ObjectiveTo investigate the effect and underlying mechanism of the Wulao Qisun prescription on pathological new bone formation in ankylosing spondylitis （AS）. MethodsSynovial fibroblasts were isolated from the hip joints of AS patients and observed under a microscope to assess cell morphology. The cells were identified using immunofluorescence staining. The isolated AS fibroblasts were divided into blank group， low drug-containing serum group， medium drug-containing serum group， high drug-containing serum group， and positive drug group. After drug intervention， cell proliferation was measured using the cell counting kit-8 （CCK-8） assay to observe fibroblast growth and determine the optimal intervention time. Alkaline phosphatase （ALP） activity was measured using the alkaline phosphatase assay. Protein expression of osteocalcin （OCN）， osteopontin （OPN）， and runt-related transcription factor 2 （Runx2） was detected by Western blot. The mRNA expression levels of Wnt5a， β-catenin， and Dickkopf-1 （DKK-1） were measured by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared with the blank group， each drug-containing serum group of Wulao Qisun prescription and the positive drug group inhibited the proliferation of AS fibroblasts and reduced ALP expression （P<0.01）. Compared with the blank group， the low drug-containing serum group of Wulao Qisun prescription downregulated β-catenin mRNA expression （P<0.05）. The medium and high drug-containing serum groups and the positive drug group significantly downregulated Wnt5a and β-catenin mRNA expression （P<0.05， P<0.01）， with the positive drug group showing the most pronounced effect （P<0.01）. The high drug-containing serum group and the positive drug group significantly upregulated DKK-1 mRNA expression （P<0.01）. Compared with the blank group， the low drug-containing serum group of Wulao Qisun prescription inhibited the expression of OPN and Runx2 proteins （P<0.05， P<0.01）， while the medium and high drug-containing serum groups and the positive drug group inhibited the expression of OCN， OPN， and Runx2 proteins （P<0.05， P<0.01）. ConclusionThe Wulao Qisun prescription can inhibit the proliferation and osteogenic differentiation of AS fibroblasts， thereby delaying the formation of pathological new bone in AS. The possible mechanism involves the regulation of Wnt/β-catenin-related gene expression， further inhibiting the transcription of downstream target genes.

Duodenum-preserving pancreatic head resection， also known as Beger surgery， has a high incidence rate of bile duct injury after surgery， while the treatment modality for bile duct injury depends on the severity of the injury， and endoscopic therapy is often challenging in case of severe bile duct injury. Recently a patient with biliary fistula after Beger surgery was admitted to Affiliated Hangzhou First People’s Hospital， Westlake University， and successful diagnosis and treatment were achieved through oral choledochoscopy-assisted percutaneous-endoscopic rendezvous technique.

Hydration status refers to the balance between the intake and discharge of water in the body. When the ingested and discharged water are roughly equal and the body is in water balance, it is the normal hydration status, and when the water intake is too little or too much, it is the "dehydration" or "overhydration status". The hydration status of the body not only affects metabolism, but also affects the functions of the urinary system, cardiovascular system, nervous system, etc. In order to further clarify the relationship between body hydration status and decompression sickness (DCS), this paper reviewed relevant studies and analyzed the interaction between hydration and decompression safety during diving. The primary causes of dehydration in diving are "hyperbaric diuresis", "immersion diuresis", breathing dry gas, heat, and cold. Dehydration not only promotes the occurrence of DCS but also reduces the aerobic work efficiency and athletic performance of divers, as well as affects cognition and mood. A study found that appropriate rehydration before and during diving can reduce the risk of DCS, which possibly associates with the increase of blood volume, plasma surface tension, and vasoconstriction. Fluid therapy is also important for those who already have DCS. This paper analyzed the amount, nature, timing, and effect of rehydration involved in the above links, comprehensively sorted out the relationship between hydration and diving safety, summarized the existing problems, and provided reference for practical application and future research.

