OBJECTIVE To provide evidence for further improving the rules governing the renewal round of national centralized drug procurement with volume-based purchasing （VBP） program for insulin.METHODS Based on publicly available policy documents， selection outcomes， and interview data， policy text analysis， descriptive statistical analysis， the Wilcoxon signed-rank test， and thematic analysis were used to compare the procurement rules and selection outcomes between the initial and renewal rounds of the national VBP programs for insulin， and to examine the mechanisms linking rule adjustments to changes in selection outcomes.RESULTS Compared with the initial round， the renewal round retained the six procurement groups and 11 bidding units， reduced the maximum valid bid price by 40%， and introduced competitive bidding selection， revival selection， and a price line for Category A products. A total of 42 products were selected in the initial round and 49 in the renewal round， including 37 that remained selected， 5 that exited， and 12 that were newly selected in the renewal round. Within the same procurement groups， the price range decreased significantly in the renewal round compared with the initial round （ P ＝0.031）， whereas the difference in average price between the two was not statistically significant （ P ＝0.063）. Domestic manufacturers were more likely to enter the A1 category， whereas multinational manufacturers were more likely to remain in categories B/C. Mechanism analysis suggested that the price line shaped the boundary of selected prices， while the classification and volume-allocation rules linked manufacturers’ bidding decisions to expected procurement volumes， potentially altering bidding incentives and corresponding to changes in the distribution of selection outcomes.CONCLUSIONS The renewal round of the insulin VBP program established an interrelated mechanism involving price boundaries， volume-based incentives， and supply constraints through the use of price lines， product classification， and contracted volume allocation. These rule adjustments corresponded to changes in the structure of selected products， price distributions， and manufacturer classifications. Future policy refinement should strengthen the coordination among reasonable price ranges， volume-based incentives， and supply performance.

BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

OBJECTIVE: To investigate the effects of 4-methylcatechol (4MC) on the migration and inflammatory response in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS), as well as its underlying mechanisms of action. METHODS: RA-FLS was isolated from synovial tissue donated by RA patients, and the optimal concentration of 4MC was determined by cell counting kit 8 method for subsequent experiments, and the effect of 4MC on the migratory ability of RA-FLS was evaluated via a cell scratch assay. An inflammation model of RA-FLS was induced by tumor necrosis factor α (TNF-α). Real-time fluorescence quantitative PCR and ELISA were employed to detect the gene and protein expression levels of interleukin-1β (IL-1β) and IL-6 in RA-FLS and their culture supernatants, respectively, thereby investigating the anti-inflammatory effects of 4MC. Western blot was used to examine the expressions of nuclear factor κB (NF-κB) signaling pathway-related proteins, including inhibitor of NF-κB-α (IKBα), phosphorylated (P)-IκBα, NF-κB-inducing kinase α (IKKα), P-IKKαβ, P-p65, and p65. Cellular immunofluorescence was utilized to detect the expression and localization of p65 in RA-FLS, exploring whether 4MC exerts its anti-inflammatory effects by regulating the NF-κB signaling pathway. Finally, a collagen-induced arthritis (CIA) mouse model was established. The anti-RA effect of 4MC in vivo was evaluated by gross observation and histological examination. RESULTS: 4MC inhibited RA-FLS migration in a concentration-dependent manner. In the TNF-α-induced RA-FLS inflammation model, 4MC significantly decreased the gene and protein expression levels of IL-1β and IL-6. Furthermore, 4MC markedly reduced the ratios of P-IΚBα/IΚBα, P-IKKαβ/IKKα, and P-p65/p65, thereby blocking the transcriptional activity of p65 by inhibiting its nuclear translocation. This mechanism effectively suppressed the activation of the TNF-α-mediated NF-κB signaling pathway. Animal studies demonstrated that 4MC [10 mg/(kg·day)] significantly lowered serum levels of IL-1β, IL-6, and TNF-α, and alleviated arthritis severity and bone destruction in CIA mice. CONCLUSION 4MC not only inhibits the migration of RA-FLS but also mitigates their inflammatory response by suppressing the NF-κB signaling pathway, thereby effectively exerting its anti-RA effects.
Synoviocytes/metabolism* ; Arthritis, Rheumatoid/metabolism* ; Animals ; Cell Movement/drug effects* ; Humans ; Catechols/therapeutic use* ; Fibroblasts/drug effects* ; Mice ; Tumor Necrosis Factor-alpha/pharmacology* ; Interleukin-1beta/metabolism* ; Interleukin-6/metabolism* ; Signal Transduction/drug effects* ; NF-kappa B/metabolism* ; Transcription Factor RelA/metabolism* ; Synovial Membrane/cytology* ; Cells, Cultured ; Male ; Arthritis, Experimental ; Anti-Inflammatory Agents/pharmacology* ; NF-KappaB Inhibitor alpha ; Inflammation

