Objective:To investigate the level of urinary serine protease(Corin) in early diabetic kidney disease(DKD) and its correlation with clinical stage.Methods:One hundred and seventy-three patients with type 2 diabetes mellitus(DM) from two tertiary A hospitals in Henan, diagnosed between April 2023 and December 2023 were selected as the research group, and 120 healthy subjects were selected as the control group. Basic clinical information and laboratory data were collected, and urinary Corin level was detected. DM patients were classified into G1-G5 stages based on estimated glomerular filtration rate(eGFR), and those in the early DKD stages(G1-G3) were further divided into A1-A3 subgroups based on urinary albumin/creatinine ratio(ACR). Spearman correlation analysis was performed to assess relationships between urinary Corin and other indicators, linear regression analysis identified factors influencing urinary Corin in early DKD patients, logistic regression analysis evaluated the risk factors for early DKD, and receiver operating characteristic(ROC) curve analysis determined the diagnostic value of urinary Corin in early DKD. Results:Urinary Corin levels were significantly higher in early DKD patients compared to healthy controls, with levels increasing as ACR rose( P<0.05). Urinary Corin was positively associated with serum creatinine( r=0.570), urea( r=0.458), cystatin C( r=0.693), ACR( r=0.616), urinary transferrin( r=0.448), urinary α1 microglobulin( r=0.507), urinary n-acetyl-β-D-glucosaminase( r=0.388) and A subgroup( r=0.692) while was negatively correlated with eGFR( r=-0.647), albumin( r=-0.312)(all P<0.05). eGFR was the only independent factor affecting urinary Corin. After adjusting for confounding factors in logistic regression analysis, urinary Corin was still an independent influencing factor for early DKD. ROC curve analysis indicated that urinary Corin had a diagnostic AUC of 0.842(95% CI 0.791-0.892, P<0.001), with a cut-off value of 2 226.04 pg/mL, sensitivity of 0.712, and specificity of 0.858 for early DKD diagnosis. Conclusions:Urinary Corin was elevated in early DKD patients and correlated with clinical stage. Urinary Corin is an independent factor of early DKD, and a reliable predictor of early DKD diagnosis.

Objective:To develop an artificial intelligence (AI)-guided intravitreal injection robot system to accurately detect the injection point on the ocular surface and guide the robotic arm to complete the intravitreal injection positioning task through 3D position calculation.Methods:The Dikablis subset of the TEyeD dataset was used.Training set, testing set, and validation set were constructed by using equal interval sampling strategy.The system read the ocular surface color RGB image with an RGBD camera, then used a PatchCrop-Transformer-based injection point detection algorithm to detect and locate key points such as the pupil, iris, and eyelid in the image.Next, it extracted the local 3D point cloud data near the injection point based on the depth information obtained by the camera.Through principal component analysis (PCA) of the local area point cloud data, the injection point and injection direction were determined.The key information was then passed to the robotic arm system.The end of the robotic arm adopted a remote center of motion (RCM) mechanism.After solving the forward and inverse kinematics, the joint movement path was obtained, and the robotic arm was controlled to move to 2 cm above the injection point.After confirmation by the doctor, the insertion, injection, and withdrawal operations were completed to ensure the stability and repeatability of the injection process.The mean square error (MSE) of key points localization and the success detection rate (SDR) within different pixel error ranges (2, 5, and 10 pixels) of the study method were compared with those of the NFDP, SLPT, and StarLoss methods, and the effects of random weight enhancement, fixed weight enhancement, and no enhancement methods on the MSE of key points localization were evaluated.The repeatability and absolute positioning accuracy of the robotic arm system were also evaluated.Results:After adding random weight enhancement, the model of this study outperformed the fixed weight enhancement and no enhancement methods in both MSE and SDR.The MSEs of the model proposed in this study for overall eye, pupil, and iris localization were 4.25, 2.41, and 1.54, respectively, which were lower than those of the NFDP, StarLoss, and SLPT methods.Within the error ranges of 5 and 10 pixels, the SDRs of the model proposed in this study were 72.09% and 92.68%, respectively, which were higher than those of the NFDP, StarLoss, and SLPT methods.The single-axis repeatability errors and absolute positioning errors of the robotic arm were within ±5 μm.Conclusions:The AI-guided intravitreal injection robot system integrates RGBD images to achieve automatic recognition of the ocular injection point and high-precision motion control through RCM mechanism design and corresponding kinematic solution methods.

