OBJECTIVE To investigate the effects and mechanisms of Lycium ruthenicum Murr. in improving sleep. METHODS Network pharmacology was employed to identify the active components of L. ruthenicum and their associated disease targets， followed by enrichment analysis. A caffeine‑induced zebrafish model of sleep deprivation was established ， and the zebrafish were treated with L. ruthenicum Murr. extract （LRME） at concentrations of 0.1， 0.2 and 0.4 mg/mL， respectively； 24 h later， behavioral changes of zebrafish and pathological alterations in brain neurons were subsequently observed. The levels of inflammatory factors [interleukin-6 （IL-6）， IL-1β， IL-10， tumor necrosis factor-α （TNF-α）]， oxidative stress markers [superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）， catalase （CAT）]， and neurotransmitters [5- hydroxytryptamine （5-HT）， γ-aminobutyric acid （GABA）， glutamic acid （Glu）， dopamine （DA）， and norepinephrine （NE）] were measured. The protein expression levels of protein kinase B1 （AKT1）， phosphorylated AKT1 （p-AKT1）， epidermal growth factor receptor （EGFR）， B-cell lymphoma 2 （Bcl-2）， sarcoma proto-oncogene，non-receptor tyrosine kinase （SRC）， and heat shock protein 90α family class A member 1 （HSP90AA1） in the zebrafish were also determined. RESULTS A total of 12 active components and 176 intersecting disease targets were identified through network pharmacology analysis. Among these， apigenin， naringenin and others were recognized as core active compounds， while AKT1， EGFR and others served as key targets； EGFR tyrosine kinase inhibitor resistance signaling pathway was identified as the critical pathway. The sleep improvement rates in zebrafish of LRME low-， medium-， and high-dose groups were 54.60%， 69.03% and 77.97%， 开发。E-mail：hjp_yft@163.com respectively， while the inhibition ratios of locomotor distance were 0.57， 0.83 and 0.95， respectively. Compared with the model group， the number of resting counts， resting time and resting distance were significantly increased/extended in LRME medium- and high-dose groups （P＜0.05）. Neuronal damage in the brain was alleviated. Additionally， the levels of IL-6， IL-1β， TNF-α， MDA， Glu， DA and NE， as well as the protein expression levels of AKT1， p-AKT1， EGFR， SRC and HSP90AA1， were markedly reduced （P＜0.05）， while the levels of IL-10， SOD， GSH-Px， CAT， 5-HT and GABA， as well as Bcl-2 protein expression， were significantly elevated （P＜0.05）. CONCLUSIONS L. ruthenicum Murr. demonstrates sleep-improving effects， and its specific mechanism may be related to the regulation of inflammatory responses， oxidative stress， neurotransmitter balance， and the EGFR tyrosine kinase inhibitor resistance signaling pathway.

OBJECTIVE To investigate the effects and mechanism of the Yishen paidu formula on renal fibrosis in rats with chronic renal failure （CRF） through the reactive oxygen species （ROS）/thioredoxin-interacting protein （TXNIP）/NOD-like receptor thermal protein domain associated protein 3 （NLRP3） pathway. METHODS Rats were randomly divided into control group， model group， Yishen paidu formula low-dose （Yishen paidu formula-L） group， Yishen paidu formula high-dose （Yishen paidu formula- H） group， Yishen paidu formula-H+pcDNA-NC group， and Yishen paidu formula-H+ pcDNA-TXNIP group， with 10 rats in each group. Except for control group， all other rats were fed a diet containing 0.5% adenine to establish a CRF model； the rats were then administered corresponding drugs or normal saline intragastrically or via tail vein， once daily， for 8 consecutive weeks. After the last administration， the levels of serum creatinine （Scr）， blood urea nitrogen （BUN）， ROS， superoxide dismutase （SOD）， malondialdehyde （MDA）， tumor necrosis factor-α （TNF-α）， interleukin （IL）-6， and IL-1β were measured in each group. Pathological changes in renal tissue were observed， and the protein expression levels of Collagen Ⅲ， α-smooth muscle actin （α-SMA）， transforming growth factor-β1 （TGF-β1）， TXNIP and NLRP3 in renal tissue were detected. RESULTS Compared with model group， the renal histopathological damage and fibrosis of rats in Yishen paidu formula-L group and Yishen paidu formula-H group were significantly alleviated. The levels of Scr， BUN， ROS， MDA， TNF- α， IL-6 and IL-1β， and the protein expressions of Collagen Ⅲ， α-SMA， TGF-β1， TXNIP and NLRP3 were significantly decreased， while SOD levels were significantly increased （P＜0.05）. Moreover， the changes were more pronounced in the Yishen paidu formula-H group （P＜0.05）. Compared with Yishen paidu formula-H+pcDNA-NC group， above indexes of rats in Yishen paidu formula-H+pcDNA-TXNIP group were reversed significantly （P＜0.05）. CONCLUSIONS Yishen paidu formula can inhibit renal fibrosis in CRF rats by suppressing the ROS/TXNIP/NLRP3 pathway.

