Background::Although significant advances have been made in the treatment of multiple myeloma (MM), leading to unprecedented response and survival rates among patients, the majority eventually relapse, and a cure remains elusive. This situation is closely related to an incomplete understanding of the immune microenvironment, especially monocytes/macrophages in patients with treatment-na?ve MM. The aim of this study was to provide insight into the immune microenvironment, especially monocytes/macrophages, in patients with treatment-na?ve MM.Methods::This study used the single-cell RNA sequencing (scRNA-seq) data of both patients with MM and heathy donors to identify immune cells, including natural killer (NK) cells, T cells, dendritic cells (DCs), and monocytes/macrophages. Transcriptomic data and flow cytometry analysis of monocytes/macrophages were used to further examine the effect of monocytes/macrophages in treatment-na?ve MM patients.Results::A significant difference was observed between the bone marrow (BM) immune cells of the healthy controls and treatment-na?ve MM patients through scRNA-seq. It is noteworthy that, through an scRNA-seq data analysis, this study found that interferon (IFN)-induced NK/T cells, terminally differentiated effector memory (TEMRA) cells, T-helper cells characterized by expression of IFN-stimulated genes (ISG +Th cells), IFN-responding exhausted T cells, mannose receptor C-type 1 (MRC1) + DCs, IFN-responding DCs, MHCII + DCs, and immunosuppressive monocytes/macrophages were enriched in patients with treatment-na?ve MM. Significantly, transcriptomic data of monocytes/macrophages demonstrated that "don’t eat me" -related genes and IFN-induced genes increase in treatment-na?ve MM patients. Furthermore, scRNA-seq, transcriptomic data, and flow cytometry also showed an increased proportion of CD16 + monocytes/macrophages and expression level of CD16. Cell-cell communication analysis indicated that monocytes/macrophages, whose related important signaling pathways include migration inhibitory factor (MIF) and interleukin 16 (IL-16) signaling pathway, are key players in treatment-na?ve MM patients. Conclusions::Our findings provide a comprehensive and in-depth molecular characterization of BM immune cell census in MM patients, especially for monocytes/macrophages. Targeting macrophages may be a novel treatment strategy for patients with MM.

Bupleuri radix is the dried root of Bupleuri radix or narrow-leaved Bupleuri radix of the umbelliferae family,and it is the most commonly used traditional Chinese medicine,which was first published in Shennong's Classic of Materia Medica.It has a variety of pharmacological effects such as anti-inflammatory,antioxidant,hepatoprotective,antitumor,antidepressant,et al.In the modern study,the extract of Bupleuri radix mainly includes a variety of chemical components such as Bupleuri radix saponin,flavonoids and volatile oil.By reviewing the relevant literature at home and abroad,this paper summarizes the research progress on the chemical composition and pharmacological effects of Bupleuri radix,and points out the future research direction to provide a certain reference basis for the subsequent research.

Objective To explore the mechanism of immediate effect regulated by acupuncture on acupoints in patients with migraine without aura(MwoA)during the interictal period.Methods A total of 28 MwoA patients were enrolled and resting-state functional magnetic resonance imaging(rs-fMRI)were performed at baseline and after acupuncture for 30 minutes.Paired t test was used to compare the differences of regional homogeneity(ReHo)and voxel-mirrored homotopic connectivity(VMHC)between two groups.Additionally,the correlation between the changes of rs-fMRI indexes and clinical scores was analyzed.Results In MwoA patients after acupuncture for 30 minutes,the mean regional homogeneity(mReHo)was decreased in the right lingual gyrus and right cere-bellum and was increased in the right middle frontal gyrus,while the z transformation voxel-mirrored homotopic connectivity(zVMHC)was significantly decreased in the bilateral cuneus compared with baseline.There was no significant correlation between imaging data and clinical scales.Conclusion Patients with MwoA after acupuncture for 30 minutes show abnormal ReHo and VMHC in multiple brain regions,which suggest that the mechanism of immediate effect may act through regulating pain-related brain regions.

