Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

High mobility group box 1 (HMGB1), when released extracellularly, plays a pivotal role in the development of spinal cord synapses and exacerbates autoimmune diseases within the central nervous system. In experimental autoimmune encephalomyelitis (EAE), a condition that models multiple sclerosis, the levels of extracellular HMGB1 and interleukin-33 (IL-33) have been found to be inversely correlated. However, the mechanism by which IL-33 deficiency enhances HMGB1 release during EAE remains elusive. Our study elucidates a potential signaling pathway whereby the absence of IL-33 leads to increased binding of P300/CBP-associated factor with HMGB1 in the nuclei of astrocytes, upregulating HMGB1 acetylation and promoting its release from astrocyte nuclei in the spinal cord of EAE mice. Conversely, the addition of IL-33 counteracts the TNF-α-induced increase in HMGB1 and acetylated HMGB1 levels in primary astrocytes. These findings underscore the potential of IL-33-associated signaling pathways as a therapeutic target for EAE treatment.
Animals ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; Astrocytes/metabolism* ; Interleukin-33/metabolism* ; HMGB1 Protein/metabolism* ; Acetylation ; Mice, Knockout ; Mice, Inbred C57BL ; p300-CBP Transcription Factors/metabolism* ; Mice ; Spinal Cord/metabolism* ; Cells, Cultured ; Female ; Signal Transduction

In the implementation process,the current medical service price item standard faces the facts,including disconnection between item establishment and clinical improvement innovation,disconnection from the masses'demand and disconnection from price management needs.The compilation of the guidelines for the establishment of medical service price items marks that the unified standardization of national medical service price items has entered the"fast lane".It reviews the policy requirements to promote the standardization and unification of the current medical service price items by compiling up item guidelines in batches,analyze the framework structure of the medical service price item guidelines,and studies the main changes of the medical service price item guidelines:integrating stock,compatible improvement,and supporting innovation.The policy suggestions to accelerate the implementation and application of the medical service price item guide include:according to the item guidelines,determine the mapping relationship between old and new items,standardize and integrate the current price items,and stop the original items;carry out cost investigation and calculation,weighted average according to the service volume,shift the price of old items,and approve the price of new items;guide public hospitals to implement item guidelines,track price implementation,monitor service number,and strengthen charge supervision.

By the end of 2024,the National Healthcare Security Administration has compiled a guide for the establishment of medical service price items covering most disciplines,and basically completed the top-level design of standardization and standardization of national medical service price items.On the basis of sorting out the ideas for the preparation of the for the medical service price item setting guidelines,and combining the practice of docking and implementing the compilation guidelines for the price items setting in typical provinces,it analyzes the impact of the docking and implementation of the item setting guidelines on medical care,medical insurance and patients and the coping strategies:clarifying the boundaries of technical specifications and price items,reforming compatible with technological improvements according to the item guidelines,and supporting major innovations;carrying out price and cost investigation of sample hospitals,scientifically and reasonably approving the integrated item price according to the item guidelines;item guidelines better reflecting the degree of operational risk,technical difficulty,labor value,optimizing the income structure of the hospital;standardizing items with item setting guidelines,promoting transparent and reasonable fees,and making patient payments more clear.

