Osteoarthritis (OA) causes chronic pain that significantly impairs quality of life, with current treatments often proving insufficient and accompanied by adverse effects. Recent research has identified the dorsal root ganglion (DRG) and its resident macrophages as crucial mediators of chronic OA pain through neuroinflammation driven by macrophage polarization. We present a novel injectable thermo-sensitive hydrogel system, KAF@PLEL, designed to deliver an anti-inflammatory peptide (KAF) specifically to the DRG. This biodegradable hydrogel enables sustained KAF release, promoting the reprogramming of DRG macrophages from pro-inflammatory to anti-inflammatory phenotypes. Through comprehensive in vitro and in vivo studies, we evaluated the hydrogel's biocompatibility, effects on macrophage polarization, and therapeutic efficacy in chronic OA pain management. The system demonstrated significant capabilities in preserving macrophage mitochondrial function, suppressing neuroinflammation, alleviating chronic OA pain, reducing cartilage degradation, and improving motor function in OA rat models. The sustained-release properties of KAF@PLEL enabled prolonged therapeutic effects while minimizing systemic exposure and side effects. These findings suggest that KAF@PLEL represents a promising therapeutic approach for improving outcomes in OA patients through targeted, sustained treatment.

Neuroinflammation is a common pathological feature of neurodegenerative diseases （NDs）. Microglia （MG）， a resident macrophage in the brain with a unique developmental origin， is the core driver of neuroinflammation. It can participate in the occurrence and development of NDs through different polarization states and play a key role in regulating neurogenesis and synapse shaping and maintaining homeostasis. MG can be divided into M1 pro-inflammatory phenotype and M2 anti-inflammatory phenotype according to its function. The inflammatory mediators released by the M1 phenotype can lead to nerve degeneration and myelin sheath damage， while the activation of the M2 phenotype is required to inhibit the inflammatory response and promote tissue repair. With the advantages of multi-pathway， multi-target， and bidirectional regulation， traditional Chinese medicine can regulate the polarization balance of MG and has dual effects on NDs such as Alzheimer's disease， Parkinson's disease， and multiple sclerosis. The active components of traditional Chinese medicine and its compound can inhibit the activation of MG by regulating phosphatidylinositol-3-kinases/protein kinase B（PI3K/Akt）， NOD-like receptor thermal protein domain associated protein 3（NLRP3）， signal transducer and activator of transcription factor1（STAT1）， nuclear transcription factor kappa B（NF-κB）， and other pathways， promote the polarization of M1 phenotype to M2 phenotype， reduce the expression of interleukin（IL）-6， tumor necrosis factor-α（TNF-α）， and other pro-inflammatory factors， and increase the secretion of IL-10， arginase-1（Arg-1）， and other anti-inflammatory factors. It can also reduce β-amyloid deposition and tau protein expression in Alzheimer's disease， alleviate dopaminergic neuronal damage in Parkinson's disease， and relieve demyelination， inflammatory cell infiltration， and related clinical symptoms of multiple sclerosis. The bidirectional regulation of the M1/M2 polarization balance of MG by traditional Chinese medicine is a potential strategy for the treatment of NDs. This paper focused on the targets of the regulation of MG polarization balance by traditional Chinese medicine monomer and its compound in the treatment of NDs， so as to further study and summarize the existing research results and provide ideas and basis for the future treatment of NDs.

