Liver ischemia-reperfusion injury (LIRI) is a pathological process involving multiple injury factors and cell types, with different stages. Currently, protective drugs targeting a single condition are limited in efficacy, and interventions on immune cells will also be accompanied by a series of side effects. In the current bottleneck research stage, the multi-target and obvious clinical efficacy of Chinese medicine (CM) is expected to become a breakthrough point in the research and development of new drugs. In this review, we summarize the roles of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in various stages of hepatic ischemia-reperfusion and on various types of cells. Combined with the current research progress in reducing ROS/RNS with CM, new therapies and mechanisms for the treatment of hepatic ischemia-reperfusion are discussed.
Reperfusion Injury/drug therapy* ; Reactive Oxygen Species/metabolism* ; Reactive Nitrogen Species/metabolism* ; Humans ; Liver/drug effects* ; Animals ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/pharmacology*

Acute pancreatitis (AP) is a life-threatening gastrointestinal disorder for which no effective pharmacological treatments are currently available. One of the pharmacological targets that merits further research is the neurokinin 1 receptor (NK1R), which is found on pancreatic acinar cells and responds to the neuropeptide substance P (SP) that participates in AP. Although a few studies have stated the involvement of SP/NK1R in neurogenic inflammation in AP development, the regulatory mechanism remains unclear. In this study, we found that following activation of NK1R by SP, β-arrestin1, a scaffold protein of NK1R, down-regulated transcription of Adss, Adsl, and Ampd in the purine nucleotide cycle, thereby inhibiting mitochondrial function through fumarate depletion. Interestingly, we identified magnolol as a new and natural NK1R inhibitor with a non-nitrogenous biphenyl core structure. It exhibited a beneficial effect on AP by restoring purine nucleotide cycle metabolic enzymes and fumarate levels. Our study not only provides new therapeutic strategies, leading compounds, and drug translation possibilities for AP, but also provides important clues for the study of downstream mechanisms driven by SP in other diseases.

Ovarian tumor (OT) is the most lethal form of gynecologic malignancy, with minimal improvements in patient outcomes over the past several decades. Metastasis is the leading cause of ovarian cancer-related deaths, yet the underlying mechanisms remain poorly understood. Psychological stress is known to activate the glucocorticoid receptor (NR3C1), a factor associated with poor prognosis in OT patients. However, the precise mechanisms linking NR3C1 signaling and metastasis have yet to be fully elucidated. In this study, we demonstrate that chronic restraint stress accelerates epithelial-mesenchymal transition (EMT) and metastasis in OT through an NR3C1-dependent mechanism involving nuclear protein 1 (NUPR1). Mechanistically, NR3C1 directly regulates the transcription of NUPR1, which in turn increases the expression of snail family transcriptional repressor 2 (SNAI2), a key driver of EMT. Clinically, elevated NR3C1 positively correlates with NUPR1 expression in OT patients, and both are positively associated with poorer prognosis. Overall, our study identified the NR3C1/NUPR1 axis as a critical regulatory pathway in psychological stress-induced OT metastasis, suggesting a potential therapeutic target for intervention in OT metastasis.

