ObjectiveTo observe the effect of Shenshu Fujian decoction on platelet-derived growth factor （PDGF）/naked cuticle homolog 2 （NKD2） /Wnt signaling pathway in rats with chronic renal failure （CRF）. MethodsSixty male SD rats were randomly divided into normal group， model group， Niaoduqing group （5 g·kg^-1）， low-dose Shenshu Fujian decoction group （5.5 g·kg^-1）， medium-dose Shenshu Fujian decoction group （11 g·kg^-1）， and high-dose Shenshu Fujian decoction group （22 g·kg^-1）， with 10 rats in each group. A CRF rat model was established by feeding a 0.5% adenine diet for 21 days. After successful modeling， intragastric administration was given once daily for 28 consecutive days. After treatment， the renal morphology of rats was observed. Serum creatinine （SCr） and blood urea nitrogen （BUN） levels were detected. Hematoxylin-eosin （HE） staining and Masson staining were used to detect renal histopathological changes， and collagen volume fraction （CVF） was calculated. Serum levels of inflammatory markers interleukin （IL）-1β and IL-6 were measured using enzyme-linked immunosorbent assay （ELISA）. The expressions of fibronectin 1 （FN1）， type Ⅰ collagen （ColⅠ）， α-smooth muscle actin （α-SMA）， platelet-derived growth factor receptor-β （PDGFR-β）， NKD2， dishevelled protein 2 （DVL2） and β-catenin in renal tissue were detected by immunohistochemistry and Western blot. ResultsCompared with the normal group， the model group showed significant renal pathological changes， a markedly increased kidney weight/body weight ratio （P<0.01）， significantly elevated CVF （P<0.01）， and notably increased serum levels of SCr， BUN， IL-1β， and IL-6 （P<0.01）. Expression levels of FN1， ColⅠ， α-SMA， PDGFR-β， NKD2， DVL2， and β-catenin in renal tissue were also significantly increased （P<0.01）. Compared with the model group， all treatment groups showed significantly decreased kidney weight/body weight ratios and CVF （P<0.01）， as well as markedly decreased serum SCr， BUN， IL-1β， and IL-6 levels. Protein expression levels of FN1， ColⅠ， α-SMA， PDGFR-β， NKD2， DVL2， and β-catenin in renal tissue were decreased， with more pronounced effects observed in the Niaoduqing， medium-dose， and high-dose Shenshu Fujian decoction groups （P<0.05， P<0.01）. ConclusionShenshu Fujian decoction improves renal function， reduces inflammation， and reverses renal fibrosis in CRF rats， possibly by downregulating the expression of PDGF/NKD2/Wnt signaling pathway-related proteins.

Objective This study aims to build a differential diagnosis model for unipolar and bipolar depression based on clinical features and blood indicators.Methods According to inclusion and exclusion criteria,participants with unipolar and bipolar depression were included,and clinical data and blood test indicators of the participants were extracted.The data were randomly divided into a training set and a testing set.Classification models were trained on the training set using extreme gradient boosting based on different feature combinations,and the performance of the models was validated on the testing set.Receiver operating characteristic(ROC),area under curve(AUC),sensitivity,specificity and accuracy were used to evaluate model performance.The SHapley additive explanations(SHAP)method was used to calculate the importance of selected features for the differential diagnosis of unipolar and bipolar depression.Results In the unipolar and bipolar depression classification model,the XGBoost model performs the best,with an AUC of 0.889,sensitivity of 0.831,specificity of 0.839,and accuracy of 0.863.The main features in this model include duration of illness,age of onset,albumin,low-density lipoprotein,blood potassium concentration,white blood cell count,platelet/lymphocyte ratio,and monocytes.Conclusion Duration of illness and hematological biomarkers,which are easily obtainable in clinical settings,can provide important support for the differential diagnosis of unipolar and bipolar depression.

