ObjectiveTo study the effect of Taikong Yangxin Pills on the metabolism of simulated weightless rats based on metabolomics and discuss the metabolism mechanism. MethodsIn the simulated space capsule environment on the ground， the rat model of simulated weightlessness was established by the tail suspension method. Rats were randomly grouped as follows： out-of-capsule control， in-capsule control， model， and high （3.0 g·kg^-1） and low （1.5 g·kg^-1） doses of Taikong Yangxin Pills， and they were administrated with corresponding drugs by gavage for 28 days. The serum levels of endogenous metabolites in rats were determined by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF/MS）. The obtained data were processed by principal component analysis （PCA） and orthogonal partial least squares-discriminant analysis （OPLS-DA） to screen for differential metabolites and potential biomarkers. MetaboAnalyst 5.0 was used for pathway enrichment analysis to explain the metabolic regulation mechanism of the drug. ResultsCompared with the out-of-capsule control group， the in-capsule control group showed elevated levels of thirteen metabolites， including 14-hydroxyhexadecanoic acid， linoleic acid， and α-linolenic acid （P<0.05）， which suggested that the space capsule environment mainly affected the metabolism of α-linolenic acid and linoleic acid in the rats. Compared with the in-capsule control group， the model group showed lowered levels of fourteen metabolites， including 4-imidazolone-5-propionic acid， isocitric acid/citric acid， and L-tyrosine （P<0.05）， which were recovered after the treatment with Taikong Yangxin pills （P<0.05）. The pathway enrichment analysis revealed that weightlessness induced by tail suspension and drug intervention mainly involved the phenylalanine， tyrosine， and tryptophan biosynthesis， tyrosine metabolism， histidine metabolism， and citric acid cycle. ConclusionThe simulated space capsule environment and simulated weightlessness induced by tail suspension can both affect the metabolism level of rats. Taikong Yangxin pills can ameliorate the metabolic abnormality in the rat model of weightlessness by regulating various amino acids and energy metabolism-related pathways.

BACKGROUND: To evaluate the efficacy and safety of the first cohort of people in China treated with a responsive neurostimulation system (Epilcure TM , GenLight MedTech, Hangzhou, China) for focal drug-resistant epilepsy in this study. METHODS: This multicenter, before-and-after self-controlled study was conducted across 8 centers from March 2022 to June 2023, involving patients with drug-resistant epilepsy who were undergoing responsive neurostimulation (RNS). The study was based on an ongoing multi-center, single-blind, randomized controlled study. Efficacy was assessed through metrics including median seizure count, seizure frequency reduction (SFR), and response rate. Multivariable linear regression analysis was conducted to explore the relationships of basic clinical factors and intracranial electrophysiological characteristics with SFR. The postoperative quality of life, cognitive function, depression, and anxiety were evaluated as well. RESULTS: The follow-up period for the 19 participants was 10.7 ± 3.4 months. Seizure counts decreased significantly 6 months after device activation, with median SFR of 48% at the 6th month (M6) and 58% at M12 ( P  <0.05). The average response rate after 13 months of treatment was 42%, with 21% ( n  = 4) of the participants achieving seizure freedom. Patients who have previously undergone resective surgery appear to achieve better therapeutic outcomes at M11, M12 and M13 ( β  <0, P  <0.05). No statistically significant differences were observed in patients' scores of quality of life, cognition, depression and anxiety following stimulation when compared to baseline measurements. No serious adverse events related to the devices were observed. CONCLUSIONS: The preliminary findings suggest that Epilcure TM exhibits promising therapeutic potential in reducing the frequency of epileptic seizures. However, to further validate its efficacy, larger-scale randomized controlled trials are required. REGISTRATION Chinese Clinical Trial Registry (No. ChiCTR2200055247).