BACKGROUND: China is seeing a growing demand for rehabilitation treatments for post-stroke upper limb spastic paresis (PSSP-UL). Although acupuncture is known to be effective for PSSP-UL, there is room to enhance its efficacy. OBJECTIVE: This study explored a semi-personalized acupuncture approach for PSSP-UL that used three-dimensional kinematic analysis (3DKA) results to select additional acupoints, and investigated the feasibility, efficacy and safety of this approach. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: This single-blind, single-center, randomized, controlled trial involved 74 participants who experienced a first-ever ischemic or hemorrhagic stroke with spastic upper limb paresis. The participants were then randomly assigned to the intervention group or the control group in a 1:1 ratio. Both groups received conventional treatments and acupuncture treatment 5 days a week for 4 weeks. The main acupoints in both groups were the same, while participants in the intervention group received additional acupoints selected on the basis of 3DKA results. Follow-up assessments were conducted for 8 weeks after the treatment. MAIN OUTCOME MEASURES: The primary outcome was the Fugl-Meyer Assessment for Upper Extremity (FMA-UE) response rate (≥ 6-point change) at week 4. Secondary outcomes included changes in motor function (FMA-UE), Brunnstrom recovery stage (BRS), manual muscle test (MMT), spasticity (Modified Ashworth Scale, MAS), and activities of daily life (Modified Barthel Index, MBI) at week 4 and week 12. RESULTS: Sixty-four participants completed the trial and underwent analyses. Compared with control group, the intervention group exhibited a significantly higher FMA-UE response rate at week 4 (χ² = 5.479, P = 0.019) and greater improvements in FMA-UE at both week 4 and week 12 (both P < 0.001). The intervention group also showed bigger improvements from baseline in the MMT grades for shoulder adduction and elbow flexion at weeks 4 and 12 as well as thumb adduction at week 4 (P = 0.007, P = 0.049, P = 0.019, P = 0.008, P = 0.029, respectively). The intervention group showed a better change in the MBI at both week 4 and week 12 (P = 0.004 and P = 0.010, respectively). Although the intervention group had a higher BRS for the hand at week 12 (P = 0.041), no intergroup differences were observed at week 4 (all P > 0.05). The two groups showed no differences in MAS grades as well as in BRS for the arm at weeks 4 and 12 (all P > 0.05). CONCLUSION: Semi-personalized acupuncture prescription based on 3DKA results significantly improved motor function, muscle strength, and activities of daily living in patients with PSSP-UL. TRIAL REGISTRATION Chinese Clinical Trial Registry ChiCTR2200056216. Please cite this article as: Huang XY, Liao OP, Jiang SY, Tao JM, Li Y, Lu XY, Li YY, Wang C, Li J, Ma XP. Three-dimensional kinematic analysis can improve the efficacy of acupoint selection for post-stroke patients with upper limb spastic paresis: A randomized controlled trial. J Integr Med. 2025; 23(1): 15-24.
Humans ; Male ; Female ; Middle Aged ; Acupuncture Points ; Upper Extremity/physiopathology* ; Biomechanical Phenomena ; Single-Blind Method ; Aged ; Stroke/therapy* ; Acupuncture Therapy/methods* ; Stroke Rehabilitation/methods* ; Adult ; Muscle Spasticity/therapy* ; Paresis/physiopathology* ; Treatment Outcome

Bone diseases, such as osteoporosis and osteoarthritis, have emerged as pressing public health concerns requiring immediate attention and resolution. Cellular therapy and tissue engineering techniques are among the most promising therapeutic approaches for such conditions. Human induced pluripotent stem cells (hiPSCs) possess remarkable capacity for indefinite self-renewal in vitro and the ability to differentiate into all somatic cell types originating from the three germ layers, thereby making them a promising source of osteoblasts. Consequently, it is crucial to establish a well-delineated system for osteogenic differentiation of hiPSCs in vitro, with the aim to generate osteoblast-like cells that conform to clinical application standards. Numerous research teams have achieved substantial advancements in both the direct osteogenic differentiation of hiPSCs and the indirect pathway via mesenchymal stem cells. In this article, we provide a comprehensive review of these two osteogenic differentiation pathways and their current applications, with the aim of serving as a valuable reference for bone regeneration technologies. Current research efforts have relied on embryoid body formation and monolayer induction methods utilizing biomaterials to develop a system that facilitates in vitro culture and osteogenic differentiation of hiPSCs. However, the existing research is primarily constrained by unclear system components and low efficiency. Therefore, the development of a stepwise and three-dimensional induction system based on stringent regulation by specific compounds is a primary research direction for the future.