Objective Using the concept of allostatic load(AL)to evaluate aging of male SD rats and the effectiveness of Zuogui Pill in naturally aging rats.Methods Naturally aging male SD rats were tested at the ages of 2,5,8,14,18,and 21 months.They were divided into an elderly control group,low-dose Zuogui Pill group,and high-dose Zuogui Pill group.Intervention with Zuogui Pill was trialed for 3 months.Blood samples were taken from the tails of rats each month,and the number of T lymphocytes and rate of apoptosis were measured by flow cytometry.Low-density lipoprotein cholesterol(LDL-c),high-density lipoprotein cholesterol(HDL-c),triglycerides(TG),total cholesterol(TC),free fatty acids(FFA),25 hydroxyvitamin D(25-OH-D),corticosterone(CORT),C-reactive protein(CRP),and interleukin-6(IL-6)were detected in rat sera.By identifying the collinearity between indicators and professional considerations,LDL-c,TC,HDL-c,FFA,TG,CORT,IL-6,CRP,25-OH-D,CD3+T cell count,and CD3+T cell apoptosis rate were included in the AL scoring.The threshold for each indicator was established with data from 5-month-old rats,and the score was 1 point below or/and above the threshold.Results The serum levels of LDL-c,TG,TC,25-OH-D,CRP,and IL-6 of rats showed significant changes with age,although the patterns of change differed.The CD3+T lymphocyte count significantly decreased with age(P＜0.01),while the apoptosis rates of CD3+,CD4+,and CD8+T lymphocytes significantly increased with age(P＜0.01).Zuogui Pill significantly increased serum CORT levels in elderly rats(P＜0.01)and reduced the apoptosis rate of CD8+T lymphocytes(P＜0.05).The AL score began to increase in rats at 5 months of age and reached its peak in those of 18 months of age.Conclusions AL can better characterize the aging process compared to a single indicator.Zuogui Pill can improve the stress response ability of aging rats and alleviate immunosenescence.

ObjectiveTo study the characteristics of imprinting template of flavonoid clusters in four Chinese medicines attributed to the lung meridian， and to establish an in vitro experimental approach for the study of the attribution of Chinese medicines to the lung meridian. MethodBased on 13 Chinese medicines， including Xanthii Fructus， Houttuyniae Herba， Fagopyri Dibotryis Rhizoma， Belamcandae Rhizoma and so on， which only belong to the lung meridian in Chinese Materia Medica（the 13^th Five-Year planning textbook of general higher education）， we identified four representative Chinese medicines， namely Houttuyniae Herba， Fagopyri Dibotryis Rhizoma， Belamcandae Rhizoma and Mori Cortex， and set up their fingerprints by high performance liquid chromatography（HPLC） and calculated the molecular connectivity indices of various components in the four Chinese medicines， the similarity to their mean value was calculated by included angle cosine method， so as to establish the quantitative relationship of construction versus imprinting ability， and to determine the order of each component in the lung meridian. A total of 7 reference substances， including chlorogenic acid， rutin， quercetin， isoquercitrin， hyperoside， epicatechin， and iridin， were selected to validate the overall conformational relationships of flavonoids of the model， as well as its predictive ability. ResultHouttuyniae Herba， Fagopyri Dibotryis Rhizoma， Belamcandae Rhizoma and Mori Cortex contained a total of 437 chemical components with an average molecular connectivity index similarity of 0.995 6. The four Chinese medicines contained a total of 204 flavonoids with an average molecular connectivity index similarity of 0.978 0， which was second only to the alkaloids with 0.985 1. The retention time（t_R） of the 7 reference substances showed a good conformational relationship with the similarity of the molecular connectivity index（t_R=831.4×S-790.3， r=0.861 4， P<0.01）， which was applicable to the in vitro attribution study of the position， similarity， and relative similarity with t_R of the cluster of 98.04% of flavonoids. Accordingly， the 1^st position was kuwanon D， with a similarity of molecular connectivity index of 0.987 7 and a t_R of 30.88 min， the 200^th position was chlorogenic acid， with a similarity of molecular connectivity index of 0.958 2 and a t_R of 6.36 min. The total first-order moment of the four Chinese medicines calculated by total statistical moment method of fingerprint was 24.26 min， ranked 21， which could characterize 99.19% of the whole， and the total first-order moment of the total peak area of the 7 reference substances in the four Chinese medicines was 20.00 min， with a rank of 46， which could characterize 98.68% of the whole. ConclusionFlavonoid clusters are suitable probes for the characterization of imprinting template for the study of the lung meridian， which can be established a quantitative imprinting method for meridian tropism of Chinese medicines in vitro.

The study was carried out to understand the changes in the ethical cognition status of laboratory animals and the effectiveness of laboratory animal ethics education among medical students in Xiangya School of Medicine of Central South University (CSU), and provide new enlightenment for further strengthening the ethical education of laboratory animals. In the study, the same self-compiled questionnaire was used to investigate the ethical cognition of experimental animals among medical students in Xiangya School of Medicine of CSU in 2011 and 2021, and 359 and 363 questionnaires were collected respectively. Through comparative analysis of the questionnaire results before and after ten years, it was found that medical students’ animal experiment operation and attitudes towards laboratory animals, cognition of experimental animal ethics knowledge and their attitude to animal experiment ethics education were significantly improved. It showed that the state of experimental animal ethics cognition among medical students in Xiangya School of Medicine of CSU had improved significantly in recent 10 years, but the cognition of experimental animal ethics knowledge was higher than the actual behavior of caring for experimental animals, and there was the phenomenon of "separation of knowledge and action". The ethics education of experimental animals needs to pay more attention to the development of students’ behavior of caring for experimental animals.

