Objective:To carry out the policy diffusion analysis of centralized and volume-based drug procurement in China in recent years,and to provide reference for the formulation of centralized and volume-based drug procurement policy.Methods:Through the official websites of the central and provincial governments,the official websites of the Health Commission and the official websites of the Medical Security Bureau,the policy documents related to centralized and volume-based drug procurement from January 1,2009 to December 31,2023 were searched.Based on the policy diffusion theory,the reference network analysis method is used to analyze the intensity,breadth and speed of policy diffusion,and the sequential analysis method of policy keywords is used to analyze the direction of policy diffusion.Results:In the two stages of the development of centralized and volume-based drug procurement policy,the number of policies issued in the medical insurance management stage reached the peak;The top ten policies with the highest diffusion intensity and breadth are all central policies,and most of them are notices and opinions.In addition,the newly promulgated policies have a faster diffusion speed.In the direction of diffusion,top-down and parallel diffusion trends are obvious.Conclusion:The diffusion of centralized and volume-based drug procurement policy in China focuses on the central policy,and the diffusion speed is increasing year by year.It is suggested to strengthen the policy coordination between the central and local governments,establish a unified national information platform for centralized drug procurement,optimize the learning and competition mechanism between governments at all levels,and give play to the advantages of"policy experiment".

OBJECTIVE: To evaluate the feasibility and tolerability of metoprolol standard dosing pathway (MSDP) in Chinese patients with acute coronary syndrome (ACS). METHODS: In this multicenter, prospective, open label, single-arm and interventional study that was conducted from February 2018 to April 2019 in fifteen Chinese hospitals. A total of 998 hospitalized patients aged ≥ 18 years and diagnosed with ACS were included. The MSDP was applied to all eligible ACS patients based on the standard treatment recommended by international guidelines. The primary endpoint was the percentage of patients achieving the target dose at discharge (V2). The secondary endpoints included the heart rate and blood pressure at V2 and four weeks after discharge (V4), and percentage of patients experiencing bradycardia (heart rate < 50 beats/min), hypotension (blood pressure < 90/60 mmHg) and transient cardiac dysfunction at V2 and V4. RESULTS: Of the 998 patients, 29.46% of patients achieved the target dose (≥ 95 mg/d) at V2. The total population was divided into two groups: target group (patients achieving the target dose at V2) and non-target group (patients not achieving the target dose at V2). There was significant difference in the reduction of heart rate from baseline to discharge in the two groups (-4.97 ± 11.90 beats/min vs. -2.70 ± 9.47 beats/min, P = 0.034). There was no significant difference in the proportion of bradycardia that occurred in the two groups at V2 (0 vs. 0, P = 1.000) and V4 (0.81% vs. 0.33%, P = 0.715). There was no significant difference in the proportion of hypotension between the two groups at V2 (0.004% vs. 0.004%, P = 1.000) and V4 (0 vs. 0.005%, P = 0.560). No transient cardiac dysfunction occurred in two groups during the study. A total of five adverse events (1.70%) and one serious adverse event (0.34%) were related to the pathway in target group. CONCLUSIONS In Chinese ACS patients, the feasibility and tolerability of the MSDP have been proved to be acceptable.

Chemical investigation of the culture extract of an endophytic Penicillium citrinum from Dendrobium officinale, afforded nine citrinin derivatives (1-9) and one peptide-polyketide hybrid GKK1032B (10). The structures of these compounds were determined by spectroscopic methods. The absolute configurations of 1 and 2 were determined for the first time by calculation of electronic circular dichroism (ECD) data. Among them, GKK1032B (10) showed significant cytotoxicity against human osteosarcoma cell line MG63 with an IC₅₀ value of 3.49 μmol·L^-1, and a primary mechanistic study revealed that it induced the apoptosis of MG63 cellsvia caspase pathway activation.
Apoptosis ; Bone Neoplasms ; Caspases ; Humans ; Osteosarcoma/drug therapy* ; Penicillium

