Nasal drug delivery efficiency is highly dependent on the position in which the drug is deposited in the nasal cavity. However, no reliable method is currently available to assess its impact on delivery performance. In this study, a biomimetic nasal model based on three-dimensional (3D) reconstruction and three-dimensional printing (3DP) technology was developed for visualizing the deposition of drug powders in the nasal cavity. The results showed significant differences in cavity area and volume and powder distribution in the anterior part of the biomimetic nasal model of Chinese males and females. The nasal cavity model was modified with dimethicone and validated to be suitable for the deposition test. The experimental device produced the most satisfactory results with five spray times. Furthermore, particle sizes and spray angles were found to significantly affect the experimental device's performance and alter drug distribution, respectively. Additionally, mometasone furoate (MF) nasal spray (NS) distribution patterns were investigated in a goat nasal cavity model and three male goat noses, confirming the in vitro and in vivo correlation. In conclusion, the developed human nasal structure biomimetic device has the potential to be a valuable tool for assessing nasal drug delivery system deposition and distribution.

Objective To investigate the characteristics and rules of tongue image in patients with chronic fatigue syndrome(CFS)with different fatigue degree.Methods Totally 917 patients with severe chronic fatigue syndrome(severe CFS group),351 patients with mild chronic fatigue syndrome(mild CFS group)and 1216 healthy controls(healthy control group)were enrolled in the physical examination center of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine.The tongue image data of subjects in the three groups were collected using TFDA-1 digital tongue and face diagnostic instrument,and the color space indexes of RGB,HSI,Lab and YCrCb were used to analyze the tongue image differences of CFS people with different fatigue degrees and the tongue image features of CFS patients with liver-qi stagnation syndrome,damp-heat stasis syndrome and spleen deficiency syndrome.Results Compared with the healthy control group,the tongue image indexes TB-R,TB-G,TB-B,TB-I,TB-L,TB-Y,TC-H,TC-I,TC-L and TC-Y increased in the severe CFS group;TB-S,TB-a,TC-S,TC-a,TC-Cr decreased(P<0.05).TB-R,TB-G,TB-B,TB-I,TB-L,TB-Y,TC-R,TC-G,TC-B,TC-I,TC-L and TC-Y increased in severe CFS group compared with mild CFS group.TB-H and TB-b increased in mild CFS group compared with healthy control group.The comparison of syndromes in severe CFS group showed that TB-a,TB-Cr,TC-S,TC-a,TC-Cr and TB-S increased in liver-qi stagnation syndrome compared to damp-heat stasis syndrome;TB-G,TB-B,TB-I,TB-L,TB-Y,TB-b,TB-Cb,TC-G,TC-B,TC-H,TC-I,TC-L,TC-Y and perAll decreased(P<0.05).Compared with spleen deficiency syndrome,TB-a,TB-Cr,TB-CON,TB-ENT,TB-MEAN,TC-a,TC-Cr,TC-CON,TC-ENT,TC-MEAN increased in liver-qi stagnation syndrome;TB-ASM,TC-S and TC-ASM decreased(P<0.05).Compared with spleen deficiency syndrome,TB-a,TB-b,TB-Cr,TB-Cb,TB-CON,TB-ENT,TB-MEAN,TC-G,TC-B,TC-H,TC-I,TC-L,TC-a,TC-Y,TC-Cr,TC-CON,TC-ENT,TC-MEAN,perAll increased;TB-ASM,TC-S and TC-ASM decreased(P<0.05).The comparison of mild CFS syndrome showed that there was no statistical significance between liver-qi stagnation syndrome and spleen deficiency syndrome(P>0.05).TB-Cr,TC-a,TC-Cr and perAll increased and TC-S decreased in damp-heat stasis syndrome compared with spleen deficiency syndrome(P<0.05).TB-S,TB-a,TB-Cr,TC-S,TC-a,TC-Cr increased,and TB-G,TB-B,TB-I,TB-Cb,TB-b,TC-b and TC-Cb decreased(P<0.05)in liver-qi stagnation syndrome compared with damp-heat syndrome.The distribution trend of TC-S was as follows:dampness-heat syndrome