Objective To systematically evaluate the efficacy of β-blocker in pediatric patients with congestive heart failure and congenital heart disease,and to provide evidence for clinician.Methods Before-and-after self-control study and randomized controlled trials were retrieved from PubMed,EMbase,the Cochrane Library,CNKI,WanFang,VIP databases,and the search time was from the establishment of the database to October 31,2023.All outcomes included left ventricular ejection fraction(LVEF),left ventricular fraction shortening,LVFS),left ventricular end-diastolic dimension(LVDD),Left ventricular end-systolic dimension(LVSD),N-terminal proB brain natriuretic peptide(NT-proBNP),heart rate,blood pressure and cardiac function improvement.Results A total of 20 trials involving 1 068 children with heart failure(dilated cardiomyopathy and endocardial fibroelastosis were included.Meta-analysis results showed that the addition of β-blockers(metoprolol succinate,bisoprolol and carvedilol)on the basis of conventional drug therapy for heart failure had significant effects on LVEF[MD=13.06,95%CI(11.67,14.45),P<0.001],LVFS[MD=6.96,95%CI(6.54,7.37),P<0.001],LVDD[MD=-6.43,95%CI(-7.58,-5.28),P<0.001]and LVSD[MD=-8.30,95%CI(-8.83,-7.76),P<0.001]were significantly improved.In addition,blood pressure,heart rate,NT-proBNP and cardiac function could also be improved.Conclusion The combination regimen of β-blockers on the basis of conventional drug therapy for heart failure can improve cardiac function and symptoms of heart failure in children with congestive heart failure.Therefore,it is recommended that β-blockers should be actively used in the conventional treatment regimen for children with congestive heart failure.

Objective To investigate the therapeutic effects of Isaria felina derived from Cordyceps sinensis combined with cyclophosphamide(CTX)in hepatoma H22 tumor-bearing mice.Methods An H22 tumor-bearing mouse model was established and mice were divided randomly into a normal control group(NC group,distilled water),model control group(MC group,distilled water),positive control group(CTX group,25 mg/kg),Isaria felina group(IF group,400 mg/kg),and combined administration group(IF+CTX group,IF 400 mg/kg+CTX 25 mg/kg),with 5 mice in each group.Distilled water and IF were administered by gavage,and CTX was administered by intraperitoneal injection.The administration cycle was 10 days.At the end of the experiment,the mean tumor volume and weight,tumor inhibition rate,q value,and immune organ index were calculated,and routine blood indexes and cytokine levels were determined.Histopathological changes in tumor tissues were observed by HE staining.Results The tumor volume and mass were significantly lower in mice in each treatment group compared with those in mice in the MC group(P＜0.05).The tumor inhibition rates in the CTX,IF,and IF+CTX groups were 49.3%,34.2%,and 72.8%,respectively,and the q value was 1.09.The numbers of white blood cells,Lymph,and platelets were significantly higher in the IF+CTX group than in the CTX group(P＜0.05).The spleen index was significantly higher in the MC group compared with that in the NC group,and significantly lower in the IF+CTX group compared with that in the MC group(P＜0.05).Serum interferon-γ levels were significantly lower in the MC group than in the NC group,and were significantly higher in the IF and IF+CTX groups compared with those in the MC and CTX groups(P＜0.05).Pathologically,tumor cells in the MC group grew well and were numerous and closely arranged,while cells in the CTX,IF,and IF+CTX groups were arranged loosely,with focal necrosis and nuclear pyknosis of necrotic cells in many places.Conclusions The combination of IF and CTX has an additive anti-tumor effect on H22 tumor-bearing mice,which can alleviate immunosuppression and have an immunomodulatory function.

