ObjectiveBased on modern analytical techniques and a depressed mouse model established by chronic unpredictable mild stress（CUMS）， to evaluate the quality marker（Q-Marker） and pharmacodynamic difference of Baihe Dihuangtang prepared by different processes. MethodsHigh performance liquid chromatography（HPLC） was used to establish the characteristic profiles of Baihe Dihuangtang， and determine the content of Q-Marker in the samples prepared by ancient and modern processes. Seventy C57BL/6J mice were randomly divided into the normal group， model group， fluoxetine group（3 mg·kg^-1）， low and high dose groups of ancient process（6.5， 26 g·kg^-1）， and low and high dose groups of modern process（6.5， 26 g·kg^-1）， with 10 mice in each group. Except for the normal group， CUMS was used to induce depression in mice from the other groups for 28 d. After successful modeling， administration groups were given the corresponding drugs by gavage every day， and the normal and model groups were given an equal volume of pure water by gavage for 21 consecutive days. Change in body mass of mice was recorded， tail suspension test and open field test were used to evaluate the depressive behavior of mice， and enzyme-linked immunosorbent assay（ELISA） was employed to determine the contents of tumor necrosis factor-α（TNF-α）， interleukin（IL）-1β and IL-6 in serum. ResultsCharacteristic profiles of Baihe Dihuangtang prepared by the two processes were established， the similarity between the two was 0.951， and 8 characteristic peaks were recognized with the reference peak of regaloside A. The results of quantitative analysis showed that the Q-Marker content was similar in Baihe Dihuangtang prepared by ancient and modern processes. The results of pharmacodynamics showed that， compared with the normal group， the model group showed increased immobility time in the tail suspension test， reduced total movement distance in the open field test， and elevated IL-1β， IL-6 and TNF-α levels in the serum（P<0.01）. Compared with the model group， the behavioral indicators of mice in the Baihe Dihuangtang treatment group were significantly improved in terms of tail suspension time and open field exercise， and the levels of IL-1β， IL-6 and TNF-α in serum were significantly reduced（P<0.05， P<0.01）. Baihe Dihuangtang prepared by the two processes both had antidepressant effects， and the difference between the two was not statistically significant in improving depressive symptoms. ConclusionQ-Marker of Baihe Dihuangtang prepared by modern and ancient methods are equivalent in content， and the pharmacological effects are consistent， indicating that dried Lilii Bulbus can replace fresh products in the preparation of Baihe Dihuangtang. This study provides a scientific basis for the development of new drugs of Baihe Dihuangtang and a reference for its rational application and clinical use.

ObjectiveBased on modern analytical techniques and a depressed mouse model established by chronic unpredictable mild stress（CUMS）， to evaluate the quality marker（Q-Marker） and pharmacodynamic difference of Baihe Dihuangtang prepared by different processes. MethodsHigh performance liquid chromatography（HPLC） was used to establish the characteristic profiles of Baihe Dihuangtang， and determine the content of Q-Marker in the samples prepared by ancient and modern processes. Seventy C57BL/6J mice were randomly divided into the normal group， model group， fluoxetine group（3 mg·kg^-1）， low and high dose groups of ancient process（6.5， 26 g·kg^-1）， and low and high dose groups of modern process（6.5， 26 g·kg^-1）， with 10 mice in each group. Except for the normal group， CUMS was used to induce depression in mice from the other groups for 28 d. After successful modeling， administration groups were given the corresponding drugs by gavage every day， and the normal and model groups were given an equal volume of pure water by gavage for 21 consecutive days. Change in body mass of mice was recorded， tail suspension test and open field test were used to evaluate the depressive behavior of mice， and enzyme-linked immunosorbent assay（ELISA） was employed to determine the contents of tumor necrosis factor-α（TNF-α）， interleukin（IL）-1β and IL-6 in serum. ResultsCharacteristic profiles of Baihe Dihuangtang prepared by the two processes were established， the similarity between the two was 0.951， and 8 characteristic peaks were recognized with the reference peak of regaloside A. The results of quantitative analysis showed that the Q-Marker content was similar in Baihe Dihuangtang prepared by ancient and modern processes. The results of pharmacodynamics showed that， compared with the normal group， the model group showed increased immobility time in the tail suspension test， reduced total movement distance in the open field test， and elevated IL-1β， IL-6 and TNF-α levels in the serum（P<0.01）. Compared with the model group， the behavioral indicators of mice in the Baihe Dihuangtang treatment group were significantly improved in terms of tail suspension time and open field exercise， and the levels of IL-1β， IL-6 and TNF-α in serum were significantly reduced（P<0.05， P<0.01）. Baihe Dihuangtang prepared by the two processes both had antidepressant effects， and the difference between the two was not statistically significant in improving depressive symptoms. ConclusionQ-Marker of Baihe Dihuangtang prepared by modern and ancient methods are equivalent in content， and the pharmacological effects are consistent， indicating that dried Lilii Bulbus can replace fresh products in the preparation of Baihe Dihuangtang. This study provides a scientific basis for the development of new drugs of Baihe Dihuangtang and a reference for its rational application and clinical use.

