ObjectiveRepetitive transcranial magnetic stimulation (rTMS), a non-invasive brain stimulation technique, offers a non-pharmacological therapeutic option for the management of Alzheimer’s disease (AD). Studies have demonstrated that ferroptosis plays a pivotal role in the pathological onset and progression of AD, and the inhibition of neuronal ferroptosis can significantly ameliorate cognitive impairments associated with AD. The imbalance of calcium ion (Ca²⁺) homeostasis is intimately associated with the pathology of AD and serves as a catalyst for the induction of ferroptosis through various pathways. This study is designed to investigate whether rTMS can ameliorate AD by inhibiting neuronal ferroptosis or maintaining calcium homeostasis, ultimately establishing a theoretical and experimental framework for the utilization of rTMS in AD treatment. MethodsAPP/PS1 AD mice were subjected to both 0.5 Hz low-frequency and 20 Hz high-frequency rTMS treatments, and the efficacy of these treatments was evaluated using novel object recognition and Morris water maze tests. ELISA was employed to quantify the levels of glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), Fe²⁺ within the hippocampi of mice from each group. HT-22 cells were induced to undergo ferroptosis via Erastin treatment, and subsequent to high- and low-frequency magnetic stimulation, cell viability was assessed using CCK-8 assay, while intracellular calcium ion concentration fluctuations were monitored using Fluo-4 AM. ResultsThe findings revealed that, when compared to normal mice, AD mice displayed a notable decline in cognitive function, accompanied by a substantial increase in ferroptosis levels and intracellular calcium ion concentrations. Both high-frequency and low-frequency applications of rTMS were found to significantly ameliorate cognitive impairments in AD mice, while also effectively mitigating the abnormal augmentation of neuronal ferroptosis and intracellular calcium ion levels. ConclusionThe present study underscores that both high-frequency and low-frequency rTMS exhibit efficacy in alleviating cognitive dysfunction in AD mice, potentially through the modulation of ferroptosis and intracellular calcium ion homeostasis.

This study aims to explore whether Albiziae Cortex-Tribuli Fructus can exert an anti-hepatic fibrosis effect by regulating the nuclear factor E2-related factor 2(Nrf2)/NOD-like receptor protein 3(NLRP3)/cysteine protease-1(caspase-1) pathway and analyze its potential mechanism. In the in vivo experiment, a mouse model of hepatic fibrosis was established by subcutaneous injection of carbon tetrachloride. The levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), collagen type Ⅳ(ColⅣ), laminin(LN), procollagen type Ⅲ(PCⅢ), and hyaluronic acid(HA) in the serum of mice were measured using a fully automated biochemical analyzer and ELISA. Hematoxylin and eosin(HE) and Masson staining were used to observe inflammation and collagen fiber deposition in the liver tissue. Western blot and RT-qPCR were employed to detect the protein and mRNA expression of collagen type Ⅰ(collagen Ⅰ), α-smooth muscle actin(α-SMA), Nrf2, NLRP3, gasdermin D(GSDMD), and caspase-1 in the hepatic tissue. In the in vitro experiment, human hepatic stellate cells(HSC-LX2) were pretreated with Nrf2 agonist or inhibitor, followed by the addition of blank serum, AngⅡ + blank serum, and AngⅡ + Albiziae Cortex-Tribuli Fructus-containing serum for intervention. Western blot was used to detect the protein expression of Nrf2, NLRP3, GSDMD, caspase-1, α-SMA, GSDMD-N, and apoptosis-associated speck-like protein(ASC) in cells. DCFH-DA fluorescence probe was used to detect the cellular ROS levels. The results from the in vivo experiment showed that, compared with the model group, Albiziae Cortex-Tribuli Fructus significantly reduced the serum levels of AST, ALT, ColⅣ, LN, PCⅢ, and HA, reduced the infiltration of inflammatory cells and collagen fiber deposition in the liver tissue, significantly upregulated the protein and mRNA expression of Nrf2 in the liver tissue, and significantly downregulated the protein and mRNA expression of collagen I, α-SMA, NLRP3, GSDMD, and caspase-1 in the liver tissue. The results from the in vitro experiment showed that Nrf2 activation decreased the protein expression of NLRP3, GSDMD, caspase-1, α-SMA, GSDMD-N, ASC, and ROS levels in HSC-LX2, while Nrf2 inhibition showed the opposite trend. Furthermore, Albiziae Cortex-Tribuli Fructus-containing serum directly decreased the expression of the above proteins and ROS levels. In conclusion, Albiziae Cortex-Tribuli Fructus can effectively improve hepatic fibrosis, and its mechanism of action may involve inhibiting pyroptosis through the regulation of the Nrf2/NLRP3/caspase-1 pathway.