Objective:To evaluate the safety and efficacy of 225Ac-prostate specific membrane antigen (PSMA) in the treatment of metastatic castration-resistant prostate cancer (mCRPC). Methods:Eleven patients (age (70.0±8.8) years) with mCRPC who were treated with 225Ac-PSMA-617 between July 2021 and October 2023 in the Affiliated Hospital of Southwest Medical University were retrospectively analyzed. In order to assess efficacy, the Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria were used to evaluate the changes in prostate specific antigen (PSA) level after the treatment. 68Ga-PSMA-11 PET/CT imaging was performed at the baseline and after the treatment, and molecular imaging response was assessed using the modified PET response criteria in solid tumors (PERCIST) 1.0. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. Toxicity was assessed by common terminology criteria for adverse events version 5.0 (CTCAE 5.0). The paired t test or Wilcoxon signed rank test was used to compare the parameters before and after treatment. Results:Post-treatment PSA levels were significantly lower than pre-treatment in 9 of 11 patients (17.83(4.74, 41.25) vs 124.33(77.85, 784.22) μg/L; z=-2.67, P=0.008), and 6 of them decreasing by more than 50% and 2 patients experienced progressive disease (PD) with PSA levels rising by more than 25%. Post-treatment 68Ga-PSMA-11 PET/CT showed that 7 patients achieved partial response (PR), 2 patients achieved stable disease (SD), and 2 patients were with PD. The OS was 12.0(10.0, 18.0) months and PFS was 8.0(6.0, 11.0) months in 11 patients. There were no statistically significant differences after therapy in WBC counts, Hb, PLT, creatinine, glomerular filtration rate, alanine aminotransferase, aspartate aminotransferase, total bilirubin ( z values: from -1.07 to 0.00, t values: from -0.77 to 1.76, all P>0.05). No grade Ⅲ/Ⅳ nephrotoxicity or salivary gland toxicity was observed. Conclusion:225Ac-PSMA-617 is a promising novel therapeutic option for mCRPC with favorable safety and tolerability.

Objective To construct a mouse model of psoriasis with spleen deficiency and dampness obstruction pattern and evaluate the model from multiple dimensions and directions,expects to provide research support for the study of traditional Chinese medicine (TCM) treatment of psoriasis with spleen deficiency and dampness obstruction pattern. Methods A mouse model of spleen deficiency and dampness obstruction pattern was established by feeding a high-fat diet,a mouse model of psoriasis vulgaris was established by externally applying imiquimod ointment,and a mouse model of psoriasis with spleen deficiency and dampness obstruction pattern was constructed by combining the above two models. Indications of spleen deficiency and dampness obstruction pattern were evaluated by comparing the body mass,food intake and water intake of mice in each group. The severity of psoriasis in mice was evaluated by comparing the area of skin lesions,PASI score,the value of transdermal water loss (TEWL),and histopathological morphological changes of skin under HE staining in each group. Flow cytometry was used to detect the expression in various cell types to evaluate the degree of inflammatory response of psoriasis in mice. Observation of adiposity index,changes in the histopathological morphology of liver tissue under HE staining,changes in the mRNA expression levels of related factors in liver tissue and adipose tissue of epididymis of mice detected by RT-qPCR,and changes of ABCA1 protein expression level of skin detected by Western Blot were used to evaluate the lipid metabolism disorders in mice. Results Compared with the mice in the psoriasis vulgaris model group,the mice in the model of psoriasis with pattern of spleen deficiency and dampness obstruction had significantly higher body mass (P<0.001),significantly lower food intake (P<0.005),and the symptoms of pattern of spleen deficiency and dampness obstruction such as greasy fur,mental fatigue,etc. appeared. The TWEL were significantly increased(P<0.001),and the PASI scores also significantly increased(P<0.001). HE results were found psoriasis-like manifestations including hypertrophy of the spinous layer and clubbed hyperplasia. The expression of CD11bhighLy6G+neutrophil subpopulation,CD11binLy6Chigh monocyte subpopulation,CD11binCD11chigh classical dendritic cell subpopulation,F4/80-CD11c+dendritic cell subpopulation was significantly increased (P<0.001). HE staining suggested that the cellular morphology of liver showed obvious vacuolated degeneration,and the index of subcutaneous white adiposity and epididymal adiposity index were both significantly increased (P<0.005). The mRNA levels of FABP4 and CD36 in liver tissue were significantly elevated(P<0.005,P<0.001),while the mRNA expression levels of ABCA1 and PPARγ in epididymal fat tissue were decreased (P<0.05,P<0.01). ABCA1 protein level in skin increased(P>0.05). Conclusion The mouse model of psoriasis with spleen deficiency and dampness obstruction pattern can be used as a reliable animal model for combining disease and pattern,which can provide a reference for further exploration of TCM in the treatment of psoriasis with spleen deficiency and dampness obstruction pattern.