Background and purpose:Deep learning methods can be used for automatic segmentation and detection of lymphocytes on pathological images.This study aimed to assess the performance of using variational autoencoding pre-training method for lymphocyte infiltration detection on pathological images,as well as the impact of removing tumor necrosis regions on model performance.Methods:Using variational autoencoding(VAE)pre-training method,pre-training was performed on a large number of unlabeled pathological images from the Cancer Genome Atlas(TCGA)database(TCGA-COAD and TCGA-READ)to obtain an auto-encoding pre-training model,and then a classifier model of lymphocyte infiltration was trained on the public data samples.To avoid confusion with necrotic regions,a Unet segmentation model for tumor necrotic regions was trained to remove the influence of tumor necrotic regions on lymphocyte identification.Results:The lymphocyte infiltration detection model pre-trained with the VAE model had an area under curve(AUC)of 0.979(95%CI:0.978-0.980),an accuracy of 92.5%(95%CI:92.3%-92.6%),a kappa value of 0.849,sensitivity of 0.908,specificity of 0.941,precision of 0.939,recall of 0.908,and F1 of 0.923 under the receiver operating characteristic(ROC)curve on the training set.The AUC for the validation set was 0.968(95%CI:0.964-0.972),the accuracy was 91.3%(95%CI:90.6%-92.0%),kappa value was 0.826,sensitivity was 0.898,specificity was 0.928,precision was 0.925,recall was 0.898,and F1 was 0.912.The results of Resnet18 model on the labeled dataset were as follows:accuracy of the validation set was 83.2%(95%CI:82.2%-84.1%),kappa value was 0.664,sensitivity was 0.823,specificity was 0.840,precision was 0.838,recall was 0.823 and F1 was 0.830.The Unet model that segmented the necrotic regions of the tumors had a final DICE of 0.78 for the training set,and 0.76 for the validation.After removing the necrotic region,the predictive performance of the pre-trained lymphocyte infiltration detection model using the VAE proposed in this article was improved to some extent,with the AUC on the validation set increasing from 0.968(95%CI:0.964-0.972)to 0.971(95%CI:0.968-0.975).The accuracy was 92.4%(95%CI:91.7%-93.0%),kappa value was 0.849,sensitivity was 0.928,specificity was 0.921,precision was 0.921,recall was 0.928,and F1 was 0.925.Conclusion:Using the variational autoencoding model pre-training method to classify the pathological pictures of lymphocyte infiltration can obtain better model performance compared with direct training,and removing the influence of tumor necrosis areas through Unet can further improve the performance of the model.

With the widespread application of diving technology, the safety of long-term diving has become a research focus. Research on the chronic health effects of long-term diving on divers mainly focuses on the respiratory system, circulatory system, nervous system, skeletal system, urinary system, as well as psychological health and sleep. Long-term diving can lead to increased lung capacity, thickening of nasal mucosa, myocardial hypertrophy, changes in heart rhythm, and hearing loss in divers. The impact of long-term diving on health is influenced by diving exposure index such as diving mode, maximum diving depth, underwater stay time, diving frequency, and number of dives, as well as individual factors such as years of diving experience, age, and medical history of divers. However, research on the effects of diving on health are inconsistent, and the potential mechanisms of health damage are unclear. Future large-scale research should be conducted under strict experimental conditions and with standardized inclusion criteria for subjects. Establishing a scientific and systematic assessment method for decompression is crucial for studying the chronic health effects of divers and enhancing understanding of relevant mechanisms to promote the development of diving industry and sport.