Objective:To investigate the relationship between intracerebral high-density foci and progressive stroke (PS) morbidity by using dual-energy CT, which can quantify the intracerebral high-density foci of patients with acute ischemic stroke after endovascular treatment.Methods:Ninety-two patients with acute ischemic stroke who received interventional treatment in Gaozhou People′s Hospital from May 2019 to August 2020, and underwent dual-energy CT scan immediately after intervention, were analyzed. The patients were divided into PS group ( n=35) and non-PS group ( n=57) according to the National Institutes of Health Stroke Scale (NIHSS) score, and the patients whose NIHSS score increased≥4 points within 72 hours of stroke were included in the PS group, while the patients whose NIHSS score increased<4 points were included in the non-PS group. The clinical data, volume of high-density foci and CT values were compared between the 2 groups. Logistic regression analysis was used to adjust for confounding factors and screen for risk factors. The correlations of the admission NIHSS score, presence and volume of high-density lesions, maximum CT (CTmax) value and average CT (CTave) value with the onset of PS were analyzed, and the receiver operating characteristic curve was used to screen predictive indicators of PS. Results:In the PS group, the NIHSS score (18.80±8.50 vs 14.40±9.58, t=2.229, P=0.028), proportion of high-density foci [29/35(82.9%) vs 32/57 (56.1%), χ 2=6.928, P=0.008], high-density focal volume [13.23 (39.33) cm 3vs 0.76 (9.82) cm 3, U=1 440.000, P<0.001], CTmax value [80.00 (92.00) HU vs 65.00 (87.50) HU, U=1 337.000, P=0.005] and CTave value [53.48 (23.79) HU vs 45.94 (55.11) HU, U=1 345.000, P=0.004] were higher than those in the non-PS group. The NIHSS score ( OR=1.054, 95% CI 1.004-1.106, P=0.033; rs=0.255, 95% CI 0.051-0.447, P=0.014), presence of high-density foci ( OR=3.776, 95% CI 1.358-10.503, P=0.011; rs=0.274, 95% CI 0.093-0.460, P=0.008), high-density focal volume ( OR=1.026, 95% CI 1.003-1.049, P=0.027; rs=0.381, 95% CI 0.183-0.560, P<0.001), CTmax value ( OR=1.006, 95% CI 1.001-1.011, P=0.014; rs=0.292, 95% CI 0.088-0.475, P=0.005) and CTave value ( OR=1.021, 95% CI 1.007-1.035, P=0.004; rs=0.299, 95% CI 0.092-0.484, P=0.004) were all risk factors affecting PS morbidity and were positively correlated with PS morbidity. The area under the receiver operating characteristic curve of NIHSS score, high-density lesion volume, CTmax value, and CTave value to predict the onset of PS was 0.652, 0.722, 0.670 and 0.674, respectively. The volume of high-density lesions had moderate predictive value for the onset of PS. Conclusions:For AIS patients, CT examination should be performed immediately after interventional operation. The volume, CTmax value and CTave value of high-density lesions newly appeared in the ischemic area are positively correlated with the onset of PS. Quantifying the volume of high-density lesions can help to predict the onset of PS.