Animals ; NF-E2-Related Factor 2/genetics* ; Liver Cirrhosis/genetics* ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Caspase 1/genetics* ; Male ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Signal Transduction/drug effects* ; Humans ; Liver/metabolism* ; Mice, Inbred C57BL ; Plant Extracts ; Tribulus

OBJECTIVE: To compare clinical effect of anterior tibial plateau fracture line and anterior tibial fenestration reduction in treating anterolateral tibial plateau column fracture combined with posterior lateral column collapse. METHODS: Fifty-two patients with Schatzker typeⅡ tibial plateau anterolateral column fracture combined with posterolateral column collapse admitted from January 2016 to December 2021 were retrospectively analyzed and divided into two groups according to fracture reduction methods. There were 27 patients in fracture line group, including 19 males and 8 females, aged from 26 to 62 years old with an average of (43.2±11.4) years old;the time from injury to operation ranged from 4 to 8 days with an average of (5.8±1.5) days;treated with reduction and internal fixation via fracture line of lateral platform front. There were 25 patients in fenestrate group, including 13 males and 12 females, aged from 22 to 69 years old with an average of (40.8±11.1) years old;the time from injury to operation ranged from 4 to 8 days with an average of (6.0±1.4) days;treated with tibial fenestration reduction and internal fixation. The amount of bone graft, operation time, fracture healing time and complications were compared between two groups. Posterior slope angle (PSA) and posterior slope angle of the lateral tibial plateau was compared before surgery, 2 days and 6 months after surgery. The knee function was evaluated by Hospital for Speical Surgery (HSS) at 2 days and 6 months after surgery, respectively. Fracture reduction was evaluated by Rasmussen anatomic score of knee joint. RESULTS: Both of group were followed up from 12 to 24 months (16.0±3.4) months. No redisplacement of fracture, internal and external inversion deformity of knee joint, or instability of knee joint were found between two groups during follow-up. In fracture line group, 1 patient occurred wound fat liquefaction and 2 patients occurred lower limb intermuscular venous thrombosis occurred. In fenestration group, 1 patient occurred joint stiffness, 1 patient occurred lower limb intermuscular venous thrombosis, and 1 patient occurred superficial wound infection;there were no significant difference in complications between two groups (P>0.05). Bone graft volume, operative time and fracture healing time in fracture line group were (3.6±2.3) cm³, (123.4±18.2) min and (13.8±1.8) weeks, while in feneplast group were (4.8±1.8) cm³, (135.5±22.5) min and (15.2±2.0) weeks, respectively;the difference between two groups was statistically significant (P<0.05). The collapse depth of lateral platform articular surface at 2 days and 6 months after surgery were (0.8±0.1) and (0.9±0.1) mm in fracture line group, which were lower than those in fenestration group (0.9±0.1) and (1.1±0.1) mm, respectively (P<0.05). After 2 days and 6 months, , PSA in fracture line group were (9.4±1.5) ° and (10.1±1.9) °, respectively, which were lower than those in fenestration group (10.5±1.5) ° and (11.3±1.9) ° (P<0.05). Rasmussen anatomical scores in fracture line group at 2 days and 6 months were 16(16, 18) and 16(14, 16) points, respectively, which were better than those in fenestrated group (16, 16) and 14(14, 16) points (P< 0.05). The collapse depth, PSA and Rasmussen anatomical score between two groups were better than those before surgery (P<0.05). There was no significant difference in HSS score between two groups at 2 days after surgery (P>0.05). At six months after surgery, HSS score in fracture line group (86.7±3.6) was higher than that in fenestration group (84.1±3.91) (P<0.05). HSS score at 6 months after surgery was better than that at 2 days after surgery (P<0.05). CONCLUSION Both anterior tibial plateau fracture line and anterior tibial fenestration could be used to treat anterolateral tibial plateau column fracture with posterior lateral column collapse. Compared with fenestration group, transfracture line group had advantages of less intraoperative bone grafting, shorter operative time, shorter fracture healing time, better articular surface reduction effect and better knee functional recovery.
