ObjectiveTo observe the effects of Danggui Shaoyaosan on macrophage polarization and renal inflammation in db/db mice with diabetic kidney disease （DKD）， and to explore its renal protective effects and underlying mechanisms. MethodsEight db/m mice were assigned to the normal group， and forty db/db mice were randomly divided into a model group， low-， medium-， and high-dose Danggui Shaoyaosan groups （8.39， 16.77， 33.54 g·kg^-1）， and an irbesartan group （0.025 g·kg^-1）. All mice were administered treatment by gavage for 12 consecutive weeks. General conditions of the mice were observed during the intervention. At the end of the 12-week intervention， 24-h urine samples were collected using metabolic cages， after which the mice were anesthetized for sample collection. Blood was collected by enucleation and centrifuged to obtain serum for the determination of glycated serum protein （GSP）， serum creatinine （SCr）， blood urea nitrogen （BUN）， total cholesterol （TC）， and triglycerides （TG）. The urinary albumin-to-creatinine ratio （UACR） was measured. Renal pathological changes were observed using hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and Masson staining. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum tumor necrosis factor-α （TNF-α）， interleukin-10 （IL-10）， and monocyte chemoattractant protein-1 （MCP-1） levels. Immunofluorescence （IF） was performed to detect F4/80 expression in renal tissue， and immunohistochemistry （IHC） was used to assess CD206 expression. Real-time quantitative polymerase chain reaction （Real-time PCR） was employed to measure the mRNA expression of TNF-α， IL-10， inducible nitric oxide synthase （iNOS）， and arginase-1 （Arg-1）. Western blot analysis was used to detect the protein expression of iNOS， Arg-1， CD86， and CD206 in renal tissue. ResultsCompared with the normal group， the model group showed increased levels of GSP， UACR， SCr， BUN， TC， and TG， elevated levels of the inflammatory factor TNF-α and the chemokine MCP-1， and decreased IL-10 levels （P<0.01）. Pathological examination revealed glomerular hypertrophy， mesangial cell proliferation with marked mesangial expansion， inflammatory cell infiltration， vacuolar degeneration of renal tubular epithelial cells， prominent glycogen deposition， and increased collagen fiber deposition. In addition， relative F4/80 fluorescence intensity was enhanced， CD206 expression in the glomeruli and renal interstitium was reduced， and TNF-α and iNOS mRNA expression was increased. IL-10 and Arg-1 mRNA expression was decreased， iNOS and CD86 protein expression was increased， and Arg-1 and CD206 protein expression was decreased （P<0.05， P<0.01）. Compared with the model group， the Danggui Shaoyaosan groups and the irbesartan group showed decreased levels of GSP， UACR， SCr， BUN， TC， and TG， reduced serum TNF-α and MCP-1 levels， and increased IL-10 levels. Renal pathological damage was improved to varying degrees. Relative F4/80 fluorescence intensity was reduced， CD206 expression in the glomeruli and renal interstitium was increased， and TNF-α and iNOS mRNA expression was decreased. IL-10 and Arg-1 mRNA expression was increased， iNOS and CD86 protein expression was reduced， and Arg-1 and CD206 protein expression was increased （P<0.05， P<0.01）. ConclusionDanggui Shaoyaosan can improve renal function and alleviate renal pathological damage in db/db mice. Its mechanism may be related to inhibiting M1 pro-inflammatory macrophage polarization， promoting M2 anti-inflammatory macrophage polarization， reducing inflammatory responses， delaying the progression of renal fibrosis， improving renal pathological injury， and thereby exerting renal protective effects.