Background Research on non-target organ damage of biological pesticides has attracted much attention. Rotenone exposure may be far beyond the occupational environment, and the exposureduring pregnancy may be increased through bioaccumulation, fruit or vegetable residues, and other forms of oral intake. At present, the effects of rotenone on placental development and its mechanism are still unknown. Objective To investigate the developmental damage of rat placenta and evaluate the expression levels of glycogen synthase kinase (GSK-3β) and beta catenin (β-catenin) followed by rotenone exposure through the placental barrier during pregnancy, as well as to propose possible associated mechanisms. Methods Eighteen sexually mature SD female infertile rats without specific pathogens were selected and divided into three groups: blank control group (0.9% saline), corn oil group, and rotenone group (corn oil + 2 mg·kg⁻¹ rotenone) by random number method, six female animals in each group. Another six male rats were selected and mated to the female rats at night with a female to male ratio of 3:1 per cage. Pregnant rats were given 0.9% saline, corn oil, and 2 mg·kg⁻¹ rotenone preparation by isovolumetric gavage once daily for the entire gestation period (19 d), and their conditions were observed after the last dose. The pregnant rats were anesthetized, and the size of the placenta and blood perfusion were detected by ultrasound the next day of the last dose of rotenone. Then, 3 pregnant rats in each group were sacrificed immediately and the placenta and umbilical cord tissues were dissected. The remaining 9 pregnant rats gave birth naturally, and the fetuses were observed for developmental evaluation and weighed. The histopathological changes of umbilical cord and placenta were observed by hematoxylin-eosin staining. The reactive oxygen species levels of placenta tissues were detected by flow cytometry. The Ca²⁺-ATPase activity of placenta tissues was detected by colorimetric method. The localization and levels of GSK-3β and β-catenin expression of placenta were detected by immunohistochemistry. The p-GSK-3β/GSK-3β and p-β-catenin/β-catenin protein expression in placental tissues were measured by Western blotting. Results No injury or death was recorded during the pregnant rats receiving rotennon administration. Adverse pregnancy outcomes such as fetal absorption and postpartum stillbirth were found in the rotenone group, and the weight of the fetal mice decreased (P<0.05). The B-ultrasound showed disc-shaped placenta with a thick middle and thin edge, smooth fetal surface, rough maternal surface, visible placental lobules, granular echotexture of the placenta with comma-like echogenic densities, and chorionic plate showing deep indentations, no calcification, degeneration, or necrosis in each group. Compared with the corn oil group, the fetal surface diameter of the placenta was reduced in the rotenone group (P<0.05). The Doppler color ultrasound showed that interplacental blood flow was reduced in the rotenone group, while interplacental blood flow was abundant in the blank control and the corn oil groups. The hematoxylin-eosin staining results showed that smooth muscle cells in the umbilical cord tissues of rats were loosely arranged, with fuzzy nuclei and inflammatory infiltration in the rotenone group. The placental trophoblast cells were small in size, disorderly arranged with nuclear fragmentation and cytoplasm turbidity. The tissue reactive oxygen species level in the rotenone group was higher than those in the other two groups (P<0.05). The Ca²⁺-ATPase activity of placental tissues was reduced in the rotenone group (P<0.05). The immunofluorescence low-magnification observation showed that GSK-3β and β-catenin were expressed in placental tissue, weak fluorescence expression in the decidua basalis, strong fluorescence expression in the labyrinthine layer structure. The labyrinthine layer under high magnification showed that compared with the blank control group and the corn oil group, the brightness of β-catenin fluorescence expression in the rotenone group decreased (P<0.05), and the brightness of GSK-3β expression increased (P<0.05). The Western blotting results showed that the expression of β-catenin and p-GSK-3β proteins decreased (P<0.01), and the expression of GSK-3β protein increased (P<0.01) in the rotenone group. No significant expression of p-β-catenin protein was detected in the placenta tissue of each group. Conclusion Rotenone exposure during pregnancy induces placental hypoperfusion, growth retardation, and oxidative stress in rats, as well as down-regulation of β-catenin and p-GSK-3β protein expression, and up-regulation of GSK-3β protein expression, which may further lead to abnormal pregnancy and fetal restricted growth.

Objective:To explore the feasibility of extracting the key plane of the normal fetal palate on the 11-13 + 6 week from tomography ultrasonography imaging based on artificial intelligence. Methods:The fetal volume datas of 235 cases of 11-13 + 6 week normal fetal were collected from the Department of Ultrasound in the Luohu District People′s Hospital of Shenzhen and Huazhong University of Science and Technology Union Shenzhen Hospital from May 2020 to April 2021. The data acquisition was completed by sonographers A and B by using the GE Voluson E10 color Doppler ultrasound diagnostic instrument. All datas were marked offline by sonographer C. Tomographic imaging was performed on all included data by sonographer D, the tomographic images were saved and the time-consuming was recorded, and the datas of the sonographer group were obtained. The labeled data were randomly divided into the training set and test set for model transfer learning and testing.The 4-fold cross-validation was adopted to record the test set image output by the model and the time consumption to obtain the intelligent group data. A senior sonographer performed image analysis on the two groups of data images. The feasibility of the intelligent model was verified by comparing the score of the plane of retronasal triangle(RTP), the acquisition rate of RTP, the acquisition rate of the fault, and the time-consuming difference between the sonographer group and the intelligent group. Results:①There was no significant difference in the overall distribution of RTP scores between the sonographer group and intelligent group [5 (5, 6) points vs 5 (5, 6) points, Z=0.355, P=0.722]. The RTP acquisition rate of the sonographer group and intelligent group was not statistically significant (78.72% vs 76.60%, χ 2=0.55, P=0.458). The consistency and correlation of RTP obtained by the two groups were high (Kappa=0.645, φ=0.646, both P<0.001). ②The effective layers of the sonographer group were 9 (8, 9) and the intelligent group was 8 (7, 9). The fault acquisition rate of the doctor group was higher than that of the intelligent group (78.72% vs 68.51%, χ 2=12.52, P=0.001). The consistency and correlation of the two groups in obtaining faults were media (Kappa=0.503, φ=0.521, both P<0.001). ③The time-consuming of the intelligent group was significantly lower than that of the sonographer group [1.50 (1.23, 1.75)s vs 26.94 (22.28, 30.48)s, Z=11.440, P<0.001]. Conclusions:This research model can quickly and accurately realize the extraction and tomography of the key plane of the normal fetal palate on the 11-13 + 6 week.