Humans ; Female ; Male ; Drug Resistant Epilepsy/therapy* ; Adult ; Young Adult ; Middle Aged ; China ; Adolescent ; Treatment Outcome ; Quality of Life ; Single-Blind Method ; Seizures ; Electric Stimulation Therapy/methods*

BACKGROUND: Arsenic trioxide (ATO) is indicated as a broad-spectrum medicine for a variety of diseases, including cancer and cardiac disease. While the role of ATO in hepatic ischemia/reperfusion injury (HIRI) has not been reported. Thus, the purpose of this study was to identify the effects of ATO on HIRI. METHODS: In the present study, we established a 70% hepatic warm I/R injury and partial hepatectomy (30% resection) animal models in vivo and hepatocytes anoxia/reoxygenation (A/R) models in vitro with ATO pretreatment and further assessed liver function by histopathologic changes, enzyme-linked immunosorbent assay, cell counting kit-8, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Small interfering RNA (siRNA) for extracellular signal-regulated kinase (ERK) 1/2 was transfected to evaluate the role of ERK1/2 pathway during HIRI, followed by ATO pretreatment. The dynamic process of autophagic flux and numbers of autophagosomes were detected by green fluorescent protein-monomeric red fluorescent protein-LC3 (GFP-mRFP-LC3) staining and transmission electron microscopy. RESULTS: A low dose of ATO (0.75 μmol/L in vitro and 1 mg/kg in vivo ) significantly reduced tissue necrosis, inflammatory infiltration, and hepatocyte apoptosis during the process of hepatic I/R. Meanwhile, ATO obviously promoted the ability of cell proliferation and liver regeneration. Mechanistically, in vitro  studies have shown that nontoxic concentrations of ATO can activate both ERK and phosphoinositide 3-kinase-serine/threonine kinase (PI3K-AKT) pathways and further induce autophagy. The hepatoprotective mechanism of ATO, at least in part, relies on the effects of ATO on the activation of autophagy, which is ERK-dependent. CONCLUSION Low, non-toxic doses of ATO can activate ERK/PI3K-AKT pathways and induce ERK-dependent autophagy in hepatocytes, protecting liver against I/R injury and accelerating hepatocyte regeneration after partial hepatectomy.
Animals ; Arsenic Trioxide ; Autophagy/physiology* ; Reperfusion Injury/prevention & control* ; Mice ; Male ; Proto-Oncogene Proteins c-akt/physiology* ; Arsenicals/therapeutic use* ; Oxides/therapeutic use* ; Liver/metabolism* ; Extracellular Signal-Regulated MAP Kinases/metabolism* ; Mice, Inbred C57BL

Objective To compare the clinical application of empirical thoracoscopic segmentectomy and precise segmentectomy planned by artificial intelligence software, and to provide some reference for clinical segmentectomy. Methods A retrospective analysis was performed on the patients who underwent thoracoscopic segmentectomy in our department from 2019 to 2022. The patients receiving empirical thoracoscopic segmentectomy from January 2019 to September 2021 were selected as a group A, and the patients receiving precise segmentectomy from October 2021 to December 2022 were selected as a group B. The number of preoperative Hookwire positioning needle, proportion of patients meeting oncology criteria, surgical time, intraoperative blood loss, postoperative chest drainage time, postoperative hospital stay, and number of patients converted to thoracotomy between the two groups were compared. Results A total of 322 patients were collected. There were 158 patients in the group A, including 56 males and 102 females with a mean age of 56.86±8.82 years, and 164 patients in the group B, including 55 males and 109 females with a mean age of 56.69±9.05 years. All patients successfully underwent thoracoscopic segmentectomy, and patients whose resection margin did not meet the oncology criteria were further treated with extended resection or even lobectomy. There was no perioperative death. The number of positioning needles used for segmentectomy in the group A was more than that in the group B [47 (29.7%) vs. 9 (5.5%), P<0.001]. There was no statistical difference in the number of positioning needles used for wedge resection between the two groups during the same period (P=0.572). In the group A, the nodule could not be found in the resection target segment in 3 patients, and the resection margin was insufficient in 10 patients. While in the group B, the nodule could not be found in 1 patient, and the resection margin was insufficient in 3 patients. There was a statistical difference between the two groups [13 (8.2%) vs. 4 (2.4%), P=0.020]. There was no statistical difference between the two groups in terms of surgical time, intraoperative blood loss, duration of postoperative thoracic drainage, postoperative hospital stay, or conversion to open chest surgery (P＞0.05). Conclusion Preoperative surgical planning performed with the help of artificial intelligence software can effectively guide the completion of thoracoscopic anatomical segmentectomy. It can effectively ensure the resection margin of pulmonary nodules meeting the oncological requirements and significantly reduce the number of positioning needles of pulmonary nodules.