ObjectiveTo investigate whether Danggui Shaoyaosan （DSS） inhibits oxidative stress and alleviates inflammation via the Ras homolog family member A （RhoA）/Rho-associated coiled-coil containing protein kinase 1 （ROCK）/nuclear factor kappa-B （NF-κB） signaling pathway， thereby delaying the progression of diabetic kidney disease （DKD） and exerting a nephroprotective effect. MethodsEight db/m mice were assigned to the normal group， and forty 8-week-old db/db mice were randomly divided into the model group， DSS low-dose group （8.39 g·kg^-1）， DSS medium-dose group （16.77 g·kg^-1）， DSS high-dose group （33.54 g·kg^-1）， and irbesartan group （0.025 g·kg^-1）， with eight mice in each group. All groups were administered the corresponding treatment by gavage once daily for 12 weeks. The normal and model groups received an equal volume of saline. During administration， changes in body weight， fasting blood glucose （FBG）， and 24 hour urinary protein （24 h UTP） were observed. After 12 consecutive weeks of administration， hematoxylin-eosin （HE） staining and Masson's trichrome staining were used to observe renal histopathological changes in each group. The levels of reactive oxygen species （ROS） in renal tissue were detected using the dihydroethidium （DHE） method. The expression levels of superoxide dismutase （SOD） and malondialdehyde （MDA） in renal tissue were determined. Serum interleukin-1β （IL-1β） and interleukin-6 （IL-6） levels were measured using enzyme-linked immunosorbent assay （ELISA）. The mRNA expression levels of RhoA， ROCK1， and NF-κB p65 in renal tissues were detected by Real-time quantitative polymerase chain reaction （Real-time PCR）. Protein expression levels of fibronectin （FN）， Collagen Ⅳ（Col Ⅳ）， transforming growth factor-β₁ （TGF-β₁）， RhoA， ROCK， and NF-κB p65 in renal tissues were determined by Western blot. ResultsCompared with the normal group， the model group showed significantly increased body weight， FBG， and 24 h UTP levels （P<0.01）， elevated serum IL-1β and IL-6 levels， enlarged glomerular volume， diffuse mesangial expansion， increased mesangial matrix， and marked collagen fiber proliferation in renal tissues. SOD activity was decreased， while MDA， ROS， RhoA， ROCK1， and NF-κB p65 mRNA expression levels were increased （P<0.01）， and the protein expression levels of FN， Col Ⅳ， TGF-β₁， RhoA， ROCK， and NF-κB p65 were also elevated （P<0.01）. Compared with the model group， the DSS low-， medium-， and high-dose groups and the irbesartan group showed reductions in body weight， FBG， and 24 h UTP， decreased serum IL-1β and IL-6 levels， varying degrees of improvement in renal histopathology， increased SOD activity， decreased MDA levels， reduced ROS expression， and significantly downregulated RhoA， ROCK1， and NF-κB p65 mRNA expression （P<0.05， P<0.01）， as well as reduced protein expression levels of FN， Col Ⅳ， TGF-β₁， RhoA， ROCK， and NF-κB p65 （P<0.05， P<0.01）. ConclusionDSS can alleviate oxidative stress and inflammation， reduce extracellular matrix deposition， and delay renal fibrosis progression in db/db mice. Its mechanism may be related to the inhibition of the RhoA/ROCK/NF-κB signaling pathway， thereby exerting a therapeutic effect on DKD.

Protein arginine methyltransferase 5 (PRMT5) acts as an oncogene in liver cancer, yet its roles and in-depth molecular mechanisms within the liver cancer immune microenvironment remain mostly undefined. Here, we demonstrated that disruption of tumor-intrinsic PRMT5 enhances CD8⁺ T-cell-mediated antitumor immunity both in vivo and in vitro. Further experiments verified that this effect is achieved through downregulation of the inhibitory immune checkpoint molecule, fibrinogen-like protein 1 (FGL1). Mechanistically, PRMT5 catalyzed symmetric dimethylation of transcription factor 12 (TCF12) at arginine 554 (R554), prompting the binding of TCF12 to FGL1 promoter region, which transcriptionally activated FGL1 in tumor cells. Methylation deficiency at TCF12-R554 residue downregulated FGL1 expression, which promoted CD8⁺ T-cell-mediated antitumor immunity. Notably, combining the PRMT5 methyltransferase inhibitor GSK591 with PD-L1 blockade efficiently inhibited liver cancer growth and improved overall survival in mice. Collectively, our findings reveal the immunosuppressive role and mechanism of PRMT5 in liver cancer and highlight that targeting PRMT5 could boost checkpoint immunotherapy efficacy.