Humans ; Male ; Female ; Middle Aged ; Tibial Fractures/physiopathology* ; Adult ; Fracture Fixation, Internal/methods* ; Aged ; Retrospective Studies ; Tibia/injuries* ; Tibial Plateau Fractures

OBJECTIVE: To analyze the MYH9 gene sequence of a patient with hereditary thrombocytopenia and diffuse large B-cell lymphoma and his family members, and to explore the relationship between MYH9 gene and tumors. METHODS: Peripheral blood samples were collected from the patients and their family members for complete blood count analysis. The platelet morphology was observed under microscope. The MYH9 gene sequence was analyzed by Whole Exon Sequencing and Sanger Sequencing. RESULTS: The mutation site c.279C>A:p.(Asn93Lys) in exon 2 of the MYH9 gene were found in patient and his family members, both presenting as thrombocytopenia. The platelet count was significantly increased after the administration of Avatrombopag. CONCLUSION A novel mutation of MYH9 was found in this study, and the case was sensitive to Avatrombopag, by exploring the relationship between the MYH9 gene and tumors, suggesting that the MYH9 gene may be associated with the development of diffuse large B-cell lymphoma.
Humans ; Myosin Heavy Chains/genetics* ; Thrombocytopenia/genetics* ; Mutation ; Male ; Lymphoma, Non-Hodgkin/genetics* ; Lymphoma, Large B-Cell, Diffuse/genetics* ; Molecular Motor Proteins/genetics* ; Pedigree

OBJECTIVE: To investigate the differences between high-frequency ultrasound-guided manual detorsion combined with surgery (MD+S) and surgery alone in the treatment of testicular torsion, and to provide some new evidence for the timely diagnosis and treatment of the disease. METHODS: We retrospectively analyzed the clinical data on 134 cases of unilateral testicular torsion within 48 hours treated in our hospital by MD+S or by surgery alone from January 2015 to May 2022. We statistically analyzed the age distribution, and duration and degrees of testicular torsion, followed by comparison between the two groups. RESULTS: In the 134 cases, the median age of onset was 15 (13－19) years old, the median onset-to-visit time was 15 (8－25) hours, and the median degree of torsion was 360° (180°－1080°). Of the total number of patients, 21 underwent testicular excision and the other 113 were treated with the testis preserved, with no statistically significant difference in age distribution between the two groups (P>0.05), and a higher rate of testis resection in those with longer duration and greater angle of torsion (P<0.05). Totally, 33 of the patients were assigned to the MD+S group and 101 to the surgery alone group. According to the actual clinical conditions and excluding those with torsion time longer than 24 hours and torsion angle greater than 720 °, 28 of the patients underwent ultrasound-guided MD+S (with 1 case of testis resection, 3.6%), and 68 received surgery alone (with 7 cases of testis resection, 10.3%). The rate of testis resection was higher in the surgery alone than that in the MD+S group, but with no statistically significant difference between the two groups (P>0.05), which was considered to be related to the small sample size in this study. CONCLUSION The popularization of testicular torsion knowledge can shorten the onset-to-visit time, and reasonable manual detorsion before emergency surgery can reduce the rate of testis resection.