Methods: From September 3, 2018, to March 23, 2024, participants with essential hypertension (receiving antihypertensive medication treatment, hypertension group) and normal blood pressure (control group) were recruited from the Cardiology Department of Shanghai Hospital of Traditional Chinese Medicine, the Coronary Care Unit of Shanghai Tenth People's Hospital, the Physical Examination Center of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, and the Gaohang Community Health Service Center. This study employed the propensity score matching (PSM) method to reduce study participants selection bias. Spectral information in the facial visible light spectrum of the subjects was collected using a flame spectrometer, and the spectral chromaticity values were calculated using the equal-interval wavelength method. The study analyzed the differences in spectral reflectance across various facial regions, including the entire face, forehead, glabella, nose, jaw, left and right zygomatic regions, left and right cheek regions as well as differences in parameters within the Lab color space between the two subject groups. Feature selection was conducted using least absolute shrinkage and selection operator (LASSO) regression, followed by the application of various machine learning algorithms, including logistic regression (LR), support vector machine (SVM), random forest (RF), Naïve Bayes (NB), and eXtreme Gradient Boosting (XGB). The reduced-dimensional dataset was split in a 7 : 3 ratio to establish a classification and assessment model for facial coloration related to primary hypertension. Additionally, model fusion techniques were applied to enhance the predictive power. The performance of the models was evaluated using metrics including the area under the curve (AUC) and accuracy. Shapley Additive exPlanations (SHAP) was used to interpret the outcomes of the models. Results: A total of 114 participants were included in both hypertension and control groups. Reflectance analysis across the entire face and eight predefined areas revealed that the hypertensive group exhibited significantly higher reflectance of corresponding color light in the blue-violet region (P < 0.05) and a lower reflectance in the red region (P < 0.05) compared with control group. Analysis of Lab color space parameters across the entire face and eight predefined areas showed that hypertensive group had significantly lower a and b values than control group (P < 0.05). LASSO regression analysis identified a total of 18 facial color features that were highly correlated with hypertension, including the a values of the chin and the right cheek, the reflectance at 380 nm and at 780 nm of the forehead. The results of the multi-model classification showed that the RF classification model was the most effective, with an AUC of 0.74 and an accuracy of 0.77. The combined model of RF + LR + SVM outperformed a single model in their classification performance, achieving an AUC of 0.80 and an accuracy of 0.76. SHAP model visualization results indicated that the top three contributors to ideal prediction results based on the characteristics from the facial spectrum were the reflectance at 380 nm across the entire face and of the nose as well as the a value of the chin. Conclusion Within the same age group, patients with essential hypertension exhibited significant and regular changes in facial color and facial spectral reflectance parameters after the administration of antihypertensive drugs. Furthermore, facial reflectance indicators, such as the overall reflectance at 380 nm and the a value of the chin, could offer valuable references for clinically assessing the drug efficacy and health status of patients with essential hypertension.

