1.Effect of Osteoking on Inflammatory Injury and NF-κB/NFATc1 Signaling Pathway in Model Mice with Postmenopausal Osteoporosis
Tiantian YU ; Ruibing FENG ; Qing WANG ; Chaowen LI ; Jiahao CHEN ; Ruixuan JIANG ; Yinshuai DING ; Yong HUANG ; Hao HU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(10):62-69
ObjectiveTo explore the possible mechanism of Osteoking (OK) on postmenopausal osteoporosis (PMOP). MethodForty adult female mice were randomly divided into a sham operation (Sham) group, osteoporosis model (OVX) group, estradiol intervention (E2) group, and OK group, with 10 mice in each group. The modeling was completed by conventional back double incision ovariectomy, and the corresponding drugs were given one week later. After 12 weeks, the body mass and uterine index of mice were measured, and the pathological changes of bone tissue and the number of osteoclasts (OCs) were determined by hematoxylin-eosin (HE) and tartrate-resistant acid phosphatase (TRAP) staining, respectively. Bone mineral density (BMD), trabecular number (Tb.N), trabecular separation (Tb.Sp), and bone volume fraction (BV/TV) were measured by microcomputed tomography (Micro-CT). The maximum load of the femur was detected by a three-point bending test. The contents of tumor necrosis factor-α (TNF-α) and bone resorption marker C-terminal telopeptide of type Ⅰ collagen (CTX-1) were measured by enzyme linked immunosorbent assay (ELISA). The protein expression levels of nuclear factor-kappa B p65 (NF-κB p65), phosphorylated nuclear factor-kappa B p65 (p-NF-κB p65), nuclear factor kappa B inhibitor alpha (IκBα), phosphorylated nuclear factor kappa B alpha (p-IκBα), nuclear factor of activated T cells 1 (NFATc1), and proto-oncogene (c-Fos) were detected by Western blot. The mRNA expressions of OCs-related specific genes matrix metalloproteinase-9 (MMP-9), NFATc1, TRAP, cathepsin K (CTSK), and c-Fos were detected by real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). ResultCompared with the Sham group, the uterine index decreased significantly in the OVX group, and the body mass (BMI) increased significantly. The structure of bone trabeculae was completely damaged, and the number of OCs increased. BMD, Tb.N, BV/TV, and maximum load decreased, while Tb.Sp was up-regulated. The levels of TNF-α and CTX-1 in serum were up-regulated. The protein expressions of c-Fos, p-NF-κB p65/NF-κB p65, NFATc1, and p-IκBα/IκBα were increased. The mRNA expressions of NFATc1, c-Fos, CTSK, TRAP, and MMP-9 were up-regulated (P<0.05, P<0.01). Compared with the OVX group, the body mass of the OK and E2 groups decreased, and the uterine index increased. The bone trabeculae increased, and the number of OCs decreased. BMD, Tb.N, BV/TV, and maximum load increased, while Tb.Sp decreased. The levels of TNF-α and CTX-1 in serum were decreased. The protein expressions of c-Fos, p-NF-κB p65/NF-κB p65, NFATc1, and p-IκBα/IκBα were decreased, and the mRNA expressions of NFATc1, c-Fos, CTSK, TRAP, and MMP-9 were decreased (P<0.05, P<0.01). ConclusionOK can inhibit the NF-κB/NFATc1 signaling pathway and reduce bone mass loss by reducing the level of inflammatory injury factors in PMOP mice, which is one of the mechanisms for treating PMOP.
