AIM To establish the HPLC fingerprints for Tanacetum tatsienense(Bureau & Franchet)K.Bremer & Humphries and to determine the contents of chlorogenic acid,quercetin-3-O-glucoside,luteolin-7-O-glucoside,luteolin-7-O-glucuronide,apigenin-7-O-glucuronide,luteolin and apigenin.METHODS The analysis was performed on a 35 ℃ thermostatic Agilent ZORBAX Extend C18 column(4.6 mm×250 mm,0.5 μm),with the mobile phase comprising of 0.5％phosphoric acid-acetonitrile flowing at 1.0 mL/min,and the detection wavelength was set at 350 nm.Subsequently,principal component analysis,partial least squares discriminant analysis and cluster analysis were carried out.RESULTS There were twelve common peaks in the fingerprints for fourteen batches of samples with the similarities of 0.761-0.975.Seven constituents showed good linear relationships within their own ranges(R2≥0.999 1),whose average recoveries were 84.00％-105.11％with the RSDs of 1.28％-2.86％.Various batches of samples were clustered into three types,and seven differential constituents were observable,containing peaks 4(luteolin-7-O-glucoside),12(apigenin),9(apigenin-7-O-glucuronide),8,11(luteolin),5(luteolin-7-O-glucuronide)and 2.CONCLUSION This precise,stable,specific and reproducible method can be used for the quality control of T.tatsienense.

With the development of small-molecule immunotherapy drugs, its combination with the programmed cell death ligand 1/programmed cell death protein 1 (PD-L1/PD-1) antibodies would provide a new opportunity for cancer treatment. Therefore, targeting PD-L1/PD-1 axis by small-molecule drug is an attractive approach to enhance antitumor immunity and considered as the next generation of tumor immunotherapy. In the present study, we investigated the anti-tumor role of salvianolic acid B (SAB) by regulating the PD-L1 level in tumors. Changes of total PD-L1 and membrane PD-L1 levels were determined by Western blot, flow cytometry and PD-1/PD-L1 interaction assays. The expression of mRNA level of PD-L1 was detected by real-time PCR. The cytotoxicity of activated peripheral blood mononuclear cell (PBMC) cells toward co-cultured tumor cells was measured by cell impedance assay and crystal violet experiment. Surface plasma resonance technique was used to analyze the direct interaction between SAB and ubiquitin carboxyl-terminal hydrolase 2 (USP2). The antitumor effect of SAB in vivo was examined by C57BL/6 mice bearing MC38 xenograft tumor (all animal experiments were conducted in accordance with the Animal Ethics Committee of the Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences). Western blot and flow cytometry assay showed that SAB can significantly downregulate the abundance of PD-L1 in RKO and PC3 cells in dose- and time-dependent manner. PD-1/PD-L1 binding assay revealed that SAB reduces the binding of tumor cells to recombinant PD-1 protein. Mechanism studies revealed that SAB can bind directly to USP2 protein and inhibit its activity, thus promote the ubiquitin-proteasome pathway degradation of PD-L1 proteins. In addition, Cell impedance and crystal violet staining indicated that SAB enhances the killing activity of co-cultured PBMC cells toward tumor cells. MC38 tumor transplanted mouse experiments revealed that SAB treatment displayed significant suppression in the growth of MC38 tumor xenografts in C57BL/6 mice with an inhibition rate of 63.2% at 20 mg·kg^-1. Our results demonstrate that SAB exerts its anti-tumor activity by direct binding and inhibiting the activity of USP2 and reducing the PD-L1 level. Our study provides an important material basis and scientific basis for the potential application of SAB in tumor immunotherapy drug targeting USP2-PD-L1 axis.