OBJECTIVE To investigate the mechanism of pachymic acid on renal injury in pregnancy induced hypertension （PIH） rats by regulating the silent information regulator transcript 1/peroxisome proliferator-activated receptor γ coactivator-1α （Sirt1/PGC-1α） pathway. METHODS Pregnant SD rats were prepared by co-caging and PIH model was induced using N-nitro-L- arginine methyl ester （L-NAME） method. PIH rats were randomly divided into model group， L-pachymic acid （low-dose pachymic acid， 10 mg/kg） group， H-pachymic acid （high-dose pachymic acid， 20 mg/kg） group， and H-pachymic acid+EX527 （20 mg/kg pachymic acid+10 mg/kg EX527） group， with 6 rats in each group. Another 6 normal pregnant rats were selected as blank group. Each group was given relevant medicine or solvent intragastrically or intraperitoneally daily， once a day， for 28 consecutive days. After the last administration， 24 h urinary protein and tail artery systolic blood pressure （SBP） were measured in pregnant rats from each group， along with the levels of serum creatinine （Scr）， blood urea nitrogen （BUN），uric acid （UA）， and cystatin C （Cys-C）. The contents of superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）， and 8-hydroxy-2′-deoxyguanosine （8-OHdG） in renal tissue， as well as the mRNA and protein expression levels of Sirt1 and PGC-1α， were also determined. Meanwhile， renal histopathological changes in rats from each group were evaluated using hematoxylin-eosin （HE） staining and periodic acid-Schiff （PAS） staining. RESULTS Compared with model group， L-pachymic acid group and H-pachymic acid group exhibited significant decreases in 24 h urine protein quantification， tail artery SBP， Scr， BUN， UA， Cys-C levels， glomerulosclerosis index score of renal tissue， renal tubular injury score， the percentage of PAS positive area， MDA and 8-OHdG （P＜0.05）. Conversely， the contents of SOD and GSH-Px， along with the mRNA and protein expression levels of Sirt1 and PGC-1α， were significantly increased （P＜0.05）. Moreover， these improvements were more pronounced in H-pachymic acid group （P＜0.05）. Compared with H-pachymic acid group， the aforementioned indicators in pregnant rats from the H-pachymic acid+EX527 group showed significant reversal （P＜0.05）. CONCLUSIONS Pachymic acid significantly ameliorates renal injury induced by PIH in rats， potentially through activation of the Sirt1/PGC-1α pathway.

The prescription of Qidong Yixin oral liquid is derived from the experience of national medical master Ren Jixue in treating viral myocarditis （VMC）. It has the functions of tonifying Qi， nourishing the heart，calming the mind， and relieving palpitations. It is used to treat VMC and angina pectoris of coronary heart disease caused by deficiency of both Qi and Yin. However，the understanding of its efficacy evidence， advantageous aspects， dosage and administration， and medication safety remains insufficient in clinical practice. Therefore，the development of the Expert Consensus on the Clinical Application of Qidong Yixin Oral Liquid （hereinafter referred to as consensus） was initiated. Consensus strictly followed the process and methods of the expert consensus on the clinical application of Chinese patent medicines of the China Association of Chinese Medicine，successively completing multiple tasks such as the consensus project initiation，determination of clinical problems，evidence search and evaluation，formation of recommendation opinions and consensus suggestions，solicitation of opinions，peer review， submission for review and release， and so on. Consensus formed a total of 10 recommendation opinions and 12 consensus suggestions，clarifying the clinical positioning，efficacy advantages，syndrome differentiation，dosage and administration，combination therapy，timing of medication，adverse reactions，contraindications， and precautions of Qidong Yixin oral liquid，indicating that it has good clinical advantages and safety in the treatment of VMC and angina pectoris of coronary heart disease，providing norms and references for physicians to safely and rationally apply Qidong Yixin oral liquid. Consensus was reviewed and approved for release by the Standardization Office of the China Association of Chinese Medicine on December 23， 2024. Standard number：GSCACM-376-2024.