Objective:To investigate the diagnostic value of cervical cell DNA ploidy analysis combined with negative costimulatory molecule B7 homolog 4 (B7-H4) and protein kinase Cδ (PKCδ) for cervical cancer.Methods:A total of 160 cervical cancer patients diagnosed and treated at Shijiazhuang People's Hospital from January 2018 to January 2022 were selected as the cervical cancer group. Meantime, 160 women who were screened for cervical cancer in our hospital during this period were selected as the control group. According to the examination results, they were divided into normal or inflammatory group ( n=52), low-grade cervical intraepithelial neoplasia (CIN) group ( n=68) and high-grade CIN group ( n=40). The automatic cell image analysis system was used to analyze the DNA ploidy of cervical cells. The levels of B7-H4 and PKCδ in serum were determined by enzyme-linked immunosorbent assay. Pearson method was used to analyze the correlation between serum B7-H4 and PKCδ; the diagnostic value of cervical cell DNA ploidy analysis combined with serum B7-H4 and PKCδ in cervical cancer was evaluated by the receiver operator characteristic (ROC) curve; multivariate logistic regression was used to analyze the risk factors of cervical cancer. Results:The numbers of DNA ploidy positive cases of cervical cells in normal or inflammatory group, low-grade CIN group, high-grade CIN group and cervical cancer group were 16 (30.8%), 27 (39.7%), 26 (65.0%) and 127 (79.4%), respectively, with a statistically significant difference ( H=55.86, P<0.001). Further pin-by-pair comparison showed that compared with normal or inflammatory groups, the proportion of DNA ploidy positive in high-grade CIN group and cervical cancer group were higher (both P<0.05). The proportion of DNA ploidy positive in cervical cancer group was higher than that in low-grade CIN group ( P<0.05). Serum B7-H4 levels in normal or inflammatory group, low-grade CIN group, high-grade CIN group and cervical cancer group were (57.21±10.21), (79.17±11.34), (92.73±15.36), (126.56±20.25) ng/ml, respectively, with a statistically significant difference ( F=285.45, P<0.001). Serum PKCδ levels were (89.34±18.29), (71.79±15.82), (53.39±11.84), (40.23±10.21) ng/ml, respectively, with a statistically significant difference ( F=216.28, P<0.001). Further pin-by-pair comparison showed that serum B7-H4 levels in normal or inflammatory groups, low-grade CIN group, high-grade CIN group and cervical cancer group increased in turn (all P<0.05). Serum PKCδ levels in normal or inflammatory groups, high-grade CIN group and cervical cancer group were decreased in turn (all P<0.05). Pearson correlation analysis showed that the serum B7-H4 and PKCδ levels in patients with cervical cancer were negatively correlated ( r=-0.47, P<0.001). ROC curve analysis showed that the area under the curve (AUC) of cervical cell DNA ploidy for cervical cancer diagnosis was 0.82 (95% CI: 0.78-0.86), and the sensitivity and specificity were 83.9% and 79.9%, respectively. The AUC of serum B7-H4 in the diagnosis of cervical cancer was 0.92 (95% CI: 0.89-0.95), the sensitivity and specificity were 95.7% and 76.1%, respectively, and the cutoff value was 111.12 ng/ml. The AUC of serum PKCδ for diagnosis of cervical cancer was 0.92 (95% CI: 0.89-0.95), the sensitivity and specificity were 85.6% and 88.9%, respectively, and the cut-off value was 54.83 ng/ml. The AUC of the combined diagnosis of cervical cancer was 0.99 (95% CI: 0.97-0.99), and the sensitivity and specificity were 98.3% and 75.9%, respectively. The AUC of the combined diagnosis of cervical cancer was higher than that of DNA ploidy ( Z=8.00, P<0.001), serum B7-H4 ( Z=4.34, P<0.001), and serum PKCδ ( Z=4.61, P<0.001) alone. Multivariate logistic regression analysis showed that high level of B7-H4 in serum ( OR=2.94, 95% CI: 1.78-4.84, P<0.001), low level of PKCδ ( OR=4.33, 95% CI: 1.88-10.00, P=0.001) and positive DNA ploidy in cervical cells ( OR=5.77, 95% CI: 2.38-13.99, P<0.001) were independent risk factors for cervical cancer. Conclusion:The positive proportion of DNA ploidy in cervical cells of patients with cervical cancer is increased, the serum B7-H4 level is increased, the PKCδ level is decreased, and cervical cell DNA ploidy analysis combined with serum B7-H4 and PKCδ has a high diagnostic value for cervical cancer.

