking ability of stroke survivors with dysarthria. It is worthy of wider clinical application.

As a key component of glutamatergic system, metabotropic glutamate receptor 5 (mGluR5) has been extensively involved in the regulation of physiological processes such as synaptic transmission, synaptic plasticity and synaptic excitation/inhibition balance.Over the past few decades, mGluR5 has been found to be closely related to multiple neurological and psychiatric disorders, thus it is of considerable interest as a drug target in the treatment of such disorders.This review summarizes the structure and distribution of mGluR5, its normal physiological function, its pathological roles in related central nervous system (CNS) diseases, as well as the current status of its drug development, in order to provide reference for further investigation.

Aim To investigate the effect of paeoniflorin(PF)on TLR2/4 pathway in AGEs-induced RAW264.7 macrophages.Methods RAW264.7 macrophages were incubated at different time points in AGEs stimulation,as well as different concentrations of PF,to optimize experimental conditions.RAW264.7 macrophages were randomly divided into five groups: control group(DMEM),bull serum albumin(BSA)group(200 mg·L-1 BSA),AGEs group(200 mg·L-1 AGEs),paeoniflorin group(200 mg·L-1 AGEs+10-5 mol·L-1 PF)and TLR2/4 inhibitor group(200 mg·L-1 AGEs+30 mg·L-1 OxPAPC).The expression of Toll-like receptor 2(TLR2),Toll-like receptor 4(TLR4),myeloid differentiation factor 88(MyD88),p-IRAK1,TIR-domain containing adaptor protein-inducing IFN-β(TRIF),interferon regulatory factor 3(IRF3),p-IRF3,NF-κB p-p65,NF-κB p65,inducible nitric oxide synthase(iNOS),tumor necrosis factor-α(TNF-α),interleukin-l β(IL-1β)and monocyte chemotactic protein-1(MCP-1)were measured by Western blot.Real-time PCR was used to detect the expression of TLR2 and TLR4 mRNA,while TNF-α,IL-1β and MCP-1 levels in cell supernatant were measured by ELISA.Results Compared with control group,AGEs significantly increased the expression of TLR2,TLR4,MyD88,p-IRAK1,TRIF,IRF3,p-IRF3,NF-κB p-p65,NF-κB p65,iNOS,TNF-α,IL-1β and MCP-1 proteins(P<0.01),as well as TLR2 and TLR4 mRNA(P<0.01).TNF-α,IL-1β and MCP-1 contents were also elevated in cell supernatant(P<0.01).The effects induced by AGEs were decreased significantly in PF and TLR2/4 inhibitor group(P<0.01).Conclusion PF plays an anti-inflammatory effect via inhibiting TLR2/4 pathway on macrophages,which may provide a new theoretical basis for the treatment of diabetic nephropathy.

Objective:To observe the effects of Yikunjing capsules on the bone histomorphometry indexes and the serum Interleukin-6 (IL-6) level in mice with osteoporosis.Methods:60 cases ofC57 female mice were randomly divided into 5 groups,such as model group (equal volume of normal saline),estrogen group (nilestriol,0.25 mg/kg),Yikunjing capsules high dose group (1.44 g/kg),Yikunjing capsules medium dose group (0.72 g/kg) and Yikunjing capsules low dose group (0.36 g/kg),sham group (equal volume of normal saline) were treated with sham operation.The mice in each group was intragastrically administrated for 70 days.Enzyme linked immunosorbent assay (ELISA) was used to detect the serum IL-6 level.The bone histomorphometry index were detected with BI-2000 Medical Image Analysis System.And the Number of blood vessels in distal femoral metaphysis of each group was measured by CT.Results:Compared with the sham group,the width and area of trabecular bone,the thickness of cortical bone,area of trabecular bone,the number of osteoblasts,the bone mineral density and the number of blood vessels in model group were significantly reduced(P＜0.05),while the number of osteoclasts and serum IL-6 level were significantly increased (P＜0.05).Compared with the model group,above indexes in estrogen group,Yikunjing capsules high,medium,low dose group were improved (P＜0.05),and the effect of Yikunjing capsules high dose group and estrogen group was almost the same (P＞0.05).Conclusion:Yikunjing capsules can rectify the bone histomorphometry indexes reduce the serum IL-6 level and increase the number of blood vessels in mice with osteoporosis,and intragastrically administrating 1.44 g/kg Yikunjing capsules could get the better effect.

Objective To evaluate the inhibitory effect of asiaticoside on bleomycin-induced skin cicatrization. Methods Thirty male C57BL/6 mice were randomly divided into three groups:negative control group,model control group,and asiaticoside group,ten in each group.In model control group and asiaticoside group,1 mg·mL-1bleomycin was subcutaneously injected into the dorsal skin of mice every day;4 h later,1 mL 0.9% sodium chloride solution 1 mL asiaticoside(20 mg·mL-1) was injected into the lesion skin in the model control group and the asiaticoside group,respectively.In the negative control group, the same volume of 0.9% sodium chloride solution was subcutaneously injected into the dorsal skin of the mice at the two time points every day.After 21 days,skin specimens were harvested to observe the histomorphology and detect myofibroblast proliferation and expression of inflammatory factors. Results The skin scar was significantly attenuated in the asiaticoside group as compared with the model control group,and the dermal thickness measured exhibited a gradual decrease in asiaticoside group.The expression of α-antismooth muscle antisbidy and infiltration of inflammatory cells were significantly lower in the asiaticoside group than in the model control group. Conclusion Asiaticoside inhibits the development of skin scar of mice by regulating proliferation and differentiation of myofibroblasts and down-regulating inflammatory cells.

Objective To investigate the pharmacokinetics of intravenously infused domestic alfentanil in the patients undergoing general anesthesia.Methods Twelve American Society of Anesthesiologists physical status Ⅰ or Ⅱ patients of both sexes,aged 18-47 yr,weighing 49-86 kg,scheduled for elective subtotal thyroidectomy under general anesthesia,were enrolled in the study.Anesthesia was induced with iv midazolam 0.02 mg/kg,alfentanil 25 μg/kg,propofol 1.5 mg/kg and rocuronium 0.8 mg/kg.The patients were endotracheally intubated and mechanically ventilated.Anesthesia was maintained with inhalation of 0.8％-2.0％ sevoflurane,iv infusion of alfentanil 1 μg · kg-1 · min-1,and intermittent iv boluses of rocuronium 10-20 mg,bispectral index value was maintained at 40-60,and infusion was stopped at 10 min before the end of surgery.Before induction of anesthesia,at 1,3,5,8,10,14,20,35,65,95 and 125 min ofalfentanil infusion,and at 5,15,30,60,120,180,240,300 and 360 min after termination of alfentanil infusion,venous blood samples were collected for determination of the plasma concentration of alfentanil (by high performance liquid chromatography-mass spectrometry/mass spectrometry).DAS 3.0 software was used to analyze the pharmacokinetic parameters of alfentanil.Results The pharmacokinetics of domestic alfentanil was best described by a two-compartment pharmacokinetic model.The distribution half-life was (1.8 ± 0.8) min,and the elimination half-life was (91±22) min.The volume of distribution at steady state was (0.38±0.12) L/kg,and the clearance was (4.3± 1.6) ml · kg-1 · min-1.The elimination of domestic alfentanil followed the first-order kinetics.Conclusion The distribution of intravenously infused domestic alfentanil is fitted to a two-compartment pharmacokinetic model with elimination following the first-order kinetics in the patients undergoing general anesthesia.