OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Iron is an essential trace element in the human body, crucial in maintaining normal physiological functions. Recent studies have identified iron ions as a significant factor in initiating the ferroptosis process, a novel mode of programmed cell death characterized by iron overload and lipid peroxide accumulation. The iron metabolism pathway is one of the primary mechanisms regulating ferroptosis, as it maintains iron homeostasis within the cell. Numerous studies have demonstrated that abnormalities in iron metabolism can trigger the Fenton reaction, exacerbating oxidative stress, and leading to cell membrane rupture, cellular dysfunction, and damage to tissue structures. Therefore, regulation of iron metabolism represents a key strategy for ameliorating ferroptosis and offers new insights for treating diseases associated with iron metabolism imbalances. This review first summarizes the mechanisms that regulate iron metabolic pathways in ferroptosis and discusses the connections between the pathogenesis of various diseases and iron metabolism. Next, we introduce natural and synthetic small molecule compounds, hormones, proteins, and new nanomaterials that can affect iron metabolism. Finally, we provide an overview of the challenges faced by iron regulators in clinical translation and a summary and outlook on iron metabolism in ferroptosis, aiming to pave the way for future exploration and optimization of iron metabolism regulation strategies.

Supracondylar humerus fractures represent the most prevalent type of upper limb fractures in pediatric patients. As a result of the interplay of external forces, muscular contractions, and periosteal reactions, these fractures are prone not only to axial displacement but also to rotational displacement in a certain degree. Rapid and accurate assessment of the rotational displacement holds a paramount importance for intraoperative realignment, choice of fixation modalities, and anticipation of postoperative function. Currently, methods to evaluate the rotational displacement involve X-ray, CT, and ultrasound, but the various assessment techniques and criteria often pose challenges in differentiation. This paper reviews the current diverse imaging modalities for assessment of the rotational displacement, aiming to translate the intricate three-dimensional spatial rotation into single-plane rotations within the coronal, sagittal, and horizontal planes, thereby aspiring to furnish those concerned with clinical guidance.

Objective To evaluate the efficacy and safety of CT-guided 125I seeds implantation for the treatment of abdominal wall incision metastasis of gastrointestinal malignancies.Methods The clinical data of 17 patients with abdominal wall incision metastasis of gastrointestinal malignancies(17 lesions in total),who received CT guided 125I seeds implantation at the Third Affiliated Hospital of Soochow University of China between January 2011 and December 2021,were collected.The treatment planning system was used to make preoperative planning for CT-guided 125I seeds implantation.Follow-up visit was performed once every 3 months to assess the local control rate,treatment-related adverse effects,and degree of pain relief.Results Successful CT-guided 125I seeds implantation was accomplished for the 17 lesions of gastrointestinal malignant tumor incision metastasis.A total of 372 125I seeds were implanted with an average of 21.9 seeds per lesion.The average prescription dose was 100 Gy per lesion.The average survival time was 9.8 months.CT scan performed at 3 months after first-time implantation showed that among the 17 lesions complete remission was obtained in 3,partial remission in 6,stable disease in 7 and progression in one,with a local control rate of 94.1％.The postoperative 6-month and 12-month local objective remission rates were 63.6％and 33.3％respectively,disease control rates were 100％and 50％respectively.Before treatment 8 patients had local pain,and 3 months after treatment pain relief was observed in 6 patients,and in 2 patients the NRS pain score was decreased by ≥ 2 points.No serious postoperative complications occurred.Conclusion For the treatment of abdominal wall incision metastasis of gastrointestinal metastasis,CT-guided 125I seeds implantation is clinically safe and effective.(J Intervent Radiol,2024,33:655-658)