Objective To develop a Traditional Chinese Medicine(TCM)syndrome diagnosis scale suitable for evaluating the overall health status of participants in long-term simulated weightlessness experiments,and preliminarily evaluate its reliability and validity.Methods Based on the understanding of the pathogenesis of TCM in different stages of long-term manned spaceflight,a scale was developed through literature research and expert consultation.Test-retest reliability and internal consistency coefficient were used to test the reliability of the scale.Item analysis and factor principal component analysis were used to evaluate the validity of the scale,and a rotating component matrix was used to analyze the correlation between each item and dimension using 36 volunteers in a 90 days head down bed rest experiment as the research subjects.Results The scale contains eight dimensions and 57 items.The reliability analysis showed that the correlation coefficient of the total score of the scale for the first and second tests of 30 participants was 0.889,indicating high stability of the scale.The Cronbach coefficient of the scale was 0.934,indicating very good internal consistency.The split half reliability after correction was 0.858,indicating a high reliability of the scale.The validity analysis showed that the difference between the high score group and the low score one for each of the 57 items was statistically significant(P<0.01),and the Pearson correlation coefficient between each item and the total score of the scale was greater than 0.4(P<0.001).The cumulative contribution rate of 8 common factors extracted using principal component factor analysis was 55.293%,and the results of rotating component matrix analysis,after applying TCM theory and expert feedback,had a coincidence of up to 87.5%with the initial 8 dimensions,indicating good structural validity of the scale.Conclusion The scale has good reliability and validity,and can diagnose TCM syndromes.It is suitable for long-term simulated weightlessness experiment and provides an objective and quantitative new method for evaluating the subjective feelings of participants.

Objective To investigate the protective effect of Qianggukangwei Recipe(QG)on myotube cell atrophy induced by simulated microgravity effect(SMG).Methods The induced differentiation mouse myotube cells(C2C12 cells)were divided into six groups.Then the 48h simulated microgravity effect(SMG)model of mouse myotube cells was established by three-dimensional gyrotron(48h-SMG group).The cells in 3 groups were treated with 2.50,1.25,0.625 mg/mL QG.The cells in the left group were treated with 2.70 μg/mL alendronate sodium as positive control group.The levels of oxidative and inflammatory factors in myotube cells were detected by kits.The protein expression levels of NF-κB/IκB protein decomposition pathway and IGF-1/PI3K/Akt protein synthesis pathway were detected by Western blotting.The IGF-1/PI3K/Akt pathway was verified by 7 μmol/L of IGF-1 inhibitor.Results As compared with the control group,oxidation and inflammation levels in myotube cells increased significantly(P<0.05).The protein expression levels of IKK,NF-κB,and MURF-1 were significantly increased by 19.9%±6.1%,189.3%±15.9%,445.0%±46.1%,and IκB was significantly decreased by 26.5%±0.1%(P<0.05).The levels of IGF-1,PI3K,p-Akt/Akt and mTOR in the IGF-1/PI3K/Akt pathway were decreased by 23.6%±0.5%,30.7%±2.7%,13.3%±1.1%,21.0%±1.6%(P<0.05).The three doses of QG could and reduce the level of cellular oxidative stress and inflammation(P<0.05).QG could also activate the IGF-1/PI3K/Akt pathway and inhibit the NF-κB/IκB pathway.Among them,the high dose of QG(2.50 mg/mL)significantly decreased the protein expression levels of IKK,NF-κB and MURF-1 by 39.9%±2.4%,48.6%±0.1%,70.0%±2.1%(P<0.05),and significantly increased the expression levels of IGF-1,PI3K,mTOR and Akt phosphorylation by 43.1%±1.1%,100.0%±7.7%,71.8%±2.5%,95.2%±12.8%(P<0.05).Conclusion QG can significantly alleviate myotube cell atrophy induced by SMG effect by regulating relevant protein synthesis and degradation pathways.

