OBJECTIVE To investigate the impact of Netupitant and palonosetron hydrochloride capsules （NEPA） on the pharmacokinetics of Paclitaxel for injection （albumin bound） （i. e. albumin-bound paclitaxel） under different intestinal microenvironment conditions. METHODS Male SD rats were divided into a normal group and a model group （n＝16）. Rats in the model group were intragastrically administered vancomycin solution to establish an intestinal disorder model. The next day after modeling， intestinal microbiota diversity was analyzed， and the mRNA expressions of cytochrome P450 3A1 （CYP3A1） and CYP2C11 in small intestine and liver tissues as well as those protein expressions in liver tissue were measured. Male SD rats were grouped as described above （n＝16）. The normal group was subdivided into the TP chemotherapy group （TP-1 group） and the TP chemotherapy+NEPA group （TP+NEPA-1 group）； the model group was subdivided into the TP chemotherapy group （TP-2 group） and the TP chemotherapy+NEPA group （TP+NEPA-2 group） （n＝8）. Rats in the TP+NEPA-1 and TP+NEPA-2 groups received a single intragastric dose of NEPA suspension （25.8 mg/kg， calculated by netupitant）. One hour later， all four groups received a single tail vein injection of albumin-bound paclitaxel and cisplatin. Blood samples were collected at different time points after the last administration. Using azithromycin as the internal standard， plasma paclitaxel concentrations were determined by liquid chromatography-tandem mass spectrometry. The main pharmacokinetic parameters were calculated using DAS 2.0 software and compared between groups. RESULTS Compared with the normal group， the model group showed significantly decreased Chao1 and Shannon indexes （P＜0.05）， significant alterations in microbiota composition and relative abundance， and significantly downregulated expressions of CYP3A1 mRNA in liver tissue and CYP2C11 mRNA in both small intestine and liver tissues （P＜0.05）. Compared with the TP-1 group， the AUC0－t， AUC0－∞， MRT0－t of paclitaxel in the TP-2 group， the cmax， AUC0－t， AUC0－∞ of paclitaxel in the TP+NEPA-1 group and TP+NEPA-2 group were significantly increased or prolonged； CL of paclitaxel in the TP-2 group， Vd and CL of paclitaxel in the TP+NEPA-1 group and the TP+NEPA-2 group were significantly decreased or shortened （P＜0.05）. Compared with the TP-2 group， cmax of paclitaxel in the TP+NEPA-2 group was significantly increased， and Vd and MRT0－t were significantly decreased or shortened （P＜0.05）. CONCLUSIONS Intestinal microbiota disorder affects the mRNA expressions of CYP3A1 and CYP2C11， leading to decreased clearance and increased systemic exposure of paclitaxel. Concomitant administration of NEPA under normal intestinal microbiota condition increases paclitaxel exposure. However， under conditions of intestinal microbiota disorder， concomitant administration of NEPA has a limited impact on paclitaxel systemic exposure.

Objective To investigate the molecular mechanisms by which SOX7 regulates the SHP-2/Wnt/β-cate-nin/ROS pathway,affecting the proliferation,invasion,and migration of colorectal cancer cells.Methods Twenty nude mice with subcutaneously transplanted tumor models were randomly divided into four groups:SOX7 NC(n=5),SOX mimic(n=5),SOX7 NC+PHPS1(n=5),and SOX7 mimic+PHPS1(n=5)to observe tumor growth.Human colorectal cancer cell line SW480 cells were transfected via lipofection and divided into six groups:SOX7 NC,SOX7 mimic,SOX7 NC+H2 O2,SOX7 mimic+H2O2,SOX7 NC+PHPS1,and SOX7 mimic+PHPS1.The ex-pression of SHP-2/Wnt/β-catenin/ROS pathway-related proteins in SW480 cells of each group was detected by Western blot.The invasion and migration capabilities of SW480 cells were assessed through scratch and Transwell invasion assays,while cell proliferation was evaluated using CCK-8.Results In vivo experiments demonstrated that tumors in the SOX7 mimic group were significantly smaller than those in the SOX7 NC group(P＜0.01).Tumors treated with PHPS1 intervention exhibited a significant increase in volume.There was no statistical significance in the difference in tumor volume between the SOX7 mimic+PHPS1 group and the SOX7 NC+PHPS1 group.In vitro experiments revealed that SOX7 mimic inhibited the expression of Wnt,β-catenin,NOX2,NOX4,PI3K,P-PI3K,AKT,P-AKT proteins(P＜0.01),and promoted the expression of p-SHP-2 protein(P＜0.01).The addition of hydrogen peroxide and SHP-2 inhibitor reversed the effects of SOX7 on SW480 cells(P＜0.05),and significantly promoted the expression levels of Wnt,β-catenin,NOX2,NOX4,PI3K,P-PI3K,AKT,P-AKT proteins,with no sig-nificant difference,while significantly reducing the expression levels of SHP-2,p-SHP-2 proteins,with no significant difference.PHPS1 inhibited the expression of SHP-2,p-SHP-2 proteins(P＜0.05)and upregulated the expression of Wnt,β-catenin,NOX2,NOX4,PI3K,P-PI3K,AKT,P-AKT proteins(P＜0.05).Scratch,Transwell invasion and migration assays,and CCK-8 experiments indicated that SOX7 suppressed the migration,invasion,and proliferation of SW480 cells through oxidative stress and the SHP-2 pathway(P＜0.01),while H2O2 and PHPS1 intervention promoted the migration,invasion,and proliferation of SW480 cells(P＜0.05).Conclusion SOX7 can suppress the proliferation,invasion,and migration of colorectal cancer by targeting the SHP-2/Wnt/β-catenin/ROS pathway.