BACKGROUND:Ankylosing spondylitis is a chronic inflammatory disease with chronic rheumatic immunity.Soft tissue ossification and fusion and spinal stiffness can cause biomechanical changes. OBJECTIVE:To reconstruct the lumbar-sacral intervertebral disc in ankylosing spondylitis patients with lumbar kyphosis by finite element analysis,and to study the range of motion of each segment of T11-S1 and the biomechanical characteristics of annulus fibrosus and nucleus pulposus. METHODS:The imaging data were obtained from an ankylosing spondylitis patient with lumbar kyphosis.The original CT image data of continuously scanned spine were imported into Mimics 21.0 in DICOM format,and T11-S1 was reconstructed respectively.The established model was imported into 3-Matic software in the format of"Stl"to reconstruct the intervertebral disc,and the fibrous intervertebral disc model was obtained.The improved model was further imported into Hypermesh software,and the vertebra,nucleus pulposus,annulus fibrosus and ligament were mesh-divided.After the material properties were given,the model was imported into ABAQUS software to observe the range of motion of each vertebral body in seven different working conditions of T11-S1,and analyze the biomechanical characteristics of each segment of annulus fibrosus and nucleus pulposus. RESULTS AND CONCLUSION:(1)The range of motion of L1 vertebrae was higher than that of other vertebrae under six different working conditions:extension,forward flexion,rotation(left and right),and lateral flexion(left and right).The maximum range of motion was 2.18° during L1 vertebral flexion,and the minimum range of motion was 0.12° during L5 vertebral extension.(2)The annular fiber flexion at L2-L3 segments was greater than the extension(P<0.05),and the annular fiber flexion at L3-L4 and L4-L5 segments was less than the extension(P<0.05).The left rotation of L1-L2 annular fibers was greater than the right rotation(P<0.05).The left flexion of the annulus was greater than the right flexion in L1-L2,L2-L3,L3-L4,L4-L5 and L5-S1 segments(P<0.05).(3)The nucleus pulposus stresses of T11-L12,L1-L2,L2-L3,L3-L4 and L4-L5 segments in forward flexion were greater than in extension(P<0.05).The left rotation of T12-L1 and L3-L4 segments was smaller than the right rotation(P<0.05),and that of T11-T12,L1-L2,and L2-L3 segments was larger than the right rotation(P<0.05).The left flexion was larger than the right flexion in the T11-S1 segment.(4)It is concluded that in ankylosing spondylitis patients with lumbar kyphosis,the minimum range of motion of the vertebral body is located at the L5 vertebral body in extension.To prevent fractures,it is recommended to avoid exercise in the extension position.During the onset of lumbar kyphosis in patients with ankylosing spondylitis,the maximum stress of the annulus fibrosus and nucleus pulposus is located in the L1-L2 segment,which is fixed and will not alter with the change of body position.The late surgical treatment and correction of deformity should focus on releasing the pressure of the annulus fibrosus and nucleus pulposus in this segment to avoid the rupture of the annulus fibrosus and the injury of the nucleus pulposus.

AIM:To observe the effect of acupuncture on adenosine A1 receptor(A1R)in the caudate puta-men(CPu)of complete Freund's adjuvant(CFA)rats,and to explore the potential mechanism of acupuncture in treat-ment of inflammatory pain.METHODS:Sixty-four 6～8-week-old male Wistar rats were randomly divided into saline group,model group(CFA group),CFA+manual acupuncture(MA)group,CFA+solvent dimethyl sulfoxide(DMSO)group,CFA+A1R agonist 2-chloro-N6-cyclopentyladenosine(CCPA)group,CFA+A1R antagonist 8-cyclopentyl-1,3-di-propylxanthine(DPCPX)group,CFA+MA+DMSO group and CFA+MA+DPCPX group.In MA groups,on the 2nd day af-ter modeling,the rats were needled at Zusanli points on both sides,30 min at a time,once per day,for 7 d.Pain threshold of plantar thermal radiation was used to observe the pain response of the rats.The content of cyclic adenosine monophos-phate(cAMP)in the CPu was detected by ELISA.The protein expression and phosphorylation levels of protein kinase A(PKA)and cAMP response element-binding protein(CREB)were detected by Western blot.The expression of A1R in the CPu was detected by immunofluorescence staining.RESULTS:Compared with saline group,CFA modeling signifi-cantly lowered the thermal pain threshold of the rats(P<0.01).Compared with CFA group,the thermal pain threshold of the rats in CFA+MA group and CFA+CCPA group was significantly increased(P<0.05 or P<0.01).Compared with CFA+ MA+DMSO group,the thermal pain threshold of the rats in CFA+MA+DPCPX group was decreased(P<0.05).Compared with CFA group,A1R protein relative expression level and positive cells in the CPu of the rats in CFA+MA group were in-creased(P<0.05 or P<0.01).Compared with saline group,cAMP content and p-CREB protein level in the CPu of the rats in CFA+MA group were decreased(P<0.05).Compared with CFA+DMSO group,cAMP content and p-CREB pro-tein level in CFA+MA+DMSO and CFA+CCPA groups were significantly decreased(P<0.01).Compared with CFA+MA+ DMSO group,the levels of cAMP,p-PKA and p-CREB in CFA+MA+DPCPX group were significantly increased(P<0.05 or P<0.01).CONCLUSION:Acupuncture on bilateral Zusanli can relieve inflammatory pain in CFA rats,and its mech-anism may be related to A1R/cAMP/p-CREB signaling pathway.