Activated fibroblasts and M2-polarized macrophages may contribute to the progression of pulmonary fibrosis by forming a positive feedback loop. This study was aimed to investigate whether fibroblasts and macrophages form this loop by secreting SDF-1 and TGF-β and the impacts of neotuberostemonine (NTS) and tuberostemonine (TS). Mice were intratracheally injected with 3 U·kg^-1 bleomycin and orally administered with 30 mg·kg^-1 NTS or TS. Primary pulmonary fibroblasts (PFBs) and MH-S cells (alveolar macrophages) were used in vitro. The animal experiments showed that NTS and TS improved fibrosis related indicators, inhibited fibroblast activation and macrophage M2 polarization, and reduced the levels of TGF-β and SDF-1 in alveolar lavage fluid. Cell experiments showed that TGF-β1 may activated fibroblasts into myofibroblasts secreting SDF-1 by activating the PI3K/AKT/HIF-1α and PI3K/PAK/RAF/ERK/HIF-1α pathways. It was also found for the first time that SDF-1 was able to directly polarize macrophages into M2 phenotype secreting TGF-β through the same pathways as mentioned above. Moreover, the results of the cell coculture confirmed that fibroblasts and macrophages actually developed a feedback loop to promote fibrosis, and the secretion of TGF-β and SDF-1 was crucial for maintaining this loop. NTS and TS may disturb this loop through inhibiting both the PI3K/AKT/HIF-1α and PI3K/PAK/RAF/ERK/HIF-1α pathways to improve pulmonary fibrosis. NTS and TS are stereoisomeric alkaloids with pyrrole[1,2-a]azapine skeleton, and their effect on improving pulmonary fibrosis may be largely attributed to their parent nucleus. Moreover, this study found that inhibition of both the AKT and ERK pathways is essential for maximizing the improvement of pulmonary fibrosis.
Animals ; Mice ; Pulmonary Fibrosis/metabolism* ; Transforming Growth Factor beta/pharmacology* ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; MAP Kinase Signaling System ; Alkaloids/pharmacology* ; Fibroblasts ; Macrophages/metabolism*

Objective:To observe the effects of intensive insulin therapy combined with glutamine on nutritional metabolism, inflammatory response, and hemodynamics in severe burn patients.Methods:Thirty-two severe burn patients who met the inclusion criteria and hospitalized in the Affiliated Huaihai Hospital of Xuzhou Medical University from June 2017 to January 2019 were recruited into a prospectively randomized controlled study. According to the random number table, the patients were divided into conventional insulin therapy alone group, conventional insulin therapy+glutamine group, intensive insulin therapy alone group, and intensive insulin therapy+glutamine group, with 8 patients in each group, with genders of 5 males and 3 females, 4 males and 4 females, 3 males and 5 females, 4 males and 4 females, and ages of (35±7), (36±9), (33±11), and (38±7) years, respectively. Patients in conventional insulin therapy alone group were treated with conventional insulin therapy on the basis of routine treatment to control the blood glucose. Patients in conventional insulin therapy+glutamine group were supplemented with alanyl-glutamine for more than 14 days in addition to the treatment in conventional insulin therapy alone group. Patients in intensive insulin therapy alone group were treated with intensive insulin therapy on the basis of routine treatment to control the blood glucose. Patients in intensive insulin therapy+glutamine group were supplemented with alanyl-glutamine in addition to the treatment in intensive insulin therapy alone group. On treatment day (TD) 1, 3, 7, and 14, the blood glucose, albumin, prealbumin, white blood cell count, procalcitonin (PCT), and C-reactive protein (CRP) of patients in the 4 groups were detected. The cardiac index (CI), stroke volume index (SVI), global end-diastolic volume index (GEDVI), systemic vascular resistance index (SVRI), extravascular lung water index (EVLWI), and pulmonary vascular permeability index (PVPI) of patients in the 4 groups on TD 1, 3, and 7 were measured. Data were statistically analyzed with Fisher′s exact probability test, one-way analysis of variance, analysis of variance for repeated measurement, and Bonferroni method.Results:All patients in the 4 groups successfully completed the study, and there were no withdrawal cases. On TD 3, 7, and 14, the blood glucose of patients in intensive insulin therapy alone group ((5.9±1.3), (5.8±0.6), (5.5±0.5) mmol/L) and intensive insulin therapy+glutamine group ((5.9±1.1), (5.6±1.1), (5.2±0.8) mmol/L) were significantly lower than those in conventional insulin therapy alone group ((9.1±0.5), (8.4±0.9), (7.4±1.1) mmol/L, P<0.05). Compared with those in conventional insulin therapy alone group, the levels of albumin of patients in conventional insulin therapy+glutamine group, intensive insulin therapy alone group, and intensive insulin therapy+glutamine group were significantly increased on TD 7 and 14 ( P<0.05). Compared with the level of albumin of patients in intensive insulin therapy+glutamine group, the levels of albumin of patients in conventional insulin therapy+glutamine group and intensive insulin therapy alone group were significantly decreased on TD 14 ( P<0.05). Compared with those in conventional insulin therapy alone group, the levels of prealbumin of patients in conventional insulin therapy+glutamine group and intensive insulin therapy alone group were significantly increased on TD 7 and 14 ( P<0.05). Compared with those in intensive insulin therapy+glutamine group, the levels of prealbumin of patients in intensive insulin therapy alone group and conventional insulin therapy+glutamine group were significantly decreased on TD 1, 7, and 14 ( P<0.05). There were no statistically significant differences in the white blood cell count, PCT, and CRP of patients in the 4 groups in pairwise comparison between groups on TD 1, 3, 7, and 14 ( P>0.05). On TD 3 and 7, the levels of cardiac index, SVI, GEDVI, and SVRI of patients in intensive insulin therapy+glutamine group were significantly higher than those in conventional insulin therapy alone group ( P<0.05), while the levels of EVLWI and PVPI were significantly lower than those in conventional insulin therapy alone group ( P<0.05). Conclusions:Glutamine combined with intensive insulin therapy can improve the hypermetabolism in patients after severe burns, reduce the decomposition and consumption of endogenous nutrient substrates, and at the same time help the recovery of cardiac function and maintenance of hemodynamic stability.