Objective:To develop an artificial intelligence (AI)-guided intravitreal injection robot system to accurately detect the injection point on the ocular surface and guide the robotic arm to complete the intravitreal injection positioning task through 3D position calculation.Methods:The Dikablis subset of the TEyeD dataset was used.Training set, testing set, and validation set were constructed by using equal interval sampling strategy.The system read the ocular surface color RGB image with an RGBD camera, then used a PatchCrop-Transformer-based injection point detection algorithm to detect and locate key points such as the pupil, iris, and eyelid in the image.Next, it extracted the local 3D point cloud data near the injection point based on the depth information obtained by the camera.Through principal component analysis (PCA) of the local area point cloud data, the injection point and injection direction were determined.The key information was then passed to the robotic arm system.The end of the robotic arm adopted a remote center of motion (RCM) mechanism.After solving the forward and inverse kinematics, the joint movement path was obtained, and the robotic arm was controlled to move to 2 cm above the injection point.After confirmation by the doctor, the insertion, injection, and withdrawal operations were completed to ensure the stability and repeatability of the injection process.The mean square error (MSE) of key points localization and the success detection rate (SDR) within different pixel error ranges (2, 5, and 10 pixels) of the study method were compared with those of the NFDP, SLPT, and StarLoss methods, and the effects of random weight enhancement, fixed weight enhancement, and no enhancement methods on the MSE of key points localization were evaluated.The repeatability and absolute positioning accuracy of the robotic arm system were also evaluated.Results:After adding random weight enhancement, the model of this study outperformed the fixed weight enhancement and no enhancement methods in both MSE and SDR.The MSEs of the model proposed in this study for overall eye, pupil, and iris localization were 4.25, 2.41, and 1.54, respectively, which were lower than those of the NFDP, StarLoss, and SLPT methods.Within the error ranges of 5 and 10 pixels, the SDRs of the model proposed in this study were 72.09% and 92.68%, respectively, which were higher than those of the NFDP, StarLoss, and SLPT methods.The single-axis repeatability errors and absolute positioning errors of the robotic arm were within ±5 μm.Conclusions:The AI-guided intravitreal injection robot system integrates RGBD images to achieve automatic recognition of the ocular injection point and high-precision motion control through RCM mechanism design and corresponding kinematic solution methods.

Objective:To investigate the level of urinary serine protease(Corin) in early diabetic kidney disease(DKD) and its correlation with clinical stage.Methods:One hundred and seventy-three patients with type 2 diabetes mellitus(DM) from two tertiary A hospitals in Henan, diagnosed between April 2023 and December 2023 were selected as the research group, and 120 healthy subjects were selected as the control group. Basic clinical information and laboratory data were collected, and urinary Corin level was detected. DM patients were classified into G1-G5 stages based on estimated glomerular filtration rate(eGFR), and those in the early DKD stages(G1-G3) were further divided into A1-A3 subgroups based on urinary albumin/creatinine ratio(ACR). Spearman correlation analysis was performed to assess relationships between urinary Corin and other indicators, linear regression analysis identified factors influencing urinary Corin in early DKD patients, logistic regression analysis evaluated the risk factors for early DKD, and receiver operating characteristic(ROC) curve analysis determined the diagnostic value of urinary Corin in early DKD. Results:Urinary Corin levels were significantly higher in early DKD patients compared to healthy controls, with levels increasing as ACR rose( P<0.05). Urinary Corin was positively associated with serum creatinine( r=0.570), urea( r=0.458), cystatin C( r=0.693), ACR( r=0.616), urinary transferrin( r=0.448), urinary α1 microglobulin( r=0.507), urinary n-acetyl-β-D-glucosaminase( r=0.388) and A subgroup( r=0.692) while was negatively correlated with eGFR( r=-0.647), albumin( r=-0.312)(all P<0.05). eGFR was the only independent factor affecting urinary Corin. After adjusting for confounding factors in logistic regression analysis, urinary Corin was still an independent influencing factor for early DKD. ROC curve analysis indicated that urinary Corin had a diagnostic AUC of 0.842(95% CI 0.791-0.892, P<0.001), with a cut-off value of 2 226.04 pg/mL, sensitivity of 0.712, and specificity of 0.858 for early DKD diagnosis. Conclusions:Urinary Corin was elevated in early DKD patients and correlated with clinical stage. Urinary Corin is an independent factor of early DKD, and a reliable predictor of early DKD diagnosis.

