1.Efficacy Connotation and Mechanisms of Shudi Qiangjin Pills Against Steroid-induced Osteonecrosis of Femoral Head Based on "Disease-Syndrome-Formula" Association Network
Zhijian CHEN ; Suya ZHANG ; Longlong DING ; Guixin ZHANG ; Bo LIU ; Baohong MI ; Yanqiong ZHANG ; Na LIN ; Weiheng CHEN ; Chunzhu GONG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):88-99
ObjectiveTo elucidate the efficacy connotation of Shudi Qiangjin pills (SQP) against liver and kidney deficiency in steroid-induced osteonecrosis of femoral head (SONFH) from the perspective of the "disease-syndrome-formula" association and to clarify the underlying mechanisms based on in vivo and in vitro experiment validation. MethodsThe chemical components and the corresponding putative targets of SQP were collected from the Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine (TCMIP) v2.0, the Encyclopedia of Traditional Chinese Medicine (ETCM) v2.0, and HERB databases. The SONFH-related genes were identified based on the differential expression profiles of peripheral blood of patients with SONFH compared to the healthy volunteers, and the disease phenotype-related targets were collected from the TCMIP v2.0 database. Then, the interaction network of "SONFH-related genes and candidate targets of SQP" was constructed based on "gene-gene interaction information", and the major network targets were screened by calculating the topological characteristic values of the network followed by the functional mining according to the Kyoto Encyclopedia of Genes and Genomes (KEGG) database and the SoFDA database. After that, the SONFH rat model was prepared by lipopolysaccharide combined with methylprednisolone injection, and 2.5, 5, 7.5 g·kg-1 SQP (once per day, equivalent to 1, 2, and 3 times the clinical equivalent dose, respectively) or 7.3×10-3 g·kg-1 of alendronate sodium (ALS, once per week, equivalent to the clinical equivalent dose) was given for 8 weeks. The effect characteristics of SQP and ALS in the treatment of SONFH were evaluated by micro-computed tomography scanning, hematoxylin and eosin staining, alkaline phosphatase (ALP) staining, immunohistochemical staining, enzyme-linked immunosorbent assay, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL)staining, and a comparative efficacy analysis was conducted with ALS. In addition, SONFH cell models were prepared by dexamethasone stimulation of osteoblasts, and the intervention was carried out with the medicated serum of SQP at the aforementioned three doses. Cell counting kit-8, ALP staining, ALP activity assay, alizarin red staining, and flow cytometry were employed to investigate the regulatory effect of SQP on osteoblasts. The expression levels of osteogenesis-related proteins and key factors of the target signaling axis were detected by quantitative real-time polymerase chain reaction and Western blot. ResultsThe network analysis results demonstrated that the candidate targets of SQP primarily exerted their therapeutic effects through key signaling pathways, including phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt), lipid metabolism and atherosclerosis, prolactin, chemokines, and neurotrophic factors pathways. These pathways were significantly involved in critical biological processes such as muscle and bone metabolism and the regulation of the "neuro-endocrine-immune" network, thereby addressing both modern medical symptoms (e.g., delayed skeletal maturation and recurrent fractures) and traditional Chinese medicine (TCM) symptoms (e.g., fatigue, aversion to cold, cold limbs, and pain in the limbs and joints in patients with SONFH characterized by liver and kidney deficiency syndrome. Among these pathways, the PI3K/Akt signaling pathway exhibited the highest degree of enrichment. The in vivo experimental results demonstrated that starting from the 4th week after modeling, the modeling group exhibited a significant reduction in body weight compared to the control group (P<0.05). After six weeks of treatment, all dosage groups of SQP showed significantly higher body weights compared to the model group (P<0.01). Compared with the normal group, the model group exhibited significant decreases in bone mineral density (BMD), bone volume fraction (BV/TV), trabecular number (Tb.N), osteocalcin (OCN), alkaline phosphatase (ALP) levels in femoral head tissue, and serum bone-specific alkaline phosphatase (BALP) (P<0.01), along with significant increases in trabecular separation (Tb.Sp), empty lacunae rate in tissue, and apoptosis rate (P<0.01). In comparison to the model group, the SQP intervention