Objective: To analyze the dynamic changes and influencing factors of HIV-1 DNA load in HIV-1 infected individuals under antiretroviral therapy (ART) in Dehong Dai and Jingpo autonomous prefecture, Yunnan province, and provide information support for the clinical use of HIV-1 DNA quantitative detection. Methods: The HIV infection cases in recent infection cohort from Dehong Center for Disease Control and Prevention during 2009-2018 were selected as study subjects. The dynamic curve of HIV-1 DNA load varrying with time was generated and logistic regression analysis was conducted to identify the risk factors for HIV-1 load in the recent follow up after ART and statistical analysis was performed by using SPSS 17.0. Results: Among the 113 HIV infection cases detected from the recent infection cohort, the recent HIV infection rate were 49.6%(56/113) males, sexual transmission cases and drug injection transmission cases accounted for 53.1% (60/113), 80.5% (91/113) and 19.5% (22/113), respectively. The dynamic changes curve showed that HIV-1 DNA load was relatively high (>800 copies /10⁶ PBMCs) before ART, and droped rapidly (<400 copies /10⁶ PBMCs) after ART for 1 year. However, HIV-1 DNA load decreased insignificantly from the second year of ART, and remained to be 269 copies/10⁶ PBMCs after ART for 6 years. Univariable logistic regression analysis indicated that OR (95%CI) of CD8, CD4/CD8 and HIV-1 DNA load were 1.00 (1.00-1.00), 0.30 (0.09-1.05) and 1.01 (1.00-1.01), respectively. Multivariable logistic regression analysis showed that OR value of HIV-1 DNA load base was 1.00 (1.00-1.01). Conclusions: HIV-1 DNA load decreased significantly in the first year of ART, then remained stable for years. HIV-1 DNA load base was the key factor associated with the decrease of HIV-1 DNA load, the lower the HIV-1 DNA load base, the lower HIV-1 DNA load. Therefore, earlier ART can contribute to the decrease of HIV-1 DNA load.
China/epidemiology* ; DNA/therapeutic use* ; HIV Infections/drug therapy* ; HIV Seropositivity ; HIV-1/genetics* ; Humans ; Male ; Viral Load

Macrophages play an important role in maintaining homeostasis of the body, and they are also one of the most abundant immune cells in the tumor microenvironment (TME). These macrophages are often called tumor-associated macrophages (TAMs), which play an important role in the development of tumor and are an important target for tumor therapy. Studies have shown that tumor growth and metastasis can be inhibited by regulating the function of macrophages, but the therapeutic efficacy was often hampered by the poor performance of the drugs such as lack of targeting, poor solubility, low bioavailability, and severe side effects. After introduction of the background of macrophage and tumor therapy, this review focuses on the research progress of nano-drug delivery systems in the modulation of the function of macrophages to enhance tumor immunotherapy. Nano-drug delivery systems are diverse in structures and functions, and can regulate macrophage functions through a variety of mechanisms. Four important aspects of macrophage modulation, which included TAMs depletion, repolarization of TAMs, promoted phagocytosis of TAMs, and combinational modulation of TAMs were summarized. Each strategy together with typical examples was reviewed and future directions in this field were also prospected.

Objective: To analyze the clinical characteristics of children with Burkitt lymphoma (BL) and to summarize the mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen. Methods: Clinical features of 436 BL patients who were ≤18 years old and treated with the CNCL-B-NHL-2017 regimen from May 2017 to April 2021 were analyzed retrospectively. Clinical characteristics of patients at disease onset were analyzed and the therapeutic effects of patients with different clinical stages and risk groups were compared. Survival analysis was performed by Kaplan-Meier method, and Cox regression was used to identify the prognostic factors. Results: Among 436 patients, there were 368 (84.4%) males and 68 (15.6%) females, the age of disease onset was 6.0 (4.0, 9.0) years old. According to the St. Jude staging system, there were 4 patients (0.9%) with stage Ⅰ, 30 patients (6.9%) with stage Ⅱ, 217 patients (49.8%) with stage Ⅲ, and 185 patients (42.4%) with stage Ⅳ. All patients were stratified into following risk groups: group A (n=1, 0.2%), group B1 (n=46, 10.6%), group B2 (n=19, 4.4%), group C1 (n=285, 65.4%), group C2 (n=85, 19.5%). Sixty-three patients (14.4%) were treated with chemotherapy only and 373 patients (85.6%) were treated with chemotherapy combined with rituximab. Twenty-one patients (4.8%) suffered from progressive disease, 3 patients (0.7%) relapsed, and 13 patients (3.0%) died of treatment-related complications. The follow-up time of all patients was 24.0 (13.0, 35.0) months, the 2-year event free survival (EFS) rate of all patients was (90.9±1.4) %. The 2-year EFS rates of group A, B1, B2, C1 and C2 were 100.0%, 100.0%, (94.7±5.1) %, (90.7±1.7) % and (85.9±4.0) %, respectively. The 2-year EFS rates was higher in group A, B1, and B2 than those in group C1 (χ²=4.16, P=0.041) and group C2 (χ²=7.21, P=0.007). The 2-year EFS rates of the patients treated with chemotherapy alone and those treated with chemotherapy combined with rituximab were (79.3±5.1)% and (92.9±1.4)% (χ²=14.23, P<0.001) respectively. Multivariate analysis showed that stage Ⅳ (including leukemia stage), serum lactate dehydrogenase (LDH)>4-fold normal value, and with residual tumor in the mid-term evaluation were risk factors for poor prognosis (HR=1.38,1.23,8.52,95%CI 1.05-1.82,1.05-1.43,3.96-18.30). Conclusions: The CNCL-B-NHL-2017 regimen show significant effect in the treatment of pediatric BL. The combination of rituximab improve the efficacy further.
Adolescent ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Burkitt Lymphoma/drug therapy* ; Child ; Disease-Free Survival ; Female ; Humans ; Lactate Dehydrogenases ; Lymphoma, B-Cell/drug therapy* ; Male ; Prognosis ; Retrospective Studies ; Rituximab/therapeutic use* ; Treatment Outcome

