With the rapid development of social economy and the continuous improvement of human living standard, the incidence, fatality and recurrence rates of cardiovascular disease (CVD) are increasing year by year, which seriously affects people's life and health. Conventional therapeutic drugs have limited improvement on the disability rate, so the search for new therapeutic drugs and action targets has become one of the hotspots of current research. In recent years, the therapeutic role of the natural compound rosmarinic acid (RA) in CVD has attracted much attention, which is capable of preventing CVD by modulating multiple signalling pathways and exerting physiological activities such as antioxidant, anti-apoptotic, anti-inflammatory, anti-platelet aggregation, as well as anti-coagulation and endothelial function protection. In this paper, the role of RA in the prevention of CVD is systematically sorted out, and its mechanism of action is summarised and analysed, with a view to providing a scientific basis and important support for the in-depth exploration of the prevention value of RA in CVD and its further development as a prevention drug.

Methods: The clinical data of 26 patients diagnosed with irreducible atlantoaxial dislocation complicated by atlantodental bony obstruction were analyzed retrospectively. All patients underwent anterior retropharyngeal atlantodentoplasty, followed by posterior occipitocervical fusion. Details including surgical duration and blood loss volume were recorded. Radiographic data such as the anterior atlantodental interval, O–C2 angle, space available for the cord, clivus–canal angle, and cervical medullary angle, and clinical data including the Japanese Orthopedic Association (JOA) score were assessed. The fusion time of the grafted bone and the development of complications were examined. Results: In patients undergoing anterior retropharyngeal atlantodentoplasty, the surgical duration and blood loss volume were 120.1±16.4 minutes and 100.6±33.5 mL, respectively. The anterior atlantodental interval decreased significantly after the surgery (p <0.001). The O–C2 angle, space available for the cord, clivus–canal angle, and cervical medullary angle increased significantly after the surgery (p <0.001). The JOA score during the latest follow-up significantly increased compared with that before the surgery (p <0.001). The improvement rate of the JOA score was 80.8%±18.1%. The fusion time of the grafted bone was 3–8 months, with an average of 5.7±1.5 months. In total, 11 patients presented with postoperative dysphagia and three with irritating cough. However, none of them exhibited other major complications. Conclusions Anterior retropharyngeal atlantodentoplasty can anatomically reduce the atlantoaxial joint with a satisfactory clinical outcome in patients with irreducible atlantoaxial dislocation with atlantodental bony obstruction.

Methods: The clinical data of 26 patients diagnosed with irreducible atlantoaxial dislocation complicated by atlantodental bony obstruction were analyzed retrospectively. All patients underwent anterior retropharyngeal atlantodentoplasty, followed by posterior occipitocervical fusion. Details including surgical duration and blood loss volume were recorded. Radiographic data such as the anterior atlantodental interval, O–C2 angle, space available for the cord, clivus–canal angle, and cervical medullary angle, and clinical data including the Japanese Orthopedic Association (JOA) score were assessed. The fusion time of the grafted bone and the development of complications were examined. Results: In patients undergoing anterior retropharyngeal atlantodentoplasty, the surgical duration and blood loss volume were 120.1±16.4 minutes and 100.6±33.5 mL, respectively. The anterior atlantodental interval decreased significantly after the surgery (p <0.001). The O–C2 angle, space available for the cord, clivus–canal angle, and cervical medullary angle increased significantly after the surgery (p <0.001). The JOA score during the latest follow-up significantly increased compared with that before the surgery (p <0.001). The improvement rate of the JOA score was 80.8%±18.1%. The fusion time of the grafted bone was 3–8 months, with an average of 5.7±1.5 months. In total, 11 patients presented with postoperative dysphagia and three with irritating cough. However, none of them exhibited other major complications. Conclusions Anterior retropharyngeal atlantodentoplasty can anatomically reduce the atlantoaxial joint with a satisfactory clinical outcome in patients with irreducible atlantoaxial dislocation with atlantodental bony obstruction.