Objective:To investigate the mechanism of excessive iodine-induced apoptosis of chorionic trophoblast cells associated with missed early miscarriage.Methods:Patients with unexplained missed early miscarriage ≤12 weeks of gestation (MA group, n = 43) and normal pregnant women (control group, n = 64) who were treated at Tianjin Central Obstetrics and Gynecology Hospital from September 2019 to September 2022 were selected as the study subjects, and villous tissues were collected for proliferating cell nuclear agtigen Ki67 immunohistochemistry and apoptosis assay, while urine samples were collected for urinary iodine content assay. Different doses of iodine were used to stimulate the cultivation of human chorionic trophoblast cell line (HTR8/SVneo) for 24 h. Cell proliferation viability was detected using cell counting kit 8 (CCK8), and apoptosis was detected using flow cytometry. Results:(1) Urinary iodine values were 159.70 (114.21, 218.73) μg/L in the control group and 210.80 (143.10, 336.70) μg/L in the MA group, the difference between the two groups was statistically significant ( Z = 2.26, P = 0.024). (2) The proportion of positive and strong positive Ki67 immunohistochemical staining of the villous tissues in the MA group was significantly lower than that in the control group (χ 2 = 37.00, P < 0.001). (3) The apoptosis rate of villous tissue in the MA group was significantly higher than that in the control group [(26.24 ± 1.06)% vs (2.96 ± 1.97)%, t = 92.23, P < 0.001]. (4) The cell proliferation rates of HTR8/SVneo in the 50, 100, 300 and 500 μg iodine groups were significantly lower than that in the 0 μg iodine group ( P < 0.05), with the 500 μg iodine group below the median lethal dose (LD 50). (5) The apoptosis rates of 0, 50 and 500 μg iodine groups were (8.79 ± 0.12)%, (9.56 ± 0.08)% and (19.86 ± 0.05)%, respectively, and the differences among the three groups were statistically significant ( F = 7.32, P = 0.007); in which the 50 and 500 μg iodine groups were higher than that of the 0 μg iodine group, and the 500 μg iodine group was higher than that of the 50 μg iodine group ( P < 0.05). Conclusions:Urine iodine content significantly increases in patients with missed early miscarriage. Excessive iodine intake may lead to a decrease in the proliferation viability and an increase in cell apoptosis of chorionic trophoblast cells.

Objective:To investigate the role of TRIZ theory in clinical teaching in orthopedic operating room.Methods:A total of 43 interns in the orthopedic operating room of our hospital from October 2019 to July 2020 were selected as control group, and 46 interns in the orthopedic operating room of our hospital from August 2020 to May 2021 were selected as observation group. The interns in the control group received traditional teaching, and those in the observation group received teaching based on TRIZ theory. The two groups were compared in terms of professional assessment results, self-evaluation, satisfaction score, and qualification of aseptic operation in orthopedic operating room. SPSS 22.0 was used to perform the t-test and the chi-square test. Results:Compared with the control group, the observation group had significantly higher theoretical knowledge score, practical skill score, and weighted total score ( t=14.90, 11.82, and 13.23, all P?0.001). Compared with the control group, the observation group also had significantly higher scores of analysis and problem-solving ability, clinical thinking, doctor-patient communication, psychological quality, clinical case analysis, self-study ability, and teaching satisfaction ( t=7.88, 11.78, 15.26, 7.94, 12.93, 9.83, and 13.22, all P?0.001). Compared with the control group, the observation group had significantly higher qualified rates of surgical hand-washing, wearing sterile surgical gowns, non-contact glove wearing; and bacteriological testing ( χ 2=4.22, 6.02, 4.92, and 7.59, P=0.040, 0.014, 0.027, and 0.006). Conclusion:TRIZ theory has a certain value in clinical teaching in orthopedic operating room and can significantly improve the scores of theoretical knowledge and practical skills, strengthen aseptic operation abilities in orthopedic operating room, and enhance the satisfaction with teaching among interns.

Metabolic-associated fatty liver disease (MAFLD), which is previously known as non-alcoholic fatty liver disease (NAFLD), represents a major health concern worldwide with limited therapy. Here, we provide evidence that ferroptosis, a novel form of regulated cell death characterized by iron-driven lipid peroxidation, was comprehensively activated in liver tissues from MAFLD patients. The canonical-GPX4 (cGPX4), which is the most important negative controller of ferroptosis, is downregulated at protein but not mRNA level. Interestingly, a non-canonical GPX4 transcript-variant is induced (inducible-GPX4, iGPX4) in MAFLD condition. The high fat-fructose/sucrose diet (HFFD) and methionine/choline-deficient diet (MCD)-induced MAFLD pathologies, including hepatocellular ballooning, steatohepatitis and fibrosis, were attenuated and aggravated, respectively, in cGPX4-and iGPX4-knockin mice. cGPX4 and iGPX4 isoforms also displayed opposing effects on oxidative stress and ferroptosis in hepatocytes. Knockdown of iGPX4 by siRNA alleviated lipid stress, ferroptosis and cell injury. Mechanistically, the triggered iGPX4 interacts with cGPX4 to facilitate the transformation of cGPX4 from enzymatic-active monomer to enzymatic-inactive oligomers upon lipid stress, and thus promotes ferroptosis. Co-immunoprecipitation and nano LC-MS/MS analyses confirmed the interaction between iGPX4 and cGPX4. Our results reveal a detrimental role of non-canonical GPX4 isoform in ferroptosis, and indicate selectively targeting iGPX4 may be a promising therapeutic strategy for MAFLD.