2.Analysis and Textual Research on Suzi Jiangqitang Based on Ancient Literature
Shengyi NI ; Jiahao WANG ; Yu LI ; Renshou CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(22):1-9
Suzi Jiangqitang is one of the classical formulas in the Catalogue of Ancient Classical Formulas (the second batch)—Han Medicine. The research method of philology was employed to systematically review the ancient documents and modern medical reports of Suzi Jiangqitang. The key information of this formula, including origin, composition, compatibility, original plants, processing method, dosage, preparation method, usage, and indications, was summarized to provide literature and data support for the development and clinical application of this formula. Suzi Jiangqitang is originally known as Zusuzi Tang, which is derived from Important Prescriptions Worth a Thousand Gold for Emergency. This formula is composed of Perillae Fructus, Pinelliae Rhizoma, Peucedani Radix, Magnoliae Officinalis Cortex, Glycyrrhizae Radix et Rhizoma, Angelicae Sinensis Radix, Citri Reticulatae Pericarpium, Perillae Folium, Jujubae Fructus, Zingiberis Rhizoma Recens, and Cinnamomi Cortex. The original plants of other herbal medicines except Peucedani Radix follow those in the 2020 edition of Pharmacopoeia of the People's Republic of China. Raw materials of Angelicae Sinensis Radix, Peucedani Radix, Cinnamomi Cortex, Citri Reticulatae Pericarpium, Perillae Folium, and Jujubae Fructus are used in this formula. Perillae Fructus, Pinelliae Rhizoma, Glycyrrhizae Radix et Rhizoma, and Magnoliae Officinalis Cortex in this formula are stir-fried, processed with alumen, stir-fried, and processed with ginger, respectively, and the fresh material of Zingiberis Rhizoma Recens is used in this formula. The recommended formula is composed of 15 g Perillae Fructus, 15 g Pinelliae Rhizoma, 6 g Angelicae Sinensis Radix, 6 g Glycyrrhizae Radix et Rhizoma, 6 g Peucedani Radix, 6 g Magnoliae Officinalis Cortex, 9 g Cinnamomi Cortex, and 9 g Citri Reticulatae Pericarpium. On the basis of the recommended dosage, other herbal medicines are crushed and mixed with five pieces of Perillae Folium, one jujube, and two ginger pieces. The mixture should be decocted in 450 mL water to reach a volume of 240 mL. After removal of the residue, the decoction should be taken warm with no time limitation. In ancient times, Suzi Jiangqitang was most commonly used to treat dermatophytosis, dyspnea with cough, red eyes, blood syndrome, globus hysteriocus, and headache. In modern times, it is commonly used for treating respiratory diseases, especially chronic obstructive pulmonary disease and dyspnea with cough. In addition, this formula is used to treat circulatory and digestive diseases, such as pulmonary heart disease, constipation, and vomiting. It is also used to treat globus hysteriocus and blood syndrome. Although the range of indications is wide, the diseases treated by Suzi Jiangqitang are generally caused by excess in the upper, deficiency in the lower, and failure of Qi to ascend or descend.
3.Visual Analysis of Current Status and Hotspots of Research on Ancient Classical Formulas Based on CiteSpace
Yu LI ; Jiahao WANG ; Hao XUE ; Luning WANG ; Renshou CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(22):20-26
ObjectiveTo analyze the current research status of the classical formulas in China and predict the future development trends, thus providing reference and suggestions for the scientific research and clinical application of classical formulas. MethodThe relevant publications were retrieved from China National Knowledge Infrastructure (CNKI) with the time interval from January 1, 2008 to August 1, 2023, and the publications were counted. CiteSpace 6.1.R6 was used for visual analysis of the authors, research institutions, and keywords. ResultA total of 847 valid publications were included in this study. The annual number of publications showed a rapid rise after 2018. The Chinese Journal of Experimental Traditional Medical Formulae was the main journal publishing the articles about ancient classical formulas in China. ZHAN Zhilai, BAI Jie, LU Tulin, FU Chaomei, and CHEN Renshou were active researchers in this field and had formed stable research teams. The China Academy of Chinese Medical Sciences and its affiliated institutions published the most articles and had close cooperation with other research institutions in China. The co-occurrence network and cluster map of keywords showed that textual research on materia medica, clinical application, quality standard, fingerprint, and mechanism of action were the core keywords. The top 3 bursts in this field were benchmark samples, quality evaluation, and origin. ConclusionThe current research on ancient classical formulas still has shortcomings such as lack of large-scale cooperation between teams and weak transformation of research achievements. At present, the research hotspots in this field mainly include textural research on key information, quality control and fingerprinting, and clinical application. The future research in this field mainly focus on benchmark samples of classical formula preparations, quality evaluation of medicinal materials, pharmacodynamic material basis, and mechanisms of classical formulas.
4.LRAE-Unet:a lightweight network for fully automatic segmentation of brain tumor from MRI
Jiahao LIN ; Yu WANG ; Hongbing XIAO ; Mei SUN
Chinese Journal of Medical Physics 2024;41(1):43-49
A lightweight residual attention enhanced Unet(LRAE-Unet)is designed for the fully automatic brain tumor segmentation.LRAE-Unet uses lightweight residual module to solve the problems of gradient disappearance and network degradation when the network layers increases,lightweight self-attention module to suppress the irrelevant areas and highlight the significant features of specific local areas,and enhanced average pooling module with a larger field of perception to reduce the space of feature map,save computing resources and avoid over-fitting.The experiment on BraTS 2019 dataset shows that the proposed method has a Dice similarity coefficient of 91.24%,88.64%and 88.32%in the segmentations of the whole tumor,tumor core and enhanced tumor,which proves its feasibility and effectiveness for brain tumor segmentation.