OBJECTIVE: To compare accuracy of anterior cervical pedicle screws between assist of rapid prototyping 3D guide plate and free-hand insertion, and evaluate the safety of two methods. METHODS: Eight adult cervical cadaver specimens after formaldehyde immersion, including 4 males and 4 females, aged 32 to 65(40.3±5.6) years old. After X-ray examination to exclude bone damage and deformity, 4 of them (3D guide plate group) randomly selected were for CT scan to obtain DICOM format data, and the data was imported into Mimics software for model, designed the ideal entry point and nail path for anterior cervicaltranspedicular screw (ATPS). After obtaining the personalized guide plate of the nail channel, it was exported as STL data, and the individual guide plate was printed by rapid prototyping and 3D printing technology. In turn, with the assistance of 3D guide plates, one-to-one personalized ATPS screws were placed on the four lower cervical cadaver specimens. Another 4 (free-hand group) lower cervical cadaver specimens were implanted with ATPS screws using free-hand technique. All specimens were performed CT thin-layer scanning and three-dimensional reconstruction after operation. The Tomasino method was used to evaluate the safety of the screws on the CT cross-sectional and sagittal images, to determine whether there was a cortical puncture of the lower and inner edges of the pedicle. According to the CT rating results, gradeⅠandⅡwere safe, and grade Ⅲ- Ⅴ were dangerous.And the accuracy of screws was recorded and analyzed between two groups. RESULTS: Two screws were inserted in each segment from C CONCLUSION The 3D printing rapid prototyping guide plate assisted insertion of the anterior cervical pedicle screw can significantly improve the accuracy and safety, and provide a theoretical basis for further clinical application.
Adult ; Aged ; Bone Plates ; Cervical Vertebrae/surgery* ; Cross-Sectional Studies ; Female ; Humans ; Male ; Middle Aged ; Pedicle Screws ; Printing, Three-Dimensional

China/epidemiology* ; Coronary Angiography ; Coronary Artery Disease/diagnosis* ; Humans ; Registries ; Risk Assessment ; Risk Factors

Objective:To observe the activation of microglia and the expression of inflammatory factors in hippocampus of mice with depression-like behavior after mother-infant separation （MS） combined with lipopolysaccharide （LPS） stress， and to explore the possible anti-depression mechanisms of Wenyang （WY）， Jieyu （JY）， and Wenyang Jieyu （WYJY） prescriptions from the perspective of warming Yang and relieving depression. Method:Seventy offspring mice were randomly divided into a normal group （n=10）， a LPS stress group （n=10）， and a modeling group （n=50）. After undergoing 8 h·d^-1 mother-infant separation during postnatal day 5 （PD₅）–PD₁₄， mice in the modeling group were further divided into the MS + LPS group， WY group， JY group， WYJY group， and fluoxetine （FLU） group， with 10 in each group. The birth date of the offspring mice was recorded as PD₀. The mice in the normal， LPS， and MS + LPS groups were fed a normal diet during PD₂₁–PD₉₀， while those in the other groups were treated with the mixtures of corresponding drugs and feed， followed by seven-day intraperitoneal injection of LPS since PD₉₁ for inducing depression. The depression-like behavior of mice in each group was detected in the open-field， O-maze， and social interaction tests. The protein expression of microglia-specific ionized calcium-binding adaptor molecule 1 （Iba-1） in the hippocampus was assayed by immunohistochemistry， and the mRNA expression of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， Iba-1， and glucocorticoid receptor （GR） by real-time fluorescence quantitative PCR （Real-time PCR）. Result:Compared with the normal group， the LPS group exhibited significantly reduced residence time at the central area within 5 min （P<0.01） and shortened total exercise distance （P<0.01）. In the MS + LPS group， the open-arm activity time and the total activity distance decreased significantly （P<0.01， P<0.05）， whereas the training， discrimination and exploration time increased significantly （P<0.01）. The expression of Iba-1 in hippocampal CA1 region of mice in the LPS and MS + LPS groups was remarkably elevated （P<0.01）. Compared with the LPS group， the MS + LPS group displayed significantly prolonged distance of 5-min exercise （P<0.05）， increased training， discrimination and exploration time （P<0.05， P<0.01）， and up-regulated Iba-1 expression in hippocampal CA1 area （P<0.01）. As revealed by comparison with the MS + LPS group， both the total 5-min exercise distance （P<0.01） and the training and discrimination time （P<0.01， P<0.05） of mice in each administration group was significantly shortened. The discrimination and exploration time of mice in the JY， WYJY， and FLU groups was significantly reduced （P<0.01）， and the expression of Iba-1 in hippocampal CA1 region of mice in each administration group was significantly down-regulated （P<0.01）. Conclusion:The warming Yang and relieving depression method helps to inhibit the occurrence and development of depression due to its efficacy in activating microglia in hippocampus of depression mice and lowering the expression of IL-1β， IL-6， and TNF-α.