OBJECTIVE To explore the clinical characteristics and risk factors for refractory drug-resistant Pseudo-monas aeruginosa infection and evaluate the prognosis so as to provide theoretical bases for effective prevention and control of the refractory drug-resistant P.aeruginosa infection.METHODS A total of 95 patients who were di-agnosed with refractory drug-resistant P.aeruginosa infection and were treated in People's Hospital of Guangdong Province from Jan.2019 to Dec.2023 were assigned as the infection group.Meanwhile,95 patients who did not have drug-resistant P.aeruginosa infection,matched by the age and hospitalization period,were chosen as the non-infection group in a case-control(1∶1 ratio).The basic information and clinical data were collected from the two groups of patients.The characteristics and risk factors for the drug-resistant P.aeruginosa infection were ana-lyzed,and the prognosis of the patients was evaluated.RESULTS Among the clinical isolates of drug-resistant P.aeruginosa,78 were isolated from respiratory secretions;there were 59 patients from intensive care unit(ICU),13 patients from respiratory medicine department and 8 patients from geriatrics department.Fever,dyspnea,moist rales and cough were the major clinical manifestations.The proportions of patients with history of respirato-ry tract disease(P＜0.001),renal disease(P=0.008),nervous system disease(P=0.005),diabetes mellitus(P=0.017),hepatic disease(P=0.007),previous utilization rate of aminoglycosides(P=0.002)and previous u-tilization rate of no less than 3 types of antibiotics were higher in the infection group than in the non-infection group.Multivariate analysis showed that the history of respiratory tract disease(OR=2.813,95％CI:1.366 to 5.792,P=0.005),history of diabetes mellitus(OR=2.465,95％CI:1.129 to 5.382,P=0.024)and history of nervous system disease(OR=2.386,95％CI:1.151 to 4.944,P=0.019)were the risk factors for the drug-resist-ant P.aeruginosa infection.The mortality rate of the infection group was 30.53％,higher than 6.32％of the non-infection group(x2=18.527,P＜0.001).CONCLUSIONS The mortality rate of the patients with drug-resistant P.aeruginosa infection is high.The history of respiratory tract disease,history of diabetes mellitus and history of nervous system disease are the major risk factors for the infection.It is necessary for the hospital to strengthen the awareness of prevention of the drug-resistant P.aeruginosa infection so as to curb the hospital-associated infection.

OBJECTIVE To standardize the main processes and related technical links of the clinical comprehensive evaluation of drugs， and provide guidance and reference for improving the quality of comprehensive evaluation evidence and its transformation and application value. METHODS The construction of Guideline for the Workflow of Clinical Comprehensive Evaluation of Drugs was based on the standard guideline formulation method of the World Health Organization （WHO）， strictly followed the latest definition of guidelines by the Institute of Medicine of the National Academy of Sciences of the United States， and conformed to the six major areas of the Guideline Research and Evaluation Tool Ⅱ. Delphi method was adopted to construct the research questions； research evidence was established by applying the research methods of evidence-based medicine. The evidence quality classification system of the Chinese Evidence-Based Medicine Center was adopted for evidence classification and evaluation. The recommendation strength was determined by the recommendation strength classification standard formulated by the Oxford University Evidence-Based Medicine Center， and the recommendation opinions were formed through the expert consensus method. RESULTS & CONCLUSIONS The Guideline for the Workflow of Clinical Comprehensive Evaluation of Drugs covers 4 major categories of research questions， including topic selection， evaluation implementation， evidence evaluation， and application and transformation of results. The formulation of this guideline has standardized the technical links of the entire process of clinical comprehensive evaluation of drugs， which can effectively guide the high-quality and high-efficient development of this work， enhance the standardized output and transformation application value of evaluation evidence， and provide high-quality evidence support for the scientific decision-making of health and the rationalization of clinical medication.

Objective:To analyze the correlation between thymus dose-volume parameters and lymphopenia in patients with early-stage breast cancer (BC) receiving adjuvant radiotherapy (RT).Methods:Medical records of 54 patients with early-stage BC who received postoperative adjuvant RT in the Second Affiliated Hospital of Soochow University from January to December 2019 were retrospectively analyzed. Absolute lymphocyte counts (ALC) were collected at 1 month before (baseline) and weekly during RT. Lymphopenia was graded based according to the common terminology criteria for adverse events version 5.0 and nadir/baseline ALC was calculated. The thymus was delineated according to anatomical boundaries in the original RT planning system. Dosimetric parameters were obtained from the dose volume histograms. Stepwise multiple linear regression analysis was used to explore the factors associated with nadir/baseline ALC. The cutoff values of dosimetric parameters for predicting ≥grade 3 lymphopenia were obtained using the receiver operating characteristic (ROC) curve.Results:The proportion of 54 patients experiencing ≥ grade 3 lymphopenia was 38.9%. The median value of thymus volume, mean dose, V 5 Gy, V 10 Gy were 14.02 cm 3, 4.95 Gy, 36.18%, and 6.61%, respectively. Stepwise multiple linear regression analysis revealed that baseline ALC ( P=0.005), quadrant location ( P=0.005) and mean thymus dose ( P<0.001) were significantly associated with nadir/baseline ALC. ROC curve analysis indicated that the cutoff values of thymus mean dose, V 5 Gy and V 10 Gy for predicting ≥ grade 3 lymphopenia were 6.12 Gy, 35.2%, and 7.4%, respectively. Conclusions:Lymphopenia in early-stage BC patients is significantly correlated with high dosimetric parameters of the thymus during postoperative adjuvant RT. Thymus may be considered as an organ at risk during RT.