Objective:To explore the role of individualized teaching method based on failure mode and effect analysis (FMEA) in the teaching of rotation interns in operating room.Methods:Twenty-three operating room rotation interns received by Zhongnan Hospital, Wuhan University from February 2019 to September 2019 were selected as the control group, and another 23 operating room rotation interns received from October 2019 to May 2020 were selected as the research group. The control group adopted the conventional teaching method, while the research group adopted the individualized teaching method based on FMEA. The theoretical knowledge and practical operation examination results before and after teaching, self-directed learning ability before and after teaching and teaching satisfaction of interns after teaching were compared between the two groups. SPSS 25.0 was used for t test, chi-square test and rank sum test. Results:After teaching, the scores of theoretical knowledge [(91.13±6.35) vs. (84.26±5.94)] and practical operation [(89.39±5.45) vs. (79.78±5.65)], self-directed learning ability of each dimension and total scores [(280.63±23.39) vs. (248.17±20.68)] of the two groups were higher than those before teaching, and the scores of theoretical knowledge and practical operation, self-directed learning ability of each dimension and total score of the research group were higher than those of the control group ( P<0.05). After teaching, the satisfaction scores on the professional quality of the teachers, the rationality of the teaching mode and the effectiveness of the teaching mode of the interns in the research group were higher than those in the control group ( P<0.05). Conclusion:In the teaching of rotation interns in operating room, the individualized teaching method based on FMEA can not only improve the examination results of interns, enhance their self-directed learning ability, but also improve their teaching satisfaction.

Lung cancer is currently one of the most common malignant tumors in the world. The occurrence and development of lung cancer, especially non-small cell lung cancer (NSCLC), are closely related to the abnormal expression of long non-coding RNA (lncRNA). lncRNA with a transcript of more than 200 nucleotides is involved in chromatin modification, transcription activation, transcription interference and other regulatory processes, and has varying degrees of regulation on the proliferation, migration, and invasion of tumor cells. It is characterized by up-regulation or down-regulation of expression. At present, there are a large number of studies on lncRNA, because lncRNA has considerable application prospects in the diagnosis, clinical treatment, drug resistance research and prognosis evaluation of NSCLC. In this paper, the overview of lncRNA, the up-regulation or down-regulation of NSCLC-related lncRNA expression, NSCLC clinical treatment and drug-resistant lncRNA were summarized.

Objective:To explore the effects of failure modes and effects analysis (FMEA) in the transfer of critically ill patients in operating room.Methods:Convenient sampling was used to include totally 50 critically ill patients from the operating room at Zhongnan Hospital of Wuhan University between January and September into a control group, and another 50 critically ill patients from the operating room from October 2019 to June 2020 into an observation group. Patients in the control group received conventional transfer management, while patients in the observation group were managed with FMEA. The adverse reactions, transfer time, and satisfaction of receiving departments were compared between the two groups of patients.Results:The total incidence of adverse reactions such as drainage tube slippage, infusion tube slippage, tracheal tube slippage, and sudden disease changes in the observation group was 6% (3/50) , which was lower than 22% (11/50) in the control group (χ 2=6.673, P<0.05) . The transfer time in the group was (26.57±3.83) min, which was shorter than (41.52±4.04) min in the control group ( t=12.672, P<0.05) . The satisfaction of receiving departments for the observation group in advance notice of the condition, preparation of first aid equipment, notification of vital signs, the condition and medication upon handover, and assistance in placement was higher than that for the control group ( P<0.05) . Conclusions:The use of FMEA in the transfer of critically ill patients in operating room can reduce the occurrence of adverse events during the transfer, shorten the transfer time, improve the satisfaction of receiving departments, and reduce the transfer risk.