The regulation of spermatogonial proliferation and apoptosis is of great significance for maintaining spermatogenesis. The single-cell RNA sequencing (scRNA-seq) analysis of the testis was performed to identify genes upregulated in spermatogonia. Using scRNA-seq analysis, we identified the spermatogonia upregulated gene origin recognition complex subunit 6 (Orc6), which is involved in DNA replication and cell cycle regulation; its protein expression in the human and mouse testis was detected by western blot and immunofluorescence. To explore the potential function of Orc6 in spermatogonia, the C18-4 cell line was transfected with control or Orc6 siRNA. Subsequently, 5-ethynyl-2-deoxyuridine (EdU) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays, flow cytometry, and western blot were used to evaluate its effects on proliferation and apoptosis. It was revealed that ORC6 could promote proliferation and inhibit apoptosis of C18-4 cells. Bulk RNA sequencing and bioinformatics analysis indicated that Orc6 was involved in the activation of wingless/integrated (Wnt)/ β-catenin signaling. Western blot revealed that the expression of β-catenin protein and its phosphorylation (Ser675) were significantly decreased when silencing the expression of ORC6. Our findings indicated that Orc6 was upregulated in spermatogonia, whereby it regulated proliferation and apoptosis by activating Wnt/β-catenin signaling.

Humans ; Pulmonary Alveolar Proteinosis/pathology*

A fluorescence endoscopic laser confocal microscope(FELCM) was used to direct the injection of sinomenine solid lipid nanoparticles(Sin-SLN) into the joint, and the in vitro effectiveness of Sin-SLN in the treatment of rheumatoid arthritis(RA) was evaluated. Sin-SLN was prepared with the emulsion evaporation-low temperature curing method. The Sin-SLN prepared under the optimal conditions showed the encapsulation efficiency of 64.79%±3.12%, the drug loading of 3.84%±0.28%, the average particle size of(215.27±4.21) nm, and the Zeta potential of(-32.67±0.84) mV. Moreover, the Sin-SLN demonstrated good stability after sto-rage for 30 days. The rabbit model of RA was established by the subcutaneous injection of ovalbumin and complete Freund's adjuvant. Five groups were designed, including a control group, a model group, a Sin(1.5 mg·kg~(-1)) group, a Sin-SLN(1.5 mg·kg~(-1)) group, and a dexamethasone(positive drug, 1.0 mg·kg~(-1), ig) group. The control group and the model group only received puncture treatment without drug injection. After drug administration, the local skin temperature and knee joint diameter were monitored every day. The knee joint diameter and the local skin temperature were lower in the drug administration groups than in the model group(P<0.05, P<0.01). FELCM recorded the morphological alterations of the cartilage of knee joint. The Sin-SLN group showed compact tissue structure and smooth surface of the cartilage. Enzyme-linked immunosorbent assay(ELISA) was employed to determine the serum le-vels of interleukin-1(IL-1) and tumor necrosis factor-α(TNF-α). The findings revealed that the Sin-SLN group had lower IL-1 and TNF-α levels than the model group(P<0.05, P<0.01). Hematoxylin-eosin(HE) staining was employed to reveal the pathological changes of the synovial tissue, which were significantly mitigated in the Sin-SLN group. The prepared Sin-SLN had uniform particle size and high stability. Through joint injection administration, a drug reservoir was formed. Sin-SLN effectively alleviate joint swelling and cartilage damage of rabbit, down-regulated the expression of inflammatory cytokines, and inhibited the epithelial proliferation and inflammatory cell infiltration of the synovial tissue, demonstrating the efficacy in treating RA.
Animals ; Rabbits ; Tumor Necrosis Factor-alpha ; Fluorescence ; Arthritis, Rheumatoid/drug therapy* ; Interleukin-1 ; Arthritis, Experimental/drug therapy*

Aim To explore whether isopropyl3-(3, 4-dihydroxyphenyl) -2-hydroxypropanoate (IDHP) could inhibit fat accumulation in liver cells by improving mitochondrial function, and alleviate the symptom of excessive fat accumulation in patients with NAFLD. Methods Cell steatosis model was established by inducing hepatocyte fat accumulation using palmitic acid and oleic acid (PA: OA molar ratio =1