Objective:To investigate the plasma differential protein expressions between patients with Alzheimer's disease (AD) and normal controls, and to search plasma protein markers or protein combinations with screening or diagnostic significance.Methods:Plasma samples from 98 patients with dementia of Alzheimer type (DAT), 102 patients with mild cognitive impairment (MCI) and 101 normal controls (NC) were collected from Wuxi Mental Health Center and Shanghai Mental Health Center from 2016 to 2018.The expression levels of 50 kinds of plasma proteins in all plasma samples were detected by Milliplex MAP assays(xMAP).Analysis of variance, regression analysis, discriminant analysis, and ROC analysis on the data were performed using SPSS 20.0 software.Results:(1)Compared with the NC group, 26 plasma proteins were up-regulated and 4 proteins were down-regulated in DAT group, while 6 proteins were up-regulated and 4 proteins were down-regulated in MCI group(all P<0.05).Compared with the NC group, 6 proteins were upregulated in both MIC group and DAT group, which were clusterin(Clust) (613.41(278.89), 761.76(358.60), 473.01(321.73)), cystatin C(Cys C) (691.88(441.34), 852.28(551.75), 548.64(545.28)), transthyretin(TTR) (207.10(168.60), 220.95(151.20), 152.89(162.70)), complement factor H(Com FH) (331.67(218.37), 361.69(124.64), 225.79(236.82)), soluble intercellular adhesion molecule-1(sICAM1) (109.30(49.47), 137.21(50.36), 87.06(57.59), and apolipoprotein E(APOE) (79.33(78.13), 79.31(68.85), 54.88(67.34)).The serum amyloid P component(SAP) was downregulated in both DAT and MCI groups(121.23(311.31), 92.39(156.62), 125.00(242.82)) compared with NC group.(2)Three sets of protein combination were screened by differential analysis, regression analysis, and discriminant analysis, including 8 proteins, 9 proteins and 7 proteins, respectively.And SAP, angiotensin (AGT), osteopontin (OPN), and complement C4 (Com C4) were the compared with NC group most frequently selected protein.The screening correct rate of three protein combinations were respectively 67.4%-71.4% for AD, 82.4%-88.4% for DAT, and 60.6%-63.5% for MCI. Conclusions:A variety of plasma proteins such as Clust, Cys C, TTR, Com FH, sICAM1, APOE are upregulated, while SAP is downregulated in AD patients.These differential protein combinations can help with early diagnosis of dementia with Alzheimer type.SAP, AGT, OPN and Com C4 may be potential markers for early screening or diagnosis of AD.