Objective To explore the prognostic impact of Qili Qiangxin capsules(QLQX)in patients with ST-segment elevation myocardial infarction(STEMI).Methods Retrospective collecting the clinical data of STEMI patients treated at PingAn Hospital affiliated to Hebei Medical University from January 2020 to January 2022,divided into QLQX group and non-QLQX group according to treatment plan.Follow-up patients for 1 year,with the main endpoint being major adverse cardiovascular and cerebrovascular events(MACCEs)at 30 d and 1 year;The secondary endpoints were cardiogenic death,myocardial reinfarction,emergency coronary revascularization,stroke,and major bleeding at 30 d and 1 year,as well as severe STEMI complications(30 d),re-admission due to heart failure(1 year),and all-cause mortality(1 year).Results A total of 210 STEMI patients were included(125 in the QLQX group and 85 in the non QLQX group).Univariate or Kaplan Meier analysis showed that the MACCE,cardiogenic death,malignant arrhythmia at 30 d,myocardial reinfarction,re-admission due to heart failure,and all-cause mortality rates in the QLQX group were significantly lower than those in the non QLQX group at 30 d and 1 year(P＜0.05),while there were no significant differences in the incidence of other observed endpoint events between the two groups(P＞0.05).In addition,QLQX may be a protective factor for MACCEs in STEMI patients(30 d:HR=0.157,95％CI 0.032 to 0.756,P=0.021;1 year:HR=0.208,95％CI 0.087 to 0.497,P=0.014).Conclusion QLQX adjuvant therapy may improve MACCEs in STEMI patients.

Objective:To investigate the value of CT imaging radiomics in predicting the therapeutic effect of extracorporeal shock wave lithotripsy (ESWL) for pancreatic duct stones.Methods:The clinical data of 167 patients with pancreatic duct stones treated with ESWL in the Department of Gastroenterology, the First People's Hospital of Hangzhou, Westlake University from July 2016 to January 2023 were retrospectively analyzed. Patients were divided into complete lithotripsy group (stone diameter ≤3 mm, n=94) and incomplete lithotripsy group (stone diameter>3 mm, n=73), according to the size of the largest residual stone after the first ESWL treatment. ITK SNAP software was used to delineate the images of pancreatic duct stones, and the artificial intelligence tool kit developed by United Shadow Company was used to extract the image radiomics characteristics. The pancreatic duct stone data set was randomly assigned into the training set ( n=118) and the test set ( n=29) in the ratio of 8∶2, and the absolute maximum normalization treatment was used, followed by peacekeeping selection through the minimum absolute contraction and selection operator (Lasso) to calculate the CT image radiomics score, and the logistic regression classifier was used to construct the ESWL treatment effect prediction model of pancreatic duct stones. Receiver operating characteristic curves (ROC) were plotted, and the area under the curve (AUC) and sensitivity, specificity, and accuracy were calculated to assess the performance of the prediction model. Decision curve analysis was used to evaluate the clinical value of CT radiomics score in the diagnosis of ESWL for pancreatic duct stones. Results:A total of 2 287 imaging radiomics characteristics were extracted, and 11 optimal imaging radiomics characteristics were finally screened by Lasso regression dimensionality reduction to establish a prediction model for ESWL treatment effect of pancreatic duct stones. The AUC values of the training set and the test set were 0.89 and 0.87, respectively, and the sensitivity, specificity, and accuracy were 82% and 79%, 82% and 82%, 82% and 80%, respectively. The AUC value in the independent validation set was 0.90, and the sensitivity, specificity, and accuracy were 78%, 90%, and 85%, respectively. The results of decision curve analysis showed that when the probability of ESWL efficacy in the diagnosis of pancreatic duct stones with CT image radiomics score was >0.05, the use of CT image radiomics score in the diagnosis of ESWL efficacy in pancreatic duct stones was more beneficial to patients in clinical practice than not.Conclusions:The treatment effect of ESWL for pancreatic duct stones can be predicted by CT imaging radiomics model.

The construction of experimental animal models plays an important supporting role in research into the mechanisms of action of Chinese medicines.There have been increasing reports of the construction and evaluation of animal models of spleen deficiency;however,the construction method have involved different standards and there has been insufficient objectification of the evaluation indexes.In this review,we summarize the construction and evaluation method of animal models of spleen deficiency from the aspects of animal selection,model establishment,macroscopic characterization,behavioral experiments,and objective indexes of spleen deficiency,with a view to providing theoretical guidance for the construction of experimental animal models of spleen deficiency and references for the selection of animal model platforms for spleen deficiency.