The research advancements in probes for deep-tissue imaging and adaptive optical imaging technologies are summarized,aiming to offer a new perspective for life science and interdisciplinary research.The review firstly gives an introduction on the probes emitting in the near-infrared-Ⅱ region,including fluorescence,bioluminescence,chemiluminescence,and persistent luminescence,and then elaborates direct sensing methods for rapid measurement and correction of wavefront distortions,as well as indirect sensing methods for correcting complex optical aberrations.The continuous updating of the above techniques and methods has enabled optical imaging to successfully penetrate deeper tissues with a remarkable reduction of background noise for higher image quality.

OBJECTIVE To analyze the clinicopathological features of laryngeal squamous carcinoma tumors and their correlation with prognosis in order to improve the understanding and diagnosis of laryngeal squamous cell carcinoma.METHODS The clinical and pathological data(including gender,age,stage,differentiation,immunohistochemistry,etc.)of 179 patients with laryngeal squamous cell carcinoma[171 males,8 females,aged 30-84(61.53±8.02)years]who were treated in Department of Otolaryngology Head and Neck Surgery,The First and Second Clinical Medical Schools of Ningxia Medical University from January 2015 to December 2022 were retrospectively studied,and the effects of various factors on prognosis were analyzed.RESULTS Among the 179 patients with laryngeal squamous cell carcinoma,the male-to-female ratio was 21.4:1,and the incidence was high in the age group of 60-79 years old(58.7%),and the youngest age of onset was 30 years old.The main clinical manifestations were hoarseness 138 cases(77.1%),sore throat 16 cases(8.9%)and pharyngeal foreign body sensation 13 cases(7.3%).Glottic type was more common in the primary site 135 cases(75.4%),and 31 cases were accompanied by cervical lymph node metastasis(17.3%).The degree of differentiation was more common in the moderately differentiated type 80 cases(44.7%).The positive rates of immunohistochemistry markers p16,EGFR(epidermal growth factor receptor),PD-1/PD-L1 and VEGF(vascular endothelial growth factor)were 20.3%,96.4%,36.4%and 77.3%,respectively.Univariate Kaplan-Meier survival analysis showed that the site of disease,lymph node metastasis,and tumor stage were significantly correlated with disease recurrence.Multivariate Cox regression analysis showed that the clinical stage of the tumor was an independent risk factor for the prognosis of the disease(HR=3.715,95%CI:1.519-9.088,P=0.04).CONCLUSION The stage of laryngeal squamous cell carcinoma,the site of the disease,and the metastasis of the lymph nodes are the main factors affecting the prognosis.The high positive expression rate of immunohistochemistry markers EGFR and VEGF is worth paying attention to Targeted therapy for patients with positive PD-1/PD-L1 testing is a promising research direction.

