Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Parkinson's disease（PD） is the second most common neurodegenerative disease in the world， which seriously affects the lives of patients. With the acceleration of aging process， the number of patients continues to rise. Its main pathological features are aggregation of α-synuclein and degenerative death of dopaminergic neurons in the substantia nigra. However， the pathogenesis of PD is still unclear. According to reports， the brain-derived neurotrophic factor（BDNF）/tyrosine kinase receptor B（TrkB） signaling pathway is highly expressed and activated in dopaminergic neurons in the substantia nigra， which is closely related to neurophysiological processes such as neurogenesis， synaptic plasticity， neuroinflammation， and oxidative stress. It plays an important role in the occurrence and development of PD. At present， the treatment methods of Western medicine for PD are mainly based on drugs such as levodopa and dopamine agonists to alleviate motor symptoms， but with the increase of dose， the adverse reactions are significantly enhanced. Traditional Chinese medicine（TCM） has attracted people to explore its therapeutic effects on PD due to its characteristics of homology of medicine and food， economy， minor adverse reactions and multi-target action. Therefore， this paper systematically reviews the role of BNDF/TrkB pathway in the pathogenesis of PD and the mechanism of TCM formulas， extracts and monomers in the treatment of PD by regulating the BNDF/TrkB pathway according to retrieving the latest research reports at home and abroad， so as to provide a reference for the clinical application of related TCM and the development of new drugs for PD.

OBJECTIVE To investigate the relationship between the expression level of endotoxin and soluble interleukin-2 receptor(sIL-2R)and the occurrence of suppurative otitis media in patients with nasopharyngeal carcinoma after radiotherapy.METHODS Seventy-nine nasopharyngeal cancer patients who received radiotherapy in Nanyang Downtown Hospital between January 2022 and July 2023 were selected as the study subjects,and they were followed up for a period of 1 year,and then grouped according to the occurrence of suppurative otitis media during the follow-up period,i.e.,21 cases in the occurringgroup and 58 cases in the non-occurring group,and the baseline data of patients in the two groups were compared,and the levels of endotoxin and sIL-2R were detected at the end of radiotherapy and analyze the relationship between endotoxin,sIL-2R and the occurrence of purulent otitis media after radiotherapy for nasopharyngeal carcinoma.RESULTS A total of 21 cases(26.58%)of 79 nasopharyngeal carcinoma patients developed suppurative otitis media after radiotherapy.Compared with the non-occurrence group,the radiotherapy time,endotoxin,sIL-2R,TNM stage Ⅲ,Eustachian tube involvement,nasal cavity structural abnormality,inflammatory reaction,and palatal sail tensor atrophy degree≥30%were high in the occurrence group,and the difference was statistically significant(all P<0.05).The results of logistic multifactorial analysis showed that inflammatory reaction,endotoxin,abnormal nasal structure,TNM stage(Ⅲ),sIL-2R,Eustachian tube involvement,duration of radiotherapy,and degree of atrophy of palatofacial tensor atrophy≥30%were all risk factors for suppurative otitis media.The results of Spearman's rank correlation analysis showed that endotoxin and sIL-2R were positively correlated with the occurrence of septic otitis media(r=0.493,0.516,P<0.001).Analysis using the ROC curve showed that:endotoxin:AUC value:0.657,sensitivity:61.90%,specificity:72.41%,accuracy:69.62%,95%CI=0.523-0.791;sIL-2R:AUC value:0.697,sensitivity:71.43%,specificity:67.24%,accuracy:68.35%,95%CI=0.566-0.829;combined test:AUC value:0.804,sensitivity:95.24%,specificity:65.52%,accuracy:73.42%,95%CI=0.705-0.903,the best value of the two combined tests.CONCLUSION The elevated levels of endotoxin and sIL-2R in patients with nasopharyngeal carcinoma after radiotherapy may be associated with suppurative otitis media.