Objective:To explore the role of mechanical hemodynamic support (MHS) in mapping and catheter ablation of patients with hemodynamically unstable ventricular tachycardia (VT), report single-center experience in a cohort of consecutive patients receiving VT ablation during MHS therapy, and provide evidence-based medical evidence for clinical practice.Methods:This was a retrospective cohort study. Patients with hemodynamically unstable VT who underwent catheter ablation with MHS at Beijing Anzhen Hospital, Capital Medical University between August 2021 and December 2023 were included. Patients were divided into rescue group and preventive group according to the purpose of treatment. Their demographic data, periprocedural details, and clinical outcomes were collected and analyzed.Results:A total of 15 patients with hemodynamically unstable VT were included (8 patients in the rescue group and 7 patients in the preventive group). The acute procedure was successful in all patients. One patient in the rescue group had surgical left ventricular assist device (LVAD) implantation, remaining 14 patients received extracorporeal membrane oxygenation (ECMO) for circulation support. ECMO decannulation was performed in 12 patients due to clinical and hemodynamic stability, of which 6 patients were decannulation immediately after surgery and the remaining patients were decannulation at 2.0 (2.5) d after surgery. Two patients in the rescue group died during the index admission due to refractory heart failure and cerebral hemorrhage. During a median follow-up of 30 d (1 d to 12 months), one patient with LVAD had one episode of ventricular fibrillation at 6 months after discharge, and no further episodes of ventricular fibrillation and/or VT occurred after treatment with antiarrhythmic drugs. No malignant ventricular arrhythmia occurred in the remaining 12 patients who were followed up.Conclusions:MHS contributes to the successful completion of mapping and catheter ablation in patients with hemodynamically unstable VT, providing desirable hemodynamic status for emergency and elective conditions.

Objective:To study the clinical characteristics of neonatal gastric perforation (NGP) and risk factors of mortality.Methods:From January, 2015 to December, 2021, clinical manifestations of neonates diagnosed with NGP in the Department of Neonatology and Neonatal Surgical Intensive Care Unit of our hospital were retrospectively analyzed. Neonates were assigned into the survival group and the death group according to their prognosis. Risk factors of mortality were analyzed using multivariate logistic regression method.Results:A total of 50 cases were enrolled, including 41 in the survival group and 9 in the death group. 38 cases were males, 34 were premature infants, 30 were low birth weight infants and 5 had history of asphyxia. The clinical manifestations included abdominal distension, tachypnea, cyanosis, poor response, fever, diminished bowel sound and redness of the abdominal wall. Abdominal X-ray indicated pneumoperitoneum. Laboratory abnormalities included leukocytosis, thrombocytopenia, elevated C-reactive protein and procalcitonin, decreased blood pH and increased lactic acid. 30 cases had perforation at the greater curvature of stomach. Perforation was larger than 3 cm in 40 cases and intestinal necrosis was identified in 14 cases. Some patients suffered from sepsis, respiratory failure, pulmonary hemorrhage, shock, coagulopathy and other related complications. The death group had significantly higher incidences of dyspnea, fever, elevated procalcitonin, blood pH<7.3, intestinal necrosis, time from onset of clinical manifestations to operation (Tm-o) >24 h and complications than the survival group ( P<0.05). Multivariate logistic regression analysis showed that pH<7.3 ( OR=9.755, 95% CI 1.363-69.800), Tm-o>24 h (OR=11.831, 95%CI 1.305-107.301), septic shock and sepsis ( OR=29.622, 95% CI 3.728-235.369) were risk factors of mortality. Conclusions:The main manifestations of NGP are abdominal distension and pneumoperitoneum. The risk factors of mortality in NGP are sepsis, blood pH<7.3 and Tm-o>24 h.

