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.

Objective To analyze the prevalence status of cardiometabolic risk factor (CMRF) and its aggregation among workers engaged in new forms of employment. Methods A total of 5 429 new employment workers (including couriers, online food delivery workers, and ride hailing drivers) who underwent health medical examinations at a tertiary hospital in Beijing City were selected as the research subjects using the judgment sampling method. Data on waist circumference, blood pressure, blood glucose, and blood lipid levels were collected to analyze their CMRF [central obesity, elevated blood pressure, elevated blood glucose, elevated triglycerides, and reduced high-density lipoprotein cholesterol (HDL-C)] and their aggregation (with ≥ 2 of the above 5 risk factors) status. Results The detection rates of central obesity, elevated blood pressure, elevated blood glucose, elevated triglycerides, and reduced HDL-C were 61.2%, 38.2%, 29.5%, 40.9% and 22.6%, respectively. The detection rates of CMRF aggregation was 57.8%. The result of multivariable logistic regression analysis showed that male, age ≥45 years, smoking, overweight, and obesity were risk factors for CMRF aggregation (all P<0.05). Conclusion The detection rate of CMRF and its aggregation among workers with new forms of employment in Beijing City is relatively high. Targeted prevention and control efforts should be strengthened for high-risk populations, especially males, workers aged ≥45 years, smokers, and those who are overweight or obese.

Objective This study investigated the regulatory effect of high mobility group protein B1 (HMGB1) in the peripheral blood of patients with primary immune thrombocytopenia (ITP) on myeloid dendritic cells (mDC) and Th17/regulatory T cells (Treg) balance. Methods The study enrolled 30 newly diagnosed ITP patients and 30 healthy controls.Flow cytometry was used to measure the proportion of mDC, Th17, and Treg cells in the peripheral blood of ITP patients and healthy controls. ELISA was conducted to quantify the serum levels of HMGB1, interleukin 6 (IL-6), IL-23, IL-17, and transforming growth factor β(TGF-β). The mRNA levels of retinoic acid-related orphan receptor γt(RORγt) and forehead box P3(FOXP3) were detected by real-time PCR. The correlation between the abovementioned cells, cytokines, and platelet count was assessed using Pearson linear correlation analysis. Results The proportion of Th17 cells and the expression levels of HMGB1, IL-6, IL-23, IL-17 and the level of RORγt mRNA in the peripheral blood of ITP patients were higher than those in healthy controls. However, the Treg cell proportion and TGF-β level were lower in ITP patients than those in healthy controls. In patients with ITP, the proportion of mDC and the level of FOXP3 mRNA did not show significant changes. The proportion of mDC cells was significantly correlated with the expression of IL-6 and IL-23. Moreover, the expression of HMGB1 showed a significant correlation with the expression of mDC, IL-6, IL-23, RORγt mRNA, and IL-17. Notably, both the proportion of mDC cells and the expression of HMGB1 were negatively correlated with platelet count. Conclusion The high expression of HMGB1 in peripheral blood of ITP patients may induce Th17/Treg imbalance by promoting the maturation of mDC and affecting the secretion of cytokines, thereby potentially playing a role in the immunological mechanism of ITP.
Humans ; Th17 Cells/cytology* ; HMGB1 Protein/genetics* ; T-Lymphocytes, Regulatory/cytology* ; Female ; Male ; Dendritic Cells/metabolism* ; Adult ; Middle Aged ; Purpura, Thrombocytopenic, Idiopathic/genetics* ; Nuclear Receptor Subfamily 1, Group F, Member 3/genetics* ; Young Adult ; Interleukin-23/blood* ; Interleukin-17/blood* ; Interleukin-6/blood* ; Forkhead Transcription Factors/genetics* ; Myeloid Cells/cytology* ; Aged