Objective:This retrospective, single-center study aimed to evaluate the efficacy and safety of programmed death-1 (PD-1) inhibitors, either as monotherapy or in combination with chemotherapy, in the management of relapse/refractory classical Hodgkin's lymphoma (R/R cHL) .Methods:A total of 35 patients with R/R cHL who received treatment at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College from September 2016 to December 2020 were enrolled in this study. Among them, 17 patients received PD-1 inhibitor monotherapy (PD-1 inhibitor group), while 18 patients received a combination of PD-1 inhibitor and chemotherapy (PD-1 inhibitor + chemotherapy group). Clinical data and follow-up information were retrospectively analyzed, and survival analysis was conducted using the Kaplan-Meier method and Cox proportional hazards model.Results:The median age of the 35 patients with R/R cHL was 29 years (range: 11-61 years), with 54.3% being male. According to the Ann Arbor staging system, 62.9% of patients presented with advanced (stage Ⅲ/Ⅳ) disease, and 48.6% had extranodal involvement. Before PD-1 inhibitor therapy, the median number of prior lines of therapy was 2 (range: 1-3). Objective responses were observed in 28 patients, including 22 complete response (CR) cases, resulting in an overall response rate (ORR) of 80.0% and a CR rate of 62.9%. Specifically, the ORR and CR rates were 64.7% and 58.8%, respectively, in the PD-1 inhibitor group and 94.4% and 66.7%, respectively, in the PD-1 inhibitor + chemotherapy group. Among the 18 patients who underwent sequential autologous hematopoietic stem cell transplantation (auto-HSCT) [13 CR and five partial response (PR) cases], eight patients received PD-1 inhibitor therapy after auto-HSCT as consolidation therapy. All patients maintained a CR status after transplantation, and they exhibited significantly improved progression-free survival (PFS) rates compared with those who did not undergo sequential auto-HSCT (4-year PFS rates: 100% vs 53.5% ; P=0.041). The incidence of immune-related adverse events was 29%, with only one patient experiencing grade≥3 adverse reactions, which indicated a favorable safety profile for the treatment approach. Conclusions:PD-1 inhibitor monotherapy demonstrates notable efficacy and sustained response in patients with R/R cHL. PD-1 inhibitors combined with chemotherapy significantly improve response rates. Additionally, for salvage therapy-sensitive patients, consolidation treatment with PD-1 inhibitors after auto-HSCT exhibits the potential for prolonging PFS.

Central nervous system (CNS) injuries, including stroke, traumatic brain injury, and spinal cord injury, are essential causes of death and long-term disability and are difficult to cure, mainly due to the limited neuron regeneration and the glial scar formation. Herein, we apply extracellular vesicles (EVs) secreted by M2 microglia to improve the differentiation of neural stem cells (NSCs) at the injured site, and simultaneously modify them with the injured vascular targeting peptide (DA7R) and the stem cell recruiting factor (SDF-1) on their surface via copper-free click chemistry to recruit NSCs, inducing their neuronal differentiation, and serving as the nanocarriers at the injured site (Dual-EV). Results prove that the Dual-EV could target human umbilical vascular endothelial cells (HUVECs), recruit NSCs, and promote the neuronal differentiation of NSCs in vitro. Furthermore, 10 miRNAs are found to be upregulated in Dual-M2-EVs compared to Dual-M0-EVs via bioinformatic analysis, and further NSC differentiation experiment by flow cytometry reveals that among these miRNAs, miR30b-3p, miR-222-3p, miR-129-5p, and miR-155-5p may exert effect of inducing NSC to differentiate into neurons. In vivo experiments show that Dual-EV nanocarriers achieve improved accumulation in the ischemic area of stroke model mice, potentiate NSCs recruitment, and increase neurogenesis. This work provides new insights for the treatment of neuronal regeneration after CNS injuries as well as endogenous stem cells, and the click chemistry EV/peptide/chemokine and related nanocarriers for improving human health.