Objective:To explore the clinical effect of observation and psychological intervention, splint or brace fixation as well as surgical treatment on habitual dislocation of the hip (HDH) and to combine the authors' data with a compilation of the cases from the literature, evaluingating the epidemiological characteristics of HDH and the treatment scheme to maintain the stability of hip joint by systematic literature review in children.Methods:A retrospective analysis of the relevant data of 11 patients (12 hips) with HDH were treated from March 2007 to March 2021, including 2 boys and 9 girls. The age of the first dislocation was 2.25 (1.66, 3.75) years old and 4.33 (3.33, 6.17) years old at the age of diagnosis. At the same time, the relevant literature reports were searched from 1932 to 2022, and 24 HDH patients reports and clinical studies were confirmed to be included in this study according to the inclusion and exclusion criteria. The data of 33 patients (38 hips) with HDH who were obtained in the literature, including 5 boys and 28 girls. The age of the first dislocation was 2.00 (1.50, 2.00) years old and 4.00 (2.55, 5.00) years old at the age of diagnosis. A total of 44 patients (50 hips) with HDH who were analyzed, including gender, age of first dislocation, age of diagnosis, mode of stimulating dislocation, side and direction of dislocation, accompanying symptoms, family history, trauma history and imaging examination. The data of 41 patients with HDH (3 patients were excluded due to lack of treatment description) were treated with observation and psychological intervention in 19 patients, splint or brace fixation in 13 patients, and surgical treatment in 9 patients. The femoral neck-stem angle, acetabular index, central edge angle (CE angle) and Reimers instability index were measured by AutoCAD software, and the hip function was evaluated by Harris standard. Meantime, the disappearance time of dislocation was recorded.Results:The average follow-up time of 44 patients (50 hips) with HDH were 4.05±2.93 years old, and the time of disappearance of dislocation after treatment were 1.28±1.19 years old. Patients were diagnosed as 7 boys and 37 girls, 30 right and 8 left as well as 6 bilateral, the age of the first dislocation was 2.64±1.54 years old and 4.52±2.64 years old at the age of diagnosis. The data of 39 patients took hip flexion, adduction, internal rotation or hip flexion and adduction as the mode of stimulating dislocation. There were 43 patients with posterior dislocation, 41 patients with an audible "click" sound during dislocation, 36 patients with painless dislocation, and 37 patients with "vacuum phenomenon" were captured at the moment of dislocation. All patients with HDH had no specific family history and obvious history of trauma. There was no significant difference in general data between observation and psychological intervention group, splint or brace fixation group as well as surgical treatment group ( P>0.05). Harris standard to evaluate hip function, CE angle and Reimers instability index of the affected side were significantly different from those before and after treatment at the moment of dislocation ( H=127.51, P<0.001; H=55.70, P<0.001; H=54.69, P<0.001). Compared with the immediate disappearance of dislocation in the surgical treatment group, the disappearance time of dislocation in the observation and psychological intervention group and the splint or brace fixation group were significantly longer, and the difference was statistically significant ( H=20.83, P<0.001). Conclusion:Without specific family history and obvious trauma at young girls, painless posterior dislocation of hip with an audible "click" sound and "vacuum phenomenon" at the moment of dislocation are the significant epidemiological characteristics of HDH. Observation and psychological intervention, splint or brace fixation are recommended as the initial treatment scheme. When conservative treatment is ineffective, surgical treatment is needed to stabilize the hip joint quickly.

A 56-year-old female was admitted to Department of Gastroenterology at Peking Union Medical College Hospital with diarrhea for seven months, and abnormal liver function for six months. She had a history of type 1 diabetes. The main clinical manifestations were recurrent fatty diarrhea and abnormal liver function, accompanied by abdominal and retroperitoneal lymphadenopathy, elevated CA19-9 and CEA. Progressive impairment of hepatic synthetic function and shrinkage of liver developed in a short period of time. The pathology of liver biopsy suggested that nodular regeneration of hepatocytes was followed by hyperplasia of thin bile ducts after submassive necrosis. Intestinal mucosa biopsies were performed twice. The pathology showed that the intestinal villi were completely blunt, accompanied with crypt hyperplasia. Goblet cells disappeared with reduced mucin. Paneth cells were barely seen without intraepithelial infiltration of lymphocytes. Rifaximin was not effective, while glucocorticoids improved clinical situation. The diagnosis of autoimmune enteropathy was finally confirmed by multidisciplinary team including departments of gastroenterology, pathology, endocrinology, hematology, infectious diseases, and rheumatology. With the administration of glucocorticoid and sirolimus, diarrhea relieved and liver function returned to normal.