Humans ; Male ; Spermatic Cord Torsion/therapy* ; Retrospective Studies ; Adolescent ; Young Adult ; Ultrasonography ; Testis/surgery* ; Adult

BACKGROUND: The association between uric acid-albumin ratio (UAR) with different diseases has been evaluated before. However, the association between UAR with spontaneous reperfusion (SR) in patients with ST-segment elevation myocardial infarction (STEMI) has not been explored. METHODS: STEMI patients admitted to our department and underwent primary coronary angiography between 1^st November 2018 and 31^st December 2020 were retrospectively enrolled. The patients were divided into the SR group and the non-SR group according to the index coronary angiography results. The association between UAR and SR was evaluated by uni-variable and multi-variable logistic analysis. Receiver operating characteristic curve analysis was used to determine the optimum cut-off level of UAR in predicting SR. RESULTS: Three hundred and fifty-seven patients were finally enrolled in our study, 55 patients were divided into the SR group and 302 patients were divided into the non-SR group. In uni-variable analysis, patients with SR were older (P = 0.032), with higher red blood cell distribution width (P < 0.001) and red blood cell distribution width-to-platelet ratio (P < 0.001), higher level of C-reactive protein (P = 0.046), higher level of uric acid (P < 0.001) compared with patients without SR. Patients with SR had a lower level of platelets (P = 0.008), lower level of on-admission B-type natriuretic peptide (P < 0.001). As for the level of UAR, STEMI patients with SR had significantly higher levels of UAR compared with STEMI patients without SR [11.1 (8.9-13.4) vs. 8.3 (6.6-10.0), P < 0.001]. Further multi-variable logistic analysis reveals that UAR was the independent risk factor of SR in different models after adjusting different variables. Receiver operating characteristic analysis showed that UAR had good predictive value in SR (AUC = 0.75, 95% CI: 0.702-0.794, P < 0.01). CONCLUSIONS Our study shows that UAR is an independent risk factor for predicting SR in STEMI patients.

In this study, we designed and synthesized 12 novel aloperine derivatives with different core structures. Among them, compound 3 with a ten-membered ring core was obtained through a special ring expansion reaction after γ-H Huffman elimination of quaternary ammonium salt, and the structure was verified by X-single crystal diffraction. Furthermore, their antiviral activity against human β-coronavirus HCoV-OC43 was evaluated by CCK-8 assay. Quaternary ammonium salt 2a and 3 had a good inhibitory effect against HCoV-OC43, and 2a had the highest anti-HCoV-OC43 activity with an EC₅₀ values of 3.77 μmol·L^-1 and a SI value of over 53.1. Schrӧdinger molecular docking results showed that both 2a and 3 might display their anti-HCoV-OC43 activity by directly acting on host TMPRSS2 and SR-B1. The results expanded the structural types of endocyclic aloperine and the function against coronavirus, and provided useful scientific data for the development of pharmaceutical applications of these compounds.