OBJECTIVE To compare the short-term efficacy of autologous frozen tragus perichondrium and fresh perichondrium in repairing tympanic membrane perforations,and to explore the clinical application value of autologous frozen tragus perichondrium.METHODS Twenty-five patients with bilateral tympanic membrane perforations from March 2021 to October 2023 were selected,including 7 males and 18 females.Bilateral tympanoplasty was completed in stages.The initial operation was set as the control group,in which the ventral perichondrium of the tragus was used for tympanoplasty,and the dorsal perichondrium of the tragus was reserved and stored at-80℃ultra-low temperature in a sterile container.The second operation was set as the observation group,in which the thawed frozen perichondrium was used for contralateral tympanoplasty.The differences in the healing rate of tympanic membrane,postoperative hearing,operation time and surgical bleeding volume were compared between the two groups.RESULTS All patients were followed up for three months.The success rate of tympanic membrane healing in the observation group was 96%(24/25),and that in the control group was 92%(23/25).There was no statistically significant difference between the two groups(χ2=0.36,P>0.05).The operation time and surgical bleeding volume of patients in the observation group were lower than those in the control group[(48.64±4.64)min vs.(67.92±5.69)min,(5.32±1.54)ml vs.(9.65±1.73)ml],and the differences were statistically significant(t=13.93,t=12.09,P all<0.05).The postoperative air conduction hearing thresholds and air-bone conduction gap of the two groups of patients were lower than those before operation(all P<0.05).There was no difference in air conduction hearing threshold,bone conduction hearing threshold and air-bone conduction difference between the groups(all P>0.05).CONCLUSION The application of autologous frozen tragus perichondrium has effectively shortened the operation time of the contralateral ear,avoided the trauma caused by taking materials again,and has the characteristics of minimally invasive and high efficiency.The method is feasible and the curative effect is accurate.

Wound infections, secondary to acute and chronic wounds caused by mechanical, thermal, chemical factors, etc, not only delay wound healing but also may lead to mortality. The prolonged or inappropriate use of antibiotics lead to the growth of drug-resistant bacteria, resulting in refractory wound infections and poor treatment outcomes, which highlights the urgent need for effective therapies. Bacteriophages show great promise in treating drug-resistant wound infections due to their effectiveness in killing drug-resistant bacteria, their good resistance against bacterial biofilm (BBF) and their absence of cytotoxicity to eukaryotic cells. However, the mechanisms underlying bacteriophages′ resistance against BBF remain incompletely understood and their antibacterial efficacy for wound infections may also vary. For this purpose, the authors reviewed the biological characteristics and mechanisms of bacteriophages and their application in antibacterial therapies for wound infections, aiming to provide a reference for further research and application of bacteriophages in the treatment of wound infections.

Objective:To explore the effect of health education based on symptom management strategy on the psychological status, self-management ability and quality of life of maintenance hemodialysis patients.Methods:A randomized controlled trial method was used. One hundred and fifty hemodialysis maintenance patients in the Blood Purification Center, Jinan People's Hospital from August 2019 to August 2020, were selected as the research subjects by convenience sampling. Patients were divided into a control group and observation group by random number table method, with 75 cases in each group. The control group was given routine health education, and the observation group was given health education based on symptom management strategies. Self-rating Anxiety Scale (SAS), self-rating Depression Scale (SDS), self-management ability scale of dialysis patients, and SF-36 quality of life scale were used to compare the improvement of negative emotion, self-management ability, and quality of life in the two groups.Results:There was no statistically significant difference between the control group and the observation group before the intervention (all P>0.05). After 3 months of intervention, the SAS and SDS scores of the patients in the observation group were (36.42 ± 4.09) and (35.74 ± 3.64) respectively, which were lower than those of the control group (46.37 ± 4.64) and (49.38 ± 2.49). The difference was statistically significant ( t=8.46, 9.42, P<0.05); the self-management score of patients in the observation group (80.11 ± 7.83) was higher than that in the control group (47.21 ± 6.62), with a statistically significant difference ( t=32.29, P<0.05); the total score of SF-36 quality of life in the observation group (594.32 ± 35.03) was higher than that in the control group (501.42 ± 32.78),with a statistically significant difference ( t=24.66, P<0.05). Conclusions:Health education based on symptom management strategy can improve the psychological status of maintenance hemodialysis patients, and has important value in improving their self-management ability and quality of life.