ObjectiveTo observe the efficacy and safety of Uyghur medicine Yangxin Dawayimixike Honey Paste （养心达瓦依米西克蜜膏， YDMHP） in the treatment of stable angina pectoris （SAP） of qi stagnation and blood stasis syndrome. MethodsA randomized ， double-blind， positive-controlled，multi-center clinical trial was conducted， in which 370 patients with SAP of qi stagnation and blood stasis syndrome were randomly divided into treatment group（279 cases）and control group（91cases）at a ratio of 3∶1. The treatment group was orally administered with YDMHP， 3 g each time， and placebo of Xuefu Zhuyu Capsule （血府逐瘀胶囊）， 2.4 g each time， while the control group was treated with Xuefu Zhuyu Capsule， 2.4 g each time， and placebo of YDMHP， 3 g each time， both twice a day for a course of 12 weeks. The primary outcome was the effect of angina pectoris symptom. The secondary outcomes include single angina symptom scores such as number of attacks， duration of attacks， pain intensity and usae of nitroglycerin scores， the total angina symptom score before and after the treatment， the usage of nitroglycerin， the exercise duration in treadmill exercise test （TET） and the Duck treadmill score among patients，the scores of Seattle Angina Questionnaire （SAQ） on five dimensions including physical limitations， anginal stability， anginal frequency， treatment satisfaction， and disease perception， and efficacy of TCM syndrome and of each single TCM symptom after treatment. The safety were evaluated by examine blood routine， urine routine， liver and kidney function， fasting blood sugar， electrocardiogram， adverse events. ResultsThe total effective rate of angina symptom in the treatment group was 71.69% （200/279）， significantly higher than 51.64% （47/91） in the control group （P＜0.01）. The curative and markedly effective rate of TCM syndrome in the treatment group was 53.05% （148/279）， which was significantly higher than 25.27% （23/91） in the control group （P＜0.01）. After treatment， scores of the number as well as duration of angina attacks and pain severity， the total score of angina symptoms， and the usage of nitroglycerin significantly decreased in both groups， and more changes were seen in the treatment group than in the control group； the scores of physical limitations， anginal stability， anginal frequency， treatment satisfaction， and disease perception in both groups significantly increased， and more improvement were shown in the experimental group regarding the anginal stability， anginal frequency and treatment satisfaction （P＜0.05 or P＜0.01）. The effects of chest pain， chest tightness， palpitation， shortness of breath and fatigue in experimental group were significantly higher than those in control group （P＜0.05 or P＜0.01）. There was no significant difference in the exercise duration of treadmill test and Duke score among patients between the two groups either before or after treatment （P＞0.05）. Adverse events occurred in 66 cases （23.66%） of the experimental group and 16 cases （17.58%） of the control group， with no statistical significance between the two groups （P＞0.05）. ConclusionThe Uyghur medicine YDMHP can effectively improve symptoms of angina pectoris， reduce the number， duration， and intensity of attacks， decrease the dosage of nitrogly-cerin and improve the individual TCM symptoms and has good safety in the treatment of SAP patients of qi stagnation and blood stasis.

Objective:To construct a remote screening network for breast cancer based on automated breast ultrasound (ABUS) and explore the value of ABUS with remote reading for breast cancer screening.Methods:We constructed a remote breast cancer screening network including one remote reading center and 48 image-acquisition centers. We recruited women to participate in breast cancer screening at one of these image-acquisition centers from January 2021 to January 2023. The technicians collected the whole breast images using the ABUS. The images were then sent to the reading center through the PVBUS System and interpreted independently by two radiologists using the Breast Imaging Reporting and Data System (BI-RADS). BI-RADS categories 1 and 2 indicate negative screening results, and women diagnosed with these categories were recommended for annual breast ultrasound screening. BI-RADS categories 3, 4, and 5 indicate positive results. Women with BI-RADS category 3 lesions were recommended for follow-up examinations every 6 months using ABUS or handheld ultrasound, while those with BI-RADS 4 and 5 lesions were suggested to undergo pathological examinations.Results:In our study, we enrolled 10 344 women who completed the ABUS screening and were followed up for more than 12 months. After remote reading, 6 164 women were diagnosed with BI-RADS category 1 and 2 626 woman were within BI-RADS category 2. In contrast, 1 404 women were within BI-RADS category 3, a total of 135 women were within BI-RADS category 4, and 15 women were within BI-RADS category 5. The positive screening rate of ABUS was 15.0% (1 554/10 344). The ABUS with remote reading had a detection rate of 3.7/1 000 (38/10 344) for breast cancer screening, with a sensitivity of 97.4% (38/39) and a specificity of 85.3% (8 789/10 305). Among the 38 breast cancer cases detected, 92.1% (35/38) were invasive carcinomas, and 63.2% (24/38) were stage 0 or Ⅰ breast cancers.Conclusions:Breast cancer screening based on ABUS with remote reading provided an efficient and feasible solution to the problem of unevenly distributed medical resources and medical staff levels in various regions of China, enabling the decentralization of high-quality medical resources and improving the accessibility of high-quality screening services. It has provided an alternative for breast cancer screening in China.