Objective:To explore the feasibility of using quantitative parameters of double contrast-enhanced ultrasound (DCUS) to noninvasively predict lymphatic metastasis in gastric cancer before operation.Methods:From December 2021 to October 2023, 119 patients undergoing gastrectomy at the Second Hospital & Clinical Medical School, Lanzhou University, were enrolled retrospectively. Based on the pathological findings, they were divided into lymph node metastasis (N1, 94 cases) and non-lymph node metastasis (N0, 25 cases) groups. All patients underwent DCUS within 3 days before surgery. Previous to DCUS, lesions′ location and ultrasonic T-staging were recorded by conventional ultrasound. Quantitative parameters such as arrival time (AT), time to peak (TTP), baseline intensity (BI), peak intensity (PI) and wash-in slope (WIS) were obtained by the time-intensity curve (TIC) automatically, and then manually calculated enhanced intensity (ΔPI=PI–BI) and enhanced time (ΔTTP=TTP–AT). Binary Logistic regression analysis was used to screen independent risk factors for predicting lymph nodes metastasis in gastric cancer, and regression models were established.Results:Statistical tests revealed significant differences in ultrasonic T-staging ( P<0.001) and degree of differentiation ( P=0.015) between N1 and N0 group. Among DCUS quantitative parameters, statistical differences in PI, ΔPI and WIS were observed between the two groups (all P<0.05), while no significant differences were found in BI, AT, TTP and ΔTTP (all P>0.05). Logistic regression analysis showed that ultrasonic T-staging and WIS were independent risk factors for predicting lymphatic metastasis. The regression model built on the above two factors performed well in predicting lymph nodes metastasis, with an area under the curve of 0.905, accuracy of 93.3% (superior to the prediction model based on DCUS quantitative parameters alone, P<0.05), sensitivity of 95.7% and specificity of 84.0%. Conclusions:DCUS quantitative parameters may be helpful to evaluate lymphatic metastasis of gastric cancer prior to surgery, and the accuracy of prediction would be improved by combing with ultrasonic T-staging.

Cases of high-temperature requirement A serine peptidase 1(HTRA1)gene heterozygous mutation associated cerebral small vessel disease are relatively rare.Early and timely diagnosis and treatment can improve prognosis.The authors reported a 37 years old male patient admitted in Department of Neurology,the Second Affiliated Hospital of Nanchang University,whose initial symptom was transient right limb weakness,imaging suggested white matter lesions and the gene screening showed HTRA1(c.854 C＞T/p.Pro285Leu)heterozygous mutation.A family survey has been conducted and the characteristics of patients in this family are as follows:they present with ischemic cerebrovascular disease,coexist with cervical or lumbar disc herniation,male patients have hair loss,some patients have cognitive dysfunction,men tend to develop the disease at an earlier age than women,and the onset age is progressively earlier from generation to generation.Therefore,for young ischemic cerebrovascular disease patients with hair loss,cognitive dysfunction,cervical or lumbar disc herniation,and obvious white matter lesions on imaging,especially those without common risk factors for cerebrovascular disease,a family history should be inquired and genetic testing should be performed to screen for HTRA1 mutations.

Objective To investigate the effects of pterostilbene on human colon cancer LoVo cells and study the regulatory mechanism of nuclear factor E2-related factor 2(Nrf2)in the process of pterostilbene acting on LoVo cells.Methods LoVo cells were treated with different concentrations(5,10,20,40,60,80,100 panol/L)of pterostilbene.Cell viability,migration,invasion,and apoptosis were examined by CCK-8,scratch,Tran-swell,and TUNEL assays,respectively.The mitochondrial membrane potential was measured by the mitochon-drial membrane potential assay kit with JC-1.The reactive oxygen species level was measured by 2',7'-dichlo-rofluorescein diacetate.The protein levels of Nrf2,phosphorylated Nrf2,heme oxygenase 1,and apoptotic pro-teins(Bcl2 and Bax)were determined by Western blotting.In addition,cell viability,Nrf2 expression,and ap-optosis rate were determined after co-application of the Nrf2-specific agonist sulforaphane.Results Compared with the control group,40,60,80,100 μmol/L pterostilbene reduced the viability of LoVo cells(P=0.014,P＜0.001,P＜0.001,P＜0.001).Pterostilbene at 5,10,20 μmol/L did not show effects on cell viability but inhibited cell migration(P=0.008,P＜0.001,P＜0.001)and invasion(all P＜0.001).Pterostilbene at 40,60,80 μmol/L increased apoptosis(P=0.014,P＜0.001,P＜0.001),promoted mitochondrial membrane potential depolarization(P=0.026,P＜0.001,P＜0.001)and reactive oxygen species accumula-tion(all P＜0.001),and down-regulated the expression of phosphorylated Nrf2(P=0.030,P＜0.001,P＜0.001),heme oxygenase 1(P=0.015,P＜0.001,P＜0.001),and Bc12(P=0.039,P＜0.001,P＜0.001)in LoVo cells.Pterostilbene at 60,80 μmol/L down-regulated Nrf2 expression(P=0.001,P＜0.001)and up-regulated Bax expression(both P＜0.001).The application of sulforaphane reversed the effects of pterostilbene on cell viability(P＜0.001),apoptosis(P＜0.001),and Nrf2 expression(P=0.022).Conclusion Pterostilbene is a compound that can effectively inhibit colon cancer cells by inhibiting the Nrf2 pathway.