Neurocritical care involves complex pathophysiological mechanisms, and its incidence is higher, injuries are more severe, and treatment is more challenging in high-altitude environments. This consensus, based on the latest domestic and international evidence-based medical data, establishes a standardized, goal-oriented framework for neurocritical care management applicable in high-altitude regions and nationwide. The consensus was developed following international standards for evidence quality assessment and underwent two rounds of Delphi expert consultation, resulting in 32 recommendation statements covering three parts: management systems, monitoring and assessment, and core strategies. Key updates include: advocating for the establishment of independent neurocritical care units and implementing precise tiered diagnosis and treatment based on the "Five Differences in Critical Care" concept; constructing a "trinity" multimodal brain monitoring system centered on cerebral blood flow, cerebral oxygenation, and brain function, emphasizing routine bedside transcranial Doppler ultrasound, cerebral oximetry, and continuous electroencephalography monitoring; shifting management strategies from mild hypothermia therapy to targeted temperature management, and defining the "446" target management pathway for the supercritical stage; emphasizing the assessment of static and dynamic cerebrovascular autoregulation functions through multimodal methods to achieve individualized optimal mean arterial pressure management; elevating cerebrospinal fluid management goals to the level of "glymphatic system" function maintenance; implementing a multidisciplinary collaborative, whole-process management model focusing on patients' long-term neurological functional outcomes; de-escalation criteria include multidimensional indicators such as recovery of brain structure, restoration of cerebrovascular autoregulation, improvement in cerebrospinal fluid dynamics, and reduction in biomarker levels; and integrating cutting-edge technologies like artificial intelligence into post-critical care management and rehabilitation planning. This consensus systematically integrates the entire process of neurocritical care management, reflecting the modern connotation of goal-oriented, dynamic, and multimodal integration in neurocritical care medicine. It aims to adapt to new trends such as deepening understanding of pathophysiological mechanisms, the integration of medicine and engineering, and the empowerment of artificial intelligence, thereby further advancing the discipline of critical care medicine.

Objective To explore the predictive effect of serum 25-hydroxyvitamin D3 [25(OH)D3] and blood lipid metabolism indexes on the occurrence of osteoporosis in type 2 diabetes mellitus (T2DM). Methods Totally 98 patients with T2DM in the hospital from January 2022 to January 2024 were classified into osteoporosis group (38 cases) and non-osteoporosis group (60 cases) by means of concurrent osteoporosis status. The levels of serum 25(OH)D3 and blood lipid metabolism indexes [high density lipoprotein (HDL), total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), VLDL] were measured in study subjects. The association of serum 25(OH)D3 and blood lipid metabolism indexes with osteoporosis was explored by Logistic regression analysis. The predictive value of serum 25(OH)D3 and blood lipid metabolism indexes on osteoporosis was analyzed by receiver operating characteristic curve (ROC). Results Serum 25(OH)D3 and HDL levels in the osteoporosis group were lower while TG and LDL levels were higher than those in the non-osteoporosis group (P<0.05). The differences in the levels of TC and VLDL were insignificant between groups (P>0.05). After logistic regression analysis, the levels of serum 25(OH)D3, HDL, TG and LDL were closely related to the occurrence of osteoporosis (P<0.05). ROC curve indicated that the area under the curve (AUC), sensitivity and specificity of combined prediction of osteoporosis by serum 25(OH)D3, HDL, TG, and LDL were 0.943, 92.11% and 85.00%, and the efficiency of combined prediction was better than that of each index alone (P<0.05). Conclusion The levels of serum 25(OH)D3, HDL, TG and LDL in T2DM are closely related to osteoporosis. Early combined monitoring of the indicators can provide reference value for clinical prediction of osteoporosis occurrence in patients with T2DM.