5.Effects of advanced bone flap versus no bone flap on the healing of osteotomy gap in high tibial osteotomy
Jiahao YU ; Dongwei WU ; Yanbin ZHU ; Yingze ZHANG
Chinese Journal of Orthopaedic Trauma 2024;26(2):96-102
To compare the effects of advanced bone flap and no bone flap on the healing of osteotomy gap in open-wedge high tibial osteotomy (OW-HTO) for the treatment of medial compartment osteoarthritis and knee inversion.Methods:A retrospective study was conducted to analyze the 85 patients who had undergone OW-HTO from March 2021 to December 2021 at Trauma Emergency Centre, The Third Hospital of Hebei Medical University for medial compartment osteoarthritis and knee inversion. The patients were divided into 2 groups according to whether bone flap was grafted. In group A of 42 patients who received advanced bone flap intraoperatively, there were 32 females and 10 males with an age of (63.7±6.6) years; in group B of 43 patients who received no advanced bone flap intraoperatively, there were 31 females and 12 males with an age of (63.2±9.4) years. The measures recorded and compared between the 2 groups included: osteotomy gap healing rates at 3, 6, 12, and 18 months postoperatively; Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Visual Analog Scale (VAS) for pain, and Knee injury and Osteoarthritis Outcome Score (KOOS) at 6 and 18 months postoperatively; medial proximal tibial angle (MPTA) and femorotibial angle at immediate postoperation and 18 months postoperation; postoperative complications.Results:The differences in preoperative general information between the 2 groups were not statistically significant, showing comparability ( P>0.05). The osteotomy gap healing rates at 3, 6, 12, and 18 months postoperatively in group A were significantly higher than those in group B ( P<0.05). The WOMAC (26.1±5.9), VAS (4.1±1.4), and KOOS (47.0±9.7) scores at 6 months postoperatively in group A were significantly lower than those in group B (31.3±8.3, 4.8±1.6, and 56.1±11.9) ( P<0.05), but the differences in the above indicators between the 2 groups at 18 months postoperatively were not statistically significant ( P>0.05). There was no statistically significant difference in MPTA or femorotibial angle at immediate postoperation between the 2 groups ( P>0.05). At 18 months postoperatively, the MPTA in group A (88.7°±1.1°) was significantly better than that in group B (87.7°±1.5°) ( P<0.05). The total complication rate in group B [27.9% (12/43)] was signifcantly higher than that in group A [2.4% (1/42)]( P<0.05). Conclusions:In the OW-HTO treatment of the patients with medial compartment osteoarthritis and knee inversion, application of an advanced bone flap to fill the osteotomy gap can accelerate the gap healing and reduces occurrence of delayed healing or non-healing of the osteotomy gap.
6.Key Information Textual Research and Quality Marker Prediction Analysis of the Ancient Classic Formula Huangqin Decoc-tion
Jiahao WANG ; Limei GU ; Hao XUE ; Yu LI ; Yu CHEN ; Ziyan LENG ; Renshou CHEN
Journal of Nanjing University of Traditional Chinese Medicine 2024;40(11):1263-1274
Huangqin Decoction is a classic formula published in the Catalogue of Ancient Classical Famous Prescriptions(the Sec-ond Batch).This paper systematically collates,researches and analyzes the ancient and modern clinical literature that records Huan-gqin Decoction,sorts out key issues such as the prescription origin,composition,medicine origin,processing method,usage and dos-age,efficacy and indications of Huangqin Decoction,and performs predictive analysis on its quality markers(Q-Marker)to provide lit-erature and theoretical support for the clinical application and preparation development of Huangqin Decoction from the entire process of textual research-preparation development-quality evaluation.After analysis and research,it is found that Huangqin Decoction is de-rived from Zhang Zhongjing's Treatise on Cold Damage.It consists of Scutellaria baicalensis,Radix Paeoniae Alba,and Glycyrrhiza,with Jujube serving as the guiding herb.The medicine origin follows the 2020 edition of the Chinese Pharmacopoeia.Scutellaria ba-icalensis and Radix Paeoniae Alba are taken in the raw form;Glycyrrhiza is lightly fried and Jujubes with sliced pieces.The doasge of medicine is 11.19 of Scutellaria baicalensis,7.46 g of Radix Paeoniae Alba and Glycyrrhiza,and jujubes are added or subtracted ac-cording to the situation.The method of preparation and administration is that all herbs are added with 2 000 mL of water,decocting to 600 mL.The decoction can be consumed warm 3 times a day at any suitable time.The formula was commonly used in ancient times for dysentery,but now it is also used for other digestive system diseases such as ulcerative colitis and chronic colitis,which are mainly characterized by diarrhea.The suggested Q-markers for Huangqin Decoction are baicalin,baicalein,wogonin,paeoniflorin,glycyrrhi-zin and glycyrrhizic acid.