Purpose: Central venous stenosis is a recurring problem affecting dialysis access patency. Increasing evidence suggests that the use of drug-coated balloons (DCBs) improves target lesion primary patency (TLPP) in dialysis access. However, few studies have investigated the use of DCBs specifically in central venous stenosis. Thus, this study presents our initial experience with DCBs in the central vein of a dialysis access circuit. Materials and Methods: This is a retrospective cohort study of all hemodialysis patients who underwent central vein angioplasty with DCB between February 2017 and March 2018 at Singapore General Hospital. We compared the primary patency post DCB angioplasty to the primary patency of the patient’s previous plain old balloon angioplasty (POBA). Results: We observed a 100% anatomic and procedural success rate with no complications. The median follow-up period was 151 days (interquartile range, 85.5- 234 days) and no patients were lost to follow-up. The 30- and 90-day TLPPs after DCB were 93.3% and 75.7%, respectively. The mean primary patency in our study group post-DCB during the follow-up period was 164 days (vs. 140 days in the POBA group). However, no statistically significant difference was detected. Conclusion DCB showed a similar TLPP to that for POBA in treating central venous stenosis with a trend toward a longer re-intervention-free period for DCB. However, there were numerous confounding factors and a well-designed randomized controlled trial is warranted to assess the true utility of DCB in treating central venous stenosis.

Objective: To establish a high performance liquid chromatography-tandem mass spectrometric method ( HPLC-MS/MS) method for the determination of PA-824 in the plasma of Beagle dogs, and study the pharmacokinetics of PA-824 in Beagle dogs. Methods:Carbamazepine was used as the internal standard, and the plasma samples were pretreated with ethyl acetate for the liquid-liquid extraction of PA-824. An Eclipse Plus C18 column (100 mm × 2. 1 mm, 3. 5 μm) was used with the mobile phase consisting of methanol-water (90 :10). The flow rate was 0. 6 ml·min-1 and the column temperature was 30 ℃. The injection volume was 5 μl and the sample analysis time was 5 min. The determination was performed with an electrospray ionization ( ESI) source in the positive multiple reaction monitoring (MRM) mode. The ion pairs were m/z 360. 1→m/z 175. 0 (collision energy of 35, solution cluster volt-age of 65) for PA-824 and m/z 237. 2→m/z 194. 0 (collision energy of 28, solution cluster voltage of 83) for carbamazepine. After the oral administration, PA-824 in plasma was measured at different time points, and then the pharmacokinetic parameters were calcu-lated by DAS 2. 0 software. Results: PA-824 showed a good linear relationship within the range of 50-10000 ng · ml-1 ( r =0. 9991). The recovery was 97. 7%-105. 1%, and the RSDs of intra-day and inter-day were less than 5. 0%. At three different dosa-ges (100, 200 and 500 mg) of PA-824, AUC0-twere (5735. 18 ± 1918. 76),(11548. 47 ± 1838. 04) and (21987. 88 ± 4587. 58) ng·min·ml-1,t1/2 were(14.17 ±5.97),(11.11 ±4.39) and (13.13 ±5.46)h,and Cmaxwere(626.66 ±188.48),(2399.13 ± 516.51) and (4861.33 ±2253.61)ng·ml-1, respectively. Conclusion:The method is simple, accurate, rapid and reproducible, and suitable for the pharmacokinetic study of PA-824 in the plasma of Beagle dogs.