Methods: The clinical data of 26 patients diagnosed with irreducible atlantoaxial dislocation complicated by atlantodental bony obstruction were analyzed retrospectively. All patients underwent anterior retropharyngeal atlantodentoplasty, followed by posterior occipitocervical fusion. Details including surgical duration and blood loss volume were recorded. Radiographic data such as the anterior atlantodental interval, O–C2 angle, space available for the cord, clivus–canal angle, and cervical medullary angle, and clinical data including the Japanese Orthopedic Association (JOA) score were assessed. The fusion time of the grafted bone and the development of complications were examined. Results: In patients undergoing anterior retropharyngeal atlantodentoplasty, the surgical duration and blood loss volume were 120.1±16.4 minutes and 100.6±33.5 mL, respectively. The anterior atlantodental interval decreased significantly after the surgery (p <0.001). The O–C2 angle, space available for the cord, clivus–canal angle, and cervical medullary angle increased significantly after the surgery (p <0.001). The JOA score during the latest follow-up significantly increased compared with that before the surgery (p <0.001). The improvement rate of the JOA score was 80.8%±18.1%. The fusion time of the grafted bone was 3–8 months, with an average of 5.7±1.5 months. In total, 11 patients presented with postoperative dysphagia and three with irritating cough. However, none of them exhibited other major complications. Conclusions Anterior retropharyngeal atlantodentoplasty can anatomically reduce the atlantoaxial joint with a satisfactory clinical outcome in patients with irreducible atlantoaxial dislocation with atlantodental bony obstruction.

OBJECTIVE: To explore the mechanism of electroacupuncture (EA) in promoting recovery of the facial function with the involvement of autophagy, glial cell line-derived neurotrophic factor (GDNF), and phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling pathway. METHODS: Seventy-two male Sprague-Dawley rats were randomly allocated into the control, sham-operated, facial nerve injury (FNI), EA, EA+3-methyladenine (3-MA), and EA+GDNF antagonist groups using a random number table, with 12 rats in each group. An FNI rat model was established with facial nerve crushing method. EA intervention was conducted at Dicang (ST 4), Jiache (ST 6), Yifeng (SJ 17), and Hegu (LI 4) acupoints for 2 weeks. The Simone's 10-Point Scale was utilized to monitor the recovery of facial function. The histopathological evaluation of facial nerves was performed using hematoxylin-eosin (HE) staining. The levels of Beclin-1, light chain 3 (LC3), and P62 were detected by immunohistochemistry (IHC), immunofluorescence, and reverse transcription-polymerase chain reaction, respectively. Additionally, IHC was also used to detect the levels of GDNF, Rai, PI3K, and mTOR. RESULTS: The facial functional scores were significantly increased in the EA group than the FNI group (P<0.05 or P<0.01). HE staining showed nerve axons and myelin sheaths, which were destroyed immediately after the injury, were recovered with EA treatment. The expressions of Beclin-1 and LC3 were significantly elevated and the expression of P62 was markedly reduced in FNI rats (P<0.01); however, EA treatment reversed these abnormal changes (P<0.01). Meanwhile, EA stimulation significantly increased the levels of GDNF, Rai, PI3K, and mTOR (P<0.01). After exogenous administration with autophagy inhibitor 3-MA or GDNF antagonist, the repair effect of EA on facial function was attenuated (P<0.05 or P<0.01). CONCLUSIONS EA could promote the recovery of facial function and repair the facial nerve damages in a rat model of FNI. EA may exert this neuroreparative effect through mediating the release of GDNF, activating the PI3K/mTOR signaling pathway, and further regulating the autophagy of facial nerves.
Rats ; Male ; Animals ; Rats, Sprague-Dawley ; Electroacupuncture ; Phosphatidylinositol 3-Kinase/metabolism* ; Facial Nerve Injuries/therapy* ; Phosphatidylinositol 3-Kinases/metabolism* ; Beclin-1 ; Glial Cell Line-Derived Neurotrophic Factor ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism* ; Autophagy ; Mammals/metabolism*

Ferroptosis is an iron-dependent cell death caused by phospholipid peroxidation damage of polyunsaturated fatty acids on cell membranes and involves several pathways, including the iron homeostasis regulatory pathway, the cystine glutamate reverse transporter (system Xc) pathway and the voltage-dependent anion channel (VDAC) pathway. Ferroptosis is involved in the development of several diseases (e. g. myocardial infarction, stroke, cancer and degenerative diseases). The ubiquitination is an important post-translational modification of various protein molecules in the organism. Studies have shown that regulating the ubiquitination of ferroptosis pathway-related molecules can control cellular ferroptosis. Targeting the ubiquitination of ferroptosis pathway-related molecules can effectively promote or inhibit ferroptosis, which is expected to be a new strategy for the treatment of cancer or cardiovascular diseases. In this paper we review the progress of the ferroptosis pathways and the ubiquitination modification of ferroptosis-related molecules.