Targeting drug delivery systems mediated by nanoparticles has shown great potential in the diagnosis and treatment of cancer. However, influences of different tumor progressions on the accumulation of nanoparticles, especially the ligand-modified active targeting nanoparticles are seldom exploited. In this work, the accumulation and penetration of RGD-modified gold nanoparticles (active AuNPs) with different sizes were investigated in orthotopic breast cancer with different tumor progressions. The results showed that the smallest active AuNPs had better accumulation and permeation effects in early tumor tissues with the relatively looser extracellular matrix, larger gaps, lower interstitial fluid pressure, and less receptor expression, which was due to size effects. However, the larger active AuNPs had better accumulation and penetration effects in late tumor tissues with highly expressed target receptors integrin α _v β ₃ because of the multivalent interactions between larger active nanoparticles and integrin α _v β ₃. In the midterm, tumor accumulation of active AuNPs was equally influenced by size effects and multivalent interactions. Therefore, RGD-modified nanoparticles with sizes of 7 and 90 nm accumulated more in tumors. This study will guide a rational design of active targeting nanoparticles for enhancing the diagnosis and treatment of tumors based on their progressions.

Gastrointestinal (GI) cancers are a leading cause of cancer morbidity and mortality worldwide. Despite advances in treatment, cancer relapse remains a significant challenge, necessitating novel therapeutic strategies. In this study, we engineered nanobody-based chimeric antigen receptor (CAR) natural killer (NK) cells targeting cadherin 17 (CDH17) for the treatment of GI tumors. In addition, to enhance the efficacy of CAR-NK cells, we also incorporated CV1, a CD47-SIRPα axis inhibitor, to evaluate the anti-tumor effect of this combination. We found that CDH17-CAR-NK cells effectively eliminated GI cancers cells in a CDH17-dependent manner. CDH17-CAR-NK cells also exhibit potent in vivo anti-tumor effects in cancer cell-derived xenograft and patient-derived xenograft mouse models. Additionally, the anti-tumor activity of CDH17-CAR-NK cells is synergistically enhanced by CD47-signal regulatory protein α (SIRPα) axis inhibitor CV1, likely through augmented macrophages activation and an increase in M1-phenotype macrophages in the tumor microenvironment. Collectively, our findings suggest that CDH17-targeting CAR-NK cells are a promising strategy for GI cancers. The combination of CDH17-CAR-NK cells with CV1 emerges as a potential combinatorial approach to overcome the limitations of CAR-NK therapy. Further investigations are warranted to speed up the clinical translation of these findings.

Objective To compare the predictive value of controlling nutritional status score(CO-NUT),prognostic nutritional index(PNI)and prognostic inflammation and nutritional index(PINI)for se-vere stroke complicating lung infection(SCLI),and to analyze the risk factors for severe SCLI occurrence.Methods A retrospective analysis on the clinical data of 98 cases of severe stroke firstly visited and treated in the nervous intensive care unit(NICU)of this hospital from August 2022 to August 2023 was performed.The patients were divided into the SCLI group and non-SCLI group according to whether or not SCLI occurring during the hospitalization.Logistic regression was used to analyze the independent risk factors influencing se-vere SCLI.The sensitivity,specificity,Youden index and Kappa value of the three tools in predicting severe SCLI were calculated,and the area under the receiver operating characteristic(ROC)curve(AUC)was plot-ted.Results Among 98 cases,there were 35 cases(35.71％)of SCLI occurrence during hospitalization.The multivariate logistic regression analysis results showed that the mechanical ventilation use(OR=1.33,95％CI:1.06-2.76),nasogastric tube use(OR=1.42,95％CI:1.25-2.68),high CONUT(OR=2.74),95％CI:2.02-3.69),low PNI(OR=0.70,95％CI:0.51-0.96)and low PINI(OR=2.51,95％CI:1.78-3.62)were the independent risk factors for severe SCLI(P＜0.05).AUC of the ROC curve of CONUT,PNI and PINI for predicting SCLI was 0.729,0.723 and 0.697 respectively.The sensitivity was 0.707,0.685 and 0.631,and the specificity was 0.872,0.764 and 0.712,respectively.The Youden index was 0.579,0.449 and 0.343 respectively,and the Kappa value was 0.621,0.534 and 0.432 respectively.Conclusion CONUT,PNI and PINI all are correlated with the SCLI risk.CONUT has the highest predictive value for SCLI.