Objective:To investigate grey matter volume changes and their correlation with the severity of anxiety in adolescents with major depressive disorder (MDD) accompanied by anxious distress specifier (ADS).Methods:From June 2022 to June 2023, totally 71 inpatients with MDD in the child and adolescent psychiatry department of Anhui Mental Health Center were included. According to the definition of ADS in the DSM-5, MDD adolescents were divided into the group with anxious distress (MDD/ADS+ group, n=44) and the group without anxious distress (MDD/ADS- group, n=27). Healthy adolescents matched in terms of gender, age, education level were recruited as the control group (HC group, n=19). Voxel-based morphometry (VBM) was used to compare changes in grey matter volume among the three groups.Grey matter volume values of brain regions with significant differences between the MDD/ADS+ group and MDD/ADS- group were collected, and their correlation with Hamilton anxiety rating scale (HAMA) score were analyzed by Pearson correlation analysis using SPSS 26.0 software. Results:Compared to the MDD/ADS- group, the MDD/ADS+ group showed a significant decrease in grey matter volume in the right dorsolateral prefrontal cortex (MNI: x=16.5, y=34.5, z=52.5, t=4.48, P<0.05) and the right cerebellum (MNI: x=49.5, y=-69.0, z=-24.0, t=5.18, P<0.05). In MDD adolescents, the grey matter volumes of the right dorsolateral prefrontal cortex and the right cerebellum were negatively correlated with HAMA score ( r=-0.249, -0.491, both P<0.05). Conclusion:In adolescents with MDD accompanied by ADS, a decrease in gray matter volume is observed in the right dorsolateral prefrontal cortex and the right superior cerebellum. These brain regions may serve as potential biological markers for the severity of anxiety in adolescents with MDD.

Objective:To explore the effect of intravenous infusion of remifentanil and remifentanil combined with esketamine on blood glucose during gastrointestinal surgery.Methods:A prospective selection of 160 patients who underwent elective gastrointestinal surgery at Nanjing Hospital and the Fourth Affiliated Hospital of Nanjing Medical University from July 2023 to October 2023 was conducted. The patients were randomly divided into a control group (remifentanil group) and an observation group (remifentanil combined with esketamine group) using a random number table method, with 80 patients in each group. Both groups were anesthetized with remifentanil. The observation group received intravenous injection of 0.5 mg/kg of esketamine during anesthesia induction, followed by maintenance at a dose of 0.12 mg/(kg·h) until the sutured skin. The control group received an equal amount of physiological saline, and the anesthesia induction and maintenance plans were the same for both groups. Two groups of intraoperative and postoperative blood glucose and insulin usage, as well as intraoperative atropine and ephedrine usage, anesthesia time, extubation time, and post anesthesia care unit (PACU) retention time were recorded. Visual Analog Scale (VAS) scores were also recorded at 6, 12, and 24 hours post surgery, as well as the incidence of complications.Results:The intraoperative blood glucose levels in the observation group were lower than those in the control group, and the blood glucose levels at 6, 12, and 24 hours postoperatively were higher than those before and during surgery. The blood glucose levels at 6 and 12 hours postoperatively were higher than those at 24 hours postoperatively, and the differences were statistically significant (all P<0.05). The proportion of patients with intraoperative and postoperative blood glucose>7 mmol/L in the observation group was significantly lower than that in the control group, and the difference was statistically significant (all P<0.05). There was no statistically significant difference in the proportion of insulin use between the two groups during surgery ( P>0.05). The postoperative insulin use in both groups was significantly higher than that during surgery, and the difference was statistically significant (all P<0.05). There was no statistically significant difference in anesthesia time between the two groups of patients ( P>0.05). The observation group had shorter extubation time and PACU retention time than the control group, and the difference was statistically significant (all P<0.05). The incidence of intraoperative heart rate (HR)<60 beats/min and mean arterial pressure (MAP)<60 mmHg in the observation group were significantly lower than those in the control group, and the differences were statistically significant (all P<0.05). The maintenance dose of propofol and remifentanil in the observation group were both lower than those in the control group, and the difference was statistically significant (all P<0.05). The proportion of additional remifentanil, the dosage of hydroxycodone used within 24 hours, and the proportion of atropine and ephedrine used in the observation group were all lower than those in the control group, and the differences were statistically significant (all P<0.05). The VAS scores of the observation group at rest and activity 12 hours after surgery were significantly lower than those of the control group, with a statistically significant difference ( P<0.05). There was no statistically significant difference in VAS scores between the two groups at other time points (all P>0.05). Conclusions:Intraoperative infusion of 0.1-0.4 μ g/(kg·min) remifentanil combined with 0.12 mg/(kg·h) esketamine can inhibit intraoperative stress induced blood glucose elevation, maintain good heart rate and mean arterial pressure, and prevent postoperative remifentanil induced hyperalgesia.