Objective:To construct a remote screening network for breast cancer based on automated breast ultrasound (ABUS) and explore the value of ABUS with remote reading for breast cancer screening.Methods:We constructed a remote breast cancer screening network including one remote reading center and 48 image-acquisition centers. We recruited women to participate in breast cancer screening at one of these image-acquisition centers from January 2021 to January 2023. The technicians collected the whole breast images using the ABUS. The images were then sent to the reading center through the PVBUS System and interpreted independently by two radiologists using the Breast Imaging Reporting and Data System (BI-RADS). BI-RADS categories 1 and 2 indicate negative screening results, and women diagnosed with these categories were recommended for annual breast ultrasound screening. BI-RADS categories 3, 4, and 5 indicate positive results. Women with BI-RADS category 3 lesions were recommended for follow-up examinations every 6 months using ABUS or handheld ultrasound, while those with BI-RADS 4 and 5 lesions were suggested to undergo pathological examinations.Results:In our study, we enrolled 10 344 women who completed the ABUS screening and were followed up for more than 12 months. After remote reading, 6 164 women were diagnosed with BI-RADS category 1 and 2 626 woman were within BI-RADS category 2. In contrast, 1 404 women were within BI-RADS category 3, a total of 135 women were within BI-RADS category 4, and 15 women were within BI-RADS category 5. The positive screening rate of ABUS was 15.0% (1 554/10 344). The ABUS with remote reading had a detection rate of 3.7/1 000 (38/10 344) for breast cancer screening, with a sensitivity of 97.4% (38/39) and a specificity of 85.3% (8 789/10 305). Among the 38 breast cancer cases detected, 92.1% (35/38) were invasive carcinomas, and 63.2% (24/38) were stage 0 or Ⅰ breast cancers.Conclusions:Breast cancer screening based on ABUS with remote reading provided an efficient and feasible solution to the problem of unevenly distributed medical resources and medical staff levels in various regions of China, enabling the decentralization of high-quality medical resources and improving the accessibility of high-quality screening services. It has provided an alternative for breast cancer screening in China.

Objective To investigate the mechanism of Yiqi Tongmai Powder(Ginseng Radix et Rhizoma,Salviae Miltiorrhizae Radix et Rhizoma,Notoginseng Radix et Rhizoma,Hirudo,Eupolyphaga Steleophaga,Rhei Radix et Rhizoma)against cerebral ischemia-reperfusion injury(CIRI)based on network pharmacology,molecular docking and experimental verification.Methods(1)The active components of Yiqi Tongmai Powder and their action targets were screened by TCMSP,TCMID and ETCM databases,the disease related targets of CIRI were screened by GeneCards,OMIM and TTD disease databases,and the intersection targets of the above targets were obtained through Venny 2.1 online platform,that is,the potential targets of Yiqi Tongmai Powder in the treatment of CIRI.The"drugs-active components-targets"network was constructed by Cytoscape 3.7.1 software,and the potential active components of Yiqi Tongmai Powder in the treatment of CIRI were screened.Protein-protein interaction(PPI)analysis of potential targets was carried out by STRING 11.0 database to screen core targets.The GO function and KEGG pathway enrichment of potential targets were analyzed by Metascape database.AutoDockTools 1.5.7 software was used to verify the molecular docking between the key active components and the core targets.(2)The rat model of CIRI was established by middle cerebral artery occlusion and reperfusion(MCAO/R).SD rats were randomly divided into sham operation group,model group,Yiqi Tongmai Powder low-dose group(0.27 g·kg-1),Yiqi Tongmai Powder high-dose group(1.08 g·kg-1)and Nimodipine group(30 mg·kg-1),with 10 rats in each group.Pre-administration began three days before the establishment of the model,once a day for seven days.The neurological deficit of MCAO/R rats was evaluated by modified neurological deficit score(mNSS).The volume of cerebral infarction was measured by TTC staining.Nissl staining was used to observe the damage of neurons in brain tissue.ELISA method was used to detect serum inflammatory factors and oxidative stress related indexes.TUNEL staining was used to detect brain tissue apoptosis.Western Blot method was used to detect the protein expressions of Bax and Bcl-2 in brain tissue.Results(1)A total of 46 active components and 178 potential targets of Yiqi Tongmai Powder in the treatment of CIRI were obtained.The key active components such as quercetin,digitalis flavonoids,kaempferol,valine and uracil were analyzed,and the core targets such as TNF,IL-6,STAT3,VEGFA,AKT1,IL-1β,CASP3,TP53,MAPK3 and EGFR were analyzed.The potential targets are involved in inflammation,oxidative stress,cell proliferation and differentiation,apoptosis and other biological processes,including cAMP,NF-κB,PI3K-Akt and other signal pathways.The main active components quercetin,flavonoids of digitalis,kaempferol and valine have good binding activity to target proteins such as TNF,IL-6,STAT3 and VEGFA.(2)Compared with the model group,the neurological deficit score of rats in each treatment group was significantly decreased(P＜0.05,P＜0.01),the area of cerebral infarction was significantly decreased(P＜0.01),and the pathological changes of ischemic necrotic area of brain tissue were improved.The number of neurons in ischemic area of brain tissue was significantly increased(P＜0.01),and the rate of neuronal apoptosis was significantly decreased(P＜0.01).The levels of serum IL-1β,IL-6,TNF-α and MDA were significantly decreased,while the activities of SOD and GSH-Px were significantly increased(P＜0.05).The protein expression of Bax in brain tissue were significantly decreased and the protein expression of Bcl-2 significantly increased(P＜0.05).Conclusion Yiqi Tongmai Powder may play an anti-CIRI effect by reducing inflammation and oxidative stress,inhibiting cell apoptosis.