Background::This systematic review aimed to examine whether dual-task (DT) training was superior to single-task (ST) training in improving DT walking, balance and cognitive functions for individuals with Parkinson’s disease (PD).Methods::Literature search was performed in the following electronic databases: PubMed, the Cochrane Library, Web of Science, and Metstr covering inception to May 10, 2023. And in order to facilitate comparison across trials, we calculated the effect size (Hedges’ g) of gait, balance, cognitive, and other parameters under both ST and DT conditions, using the mean change score and standard deviation (SD) of change score of the experimental and control groups. Randomized controlled trials that examined the effects of DT motor and cognitive training in individuals with Parkinson’s disease were included for this systematic review.Results::A total of 214 participants recruited from six articles (actually five trials) were involved in this review. In terms of walking ability, only double support time and stride time variability showed significant between-group difference (Hedges’ g = 0.34, 0.18, respectively). Compared to ST training group, DT training group had a more improvement effect in laboratory balance measurement (Hedges’ g = 0.18, 1.25), but no significant improvement in clinical balance measurement. No significant between-group differences were observed, thus its training effect on cognitive function was inconclusive.Conclusions::The DT training failed to achieve promising results better than ST training in improving DT walking and balance functions for individuals with PD. Any firm conclusion cannot be drawn at present, due to the limited number of eligible publications. Larger sample size and high-quality studies are needed to investigate the effectiveness of DT training in individuals with PD.

Objective:To establish the fingerprints of Microctis Folium by ultra high performance liquid chromatography (UPLC); To determine the contents of three flavonoids in the Microctis Folium; To evaluate the quality difference of Microctis Folium from different producing areas. Methods:The fingerprints were performed on Agilent ZORBAX SB C18 column (2.1 mm×150 mm,1.8 μm). The mobile phase was acetonitrile - 0.1 % acetic acid solution with gradient elution at a flow rate of 0.30 ml/min. The column temperature was 30 ℃ and the detection wavelength was 315 nm. The common fingerprint peaks were identified by UPLC-mass spectrometry, and the identification results were confirmed by comparison of reference materials. Waters Cortecs T3 C18 chromatographic column (2.1 mm × 100 mm,1.6 μm) was used for content determination. The mobile phase was methanol-0.1 % formic acid solution with gradient elution at a flow rate of 0.35 ml/min. The column temperature was 30 ℃ and the detection wavelength was 339 nm. The contents of vitexin, isovitexin and narcissoside in 15 batches of Microctis Folium from different habitats were determine. Results:There were 11 common peaks in the fingerprint of Microctis Folium. Identified by mass spectrometry and confirmed by reference substance,10 chemical components were identified, including caffeic acid, p-hydroxycinnamic acid, ferulic acid, vitexin, isovitexin, kaempferol-3-O-rutoside, astragaloside, narcissoside, isorhamnetin-3-O-glucoside and linden glycoside. The similarity between the fingerprints of 15 batches of Microctis Folium and the control fingerprint was greater than 0.95, indicating that the overall similarity of the fingerprints of Microctis Folium from different producing areas was high. The total contents of three active components were 3.23-5.64 mg/g in Yangjiang City, Guangdong, 3.60-5.78 mg/g in Zhanjiang City, Guangdong, 4.68-5.73 mg/g in Yulin City, Guangxi and 3.87-5.21 mg/g in Wuzhishan City, Hainan . There was no significant difference in the content of three active components in different producing areas. Conclusion:The fingerprints and the determination method established in the study are stable and feasible, which can be used for the quality evaluation of Microctis Folium.

At present, discipline construction has gradually become the core theme of the development of clinical pharmacy in hospitals. As a key construction project unit of clinical pharmacy in Shanghai, from August 2017 to October 2019, the Obstetrics and Gynecology Hospital of Fudan University continued to promote the clinical pharmacy from four aspects: improving the practical ability of clinical pharmacists, building the information and automatic clinical pharmaceutical service mode, establishing the talent training echelon and promotion system, and strengthening the capacity of clinical transformation research and construction.

Gene therapy represents a promising treatment for the Alzheimer׳s disease (AD). However, gene delivery specific to brain lesions through systemic administration remains big challenge. In our previous work, we have developed an siRNA nanocomplex able to be specifically delivered to the amyloid plaques through surface modification with both CGN peptide for the blood-brain barrier (BBB) penetration and QSH peptide for -amyloid binding. But, whether the as-designed nanocomplex could indeed improve the gene accumulation in the impaired neuron cells and ameliorate AD-associated symptoms remains further study. Herein, we prepared the nanocomplexes with an siRNA against -site amyloid precursor protein-cleaving enzyme 1 (BACE1), the rate-limiting enzyme of A production, as the therapeutic siRNA of AD. The nanocomplexes exhibited high distribution in the A deposits-enriched hippocampus, especially in the neurons near the amyloid plaques after intravenous administration. In APP/PS1 transgenic mice, the nanocomplexes down-regulated BACE1 in both mRNA and protein levels, as well as A and amyloid plaques to the level of wild-type mice. Moreover, the nanocomplexes significantly increased the level of synaptophysin and rescued memory loss of the AD transgenic mice without hematological or histological toxicity. Taken together, this work presented direct evidences that the design of precise gene delivery to the AD lesions markedly improves the therapeutic outcome.