Objective:To explore the correlation between glycated hemoglobin variability index (HGI) and carotid artery plaque in patients with type 2 diabetic kidney disease (DKD).Methods:This cross-sectional study included 620 DKD patients admitted to the Department of Endocrinology in the First Affiliated Hospital of Nanjing Medical University from June 2019 to June 2022. Basic demographic and laboratory data, including age, disease duration, body mass index (BMI), blood pressure, fasting blood glucose (FBG), glycated hemoglobin (HbA 1c), lipid profile, and urinary albumin excretion rate (UAER), were collected for all participants. A linear regression equation was developed based on FPG and HbA 1c to calculate the HGI level of each patient. The patients were divided into low HGI group, medium HGI group, and high HGI group based on the tertiles of HGI. The detection rate of carotid artery plaque in the three HGI groups was analyzed. The patients were further divided into the non-plaque group (254 cases) and plaque group (366 cases) based on the presence or absence of carotid artery plaque. Binary logistic regression analysis was used to identify the risk factors for carotid artery plaque in DKD patients. Results:Among the DKD patients, the detection rate of carotid artery plaque was 59%. Compared with the non-plaque group, the patients in the plaque group had older age (60.52 years, t=-7.71), longer disease duration (10 years, Z=-4.17), higher systolic blood pressure (141.9 mmHg, t=-3.29), higher HbA 1c (9.2%, Z=-2.17), higher HGI (-0.20%, Z=-3.43), higher urea nitrogen (6.87 μmol/L, Z=-3.96), higher creatinine (77 mmol/L, Z=-4.05), and higher UAER (234.25 mg/24 h, Z=-5.59) (all P<0.05). The detection rate of carotid artery plaque in the low HGI group, medium HGI group and high HGI group was 50.5%, 57.9% and 68.5%, respectively, with a statistically significant difference among the three groups (χ 2=14.15, P=0.001). Age, UAER, and HGI were identified as risk factors for carotid artery plaque ( OR=1.051, 2.775 and 1.474, all P<0.05). The risk of carotid artery plaque in the high HGI group was 2.142 times of that in the low HGI group. After adjusting for confounding factors such as age, gender, disease duration, BMI, blood pressure, lipid profile and UAER, the risk of carotid artery plaque in the high HGI group was 2.558 times of that in the low HGI group. Conclusion:HGI is significantly elevated in DKD patients with carotid artery plaque, and the detection rate of carotid artery plaque increases with HGI level. Elevated HGI is an independent risk factor for carotid artery plaque in DKD patients.

AIM: To investigate the distribution characteristics of methylenetetrahydrofolate reductase (MTHFR) gene polymorphism and its correlation with blood Hcy in hypertensive patients and to provide reference for the prevention and treatment of H-type hypertension in southern Anhui Province. METHODS: A total of 657 hypertensive patients were treated in our hospital from October 2019 to August 2020 were selected as the research objects. The MTHFR C677T and A1298C loci were genotyped by fluorescence staining in situ hybridization, and the blood Hcy concentration was determined by the enzyme cycle method. The distribution characteristics of MTHFR gene in the Han nationality hypertensive population in southern Anhui Province were analyzed, and compared with the reported MTHFR gene distribution data of hypertensive populations in other regions and ethnic groups. RESULTS: Among the 657 patients, the distributions of CC, CT and TT types at the C677T site of MTHFR gene were 212(32.27%), 321 (48.86%), 124(18.87%), and the distribution of AA, AC, and TT types at the A1298C site were 467 (71.08%), 171(26.03%), 19(2.89%). There was no gender difference in the distribution of the two loci of this gene in the hypertensive population in southern Anhui Province (P > 0.05). The distribution frequency of CC genotype at C677T locus is lower than that in Foshan and Guangxi, but higher than that in Henan, Xinjiang and Inner Mongolia; the frequency of CT genotype is higher than that in Foshan and Guangxi; the frequency of TT genotype is higher than that in Foshan and Guangxi. Guangxi region was lower than Henan region, Xinjiang region and Inner Mongolia region, and the difference was statistically significant (P < 0.05). The mean blood Hcy of 657 patients was (15.8 ± 7.80) μmol/L, of which 510(77.62%) were in line with the diagnosis of H-type hypertension. The level of Hcy in males was significantly higher than that in females, and the difference was statistically significant (P < 0.000 1). Compared with the different genotypes of the C677T locus, the TT type was higher than the CT type and CC type, and the difference was statistically significant (P < 0.05). There was no significant difference in Hcy levels between different genotypes at the A1298C locus (P > 0.05). CONCLUSION: The distribution of MTHFR gene polymorphism in the Han nationality hypertensive population in southern Anhui is significantly different from other regions, and it is also significantly related to the level of Hcy, which has obvious regional characteristics. The genetic detection technology combined with the determination of Hcy concentration can provide a scientific basis for the prevention and treatment of H-type hypertension in southern Anhui Province.