Objective To compare the detection rates of X-ray,ultrasound,computed tomography(CT)and cone beam CT(CBCT)for submandibular gland calculi in different positions,and to explore the auxiliary value of 3-dimensional visualization technology in diagnosis and treatment of submandibular gland calculi.Methods The X-ray,ultrasound,CT and CBCT examination data of 113 patients with submandibular gland calculi at General Hospital of Ningxia Medical University from Nov.2014 to Mar.2021 were retrospectively analyzed.The detection rates and overall detection rates of the 4 imaging methods for calculi in different positions were compared.Mimics 19.0 software and CBCT data were used for 3D reconstruction imaging,visually displaying the location,size,morphology,and number of calculi from a visual perspective.Results There was no significant difference in the total detection rate of submandibular gland calculi between CBCT and CT(98.2％[111/113]vs 95.6％[108/113],P＞0.05),but both were significantly higher than that of X-ray(65.5％,74/113)and ultrasound(73.5％,83/113).The detection rates of ultrasound for calculi in the anterior and middle ducts were the lowest(63.6％[21/33]and 72.2％[26/36],respectively),which were significantly different from those of CBCT(97.0％[32/33]and 100.0％[36/36],respectively)and CT(93.9％[31/33]and 97.2％[35/36],respectively)(all P＜0.05).The detection rate of X-ray for calculi in the posterior duct was significantly lower than that of ultrasound,CBCT,and CT(40.9％[18/44]vs 81.8％[36/44],97.7％[43/44],and 95.5％[42/44],all P＜0.01).After CBCT data were imported into Mimics 19.0 software,submandibular gland calculi with different sizes,shapes,or numbers were successfully visualized and reconstructed.The reconstructed image was clear,and anatomical position relationship between the calculi and the mandible was visualized.Conclusion CBCT has good application value in the diagnosis of submandibular gland calculi and can replace traditional CT for the diagnosis of sialolithiasis.Clinically,CBCT examination can be directly performed for accurate diagnosis of calculi in the posterior duct which are not detected by double coincidence diagnosis but are indicated by ultrasound.For calculi in the anterior and middle ducts,X-ray and CBCT are preferred.Visualization technology helps clinical patient education and the development of personalized preoperative treatment plans.

Palliative and hospice care is an emerging medical care model for the development of modern medicine,and its emergence is not only a sign of social demand and the development of human civilization,but also an important manifestation of the change in the modern medical model.Hospice care is the final stage of palliative care,which is of great significance for the end-of-life treatment of incurable diseases.Palliative and hospice care has become an independent discipline in many countries,and its development has been rapid.However,the develop-ment of hospice and palliative care in China is not satisfactory,and the lack of money and human resources are the main reasons limiting its development.Many scholars have carried out a lot of useful practices in this regard.How to explore a road of hospice and palliative care development suitable for China′s national conditions is an urgent problem to be solved.By reviewing domestic and foreign literature,this paper summarizes the development mode and payment method of palliative and hospice care abroad,identifies the challenges encountered in the practice of hospice care in China,and draws on the development experience of palliative and hospice care in foreign countries.We aimed to identify pain points and difficulties faced in developing palliative and hospice care in China,so as to better serve patients at the end of life,gradually promote the concept of palliative and hospice care,and contribute to the sustainable development of palliative and hospice care in China.