Objective To investigate the relations between psychiatric disability and co-morbid disability caused by injury,severity of the disabilities,as well as the unmet health care need among people living with both disabilities.Methods Data collected through both the Second China National Sample Survey on Disabilities in 2006 and the Follow-up Studies in 2009,were utilized.Sampling weights were considered to appropriately estimate situations in the total Chinese population.Results Among people with psychiatric disability,2.7％ of them were affected by other injurycaused disabilities as visual,hearing,speech,psychical and intellectual disabilities.Among people with disability that caused by injuries,1.8％ of them were living with psychiatric disability as well.The prevalence rates of psychiatric disability and injury caused disability were as 0.94％ and 0.63％,respectively.More than half of the co-morbid people were living with profound disabilities while 46.32％ of the people living with both disabilities developed co-morbid disabilities in the same year.Data from the follow-up program showed that 56.25％ of the people living with co-morbid disabilities did not receive any psychiatric treatment which were in need.Conclusion There seemed a close but bidirectional relationship existed between the mental disorders and injuries that calling for better mental health services provided for people with psychiatric disabilities.

OBJECTIVETo investigate the possibility of using melanoma antigen-1 (MAGE-1) peptide as a tumor vaccine to treat hepatocellular carcinoma (HCC).

METHODSThe expressions of MAGE-1 in 8 HCC cell lines and in liver cancer tissue from a patient were detected using RT-PCR. The type of human leucocyte antigen I(HLA I) of both 8 HCC cell lines and peripheral blood mononuclear cells of the patient was detected using a microcytotoxicity method to screen out target cell lines for the cytotoxicity assay. Peripheral blood mononuclear cells from the HCC patient pulsed with an MAGE-1 peptide (NYKCRFPEI) were used as antigen presenting cells. Autogenous peripheral blood mononuclear cells were stimulated with antigen presenting cells every 7 days for 4 times to elicit cytotoxic T lymphocytes. The phenotype of effector cells was analyzed using flow cytometry. The cytotoxicity of effector cells was detected with a lactate dehydrogenase releasing assay.

RESULTSThe expressions of both MAGE-1 and HLA-A24 were detected in BEL7405 cell line which were used as the positive target cell line in the cytotoxicity assay. The expression of MAGE-1 alone was detected in HLE, BEL7402, BEL7404, QGY7703 and SMMC7721 cell lines, and the expression of neither MAGE-1 nor HLA-A24 was shown in QGY 7701 and HpG2 cell lines. The last 7 cell lines could be used as negative target cell lines in the cytotoxicity assay. Peripheral blood mononuclear cells expanded 32 folds during 28-day culture. The ratio of CD3(+) T cells increased by 16% (from 54% to 70%), and the ratio of CD8(+) T cells increased by 20% (from 36% to 56%) during 28-day culture. When the ratio of effector cells to target cells was 10:1, effector cells exhibited 62.5% cytotoxicity against autogenous lymphoblasts pulsed with the peptide (NYKCRFPEI) of MAGE-1 antigen, 40.25% cytotoxicity against BEL7405 cells, compared with 17.88% cytolysis observed against autogenous lymphoblasts, 19.55% against HLE cells, and 1.6% against QGY7701 cells. When the ratio of effector cells to target cells was 3.3:1, the cytotoxicity of effector cells against the peptide pulsed autogenous lymphoblasts was 53.6%, which was much higher against autogenous lymphoblasts, HLE cells and QGY7701 cells at 15.6%, 13% and 1%, respectively.

CONCLUSIONThe results demonstrate that cytotoxic T lymphocytes with the ability to specifically lyse target cells expressing both MAGE-1 and HLA-A24 could be successfully induced by the MAGE-1 peptide NYKCRFPEI in vitro. This indicates that a good result might be anticipated if this peptide is used as a tumor vaccine to treat HLA-A24 HCC patients.

Adult ; Antigens, Neoplasm ; Cancer Vaccines ; immunology ; Carcinoma, Hepatocellular ; immunology ; HLA-A Antigens ; analysis ; HLA-A24 Antigen ; Humans ; Liver Neoplasms ; immunology ; Male ; Melanoma-Specific Antigens ; Neoplasm Proteins ; genetics ; immunology ; RNA, Messenger ; analysis ; T-Lymphocytes, Cytotoxic ; immunology ; Tumor Cells, Cultured