7.SiO2 Induces Iron Overload and Ferroptosis in Cardiomyocytes in a Silicosis Mouse Model
Wang YONGHENG ; Li NING ; Guan YI ; LI TONG ; Zhang YUXIU ; Cao HONG ; Yu ZHIHUA ; Li ZHIHENG ; Li SHUOYAN ; Hu JIAHAO ; Zhou WENXIN ; Qin SISI ; Li SHUANG ; Yao SANQIAO
Biomedical and Environmental Sciences 2024;37(6):617-627
Objective The aim of this study was to explore the role and mechanism of ferroptosis in SiO2-induced cardiac injury using a mouse model. Methods Male C57BL/6 mice were intratracheally instilled with SiO2 to create a silicosis model.Ferrostatin-1(Fer-1)and deferoxamine(DFO)were used to suppress ferroptosis.Serum biomarkers,oxidative stress markers,histopathology,iron content,and the expression of ferroptosis-related proteins were assessed. Results SiO2 altered serum cardiac injury biomarkers,oxidative stress,iron accumulation,and ferroptosis markers in myocardial tissue.Fer-1 and DFO reduced lipid peroxidation and iron overload,and alleviated SiO2-induced mitochondrial damage and myocardial injury.SiO2 inhibited Nuclear factor erythroid 2-related factor 2(Nrf2)and its downstream antioxidant genes,while Fer-1 more potently reactivated Nrf2 compared to DFO. Conclusion Iron overload-induced ferroptosis contributes to SiO2-induced cardiac injury.Targeting ferroptosis by reducing iron accumulation or inhibiting lipid peroxidation protects against SiO2 cardiotoxicity,potentially via modulation of the Nrf2 pathway.
8.Comparison of myocardial protection in pediatric patients undergoing living-donor liver transplantation performed under propofol- versus desflurane-based anesthesia
Jiahao ZHI ; Yimei CAO ; Yingli CAO ; Hengchang REN ; Lili JIA ; Yiqi WENG ; Hongyin DU ; Wenli YU
Chinese Journal of Anesthesiology 2023;43(3):265-268
Objective:To compare the myocardial protection in pediatric patients undergoing living-donor liver transplantation (LDLT) performed under propofol- versus desflurane-based anesthesia. Methods:Sixty American Society of Anesthesiologists Physical Status classification Ⅲ or Ⅳ pediatric patients of both sexes, aged 5-24 months, weighing 5-15 kg, scheduled for elective LDLT under general anesthesia, were divided into 2 groups ( n=30 each) using a random number table method: propofol group (group P) and desflurane anesthesia group (group D). During anesthesia maintenance, propofol 5-10 mg·kg -1·min -1 was intravenously infused in group P, desflurane 0.65 MAC-1.30 MAC was inhaled in group D. At 5 min after induction of anesthesia, at 1 h of reperfusion, at the end of surgery, at 1, 2, 3, 7 and 14 days after surgery, and on the day of discharge, the concentrations of serum high-sensitivity cardiac troponin I, creatine kinase isoenzyme, N-terminal pro-B-type natriuretic peptide were determined by enzyme-linked immunosorbent assay, the occurrence of nausea and vomiting, agitation, and shivering, postoperative tracheal extubation time, intensive care unit stay time, and postoperative length of hospital stay were recorded within 24 h after surgery. Results:Compared with group P, the concentrations of serum high-sensitivity cardiac troponin I and creatine kinase isoenzyme were significantly decreased after surgery, the extubation time and intensive care unit stay time were shortened ( P<0.05), and no significant change was found in serum N-terminal pro-B-type natriuretic peptide concentrations, postoperative length of hospital stay and incidence of postoperative adverse effects at each time point in group D ( P>0.05). Conclusions:Desflurane has better myocardial protection than propofol in pediatric patients undergoing LDLT, which is helpful for early prognosis.