Objective:To develop and validate the models based on mixed enhanced computed tomography (CT) radiomics and deep learning features, and evaluate the efficacy for differentiating pancreatic adenosquamous carcinoma (PASC) from pancreatic ductal adenocarcinoma (PDAC) before surgery.Methods:The clinical data of 201 patients with surgically resected and histopathologically confirmed PASC (PASC group) and 332 patients with surgically resected histopathologically confirmed PDAC (PDAC group) who underwent enhanced CT within 1 month before surgery in the First Affiliated Hospital of Naval Medical University from January 2011 to December 2020 were retrospectively collected. The patients were chronologically divided into a training set (treated between January 2011 and January 2018, 156 patients with PASC and 241 patients with PDAC) and a validation set (treated between February 2018 and December 2020, 45 patients with PASC and 91 patients with PDAC) according to the international consensus on the predictive model. The nnU-Net model was used for pancreatic tumor automatic segmentation, the clinical and CT images were evaluated, and radiomics features and deep learning features during portal vein phase were extracted; then the features were dimensionally reduced and screened. Binary logistic analysis was performed to develop the clinical, radiomics and deep learning models in the training set. The models' performances were determined by area under the ROC curve (AUC), sensitivity, specificity, accuracy, and decision curve analysis (DCA).Results:Significant differences were observed in tumor size, ring-enhancement, upstream pancreatic parenchymal atrophy and cystic degeneration of tumor both in PASC and PDAC group in the training and validation set (all P value <0.05). The multivariable logistic regression analysis showed the tumor size, ring-enhancement, dilation of the common bile duct and upstream pancreatic parenchymal atrophy were associated with PASC significantly in the clinical model. The ring-enhancement, dilation of the common bile duct, upstream pancreatic parenchymal atrophy and radiomics score were associated with PASC significantly in the radiomics model. The ring-enhancement, upstream pancreatic parenchymal atrophy and deep learning score were associated with PASC significantly in the deep learning model. The diagnostic efficacy of the deep learning model was highest, and the AUC, sensitivity, specificity, and accuracy of the deep learning model was 0.86 (95% CI 0.82-0.90), 75.00%, 84.23%, and 80.60% and those of clinical and radiomics models were 0.81 (95% CI 0.76-0.85), 62.18%, 85.89%, 76.57% and 0.84 (95% CI 0.80-0.88), 73.08%, 82.16%, 78.59% in the training set. In the validation set, the area AUC, sensitivity, specificity, and accuracy of deep learning model were 0.78 (95% CI 0.67-0.84), 68.89%, 78.02% and 75.00%, those of clinical and radiomics were 0.72 (95% CI 0.63-0.81), 77.78%, 59.34%, 65.44% and 0.75 (95% CI 0.66-0.84), 86.67%, 56.04%, 66.18%. The DCA in the training and validation sets showed that if the threshold probabilities were >0.05 and >0.1, respectively, using the deep learning model to distinguish PASC from PDAC was more beneficial for the patients than the treat-all-patients as having PDAC scheme or the treat-all-patients as having PASC scheme. Conclusions:The deep learning model based on CT automatic image segmentation of pancreatic neoplasm could effectively differentiate PASC from PDAC, and provide a new non-invasive method for confirming PASC before surgery.