Objective: To explore the molecular features of chronic myelomonocytic leukemia (CMML) . Methods: According to 2022 World Health Organization (WHO 2022) classification, 113 CMML patients and 840 myelodysplastic syndrome (MDS) patients from March 2016 to October 2021 were reclassified, and the clinical and molecular features of CMML patients were analyzed. Results: Among 113 CMML patients, 23 (20.4%) were re-diagnosed as acute myeloid leukemia (AML), including 18 AML with NPM1 mutation, 3 AML with KMT2A rearrangement, and 2 AML with MECOM rearrangement. The remaining 90 patients met the WHO 2022 CMML criteria. In addition, 19 of 840 (2.3%) MDS patients met the WHO 2022 CMML criteria. At least one gene mutation was detected in 99% of CMML patients, and the median number of mutations was 4. The genes with mutation frequency ≥ 10% were: ASXL1 (48%), NRAS (34%), RUNX1 (33%), TET2 (28%), U2AF1 (23%), SRSF2 (21.1%), SETBP1 (20%), KRAS (17%), CBL (15.6%) and DNMT3A (11%). Paired analysis showed that SRSF2 was frequently co-mutated with ASXL1 (OR=4.129, 95% CI 1.481-11.510, Q=0.007) and TET2 (OR=5.276, 95% CI 1.979-14.065, Q=0.001). SRSF2 and TET2 frequently occurred in elderly (≥60 years) patients with myeloproliferative CMML (MP-CMML). U2AF1 mutations were often mutually exclusive with TET2 (OR=0.174, 95% CI 0.038-0.791, Q=0.024), and were common in younger (<60 years) patients with myelodysplastic CMML (MD-CMML). Compared with patients with absolute monocyte count (AMoC) ≥1×10(9)/L and <1×10(9)/L, the former had a higher median age of onset (60 years old vs 47 years old, P<0.001), white blood cell count (15.9×10(9)/L vs 4.4×10(9)/L, P<0.001), proportion of monocytes (21.5% vs 15%, P=0.001), and hemoglobin level (86 g/L vs 74 g/L, P=0.014). TET2 mutations (P=0.021) and SRSF2 mutations (P=0.011) were more common in patients with AMoC≥1×10(9)/L, whereas U2AF1 mutations (P<0.001) were more common in patients with AMoC<1×10(9)/L. There was no significant difference in the frequency of other gene mutations between the two groups. Conclusion: According to WHO 2022 classification, nearly 20% of CMML patients had AMoC<1×10(9)/L at the time of diagnosis, and MD-CMML and MP-CMML had different molecular features.
Humans ; Aged ; Middle Aged ; Leukemia, Myelomonocytic, Chronic/genetics* ; Prognosis ; Splicing Factor U2AF/genetics* ; Mutation ; Myelodysplastic Syndromes/genetics* ; Leukemia, Myeloid, Acute/genetics*

Objective: To explore the application and efficacy of paclitaxel liposome in the treatment of advanced breast cancer among Chinese population in the real world. Methods: The clinical characteristics of patients with advanced breast cancer who received paclitaxel liposome as salvage treatment from January 1, 2016 to August 31, 2019 in 11 hospitals were collected and retrospectively analyzed. The primary outcome was progression free survival (PFS), and the secondary outcome included objective response rate (ORR) and safety. The survival curve was drawn by Kaplan-Meier analysis and the Cox regression model were used for the multivariate analysis. Results: Among 647 patients with advanced breast cancer who received paclitaxel liposome, the first-line treatment accounted for 43.3% (280/647), the second-line treatment accounted for 27.7% (179/647), and the third-line and above treatment accounted for 29.1% (188/647). The median dose of first-line and second-line treatment was 260 mg per cycle, and 240 mg in third line and above treatment. The median period of paclitaxel liposome alone and combined chemotherapy or targeted therapy is 4 cycles and 6 cycles, respectively. In the whole group, 167 patients (25.8%) were treated with paclitaxel liposome combined with capecitabine±trastuzumab (TX±H), 123 patients (19.0%) were treated with paclitaxel liposome alone (T), and 119 patients (18.4%) were treated with paclitaxel liposome combined with platinum ± trastuzumab (TP±H), 108 patients (16.7%) were treated with paclitaxel liposome combined with trastuzumab ± pertuzumab (TH±P). The median PFS of first-line and second-line patients (5.5 and 5.5 months, respectively) were longer than that of patients treated with third line and above (4.9 months, P<0.05); The ORR of the first line, second line, third line and above patients were 46.7%, 36.8% and 28.2%, respectively. Multivariate analysis showed that event-free survival (EFS) and the number of treatment lines were independent prognostic factors for PFS. The common adverse events were myelosuppression, gastrointestinal reactions, hand foot syndrome and abnormal liver function. Conclusion: Paclitaxel liposomes is widely used and has promising efficacy in multi-subtype advanced breast cancer.
Humans ; Female ; Breast Neoplasms/chemically induced* ; Paclitaxel/adverse effects* ; Liposomes/therapeutic use* ; Retrospective Studies ; Treatment Outcome ; Trastuzumab/therapeutic use* ; Capecitabine/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/adverse effects*