OBJECTIVE To analyze technical and legal information of patents in the field of antigen immunoassay technology, and to provide advice to related enterprises on R&D direction and patent layout. METHODS Using patent analysis means combined with data visualization presentation, the R&D trends and research hotspots in the field of immunoassays of Abbott, Wondfo Bio, BGI Genomics and other related companies were systematically analyzed. RESULTS Abbott's patent layout in the field of immunoassay was more comprehensive and occupied a dominant position in international competition. Although the immunoassay technologies of Chinese enterprises had their own expertise, the industrial layout and the comprehensiveness of patent layout were weak. CONCLUSION Chinese enterprises should strengthen interdisciplinary research and strive for breakthroughs in the direction of cutting-edge technologies such as multiplex multi-pathogen high-throughput detection, magnetic particle chemiluminescence detection and microfluidic chip detection, as well as choosing appropriate patent protection strategies considering their own characteristics.

OBJECTIVE To know about the development trend of small nucleic acid drugs in the world ，to provide reference for the research and development of small nucleic acid drug in China. METHODS By searching the academic literature and patents related to small nucleic acid drugs through the Web of Science literature database and PatSnap patent database from Jan. 1980 to Dec. 2021，research and development situation of small nucleic acid drugs were revealed comprehensively by analyzing research enthusiasm，R&D countries ，R&D institutions and technical topics of small nucleic acid drugs. RESULTS & CONCLUSIONS A total of 59 819 documents and 37 645 patent groups were included. The global trend of small nucleic acid drug literature publication and patent application could be divided into three stages. From 2003 to 2021，the research enthusiasm for small nucleic acid drugs continued to increase. The United States ，China，Japan and Germany were the main research and development countries for small nucleic acid drugs. The number of document publications （25 703，15 927 papers）and patent applications （14 240、8 937 groups） in the United States and China were ahead of other countries ，and the research and development activities were relatively strong. Moreover，the number of document publications and patent applications in China in this field had grown rapidly in recent years. The R&D institution with the largest number of publications was the University of California （2 499 papers），the R&D institution with the largest number of patent applications was the American Ionis Corporation （1 378 groups），and the Chinese Academy of Sciences （1 580 papers）had been shortlisted among the top 10 document producing institutions in the world. However ，our country ’s research and development in this field are mostly based on basic research ，and the research on industrial application is slightly insufficient. The research focus in the field of small nucleic acid drugs mainly focuses on nucleic acid sequences and their modification and improvement and drug loading technology. RNA interference technology has gradually become a hot technology for small nucleic acid drugs.

AIM: To explore the effect of lienal polypeptide injection (LPI) on platelet production in ITP model mice with primary immune thrombocytopenia. METHODS: SPF Kunming mice were divided into groups by random number table method, and the ITP model of mice was induced by intraperitoneally injected of rabbit anti-mouse platelet serum APS every other day. At the set time, blood was collected through caudal vein to detect the changes in the number of platelets, red blood cells and white blood cells in each group. Meanwhile, the thymus and spleen indexes were calculated. Megakaryocytes were classified and counted by means of bone marrow smear. Finally, the expression levels of TPO, SCF, IL-3, IL-6, IL-11, β-TG, TGF-β1 and PF-4 in serum were detected by ELISA. RESULTS: LPI significantly increased platelets count in ITP model mice, but had no effect on red blood cells and white blood cells. Thymus and spleen index decreased significantly. The number of megakaryoblasts and thrombocytopenia megakaryocytes in the bone marrow of mice increased, but the number of promegakaryocytes, granular megakaryocytes and naked megakaryocyte did not change significantly. Serum sytokines SCF, IL-3 and IL-6 were significantly increased, while PF-4 was decreased significantly. CONCLUSION: LPI may increase the platelet count in ITP mice by up regulating the levels of IL-3, IL-6, SCF and down regulating the level of PF-4, which has guiding significance for clinical promotion application of LPI.