Receptor-interacting serine/threonine-protein kinase 3(RIPK3),a member of the RIP kinase family,plays an important role in cell death,especially in necroptosis. In addition,RIPK3 is also involved in apoptosis and pyroptosis,suggesting that RIPK3 may be the intersection of multiple cell death and it possesses the potential to be a target for precise regulation of cell death. According to the kinase binding mode,current RIPK3 inhibitors can be classified into type ,type Ⅱ and other types. This review summarizes the research progress in the role of RIPK3 in cell death and its inhibitors,which is of great significance in seeking drugs for the treatment of injury-related diseases.

Objective To analyze the clinical efficacy of the Qianyang Fengsui Dan(combined with flying needle therapy)in the treatment of kidney-yang deficiency type of insomnia.Methods A retrospective study was conducted to select 82 patients with insomnia admitted to the Department of Traditional Chinese Medicine of Dezhou Hospital of Traditional Chinese Medicine from November 2020 to November 2021,and they were divided into an observation group and a control group according to whether or not they were treated with Qianyang Fengsui Dan combined with flying needle therapy,with 41 cases in each group.The control group was treated with Estazolam,while the observation group was treated with Qianyang Fengsui Dan combined with flying needle therapy on the basis of the treatment of the control group,and the course of treatment was 1 month.The changes of Pittsburgh Sleep Quality Index(PSQI)scores and Epworth Sleepiness Scale(ESS)scores,as well as polysomnographic parameters were observed before and after treatment in the two groups.The changes of γ-aminobutyric acid(GABA),glutamate(GA),substance P(SP),and neuropeptide Y(NPY)levels were compared before and after treatment between the two groups.And followed up for 1 year to compare the incidence of relapce of the two groups of patients.Results(1)The total effective rate was 95.12%(39/41)in the observation group and 63.41%(26/41)in the control group,and the efficacy of the observation group was superior to that of the control group,and the difference was statistically significant(P＜0.05).(2)After treatment,PSQI scores and ESS scores of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving PSQI scores and ESS scores,and the differences were statistically significant(P＜0.05).(3)After treatment,sleep efficiency,awakening time,sleep latency,REM,and total sleep time were significantly improved in the two groups(P＜0.05),and the observation group was significantly superior to the control group in improving sleep efficiency,awakening time,sleep latency,REM,and total sleep time,and the differences were statistically significant(P＜0.05).(4)After treatment,the serum GABA,GA,SP,and NPY levels of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving the serum GABA,GA,SP,and NPY levels,and the differences were all statistically significant(P＜0.05).(5)After treatment,follow-up for 1 year,the recurrence rate of the observation group was 0,and there were 7 cases of recurrence in the control group,and the recurrence rate of the control group was 17.07%(7/41),and the recurrence rate of the observation group was lower than that of the control group,and the difference was statistically significant(P＜0.05).Conclusion The combination of flying needle therapy and Qianyang Fengsui Dan can effectively relieve insomnia and fatigue in patients with insomnia,reduce daytime drowsiness,regulate the release of blood monoamine neurotransmitters,and reduce the relapse rate,and its efficacy is superior to that of simple western medicine treatment.