Humans ; Comorbidity ; Diabetes Mellitus/genetics* ; East Asian People ; Hypertension/genetics* ; Hypertriglyceridemia/genetics* ; Obesity/genetics* ; Receptors, Calcitriol/genetics*

This study aimed to investigate the effect of Jiaotai Pills on protein expression in the hippocampus of the rat model of chronic unpredictable mild stress(CUMS)-induced depression by quantitative proteomics and explore the anti-depression mechanism of Jiaotai Pills. The SD rats were randomized into control, model, Jiaotai Pills, and fluoxetine groups(n=8). Other groups except the control group were subjected to CUMS modeling for 4 weeks. After 4 weeks of continuous administration, the changes of behavior and pathological morphology of the hippocampal tissue were observed. Proteins were extracted from the hippocampal tissue, and bioinformatics analysis was performed for the differentially expressed proteins(DEPs) identified by quantitative proteomics. Western blot was employed to verify the key DEPs. The results showed that Jiaotai Pills significantly alleviated the depression behaviors and hippocampal histopathological changes in the rat model of CUMS-induced depression. A total of 5 412 proteins were identified in the hippocampus of rats, including 65 DEPs between the control group and the model group and 35 DEPs between the Jiaotai Pills group and the model group. There were 16 DEPs with the same trend in the Jiaotai Pills group and the control group, which were mainly involved in sphingolipid, AMPK, and dopaminergic synapse signaling pathways. The Western blot results of Ppp2r2b, Cers1, and Ndufv3 in the hippocampus were consistent with the results of proteomics. In conclusion, Jiaotai Pills may play an anti-depression role by modulating the levels of Ppp2r2b, Cers1, Ndufv3 and other proteins and regulating sphingolipid, AMPK, and dopaminergic synapse signaling pathways.
Rats ; Animals ; Rats, Sprague-Dawley ; Depression/drug therapy* ; AMP-Activated Protein Kinases/metabolism* ; Proteomics ; Hippocampus ; Stress, Psychological/metabolism* ; Sphingolipids/metabolism* ; Disease Models, Animal ; Drugs, Chinese Herbal