Objective: To explore the relationship between serum level of high-sensitivity cardiac troponin T (hs-cTnT) and atrial ifbrillation (AF) occurrence in patients with stable coronary artery disease (CAD).
Methods: A total of 1011 patients with stable CAD treated in our hospital from 2013-01 to 2015-09 were retrospectively studied. According to quartiles of hs-cTnT, the patients were divided into 4 groups: Group① the patients with hs-cTnT≤7ng/L, n=283, Group② hs-cTnT 7-10ng/L,n=238, Group③ hs-cTnT 10-15ng/L,n=272 and Group④ hs-cTnT>15ng/L,n=218. The relationship between hs-cTnT level and AF occurrence rate was studied; the risk factors for AF occurrence were explored by multi stepwise Logistic regression analysis.
Results: There were 127/1011 (12.6%) patients combining AF and 884 (87.4%) with simple type stable CAD. AF patients had the higher serum level of hs-cTnT than non-AF patients 17.0 (12.0, 25.0) ng/L vs 10.0 (7.0, 13.0) ng/L,P<0.01. With baseline hs-cTnT level increasing, AF occurrence rates were elevated from group① to Group④ as 4.6% (13/283), 4.6% (11/238), 11.0% (30/272) and 33.5% (73/218), Ptrend<0.05. Multi stepwise Logistic regression analysis revealed that with adjusted common risk factors of age and gender, the risk for stable CAD patients suffering from AF in Group④ was 5.324 times higher than group① (95% CI 2.285-12.405,P<0.01).
Conclusion: Increased serum level of hs-cTnT was closely related to AF occurrence in patients with stable CAD.

Objective To analyze the epidemiological characteristics of measles in the floating population in Daxing District from 2002 to 2015 and to provide a specific guidance for the control and preven-tion of measles. Methods The epidemiological characteristics of measles in the floating population in Dax-ing District were analyzed based on the data collected from Diseases Reporting Information System and Ques-tionnaires for measles cases. Results A total of 1 263 measles cases were reported in the floating population in Daxing District from 2002 to 2015, accounting for 73. 09% of all reported cases in that area. Among the 1 263 measles cases, 1 027 cases (81. 31%) were reported from March to June. The top 5 towns with high incidence of measles were Huangcun, Jiugong, Xihongmen, Yizhuang and Yinghai, from which 80. 29% of measles cases were reported. Age distribution of the measles cases showed that 145 cases were children younger than 8 months, 412 cases were children aged 8 months to 14 years old and the rest 706 cases were a-bove 14 years old. And of all cases, only 224 cases had measles vaccine immunization history. Conclusion It is necessary to maintain the high vaccination rate of 3 doses of measles vaccine by multi-approaches and increase the immunization rate in migrant workers. Moreover, strengthen the surveillance for measles is also an effective way for measles control and elimination.

Objective To explore the clinical effect of the open and laparoscopic surgery in the treatment of ectopic pregnancy to retain the clinical efficacy of reproductive function analysis. Methods Four hundred and fifty-six patients with ectopic pregnancy were selected as our subjects. Two hundred and eleven cases were served as laparotomy group( open),and 245 cases were laparoscopic group( laparoscopic). The data of intraoperative blood loss,operative time,postoperative anal exhaust time,average hospital stay,tubal patency rate,intrauterine pregnancy rate and again repeat ectopic pregnancy rate were recorded. Results Patients in two groups were successfully completed surgery. The operative time,intraoperative blood loss,postoperative anal exhaust time,average hospitalization time were(55. 1 ± 13. 5)min,(63. 5 ± 18. 3)ml,(25. 7 ± 5. 6)h,(6. 1 ± 2. 0)d respectively in laparotomy group,and(41. 3 ± 15. 5)min,(41. 1 ± 13. 3)ml,(13. 5 ± 5. 1)h,(3. 6 ± 1. 4)d respectively in laparoscopic group,and the differences were significant( t =2. 045,2. 263,3. 131, 3. 152,P﹤0. 05). The tubal patency rate,intrauterine pregnancy,ectopic pregnancy rate in laparotomy group were 81. 0%( 171/211 ),59. 7%( 126/211 ) and 26. 5%( 56/211 ) respectively,and 75. 5%( 185/245 ), 53. 5%( 131/245 ) and 22. 9%( 56/245 ) respectively in laparoscopic group,and the differences were not significant(χ2 =2. 254,2. 130,1. 242;P ﹥0. 05 ). Conclusion Laparoscopic surgery in the treatment of ectopic pregnancy is superior to laparotomy in terms of small trauma,less bleeding,faster recovery,shorter hospitalization time,and postoperative tubal patency rate.