Traditional decoction pieces have low efficiency, poor batch-to-batch consistency, and irregular physical form, making it difficult to meet the demands of modern automated production and precise and rapid clinical blending. Therefore, this study aims to develop a new type of granular drinking tablet to meet the demand for high-quality development in the traditional Chinese medicine industry. In the current study, the differences and similarities between the new Lonicerae Japonicae Flos (LJF) granular drinking tablets and the traditional ones were evaluated based on the flowability, the paste rate of the standard soup, the characterization fingerprint, the degree of pasting, the content of active ingredients, the transfer rate, and its traditional antipyretic and anti-inflammatory efficacy, using the traditional LJF decoction piece as a reference. The flowability experiments showed that the flowability of medium-sized granules (10-24 mesh) was significantly better than that of traditional drinking tablets (P < 0.01); the results of the paste rate showed that there was no significant difference between the different particle sizes and the original decoction pieces (P > 0.05), but the small particle sizes (24-65 mesh) had poor decoction clarity and gelatinization; the transfer rate was calculated as chlorogenic acid and luteoloside, and there was no significant difference in the transfer rate between traditional slices and different particle sizes (P > 0.05); the pharmacological results showed that the contents of rat tumor necrosis factor-α (TNF-α), rat interleukin-1β (IL-1β) and rat prostaglandin E₂ (PGE₂), xylene ear swelling inhibition rate and granuloma inhibition rate showed that there was no significant difference between the traditional and new granule decoction pieces (P > 0.05). In this study, by examining the fluidity, paste rate, paste degree, and antipyretic and anti-inflammatory effects of the new granular decoction piece of LJF, it was initially revealed that the new granular drinking tablets of LJF were consistent with the basic properties and pharmacological effects of the commercially available traditional drinking tablets. Still, the new granular tablets were characterized by high utilization rate, homogeneous quality, and ease of clinical transfer, which had a good prospect for application. The animal experiment was approved by the Ethics Committee of the China Academy of Chinese Medical Sciences (approval number. 2022B214).

Objective To investigate the role of inhibition of Runt-associated transcription factor 1(Runx1)expression in arterial interventional chemotherapy for lung cancer in rats.Methods A549 cells were randomly divided into control group(normal cultured cells),si-NC group(transfected with si-NC plasmid),si-Runx1 group(transfected with si-Runx1 plasmid).Cell proliferation was detected by cell counting kit-8(CCK-8)assay,and the relative expression level of protein was detected by Western blotting.Rats were randomly divided into model group(constructed lung cancer transplanted tumor rats),sh-Runx1 group(knockdown Runx1 expression),OXA arterial group(single arterial interventional chemotherapy),sh-Runx1+OXA group(knockdown Runx1+intravenous chemotherapy),sh-Runx1+OXA arterial group(knockdown Runx1+arterial interventional chemotherapy).After continuous treatment for 3 weeks,tumor volume and weight were measured,TdT mediated dUDP nick end labeling(Tunel)assay was used to detect tumor apoptosis,and Western blot assay was used to detect the expression of migration and invasion-related proteins.Results The survival rates of A549 cells in the control group,si-NC group and si-Runx1 group were(100.00±5.13)％,(99.56±3.44)％and(60.96±7.00)％,respectively;the expression levels of Runx1 protein were 0.84±0.06,0.85±0.06 and 0.20±0.03,respectively.Compared with the control group and si-NC group,the cell survival rate and Runx1 protein expression level in the si-Runx1 group were significantly decreased(all P＜0.05).The tumor volume of the model group,sh-Runx1 group,OXA arterial group,sh-Runx1+OXA group and sh-Runx1+OXA arterial group after the last treatment were(1 069.58±121.79),(819.30±6.98),(639.34±66.64),(486.91±29.88),(416.57±21.58)mm3,respectively;the apoptosis rates were(4.32±0.36)％,(13.95±1.22)％,(15.46±1.14)％,(23.71±2.01)％,(31.16±3.04)％,respectively;the expression levels of E-cadherin protein were 0.31±0.05,0.61±0.07,0.67±0.09,0.92±0.07,1.23±0.13,respectively.The above indexes of sh-Runx1 group,OXA arterial group,sh-Runx1+OXA group and sh-Runx1+OXA arterial group were compared with those of the model group,and the difference was statistically significant(all P＜0.05).The above indexes of sh-Runx1+OXA arterial group were compared with those of sh-Runx1,OXA arterial group and sh-Runx1+OXA group,and the difference was statistically significant(all P＜0.05).Conclusion inhibition of Runx1 can enhance the apoptosis induction and cell metastasis inhibition of arterial interventional chemotherapy in lung cancer rats.