Objective The study aimed to investigate the impact of rare earth elements(REEs)exposure on pregnancy outcomes of in vitro fertilization-embryo transfer(IVF-ET)by analyzing samples from spouses. Methods A total of 141 couples were included.Blood and follicular fluid from the wives and semen plasma from the husbands,were analyzed for REEs using inductively coupled plasma mass spectrometry(ICP-MS).Spearman's correlation coefficients and the Mann-Whitney U test were used to assess correlations and compare REE concentrations among three types of samples,respectively.Logistic models were utilized to estimate the individual REE effect on IVF-ET outcomes,while BKMR and WQS models explored the mixture of REE interaction effects on IVF-ET outcomes. Results Higher La concentration in semen(median 0.089 ng/mL,P=0.03)was associated with a lower fertilization rate.However,this effect was not observed after artificial selection intervention through intracytoplasmic sperm injection(ICSI)(P=0.27).In semen,the REEs mixture did not exhibit any significant association with clinical pregnancy. Conclusion Our study revealed a potential association between high La exposure in semen and a decline in fertilization rate,but not clinical pregnancy rate.This is the first to report REEs concentrations in follicular fluid with La,Ce,Pr,and Nd found at significantly lower concentrations than in serum,suggesting that these four REEs may not accumulate in the female reproductive system.However,at the current exposure levels,mixed REEs exposure did not exhibit reproductive toxicity.

Objective:To explore the influencing factors for falls in inpatients during the rehabilitation period of stroke and research humanistic care strategies.Methods:Using a retrospective case-control study design,32 stroke patients who experienced falls in the rehabilitation department of the Second Affiliated Hospital of Xi'an Jiaotong University from January 2019 to December 2022 were selected as the observation group,and 64 stroke patients who were hospitalized in the same department during the same period and did not suffer from falls were matched 1:2 by age and gender as the control group.Logistic regression analysis was used to determine the influencing factors for falls in inpatients during the rehabilitation period of stroke.Results:The results of multivariate analysis showed that a history of falls(OR=8.688,P=0.036),a fall risk score(OR=1.615,P=0.018),sleep disorders(OR=5.378,P=0.031),malnutrition(OR=11.071,P=0.035),and osteoporosis(OR=15.831,P=0.006)were the independent risk factors for falls in inpatients during the rehabilitation period of stroke.Conclusion:There are many influencing factors for falls in inpatients during the rehabilitation period of stroke.Medical staff should take effective intervention measures based on different risk factors and implement humanistic care to reduce the incidence of falls in inpatients during the rehabilitation period of stroke.

Objective:To summarize the clinical features of transient neonatal myasthenia gravis (TNMG).Methods:We retrospectively collected the clinical data of an neonate diagnosed with TNMG in the department of Neonatology at the Affiliated Hospital of North Sichuan Medical College. Literature was retrieved from databases including CNKI, VIP, Wanfang, the Chinese Medical Journal Full Text database, the Chinese biomedical literature database, PubMed, Embase, Web of Science, The Cochrane library, and Medline. Search terms were "neonatal"、"pregnancy"OR"pregnant"OR"maternal"、"myasthenia"OR "myasthenia gravis"、"transient myasthenia gravis"OR"transitory myasthenia gravis"OR"temporary myasthenia gravis"、"congenital myasthenia gravis"OR"geneogenous myasthenia gravis". Searching period was from establishment of database to May 31st 2023. We summarize the clinical characteristics, treatment, and prognosis of reported cases with TNMG.Results:This patient is a full-term male infant who experienced decreased muscle tone, weak crying, and difficulty breathing 10 min after birth. His mother had a history of myasthenia gravis for 13 years. On the second day of birth, his neostigmine test was positive. So he was diagnosed with TNMG and treated with respiratory support and intravenous human immunoglobulin. His symptoms were relieved at day 10 and resolved by day 20. No abnormalities were observed during follow-up up to 6 months of age. A total of 7 Chinese papers and 13 English papers were retrieved, reporting 39 cases in total including this patient. Mothers of 34 cases (87.2%) were diagnosed with MG before delivery, and the other 5 mothers (12.8%) were diagnosed with MG after delivery. The main clinical manifestations in neonates were reduced muscle tone (29 cases, 74.4%), weak crying (23 cases, 59.0%), dyspnea (20 cases, 51.3%), and feeding difficulties (18 cases, 46.2%). 33 cases (84.6%) developed symptoms within the first day after birth, 6 cases (15.4%) had symptoms between day 2 and day 4. Most patients had a disease course for 2-6 weeks (29 cases, 74.4%). 27 cases (69.2%) underwent neostigmine test, all were positive. 30 cases (76.9%) were treated with cholinesterase inhibitors, 5 cases (12.8%) received IVIG and 1 case (2.6%) received an exchange transfusion. Out of the 39 cases, 33 cases (84.6%) were cured and discharged, 6 cases (15.4%) died. The causes of death were pulmonary infection and respiratory failure. Among the 17 patients with follow-up records, except for 1 case who only followed up to 2 months old and had slightly worse head upright, the rest of the children had normal physical and neurological development.Conclusions:TNMG may occur in infants that were born to MG mothers, most of the patients with TNMG develop symptoms on the first day after birth, a few patients develop symptoms 3-4 d after birth. Neostigmine test, serum MG antibody test should be performed to assist diagnosis. Cholinesterase inhibitors and symptomatic support are the main treatment options. TNMG generally have a good prognosis after treatment.