OBJECTIVE To investigate the improvement effect and mechanism of different extracts from Tylophora yunnanensis on non-alcoholic steatohepatitis （NASH）. METHODS Normal human liver LO2 cells were induced to steatosis by free fatty acid， then were divided into normal group， model group， silybin group （100 μmol/mL）， T. yunnanensis ethanol extracts （TYS） group （50 μg/mL）， T. yunnanensis ethyl acetate extracts （TYSA） group （50 μg/mL）， and T. yunnanensis n-butanol extracts （TYSB） group （50 μg/mL）. After 24 hours of drug intervention， the deposition of lipid droplets was observed in LO2 cells in each group. The contents of total cholesterol （TC）， triacylglycerol （TG）， malondialdehyde （MDA） and glutathione （GSH）， the activities of aspartate transaminase （AST）， alanine transaminase （ALT） and superoxide dismutase （SOD）， the mRNA expressions of Kelch-like ECH-associated protein 1（ Keap1）， nuclear factor E2-related factor 2（ Nrf2） and heme oxygenase 1（ HO- 1） were detected. NASH rat model was induced by a high-fat diet， and then divided into normal group， model group， silybin group （12.6 mg/kg）， TYS group （80 mg/kg）， TYSA group （80 mg/kg） and TYSB group （80 mg/kg）， with six rats in each group. The liver indexes of rats in each group were calculated after 6 weeks of drug intervention. The liver histopathological changes were observed， and the contents of TC， TG， HDL-C and LDL-C， AST and ALT activities in serum， the contents of MDA and GSH， SOD activities in liver tissue were detected. RESULTS Compared with model group， TYS， TYSA and TYSB could reduce lipid droplet deposition， intracellular TC， TG and MDA contents， AST and ALT activities， and increase SOD activity， GSH content， and Keap1， Nrf2， HO-1 mRNA expression levels in LO2 cells after steatosis to varying degrees， with some differences being statistically significant （P＜0.05）. They also significantly improved liver injury in NASH model rats， reduced their liver indexes， TC， TG， LDL-C and MDA contents， AST and ALT 1-042） activities， and increased HDL-C （except for TYS and TYSB）， GSH contents and SOD activity， with TYSA having the most significant effect （P＜0.05）. CONCLUSIONS TYS， TYSA and TYSB have a certain improvement effect on NASH， among which TYSA has the most obvious effect. Its mechanism of action may be related to upregulating the Keap1/Nrf2/HO-1 signaling pathway and inhibiting oxidative stress

OBJECTIVE To study the improvement effects of different polar parts fro m total f lavonoids of Scutellaria amoena on non-alcoholic fatty liver disease （NAFLD）model rats. METHODS The total flavonoids of S. amoena （SAF）were extracted by reflux extraction with ethanol ，suspended with water ，and then extracted with ethyl acetate and n-butanol in order to obtain the extraction parts of SAF （recorded as SAFA and SAFB respectively ）. Thirty-six rats were randomly divided into normal group （n＝ 6）and modeling group （n＝30）. Modeling group was given high-lipid diet to induce NAFLD model. After modeling ，modeling group was randomly divided into model group （normal saline ），fenofibrate group （positive control ，20 mg/kg），SAF group （300 mg/kg），SAFA group （300 mg/kg）and SAFB group （300 mg/kg）；they were given relevant intragastical administration ，once a day，for consecutive 6 weeks. After last administration ，the liver index was calculated ；the levels of total cholesterol （TC）， triacylglycerol（TG），aspartate transaminase （AST），alanine transaminase （ALT），high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C） in serum ，the levels of superoxide dismutase （SOD），glutathione peroxidase （GSH-Px），malondialdehyde（MDA），interleukin-1β（IL-1β），IL-6 and tumor necrosis factor-α（TNF-α）in liver tissue were detected；the pathomorphological changes of liver tissue were observed. RESULTS Compared with normal group ，the liver index ， the levels of TC ，TG，AST，ALT，LDL-C，MDA，IL-1β， IL-6 and TNF-α in serum/liver tissue of model group were all increased significantly （P＜0.05）， while the levels of HDL-C，SOD and GSH-Px were all decreased significantly （P＜0.05）. Compared with model group ，except there was no statistical significance in the serum levels of HDL-C and ALT in SAFA group （P＞0.05），above indexes in serum/liver tissue of rats in groups of polar parts from total flavonoids of S. amoena were significantly improved （P＜0.05）；inflammatory cell infiltration and fatty vacuoles in liver tissue were significantly improved. Compared with SAF group and SAFA group ，the levels of TC，TG，AST，MDA，IL-6 and TNF-α were decreased significantly in SAFB group（P＜0.05），while the level of SOD was increased significantly （P＜0.05）；pathomorphological changes of liver tissue were improved more significantly. CONCLUSIONS Each polar part from total flavonoids of S. amoena can improve NAFLD by regulating oxidative stress and inhibiting the secretion of inflammatory factors. The n-butanol polar part has more obvious effect .