Purpose To investigate the relationship between imaging characteristics and shunt grading in acute cerebral infarction patients with right-to-left shunt.Materials and Methods The clinical and imaging data of 697 acute cerebral infarction patients who were hospitalized in the Second Affiliated Hospital of Nanchang University from January 2019 to December 2021 were collected,and the patients were divided into right-to-left shunt negative group(443 cases)and right-to-left shunt positive group(254 cases)according bubble test,compared the difference in demographic data and imaging characteristics between the two groups.In the shunt positive group,the imaging characteristics of the two groups of patients and their relationship with the shunt grade were analyzed.Results There were no statistical differences in gender,age,smoking,hyperlipidemia and history of coronary heart disease between the two groups(P>0.05),but there were statistical differences in the history of hypertension(OR=0.533,95%CI 0.380-0.748),diabetes(OR=0.649,95%CI 0.422-0.999)and cerebral infarction(OR=0.275,95%CI 0.136-0.555)(all P<0.05).The imaging characteristics of the two groups of patients showed that there were significant differences in the number of infarct foci(χ2=53.957,4.219;both P<0.05),but there was no statistical difference in the infarct location between the two groups(P>0.05).Among the patients with acute cerebral infarction combined with positive bubble test,the imaging manifestations of grading I and II patients were mainly unilateral anterior circulation or posterior circulation infarction,and deep and single infarction were more common.In patients with grading III and IV shunts,multiple infarcts with combined bilateral anterior and posterior circulations were more common.Conclusion The imaging manifestations of patients with acute cerebral infarction combined with right-to-left shunt have their own characteristics.Bubble test has high sensitivity in the diagnosis of right-to-left shunt.The comprehensive analysis can provide certain guidance for clinical practice.

Objective:To establish a HPLC method for determinating 9 components simultaneously in Swertia chirayita. Methods:By useing water Sunfire C18 column (4.6 mm× 250 mm,5 μm); Gradient elution was carried out with methanol-0.05% phosphoric acid solution as mobile phase. Setting the column temperature at 30 ℃, the flow rate at 1.0 ml/min, and the detection wavelength at 254 nm.Results:9 components showed good linear relationship within the injection quality range. The recovery rates of wertiamarin, Gentiopicroside, Angelica glycosides,Mangiferin, Isolysine, Gentianoside, Diol glycoside, 8-hydroxy-1,3,5 trimethoxyketone, and Daisy leaf gentinone were 95.38%, 92.41%, 95.14%, 91.87%, 92.24%, 92.51%, 95.08%, 91.72%, 95.74% ( n=6). Conclusion:The method is simple, efficient, sensitive, accurate, economical and practical, with repeatability and stability. It could provide reference for the quality control and comprehensive utilization of Swertia chirayita.

ObjectiveTo observe the effect of augmented reality training based on enriched environment on walking dysfunction after stroke. MethodsFrom January, 2021 to June, 2022, 36 stroke patients in the Affiliated Suzhou Hospital of Nanjing University Medical School were randomly divided into control group (n = 18) and experimental group (n = 18). Both groups received conventional rehabilitation treatment. The control group was supplemented with conventional walking training, and the experimental group was supplemented with augmented reality training based on enriched environment, for four weeks. They were assessed with Berg Balance Scale (BBS), Timed Up and Go Test (TUGT), 10-meter walk test (10MWT) and Barthel Index (BI) before and after treatment, and the gait parameter was compared. ResultsNo adverse event occurred during treatment. After treatment, the BBS score, TUGT time, 10MWT speed, BI, gait speed, gait frequency and the proportion of single-leg support on the affected side significantly improved in both groups (|t| > 5.161, P < 0.001). All the above indexes were better in the experimental group than in the control group (|t| > 2.106, P < 0.05), except for BI (t = 1.099, P = 0.282). ConclusionAugmented reality training based on enriched environment could improve the walking function of paitents after stroke, which is better than conventional walking training.