9.Risk factors for early acute lung injury after pediatric living-related liver transplantation and the predictive value
Yingli CAO ; Mingwei SHENG ; Chen ZHANG ; Jiahao ZHI ; Yimei CAO ; Hongyin DU ; Wenli YU
Chinese Journal of Anesthesiology 2023;43(3):274-277
Objective:To identify the risk factors for early acute lung injury (ALI) after living-related liver transplantation in pediatric patients and evaluate the value of the risk factors in prediction of ALI.Methods:Perioperative data of patients were obtained through the electronic medical records system. Patients were divided into non-ALI group and ALI group according to whether ALI occurred within the first week after surgery. The risk factors of which P values were less than 0.05 would enter the multiple logistic regression analysis to stratify ALI-related risk factors. Area under the ROC curve was used to analyze the value of the risk factors in prediction of postoperative ALI. Results:A total of 67 patients were enrolled, including 45 cases in non-ALI group and 22 cases in ALI group. Increased intraoperative blood transfusion volume and up-regulated expression of miR-122 and miR-21 were independent risk factors for the occurrence of postoperative ALI ( P<0.05), and the area under the ROC curve (95% confidence interval) of serum miR-122 and miR-21 expression was 0.946 (0.875 to 1.00), with sensitivity and specificity of 95% and 90%, respectively. Conclusions:Increased intraoperative blood transfusion volume and up-regulated expression of serum miR-122 and miR-21 are independent risk factors for early postoperative ALI, and serum miR-122 and miR-21 levels have a high value in prediction of the development of postoperative ALI in pediatric patients undergoing living-related liver transplantation.
10. AGEs in DRG Participates in Gastric Hypersensitivity by Regulating Expression of Kv4.2 in Diabetes Mellitus Rat Model
Jiahao WANG ; Ting YU ; Liuqin JIANG
Chinese Journal of Gastroenterology 2023;27(5):263-269
Background: Diabetic gastroparesis (DGP) is one of the most common complications of diabetes mellitus (DM), and its main symptoms include upper abdominal pain, nausea, vomiting, abdominal distension, etc. Gastric hypersensitivity is the main pathogenesis of DGP. Advanced glycation end products (AGEs) is the initiating factor of chronic complications of DM, and its relationship with gastric hypersensitivity has not yet been clear. Kv4.2 channel plays an important role in regulating visceral sensation. Subunit inactivation of Kv4.2 can reduce potassium current, enhance pain sensation, and increase gastric sensitivity. Aims: To investigate the mechanism of AGEs participating in gastric hypersensitivity by regulating the expression or activity of Kv4.2 channel in DM rat model. Methods: Fifty⁃four rats were randomly divided into control group, DM group and DM+AG group. Streptozocin (STZ) was intraperitoneally injected to induce DM rat model. Blood glucose, body weight, gastric sensitivity and gastric emptying rate were monitored. Western blotting and ELISA were used to detect CML content in stomach tissue and serum, respectively. The expression of RAGE and its co⁃expression with Kv4.2 in dorsal root ganglia (DRG) neurons were detected by immunofluorescence. Western blotting was used to detect RAGE expression and phosphorylation levels of ERK1/2 and Kv4.2 in DRG neurons. Results: Compared with control group, gastric sensitivity was significantly increased in DM group (P<0.01), gastric emptying rate was significantly decreased (P<0.05), AGEs marker CML content in serum and gastric tissue were significantly increased (P<0.05), co ⁃ expression rate of RAGE and Kv4.2 in DRG neurons was significantly increased (P<0.01), and phosphorylation levels of ERK1/2 and Kv4.2 were up⁃regulated (P<0.05). After intervention with AG, above⁃mentioned indices were significantly ameliorated (P<0.05). Conclusions: AGEs is an upstream factor leading to gastric hypersensitivity in DM rat model. AGEs increases the excitability of DRG neurons by inhibiting Kv4.2 channel, leading to gastric hypersensitivity. RAGE and ERK1/2 signal may be involved in the above process.

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