Background and purpose:Currently,for patients with mid-to-low locally advanced rectal cancer and potentially resectable T4bM0 colon cancer,guidelines recommend neoadjuvant therapy strategies to enhance the response rate and increase the likelihood of conversion surgery.Among these patients,ypⅢ stage colorectal cancer(CRC)is assessed using the Union for International Cancer Control(UICC)/American Joint Committee on Cancer(AJCC)TNM staging system for postoperative pathological features.However,neoadjuvant therapy can lead to lymph node regression in the surgical area,resulting in an insufficient number of detected lymph nodes(less than 12),preventing classification according to conventional TNM staging.Thus,TNM staging often fails to predict the prognosis of ypⅢ patients who have undergone neoadjuvant therapy.This study aimed to evaluate the prognostic value of the positive lymph node ratio(LNR)in ypⅢ stage CRC patients treated with neoadjuvant therapy.Methods:Retrospective data was collected from ypⅢ stage CRC patients who received neoadjuvant therapy and underwent radical surgery at Fudan University Shanghai Cancer Center between 2008 and 2018.Collect clinical pathological characteristics such as age,gender,primary tumor location,tumor differentiation grade,pathological staging,and whether the patient has relapsed or died during follow-up at the time of surgery.Inclusion criteria:CRC patients who have received neoadjuvant therapy and surgery and have been confirmed to be stage Ⅲ by postoperative pathological examination.Exclusion criteria:① Preoperative imaging examination or intraoperative exploration reveals distant organ metastasis;② History of malignant tumors in the past;③ Multiple primary CRC.This study was approved by the medical ethics committee of Fudan University Shanghai Cancer Center(ethics number:050432-4-2108*).The R software survminer package(surv_cutpoint algorithm)was used to calculate the optimal cutoff value for LNR relative to disease-free survival(DFS),and patients were divided into low and high LNR groups accordingly.Clinical pathological characteristics and DFS were compared between the two groups.COX proportional hazards regression models were employed to identify adverse pathological features,and survival plots along with prediction models for DFS were generated using the survival and rms packages.Results:A total of 489 patients were included,comprising 289 males and 200 females,with a median age of 56 years(23-80 years)and a median follow-up time of 1 062 d.During the follow-up period,164 patients(33.5%)died.In the entire cohort,204(41.7%)patients had fewer than 12 lymph nodes detected.The optimal cutoff value for LNR was 0.29,classifying 317 patients into the low LNR group(LNR≤0.29)and 172 patients into the high LNR group(LNR＞0.29).The high LNR group exhibited shorter DFS compared to the low LNR group[hazard ratio(HR)=2.103,95%CI:1.582-2.796,P＜0.000 1].Multivariate COX regression indicated that LNR was an independent prognostic factor for DFS(HR=1.825,95%CI:1.391-2.394,P＜0.001).The inclusion of LNR in a multicategory DFS nomogram prediction model effectively assessed DFS in stage Ⅲ CRC patients who had undergone neoadjuvant therapy.Conclusion:LNR is an independent prognostic factor for ypⅢ stage CRC patients,showing good predictive power for DFS when combined with other adverse pathological features.Therefore,incorporating LNR as a supplement to TNM staging can improve the accuracy of CRC prognosis assessment.

[Objective] To evaluate the efficacy and safety of zero-pressure percutaneous nephrolithotomy (PCNL) combined with hands-free pneumatic lithotripsy in the one-stage treatment of calculous pyonephrosis in the non-acute infection phase. [Methods] Clinical data of 15 patients' treated during Feb.2022 and Dec.2023 were retrospectively analyzed.Double-sheath negative pressure PCNL was adopted, with zero-pressure gravity perfusion where the perfusion height was at the level of the patients' kidney, not exceeding 20 cm above the kidney.Pneumatic lithotripsy was performed without the need to hold the device with hand. [Results] The median stone diameter was 28 (range 22—40) mm, with a median stone density of 1028 (range 765—1305) Hu.All operations were successful.The median operation time was 55 (range 35—90) min.Postoperative low fever (Clavien grade Ⅰ) occurred in 1 case, and high fever (Clavien grade Ⅱ) occurred in 1 case, with no complications of Clavien grade Ⅲ or above.The initial stone-free rate was 73.3%, and the stone-free rate after one month was 93.3%. [Conclusion] For patients with calculous pyonephrosis in the non-acute infection phase, one-stage treatment using zero-pressure PCNL combined with hands-free pneumatic lithotripsy demonstrates good efficacy and safety.