OBJECTIVE To investigate the actual construction and operation status of established and under-construction centralized （cloud） prescription review centers （shortened for “prescription review center”） of close-knit county-level medical consortium in a certain city， so as to provide reference for improving the construction quality of the prescription review center. METHODS An online questionnaire survey was conducted to collect the data from 51 established and under-construction prescription review center in the city， covering basic information， funding sources， talent management， system construction， review rule maintenance， prescription review practices， prescription evaluation， data utilization， and current challenges. The collected data were summarized and analyzed. RESULTS A total of 51 valid questionnaires were retrieved， covering 32 established and 19 under-construction prescription review center. Among the 32 established prescription review centers， the main funding sources for their construction came from government financial allocations， accounting for 56.25%. Only 25.00% of prescription review center had review pharmacists who fully met national qualification requirements， and just 55.00% updated more than 10 review rule entries per month on average. Outpatient prescription verification realized full coverage， but 37.50% of prescription review centers only supported rationality verification of single prescriptions， and 50.00% could not retrieve laboratory and examination results to assist in prescription review. Additionally， 40.62% of prescription review center had not regularly conducted prescription evaluations for primary care institutions. The data from prescription review center was mainly used to support medication monitoring. Among the 19 prescription review centers currently in the planning stage， 63.16% had no identified funding sources. CONCLUSIONS The operation and construction of prescription review center in the city face challenges， such as funding shortages， absence of collaborative incentive mechanisms， and insufficient manpower.It is suggested that the state should issue a unified standard for the construction of the prescription review center as soon as possible， and local health administrative departments should formulate supporting policies and clarify assessment indicators in combination with the actual situation of the region.

Objective: To characterize the serological profile, RHD genetic spectrum, and their frequencies among pregnant women preliminary screened as RhD-negative and weak positive in Qingdao and surrounding areas, and correlate these findings with unexpected antibody detection results, thereby providing testing recommendations and suggestions for such individuals. Methods: Blood samples of pregnant women who were initially identified as RhD negative and weak positive in hospitals in Qingdao and surrounding areas over the past five years were collected. Different cloned IgG anti-D antibodies were used for RhD negative confirmation experiments. RHD genotyping was performed by combining PCR-SSP and Sanger sequencing. Unexpected antibody screening and identification were carried out using test tube method and microcolumn gel card. The immunologic status of newborns delivered by anti-D pregnant women was also tracked. Results: A total of 602 blood samples were collected from pregnant women initially identified as RhD-negative and weak positive. Among them, 569 (94.5%) were confirmed as RhD-negative in the RhD confirmation test, and 33 (5.5%) were D variant phenotype. Except for 4 cases where no definite mutations were found, gene analysis revealed 474 (78.7%) D-negative cases with 5 genotypes (RHD 01N.01, RHD 01N.03, RHD 01N.16, RHD 01N.05, and 1 new allele), 90 (15.0%) Del cases with 2 genotypes (RHD 01EL.01, and RHD 01EL.18), 23 (3.8%) weak D cases with 2 genotypes (RHD 15 and 1 new allele), and 11 (1.8%) partial D cases with 2 genotypes (RHD 06.03.01 and RHD 05.04). Anti-D and complex antibodies containing anti-D were detected in 96 RhD-negative and partial D pregnant women (15.9%). After injection of anti-D immunoglobulin, One O-type RhD-negative pregnant woman delivered a newborn with hyperbilirubinemia. The newborn was typed to be B Del, and anti-D was detected in both serum and eluate. Conclusion: The serological profiles, RHD gene types and frequencies among RhD negative pregnant women in Qingdao and surrounding areas are basically consistent with domestic published data. Pregnancy can stimulate anti-D production in D-negative and partial D individuals. However, anti-D antibody has not been detected in Del type pregnant women. Since anti-D immunoglobulin can binds to Del type red blood cells, its administration is not recommended for Del type pregnant women.

Background/Aims: Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific protease 29 (USP29) plays pivotal roles in hepatic ischemiareperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression. Methods: USP29 expression was assessed in liver samples from MASLD patients and mice. The role and molecular mechanism of USP29 in MASLD were assessed in high-fat diet-fed and high-fat/high-cholesterol diet-fed mice and palmitic acid and oleic acid treated hepatocytes. Results: USP29 protein levels were significantly reduced in mice and humans with MASLD. Hepatic steatosis, inflammation and fibrosis were significantly exacerbated by USP29 deletion and relieved by USP29 overexpression. Mechanistically, USP29 significantly activated the expression of genes related to fatty acid β-oxidation (FAO) under metabolic stimulation, directly interacted with long-chain acyl-CoA synthase 5 (ACSL5) and repressed ACSL5 degradation by increasing ACSL5 K48-linked deubiquitination. Moreover, the effect of USP29 on hepatocyte lipid accumulation and MASLD was dependent on ACSL5. Conclusions USP29 functions as a novel negative regulator of MASLD by stabilizing ACSL5 to promote FAO. The activation of the USP29-ACSL5 axis may represent a potential therapeutic strategy for MASLD.