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.

Chronic pain, frequently comorbid with neuropsychiatric disorders, significantly impairs patients' quality of life and functional capacity. Accumulating evidence implicates the chemokine CCL2 and its receptor CCR2 as key players in chronic pain pathogenesis. This review examines the regulatory mechanisms of the CCL2/CCR2 axis in chronic pain processing at three hierarchical levels: (1) Peripheral Sensitization: CCL2/CCR2 modulates TRPV1, Nav1.8, and HCN2 channels to increase neuronal excitability and CGRP signaling and calcium-dependent exocytosis in peripheral nociceptors to transmit pain. (2) Spinal Cord Central Sensitization: CCL2/CCR2 contributes to NMDAR-dependent plasticity, glial activation, GABAergic disinhibition, and opioid receptor desensitization. (3) Supraspinal Central Networks: CCL2/CCR2 signaling axis mediates the comorbidity mechanisms of pain with anxiety and cognitive impairment within brain regions, including the ACC, CeA, NAc, and hippocampus, and it also increases pain sensitization through the descending facilitation system. Current CCL2/CCR2-targeted therapeutic strategies and their development status are discussed, highlighting novel avenues for chronic pain management.
Humans ; Chronic Pain/physiopathology* ; Animals ; Neuroglia/metabolism* ; Chemokine CCL2/metabolism* ; Receptors, CCR2/metabolism*

Venetoclax,a BCL-2 inhibitor that induces apoptosis,is primarily employed to treat hematological malignancies and has been shown to substantially improve complete response(CR)in patients with acute myelogenous leukemia(AML).However,with the widespread clinical application of venetoclax,cases of acquired drug resistance have emerged.To address this issue,extensive research has been con-ducted to explore ferroptosis as an alternative programmed cell death pathway that reverses venetoclax resistance.This review discusses the potential mechanisms of acquired resistance to venetoclax in hematological malignancies,provides an overview of several crucial regu-latory pathways associated with abnormal energy metabolism-induced ferroptosis in tumor cells,and summarizes various approaches to modulate energy metabolism in tumor cells to alter ferroptosis and potentially reverse acquired resistance to venetoclax,ultimately guiding the clinical application of venetoclax.

Fifty outpatients of newly diagnosed hypertension (NDH,with course of disease ≤ 3 months) and 50 patients with routinely revisit hypertension (RRH,with course of disease ≥ 1 year) were consecutively enrolled respectively from February 2010 to July 2010.They were asked to complete the Beck Depression Inventory (BDI),Spielberger State-Trait Anxiety Inventory (STAI) and the SF-36 questionnaire.The results showed that compared with the RRH group,the NDH group were more worried about being diagnosed as hypertension,dependence and side effects of antihypertensive drugs and complications of hypertension (all P ＜ 0.05).The NDH group displayed significantly higher level of anxiety compared with that of the RRH group (P ＜ 0.001).No significant differences were found in depression and 8 dimensions of SF-36 forms between two groups (P ＞ 0.05).The results indicated that patients of NDH have significant higher level of anxiety than that of RRH,they should be given more psychological intervention and appropriate health education.