Objective::Microchannels are associated with the progression of atherosclerotic vulnerable plaques. However, in patients with culprit optical coherence tomography (OCT)-defined plaque erosion, the knowledge of microchannels and culprit lesion vulnerability is limited. The aim of this study was to investigate culprit lesion characteristics in patients with ST-segment elevated myocardial infarction (STEMI) caused by plaque erosion with and without microchannels using OCT.Methods::In all, 348 STEMI patients with plaque erosion who underwent OCT of the culprit lesion at the 2 nd Affiliated Hospital of Harbin Medical University (Harbin, China) from August 2014 to December 2017 were included and divided into the microchannel group ( n= 116, 33.3%) and no-microchannel group ( n = 232, 66.7%). The clinical characteristics and OCT-derived plaque features were compared between both groups. Results::Among the 348 STEMI patients with plaque erosion, culprit lesions with microchannels had higher incidence of lipid plaque (59.5% vs. 45.3%, P= 0.012); calcification (41.4% vs. 24.6%, P= 0.002); spotty calcification (30.2% vs. 18.1%, P= 0.014); macrophages accumulation (72.4% vs. 45.7%, P < 0.001); and cholesterol crystals (32.8% vs. 14.2%, P < 0.001) than those without microchannels. In addition, minimal lumen area was smaller ((1.9 ± 0.9) mm 2vs. (2.8 ± 2.3) mm 2, P < 0.001) and lumen area stenosis was greater ((71.3% ± 13.4%) vs. (65.3% ± 19.3%), P= 0.001) in the microchannel group than in the no-microchannel group. Conclusion::In patients with STEMI caused by plaque erosion, one-third manifested typical microchannel characteristics, and those with microchannels were associated with more severe luminal stenosis and more vulnerable plaque features than those without microchannels.

Objective::Microchannels are associated with the progression of atherosclerotic vulnerable plaques. However, in patients with culprit optical coherence tomography (OCT)-defined plaque erosion, the knowledge of microchannels and culprit lesion vulnerability is limited. The aim of this study was to investigate culprit lesion characteristics in patients with ST-segment elevated myocardial infarction (STEMI) caused by plaque erosion with and without microchannels using OCT.Methods::In all, 348 STEMI patients with plaque erosion who underwent OCT of the culprit lesion at the 2 nd Affiliated Hospital of Harbin Medical University (Harbin, China) from August 2014 to December 2017 were included and divided into the microchannel group ( n= 116, 33.3%) and no-microchannel group ( n = 232, 66.7%). The clinical characteristics and OCT-derived plaque features were compared between both groups. Results::Among the 348 STEMI patients with plaque erosion, culprit lesions with microchannels had higher incidence of lipid plaque (59.5% vs. 45.3%, P= 0.012); calcification (41.4% vs. 24.6%, P= 0.002); spotty calcification (30.2% vs. 18.1%, P= 0.014); macrophages accumulation (72.4% vs. 45.7%, P < 0.001); and cholesterol crystals (32.8% vs. 14.2%, P < 0.001) than those without microchannels. In addition, minimal lumen area was smaller ((1.9 ± 0.9) mm 2vs. (2.8 ± 2.3) mm 2, P < 0.001) and lumen area stenosis was greater ((71.3% ± 13.4%) vs. (65.3% ± 19.3%), P= 0.001) in the microchannel group than in the no-microchannel group. Conclusion::In patients with STEMI caused by plaque erosion, one-third manifested typical microchannel characteristics, and those with microchannels were associated with more severe luminal stenosis and more vulnerable plaque features than those without microchannels.