ObjectiveTo explore the protective effects and potential mechanism of Zuogui Jiangtang Yishen prescription （ZJYP） in Goto-Kakizaki （GK） rats with early-stage diabetic kidney disease （DKD）. MethodFifty 12-week-old male GK rats were included in this study. DKD was induced after one month of high-fat feeding， with fasting blood glucose （FBG） ≥ 11.1 mmol·L^-1 and urinary albumin/creatinine ratio （ACR） ≥ 30 mg·g^-1 used as model criteria. After successful modeling， DKD rats were randomly divided into five groups （n=10 in each group）： the model group， the western medicine group treated with dapagliflozin （1.0 mg·kg^-1·d^-1）， low-， medium-， and high-dose ZJYP groups （4.9， 9.9， 19.9 g·kg^-1·d^-1 by gavage）. Ten Wistar rats served as normal controls， with both the normal and model groups receiving physiological saline in the same volume as the treatment groups by gavage for 8 weeks. The urinary ACR， FBG， body weight， and liver and kidney functions of the rats were observed. Renal tissues were subjected to haematoxylin-eosin （HE） and periodic acid-Schiff （PAS） staining and examined under an electron microscope to observe pathological changes. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to detect miRNA-27a， Wnt， and β-catenin mRNA and protein expression levels in renal tissues. ResultCompared with the results in the normal group， the FBG levels in DKD rats of the model group increased significantly at 0， 2， 4， 6， and 8 weeks of drug intervention （P<0.05）， and urinary ACR increased significantly at 0， 4， 8 weeks （P<0.05）. Renal pathological staining and electron microscopy revealed an increase in mesangial cells and matrix， slight thickening of the basement membrane， and increased interstitial fibrosis and renal tubular atrophy in the model group. The mRNA expression levels of miRNA-27a， Wnt， and β-catenin were significantly higher in the model group than in the normal group （P<0.05）. Renal Wnt and β-catenin protein levels were also significantly higher in the model group （P<0.05）. After drug intervention， the FBG levels in the low-， medium-， and high-dose ZJYP groups showed a dose-dependent decrease compared with those in the model group at 6 and 8 weeks （P<0.05）. The urinary ACR also showed a dose-dependent decrease in the low-， medium-， and high-dose ZJYP groups， but the differences were not statistically significant. There were no significant differences in liver function， renal function， renal index， or routine blood lipid test results among the low-， medium-， and high-dose ZJYP groups. Renal glomerular and tubular lesions were milder in the ZJYP groups and the western medicine group than in the model group， with similar pathological changes observed in the high-dose ZJYP group and the western medicine group. The renal mRNA levels of miRNA-27a， Wnt， and β-catenin were significantly lower in the high-dose ZJYP group （P<0.05）， and renal Wnt and β-catenin protein levels were significantly lower in both the western medicine group and the high-dose ZJYP group compared with the levels in the model group （P<0.05）. The Wnt and β-catenin protein levels were lower in the renal tissues of the low- and medium-dose ZJYP groups compared with the levels in the model group， but the differences were not statistically significant. ConclusionZJYP can effectively improve glucose metabolism and alleviate early damage in DKD rats， thereby delaying the progression of DKD. Its mechanism may be related to the inhibition of the miRNA-27a/Wnt/β-catenin signaling pathway in renal tissues.

Lipopolysaccharides (LPS) are major outer membrane components of Gram-negative bacteria. Unlike most Gram-negative bacteria, Acinetobacter baumannii can still survive and acquire polymyxin resistance after complete loss of LPS. Previous studies of LPS-deficient Acinetobacter baumannii mostly focused on LPS-deficient strains induced by polymyxin, whose background was complex and unstable. To investigate LPS loss-mediated polymyxin resistant-Acinetobacter baumannii, this study constructed a stable and clear background LPS-deficient strain by knocking out lpxC gene in Acinetobacter baumannii ATCC 19606 with CIRSPR/Cas9, and then studied the phenotypic changes of the lpxC-deficient strain including morphology, growth rate, antibiotic susceptibility, virulence, membrane permeability, and membrane potential. Animal experiments were approved by the Animal Care and Welfare Committee Institute of Medicinal Biotechnology, CAMS and PUMC (approval number: IMB-20240119D₉). The results indicated that the lpxC gene of Acinetobacter baumannii ATCC 19606 was successfully knocked out. After losing the lpxC, the strain underwent the morphological change from rod-shaped to spherical. Furthermore, it leads to reduced growth rate, enhanced membrane permeability, decreased membrane potential, lower virulence, and increased antibiotic susceptibility to β-lactams, quinolones, aminoglycosides, macrolides, glycopeptides. The lpxC deletion results in significant changes in membrane homeostasis and adaptability of Acinetobacter baumannii. Understanding the phenotypic changes of colistin-resistant Acinetobacter baumannii mediated by LPS loss is useful for exploring the resistance mechanism of Acinetobacter baumannii and developing new therapeutic strategies.