Objective To systematically review the efficacy and safety of reduced versus standard doses of CDK4/6 inhibitors in patients with HR+/HER2-advanced breast cancer.Methods PubMed,Web of Science,Cochrane Library,Embase,CNKI,WanFang Data,VIP,databases were electronically searched to collect randomized controlled trials(RCTs)on HR+/HER2-advanced breast cancer patients treated with reduction of CDK4/6 inhibitor dose and standard dose from inception to April 1,2025.Two reviewers independently screened the literature,extracted data,and assessed the risk of bias of the included studies.Meta-analysis was performed using RevMan 5.1 software.Results A total of 14 RCTs involving 4,958 patients were included.The results of Meta-analysis showed that there was no statistically significant difference in PFS[HR=1.01,95％CI(0.92,1.11),P=0.81]and OS[HR=0.78,95％CI(0.52,1.18),P=0.25]in the dose-reduced group and the standard dose group,while ORR[RR=0.83,95％CI(0.71,0.96),P=0.01]and incidence of grade 3 and above neutropenia[RR=0.42,95％CI(0.21,0.85),P=0.02]in the dose-reduced group were significantly better than those in the standard dose group.Conclusions Current evidence shows that the dose reduction of CDK4/6 inhibitors can considerably reduce the incidence of grade 3 and above neutropenia without affecting PFS and OS.

The release of the medical service price item guide is an important content of deepening the reform of medical service price,and is also a major measure to unify and standardize the medical service price item.Taking the Nursing Medical Service Price Item Proposal Guide(hereinafter referred to as the Nursing item Proposal Guide)as an example,it introduces the preparation ideas,framework structure design and item element changes of the nursing item proposal guide,sorts out the progress of docking and implementation of the Nursing Item Proposal Guide in typical provinces,and makes comparisons to obtain inspiration for accelerating the implementation of the item proposal guide in other regions:ensure the participation of clinical and price experts,mapping old and new items and integrating elements according to item guidelines;comprehensive use of cost pricing,reference pricing and value pricing,check and standardize the integrated item price;to standardize the integration of new item price adjustment and medical insurance payment policy coordination,forming a positive superposition effect;make a list of consumables that can be charged separately,and do a good job in the connection between product registration and price medical insurance policies;strengthen publicity and training,update information systems,monitor service volume,and track the effect of price policy implementation.

Objective To systematically review the efficacy and safety of reduced versus standard doses of CDK4/6 inhibitors in patients with HR+/HER2-advanced breast cancer.Methods PubMed,Web of Science,Cochrane Library,Embase,CNKI,WanFang Data,VIP,databases were electronically searched to collect randomized controlled trials(RCTs)on HR+/HER2-advanced breast cancer patients treated with reduction of CDK4/6 inhibitor dose and standard dose from inception to April 1,2025.Two reviewers independently screened the literature,extracted data,and assessed the risk of bias of the included studies.Meta-analysis was performed using RevMan 5.1 software.Results A total of 14 RCTs involving 4,958 patients were included.The results of Meta-analysis showed that there was no statistically significant difference in PFS[HR=1.01,95％CI(0.92,1.11),P=0.81]and OS[HR=0.78,95％CI(0.52,1.18),P=0.25]in the dose-reduced group and the standard dose group,while ORR[RR=0.83,95％CI(0.71,0.96),P=0.01]and incidence of grade 3 and above neutropenia[RR=0.42,95％CI(0.21,0.85),P=0.02]in the dose-reduced group were significantly better than those in the standard dose group.Conclusions Current evidence shows that the dose reduction of CDK4/6 inhibitors can considerably reduce the incidence of grade 3 and above neutropenia without affecting PFS and OS.