Objective:To observe the activation of microglia in hippocampus of depressed and anxious mice induced by maternal separation with acute restraint stress and the expression of interleukin-1β（IL-1β），interleukin-6（IL-6），tumor necrosis factor-α（TNF-α）， investigating the mechanism of Wenyang Jieyu prescription in treating anxiety and depression. Method:Eighty four male C57BL offspring were randomly divided into control group， acute restraint stress group and model group on postnatal day 0（PD0）. Maternal separation combined with acute restraint stress was used to prepare anxious and depressed model mice， dividing the model mice into model group， Wenyang， Jieyu， Wenyang Jieyu and fluoxetine group according to random number table method. During the period of PD21-PD90， the control， acute restraint stress and model mice were fed with normal diet， with the other groups fed with corresponding medicine mixed diet. The Wenyang， Jieyu and Wenyang Jieyu groups were given 5.85， 12.03 and 16.71 g·kg^-1·d^-1 respectively. The fluoxetine group was given 2.60 mg·kg^-1·d^-1. Open field， zero maze test and social interaction tests were used to evaluate the anxiety and depression of model mice. The expression of Iba-1 in hippocampal microglia was detected by immunohistochemistry（IHC）. The mRNA expression of IL-1β， IL-6， TNF-α， Iba-1 and glucocorticoid receptor（GR）were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. Result:Compared with the control group， total movement distance and time spent in central zone in 5 min of the model mice significantly decreased（P<0.01）， time spent in opened arm and total movement distance decreased significantly（P<0.05，P<0.01）， investigation time during testing and training increased significantly（P<0.01）. The expression of Iba-1 protein and mRNA，IL-1β，IL-6，TNF-α mRNA significantly increased（P<0.01）， the expression levels of GR mRNA significantly decreased（P<0.01）. The result of IHC staining showed that microglia were over activated. Compared with the model group， total movement distance and time spent in central zone in 5 min of mice in the Wenyang Jieyu and fluoxetine group significantly increased（P<0.05，P<0.01）.Time spent in opened arm significantly increased（P<0.01）. Investigation time during testing and training significantly decreased（P<0.05，P<0.01）. The expression of Iba-1 protein and mRNA，IL-1β，IL-6，TNF-α mRNA significantly decreased（P<0.05，P<0.01）. The expression of GR mRNA increased significantly（P<0.05，P<0.01）. IHC staining showed the microglia recovered. Time spent in opened arm of mice in the Wenyang group and Jieyu group significantly increased （P<0.01）， time spent investigating during testing decreased significantly （P<0.05）， the expression levels of Iba-1 protein and mRNA，IL-6 mRNA significantly decreased （P<0.05，P<0.01）. The expression of GR mRNA of mice in the Wenyang group significantly increased （P<0.05）， the expression of TNF-α mRNA significantly decreased （P<0.05）. Total movement distance of mice in the Jieyu group increased significantly （P<0.01）， time spent investigating during training decreased significantly （P<0.05），the expression level of IL-1β mRNA significantly decreased （P<0.05）. IHC staining showed that microglia recovered partly in both groups. Conclusion:The comprehensive curative effect and pharmacological action of Wenyang Jieyu prescription were better than Wenyang prescription and Jieyu prescription. Wenyang Jieyu prescription can treat anxiety and depression in maternal separation and acute restraint stress mice， its possible mechanism may be related to the decreased activation of microglia， down-regulation of IL-1β，IL-6，TNF-α expression and up-regulation of GR expression.