ObjectiveTo investigate the mechanisms of Panax notoginseng saponins （PNS） in inhibiting high shear-induced platelet aggregation and thrombosis via the Piezo1-mediated calcium signaling pathway. MethodBioflux1000z was used for the microfluidic assay， where platelets were stimulated with physiological shear rate （500 s^-1）， pathological shear rate （12 000 s^-1）， or Piezo1 agonist Yoda1 under the physiological shear rate （500 s^-1）. The shear-induced platelet calcium influx and the binding of platelet with von Willebrand factor （vWF） were measured by flow cytometry. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the vWF release from platelets. The microfluidic channels were used to determine the vWF-mediated platelet aggregation and integrin αⅡbβ3 activation. A mouse model of arterial thrombosis induced by high shear stress combined with endothelial injury was established. The ultrasonic Doppler flow meter was used to monitor the cyclic flow reduction （CFR） caused by the repeated formation and shedding of thrombi， and flow cytometry was employed to examine platelet-vWF binding， on the basis of which the effect of PNS on high shear-induced arterial thrombosis was evaluated. ResultThe microfluidic assay showed that PNS decreased the high shear rate （12 000 s^-1） or Yoda1-induced calcium influx， platelet-vWF binding， vWF-mediated platelet-fibrinogen binding， and vWF release from platelet alpha-granules in a dose-dependent manner. In the mouse model of high shear-induced thrombosis， PNS markedly reduced the CFR and occlusion time of the common carotid artery and inhibited platelet-vWF binding. ConclusionPNS can mitigate pathological shear-induced platelet aggregation and arterial thrombosis via influencing Piezo1/GPIbα-vWF signaling.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.

Objective To investigate the morphological characteristics of bone marrow in RUNX1-RUNX1T1 fusion gene-positive AML.Methods From January 2017 to January 2023,20 cases of RUNX1-RUNX1T1 fusion gene-positive AML patients newly diagnosed in this hospital were selected as group A,20 cases of AML patients without fusion gene were selected as group B,and 24 cases of PML-RARA fusion gene-positive AML patients were selected as group C.Results of bone marrow morphology,immunology,cytogenet-ics and molecular biology were analyzed retrospectively.The morphological characteristics in similar cases combined with domestic and foreign literature were summarized.Results The number of promyelocytes in group A increased in different degrees,the difference was statistically significant compared with group B(P＜0.05),and the difference was also statistically significant compared with group C(P＜0.001).In group A,some promyelocytes had abnormal morphology,and the mRNA level of fusion gene was positively correlated with the number of promyelocytes(r=0.478,P=0.039).Patients with expressions of CD56,CD19 and c-Kit mutation in group A was much more than that in group B(P＜0.05).No significant difference was detected in remission rate after the first course of chemotherapy between group A and group B(P＞0.05).Besides,the simultaneous expression of CD56 and CD19 in group A was easy to accompany the loss of sex chromosome.Conclusion AML with positive RUNX1-RUNX1T1 fusion gene could be identified with bone marrow mor-phology,immunology,cytogenetics and molecular biology.Granulocyte in the bone marrow is prone to differ-ent degrees of pathological hematopoiesis with great variability.The increased number and abnormal morphol-ogy of promyelocytes in bone marrow may be one of the morphologic features of AML with positive RUNX1-RUNX1T1 fusion gene.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective To investigate the effectiveness of team-based learning(TBL)combined with research-based learning(RBL)in enhancing evidence-based nursing practice skills of undergraduate nursing interns.Methods A total of 114 undergraduate nursing students who interned in the operating room of a ⅢA hospital in Guangzhou from July 2021 to April 2022 were selected as study subjects.A randomized cluster sampling method based on a random number table was used to divide the students into a control group and a trial group.The control group received traditional teaching methods,while the trial group was taught using a combination of TBL and RBL.The two groups were compared in terms of evidence-based practice skills,critical thinking abilities,and their evaluations on the teaching methods.Results The differences in evidence-based practice skills and critical thinking abilities before and after the internship were significantly higher in the observation group compared to the control group(t=35.108,35.897;both P<0.05).Additionally,post-internship evaluation scores for the teaching methods in the trial group were significantly higher than those in the control group(t=-17.580,P<0.05).Conclusion TBL combined with RBL effectively enhances the evidence-based nursing practice skills and critical thinking abilities of undergraduate nursing interns.This approach also improves students'evaluations on the teaching methods and fosters the cultivation of excellent clinical evidence-based nursing professionals.