Objective:To understand the dilemma of active management in young and middle-aged postoperative patients with lumbar disc herniation, in order to provide reference for the formulation of active intervention program of self-health management meeting the needs of patients.Methods:Using the phenomenological research method, a total of 16 middle-aged and young patients with lumbar disc herniation were selected for semi-structured in-depth interviews, and the themes were analyzed and extracted by Colaizzi 7-step analysis method.Results:Three themes and nine sub-themes were extracted namely, inadequate disease response capacity and response resources (lack of disease symptom management capacity, limited access to disease management information, difficult use of disease management information, difficulty in maintaining positive self-management for a long time (forced to stop behavior change due to stress, lack of motivation to achieve good behavior change, doubts about the effectiveness of self-management) and multi-dimensional negative emotions (contrast between maintaining independence and dependence on others, fear of being misunderstood, fear of relapse) .Conclusions:Medical staff should provide comprehensive health information services for young and middle-aged postoperative patients with lumbar disc herniation, improve the out-of-hospital follow-up mechanism with the help of information technology, further improve family and social support strategies, reduce the difficulties faced in the process of active management and achieve long-term active disease management.

This paper reviewed literature at home and abroad, clarified the definition of drug literacy, elucidated the association between drug literacy and secondary preventive drug in stroke patients, analyzed the feasibility and limitations of existing drug literacy assessment tools in stroke patients, summarized the research status of drug literacy in stroke patients, so as to provide reference for the evaluation and intervention of drug literacy in stroke patients in China.

Frailty in elderly patients undergoing arthroplasty increases the risk of postoperative complications, prolongs hospital stays, delays the rehabilitation process, and aggravates the economic burden. Frailty is a dynamic condition, and early detection and effective intervention can delay its progression. Therefore, early assessment of frailty status in patients is necessary. Currently, there are numerous frailty assessment tools, but the selection of these tools lacks a solid basis. This paper reviews the impact of frailty on the physical condition of elderly arthroplasty patients, as well as the content, application, advantages, and limitations of existing frailty assessment tools at home and abroad. Furthermore, it summarizes the problems in the process of frailty assessment and puts forward prospects, aiming to provide reference for the identification and assessment of frailty in elderly arthroplasty patients in the future.

To further standardize the sedation and analgesia treatment for neurocritical care patients, the National Center for Healthcare Quality Management in Neurological Diseases and Chinese Society of Critical Care Medicine organized national experts in this fields to form Working group of the Expert consensus on sedation and analgesia for neurocritical care patients in order to update the Expert consensus on sedation and analgesia for patients with severe brain injury (2013) based on evidence-based medicine. This update aims to provide scientific guidance for the clinical diagnosis and treatment of neurocritical care patients. The working group followed the definition of clinical practice guidelines by the Institution of Medicine (IOM) and the World Health Organization guidelines development handbook and Guidelines for the formulation/revision of clinical guidelines in China (2022) to register and draft the Expert consensus on sedation and analgesia for neurocritical care patients. The working group will strictly adhere to the consensus development process to formulate and publish the Expert consensus on sedation and analgesia for neurocritical care patients (2023). This protocol primarily introduces the development methodology and process of the Expert consensus on sedation and analgesia for neurocritical care patients (2023), including the purpose of the update, the target population, the composition of the consensus development working group, the presentation and collection of clinical questions, evidence evaluation and summarization, and the generation of recommended opinions. This will make the consensus development process more standardized and transparent.
Humans ; Consensus ; Analgesia ; Analgesics/therapeutic use* ; Pain Management ; Critical Care