OBJECTIVE: To assess the effect and safety of Reyanning Mixture (RYN) in treating asymptomatic or mild severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adolescents. METHODS: This is a prospective, open-label, randomized controlled trial. Patients aged 1-17 years and diagnosed with asymptomatic or mild coronavirus disease-2019 (COVID-19) were assigned to an intervention group (RYN plus standard care) and a control group (standard care) according to a randomization list. The primary outcomes were SARS-CoV-2 negative conversion time. Secondary outcomes included negative conversion rate on days 3 and 7, hospital length of stay, symptom relief rate, new-onset symptoms of asymptomatic infected patients, and progressive disease rate. The cycle threshold (Ct) values of ORF1ab or N genes were also tested. RESULTS: A total of 214 patients in the intervention group and 217 in the control group were analyzed. The SARS-CoV-2 negative conversion time was significantly shortened in the intervention group [5 days (interquartile range (IQR): 5-6) vs. 7 days (IQR: 6-7), P<0.01]. By days 3 and 7, the negative conversion rates were significantly higher in the intervention group (day 3: 32.7% vs. 21.2%, P=0.007; day 7: 75.2% vs. 60.8%, P=0.001). Ct values significantly increase on day 2 [ORF1ab gene: 35.62 (IQR: 29.17-45.00) vs. 34.22 (IQR: 28.41-39.41), P=0.03; N gene: 34.97 (IQR: 28.50-45.00) vs. 33.51 (IQR: 27.70-38.25), P=0.024] and day 3 [ORF1ab gene: 38.00 (IQR: 32.72-45.00) vs. 35.81 (IQR: 29.96-45.00), P=0.003; N gene: 37.16 (IQR: 32.01-45.00) vs. 35.26 (IQR: 29.09-45.00), P=0.01]. No significant difference was found in hospital length of stay between the two groups (P>0.05). Symptoms of cough were significantly improved (82.2% vs. 70.0%, P=0.02) and wheezing was significantly reduced (0.7% vs. 12.9%, P<0.01) in the intervention group compared with the control group. During the trial, no disease progression or serious adverse events were reported. CONCLUSION Adding RYN to standard care may be a safe and effective treatment for children with asymptomatic and mild SARS-CoV-2 infection. (Registration No. ChiCTR2200060292).

Objective:To explore our self-designed classification system of irreducible intertrochanteric fractures based on reduction stage and bone block position and to evaluate the reduction techniques guided by the classification system.Methods:A retrospective study was conducted to analyze the data of 115 patients with irreducible intertrochanteric fracture who had been admitted to Department of Orthopedics, Beijing Hospital from September 2014 to November 2022. There were 24 males and 91 females with a mean age of (80.9±11.0) years. The reduction for the fractures was divided into a diaphysis reduction stage (Phase Ⅰ) and a cortical reduction stage (Phase Ⅱ). Based on the relative positions of the intraoperative bone blocks, Phase Ⅰ was divided into an anterior and posterior interlocking type (Phase Ⅰa) and a distal bone block sinking displacement type (Phase Ⅰb) while Phase Ⅱ into a proximal lifting type (Phase Ⅱa), a posterior angulation type (Phase Ⅱb), a positive support type (Phase Ⅱc), and a negative support type (Phase Ⅱd). Depending on the difficulties encountered in different reduction stages, corresponding close reduction strategies (such as top rod support, percutaneous prying, and Joystick technique) were adopted to restore the proximal femoral neck shaft angle, anteversion angle, anterior medial cortex, and length of the affected limb before fixation with intramedullary nails. Recorded were the patient's surgical time, intraoperative bleeding, quality of postoperative reduction, fracture union time, and complications.Results:The surgical time for this group of patients was 70.0(60.0, 92.0) minutes, and the intraoperative blood loss 200.0 (170.0, 200.0) mL. According to the standards by Baumgaertner et al., the quality of postoperative reduction was evaluated as excellent in 103 cases and as good in 12 cases, with an excellent and good rate of 100.0% (115/115). Of the 115 patients, 86 were followed up for more than 6 months to reveal fracture union in all after a duration of 6.0 (4.0, 8.0) months. One patient died of an acute cardiovascular event in the hospital 5 days after surgery. Two patients lost their mobility within 3 months after surgery due to acute cerebral infarction. There was no internal fixation failure requiring secondary surgery or no incision infection.Conclusion:Guided by our self-designed classification system of irreducible intertrochanteric fractures based on the intraoperative reduction stage and the relative position of bone block, real time intraoperative fluoroscopy images can be used to effectively clarify the difficulty of fracture reduction in stages so that corresponding reduction strategies can be adopted, leading to fine clinical efficacy.