Objective To explore the effects of electromagnetic field(EMF)on thechange of Ca2+ in osteolbast from the qualitative and quantitative perspectives,and try to identify the role of Ca2+in EMF regulation on osteoblast proliferation and differentiation.Methods A platform was established for generating sine EMF with a frequency of 38.7 Hz and a strength of 1.5 mT.The MC3T3-E1 osteoblasts were randomly divided into control group and experimental group(EMF intervention for 8 h per day).CCK8 was used to detect osteoblast proliferation,ALP staining to detect osteoblast differentiation,and Ca2+fluorescence probes and flow cytometer to detect the Ca2+concentration in osteoblasts.Results CCK8 result showed that EMF intervention for 48,72,96 and 120 h could significantly promote osteoblast proliferation.After 14 days of EMF intervention,the positive expression of ALP was significantly higher in EMF group than in control group.Ca2+fluorescent staining and flow cytometry results revealed that EMF intervention could increase the Ca2+in osteoblasts.Conclusion The EMF-induced upregulation of Ca2+ signal in osteoblasts may be closely related to the promotions of osteoblast proliferation and differentiation by EMF,but which Ca2+-related biosignaling pathways are involved in the EMF promoting osteoblast proliferation and differentiation remains to be further investigated.

Baihe Dihuangtang is a famous classical formula that has been respected by physicians in the past and is still used today. It was first recorded in ZHANG Zhongjing's Synopsis of the Golden Chamber， and is composed of Lilii Bulbus and Rehmanniae Radix juice. This paper systematically reviewed the research progress of historical evolution， pharmacological activities and clinical applications of Baihe Dihuangtang in recent years， and found that there was no major changes in the composition， decoction method and indications of this formula since the Han dynasty. According to the herbal textual research， the fleshy scaly leaves of Lilium brownii var. viridulum should be selected for Lilii Bulbus in this formula， and the tuberous roots of Rehmannia glutinosa were selected for Rehmanniae Radix. According to the dosage conversion of ancient and modern times， the dosage is 245 g of fresh Lilii Bulbus and 400 g of fresh Rehmanniae Radix， and the ratio of their juice is 1∶1. Its efficacy is to nourish Yin and clear heat， and to tonify the heart and lungs， which is used to treat the heart and lung Yin deficiency syndrome of lily disease. Modern pharmacological studies have shown that the research on the pharmacological effects of Baihe Dihuangtang mainly focuses on anti-depressant， anti-anxiety， improving insomnia and regulating metabolism， and it is mostly used clinically for neurological disorders such as depression， anxiety and insomnia. The quality marker（Q-Marker） of Baihe Dihuangtang were predicted according to the principles of ingredient specificity， component validity， component measurability， formula compatibility， and quality transmissibility and traceability， and it was determined that catalpol， rhmannioside D， regaloside A， regaloside B， regaloside C， and acteoside could be selected as potential Q-Markers of Baihe Dihuangtang， which could provide scientific reference for the establishment of the quality control system and the development of compound preparation of this famous classical formula.

Objective To analyze the clinical efficacy of transcatheter tricuspid valve replacement (TTVR) in cardiac implantable electronic lead-related tricuspid regurgitation (TR). Methods The patients with severe TR who underwent LuX-Valve TTVR in 9 Chinese medical centers from June 2020 to August 2021 were retrospectively enrolled. They were divided into a cardiac implantable electronic device (CIED) group and a non-CIED group based on whether they had pre-existing CIED implantation. Success of the procedure was defined as safe implantation of the LuX-Valve and complete withdrawal of the delivery system. Prognostic improvement was defined as a decrease of TR grade to≤2+ and an improvement of cardiac function by≥2 grades. Surgical success and postoperative prognosis were compared between the two groups. Results A total of 190 patients were collected, including 50 males and 140 females with a mean age of 66.2±7.8 years. There were 29 patients in the CIED group, and 161 patients in the non-CIED group. In the CIED group, 28 patients were implanted with a permanent pacemaker and 1 patient with a cardioverter-defibrillator. Preoperative New York Heart Association (NYHA) cardiac function class, TR degree, left ventricular ejection fraction, tricuspid annular plane systolic excusion, and cardiac risk scores were comparable between the two groups (P>0.05). Postoperative TR was reduced to≤2+ in all patients, and there was no statistical difference in the incidence of perivalvular leakage between the two groups (P=0.270). Postoperative CT of CIED patients showed the valve was in place, and the lead was not extruded, twisted, or deflected. The in-hospital mortality of the two groups were 10.3% and 1.9%, respectively, and the difference was statistically significant (P=0.047). In addition, there was no statistical difference between the two groups in terms of postoperative improvement of cardiac function and mortality in the 1- and 2-year follow-up. Conclusion TTVR is feasible, safe, and effective in patients with CIED implantation, and the pre-existing lead has no significant effect on the clinical efficacy.