Compared with conventional radiotherapy, FLASH radiotherapy has advantages in protecting normal tissues, while the dose rate is increased by more than 100 times. If the shielding design of the treatment room is carried out according to the existing standard, the thickness and cost of the shielding wall will be significantly increased, or even hardly to meet the requirement of the standards, resultsing in the failure of the application of FLASH radiotherapy. By investigating the domestic and foreign standards and literature, this paper analyzes the challenges brought by FLASH radiotherapy technology to the shielding design of radiotherapy treatment room in China. Dose rate control standards adopted by different countries in the shielding design are emphatically compared as well. In several countries, the average dose rate under the actual treatment conditions was considered in the shielding design. In China, the method of instantaneous dose rate taking acount of occupancy factor is adopted. However, if FLASH radiotherapy technology is applied, the requirement of instantaneous dose rate will be difficult to meet. In order to improve the high dose rate radiotherapy technology such as FLASH radiotherapy, the revision of the existing standards is advised if the authorized limits are not changed. To use the average dose rate limit within a certain period of time for control, or to raise the control standard in the case of flash radiotherapy, are also avaliable.

【Objective】 To determine the optimal process conditions for efficiently extracting human prothrombin complex concentrates from human plasma. 【Methods】 Using human plasma as the materials and the yield of prothrombin complex concentrates as the evaluation standard, the preparation process parameters were studied and optimized through design of exporement(DOE), orthogonal experiments, and single factor experiments. 【Results】 The optimal process conditions were as follows: DEAE Sephadex A50 gel was selected, which balanced to pH 7.6, and then the amount of 1.7-2.5 g/L of plasma weight is added into the cryoprecipitate supernatant for adsorption for 40 minutes; Washing solution (0.15-0.175 mol/L sodium chloride) with 3 times the volume of gel was washed 3 times, and eluent (0.5-2.0 mol/L sodium chloride) was washed 3 to 5 times; Add stabilizer (heparin 35 IU, sodium chloride 0.1 mol/L) for ultrafiltration dialysis. 【Conclusion】 By using the optimized process mentioned above, the yield(measured by human coagulation factor IX)can reach 620 000 to 630 000 IU/ton of plasma, which is suitable for large-scale production.

Objective:To investigate the value of plasma Epstein-Barr virus (EBV) DNA detection in the screening of nasopharyngeal carcinoma (NPC) and its clinical application in non-high-risk areas.Methods:Plasma EBV DNA results in 1 153 newly diagnosed nasopharyngeal carcinoma patients who were treated in Sichuan Cancer Hospital from 2015 to 2020 and 244 healthy control cases with matched sex and age were retrospectively analyzed. EBV DNA were detected by quantitative real-time PCR. Positive rate of EBV DNA was determined by the cutoff value of 400 (≥400 copies/ml as positive) and optimization threshold method (presence of S amplification curve as positive). Further analyses were conducted to compare EBV DNA load in different clinical stage, TNM stage and regions distribution characteristics. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic value of the cutoff value of 400 and optimization threshold method for NPC.Results:Compared with healthy controls, EBV DNA increased significantly in newly diagnosed NPC patients ( P<0.001). Both evaluation methods revealed that the EBV DNA positive percentage increased with TNM and clinical stage ( P<0.001). With 400 copies/ml as cutoff value, the diagnostic sensitivity and specificity were 40.85% and 100%, respectively. The area under the curve was 0.704 (95% CI 0.676-0.733, P<0.001). Evaluated by the optimization threshold method, the sensitivity and specificity could improve to 82.0% and 99.2%, respectively, and the area under the curve reached 0.910 (95% CI 0.894-0.924, P<0.001). Conclusions:In the low prevalence area of nasopharyngeal carcinoma, the sensitivity for diagnosis of nasopharyngeal carcinoma is only 40.9% by the 400 copies/ml cutoff value method. The optimization threshold method is a better choice to improve the diagnostic sensitivity without lowering the diagnostic specificity.