Objective This study aimed to develop an experimental animal platform for evaluating the feasibility and safety of intelligent acupuncture robots and to lay the foundation for further research.Methods Six 2-month-old Guangxi Bama miniature pigs were used as experimental subjects for acupuncture verification after anesthesia.First,manual acupuncture verification was carried out.Six acupoints were selected for each experimental animal and the needles were left for 20 min after the lifting,inserting,and twisting manipulation.Before and after controls were included.The experiment was carried out for 28 days,and each experiment was conducted once every 2 days for a total of 10 times.After verification of manual acupuncture,a point 10 mm from each of the six selected acupoints was selected,with a total of 12 points,and acupuncture operations were carried out on the experimental animals using the intelligent acupuncture module of the acupuncture robot at different frequencies and angles,to further verify the stability and feasibility of the animal platform.Results Routine safety-related blood indicators and blood biochemistry indicators after the procedure were normal and stable compared with those before the procedure.The average heart rate of the animals was 124 beats/min,the average blood pressure was 87/36 mmHg,and the average body temperature of was 36℃at a room temperature of 25℃,with no significant change in body temperature during and after the experiment.On the basis of this experimental platform,acupuncture manipulation using the intelligent acupuncture module of the acupuncture robot was completed successfully,with no abnormalities related to acupuncture such as bending,breaking,or stagnation of needles during the experimental process,and the experimental animals showed no obvious abnormalities.Conclusions This study established a stable experimental animal platform for evaluating the feasibility and safety of acupuncture carried out by intelligent acupuncture robots,based on the existing experimental method of miniature pigs.These result lay a foundation for further research related to the use of intelligent acupuncture robots.

Objective:To explore the efficacy and safety of whole-brain low-dose radiotherapy(LDRT)combined with PD-1 inhibitor sin-tilimab and intrathecal pemetrexed(IP)for the treatment of refractory non-small cell lung cancer(NSCLC)with leptomeningeal metastases(LM).Methods:Retrospective analysies were was performed on eight NSCLC patients with LM at the West China Hospital of Sichuan Uni-versity from December 2022 to May 2024.Among the eight patients,there were four were males and four were females,with a median age of 49 years(rangeing,between 34 to 58 years).All patients were treated with whole-brain LDRT combined with immune checkpoint inhibit-or(ICI)and intrathecal chemotherapy regimens,and the therapeutic efficacy was evaluated according to the Response Assessment in Neuro-Oncology(RANO)criteria and the Karnofsky physical status(KPS)score.Adverse reactions were assessed according to the Common Criteria for the Evaluation of Adverse Events(CTCAE version 5.0).Survival analysis was performed using the Kaplan-Meier method.The classification proportion of cerebrospinal fluid subsets before and after treatment was analyzed using by single-cell sequencing,and the differential ana-lysis of gene expression in parallel cells was performed.Results:The best clinical treatment effects in eight patients were were evaluated us-ing the RANO criteria:five patients(62.5%)were evaluated as improved and three(37.5%)as stable.The median KPS score of the eight pa-tients was 30(20-50)before treatment,which was significantly improved to 60(40-90)after treatment(P=0.000 9).The remission rate of neurological symptoms was 100%(8/8)in eight patients.The median neurological progression-free survival(NPFS)was 12 months.The res-ults of single-cell sequencing in CSF of patientss(P1)showed that the proportion of T cells in the patient samples after whole-brain LDRT treatment was significantly higher than that before treatment(6.08%vs.68.87%),and the proportion of tumor cells was significantly lower(12.92%vs.0.6%).The differential analysis of gene expression showed that CCL5 and CXCL13 were significantly upregulated in T cells of CSF after WB-LDRT treatment.Conclusions:The combination of whole-brain LDRT with ICI and IP in the treatment of NSCLC with LM can signific-antly alleviate neurological symptoms,improve quality of life and prolong the NPFS of patients,which is a safe and effective treatment.