Objective:To establish a visualized nomogram which can predict the rate of 30-day complications in the elderly patients after hip fracture.Methods:A retrospective study was conducted to analyze the clinical data of 1,074 patients with hip fracture aged 60 years and over who had been admitted to Department of Orthopedics, Beijing Hospital from January 2010 to December 2017. There were 335 males and 739 females with an average age of (80.3±7.3) yeas, 529 intertrochanteric fractures of the femur (all fixed with intramedullary nails after closed reduction), and 545 femoral neck fractures (including 470 ones treated with artificial femoral head replacement and 75 ones treated with artificial total hip replacement). The duration between injury to operation was (6.2±3.7) d. After the complications within 30 days after surgery were recorded, the risk factors for postoperative complications were screened using the binary multi-factor logistic regression analysis. The visualized nomogram and calibration graph were established with the risk factors screened.Results:Of the 1,074 patients, 28.49% (306/1,074) suffered from 30-day complications. The multivariate regression analysis showed that age ( OR=1.050, 95% CI: 1.022 to 1.080, P=0.001), time from injury to surgery ( OR=1.043, 95% CI: 1.005 to 1.083, P=0.027), white blood cell count ( OR=1.093, 95% CI: 1.033 to 1.158, P=0.002), serum albumin level ( OR=0.930, 95% CI: 0.883 to 0.980, P=0.007), troponin I ( OR=195.983, 95% CI: 2.224 to 17,268.296, P=0.021), respiratory system comorbidities ( OR=2.020, 95% CI: 1.287 to 3.170, P=0.002),cardiovascular comorbidities ( OR=1.388, 95% CI: 1.098 to 1.754, P=0.006), and neurological system comorbidities ( OR=1.778, 95% CI: 1.346 to 2.349, P<0.001) were the risk factors for 30-day complications after surgery in elderly patients with hip fracture. Based on these risk factors, a nomogram was created, with an area under the curve of 0.714. The calibration graph showed that the incidence predicted was close to that measured. Conclusion:The present study has established a visualized nomogram which can predict the rate of 30-day complications in the elderly patients after hip fracture based on age, time from injury to surgery, white blood cell count, serum albumin levels, troponin I, and cardiovascular, respiratory and neurological complications.

Objective To investigate the clinical efficacy and safety of the Camrelizumab combined with Shenqi Fuzheng injection of advanced non-squamous non-small cell lung cancer(NSCLC).Methods Patients with advanced squamous NSCLC diagnosed and treated in the department of medical oncology of The First Affiliated Hospital of Xi'an Jiaotong University from January 2018 to January 2023 were selected as the study subjects,and all patients were treated with pemetrexed combined with carboplatin chemotherapy.On the basis of the chemotherapy regimen,patients were divided into the Camrelizumab group(treated with Carelizumab)and the Camrelizumab+SFI group(treated with Camrelizumab+SFI).The short-term and long-term efficacy were evaluated using objective response rate(ORR),disease control rate(DCR),progression free survival(PFS),and overall survival(OS).Survival data were analyzed using Kaplan-Meier method.The occurrence of side effects the adverse drug reactions was evaluated according to the common terminology standard for adverse events(CTCAE 4.03).Results A total of 95 patients with advanced NSCLC were included in this study.Among them,48 patients were in the Camrelizumab group,and 47 patients were in the Camrelizumab+SFI group.The ORR of advanced non-squamous NSCLC patients in the Camrelizumab+SFI group and Carolizumab group were 59.57％and 45.83％,respectively(x2=1.799,P=0.180),with DCR of 78.72％and 58.33％,respectively(x2=4.569,P=0.033).The median PFS(8.87 months vs.6.30 months,P=0.001 7)and median OS(9.13 months vs.7.73 months,P=0.037)of patients in the Camrelizumab+SFI group were significantly higher than those in the Camrelizumab group.In addition,there was no significant difference in the incidence of adverse reactions between two groups(P＞0.05).Conclusion Camrelizumab combined with Shenqi Fuzheng injection can improve the disease control rate and prolong the PFS and OS of patients with advanced non-squamous NSCLC.