groups showed significant improvements in BMD, BV/TV and Tb.N (P<0.01), significant reductions in Tb.Sp, empty lacunae rate and apoptosis rate (P<0.05), and significant increases in protein levels of OCN and ALP as well as BALP content (P<0.05). The in vitro experimental results revealed that all dosage groups of SQP medicated serum showed no toxic effects on osteoblast. Compared with the normal group, the model group displayed significant suppression of osteoblast proliferation activity, ALP activity, and calcified nodule formation rate (P<0.01), significant decreases in mRNA transcription levels of OCN and Runt-related transcription factor 2 (RUNX2) (P<0.01), significant reductions in protein content of osteopontin (OPN), typeⅠ collagen (ColⅠ)A1, B-cell lymphoma-2 (Bcl-2), PI3K, and phosphorylated (p)-Akt (P<0.01), and a significant increase in apoptosis rate (P<0.01). Compared with the model group, the SQP medicated serum intervention groups exhibited significant increases in proliferation activity, ALP activity, calcified nodule formation rate, mRNA transcription levels of OCN and RUNX2, and protein content of OPN, ColⅠA1, Bcl-2, PI3K, and p-Akt (P<0.05), along with a significant decrease in apoptosis rate (P<0.01). ConclusionSQP can effectively reduce the disease severity of SONFH with liver and kidney deficiency syndrome and improve bone microstructure, with the therapeutic effects exhibiting a dose-dependent manner. The mechanism may be related to its regulation of key processes such as muscle and bone metabolism and the correction of imbalances in the "neuro-endocrine-immune" network, thereby promoting osteoblast differentiation and inhibiting osteoblast apoptosis. The PI3K/Akt signaling axis is likely one of the key pathways through which this formula exerts its effects.
2.Reassessment of non-acute occlusion in intracranial flow diverter implantation: an animal experimental study based on optical coherence tomography, intravascular ultrasound, and pathological correlation
Zhuangzhuang WEI ; Qi TIAN ; Shuailong SHI ; Jie YANG ; Ji MA ; Zhen LI ; Haiqiang SANG ; Yi TANG ; Yuncai RAN ; Yong ZHANG ; Baohong WEN ; Shanshan XIE ; Jinjuan CHEN ; Enjie LIU ; Xinwei HAN ; Tengfei LI
Chinese Journal of Neurology 2025;58(6):607-614
Objective:To investigate and summarize the imaging and pathological features of non-acute occlusion following flow diverter (FD) implantation in animal models.Methods:Four experimental pigs (experimental group) that experienced non-acute occlusion (occlusion time exceeding 24 hours) within the FD stent implanted in the common carotid artery, and 19 pigs (control group) that did not experience stent occlusion during the same period were involved. Using an interventional approach under digital subtraction angiography (DSA), the 4 occluded FD lumens were mechanically opened. Optical coherence tomography (OCT), intravascular ultrasound (IVUS) and histopathological examinations were performed to evaluate the intraluminal composition and characteristics of the occlusive tissues. These findings were compared with non-occluded FD stents to summarize the imaging and pathological changes within the occluded FD lumen.Results:The occlusion times of the FD stents in the 4 experimental pigs were 16 weeks, 20 weeks, 20 weeks, and 24 weeks postoperatively. All occluded stents were successfully recanalized under DSA, with a technical success rate of 4/4. Among the 19 non-occluded FD stents, OCT and IVUS revealed uniform (16 stents) or non-uniform (3 stents) neointimal coverage of the stent struts, presenting as homogeneous high/slightly high signal intensity or medium echogenicity. Histopathological examination indicated that the neointima was primarily composed of smooth muscle cells and a small amount of fibrous connective tissues. In contrast, the 4 occluded FD stents demonstrated excessive neointimal proliferation and plaque formation, leading to luminal loss, as shown by OCT and IVUS. The occlusion tissues predominantly presented as homogeneous high signal intensity with weak attenuation (fibrous plaques) on OCT, with some regions showing blurred low signal intensity and strong attenuation (lipid plaques). IVUS presented homogeneous echogenicity (fibrous plaques) and hypoechogenic zones (lipid plaques). Histopathological examination showed that the occlusion tissues mainly consisted of smooth muscle cells, fibrous connective tissues, and lipids, accompanied by numerous foam cells and a minor presence of inflammatory cells.Conclusions:Histopathological examinations confirm that non-acute occlusion of FD is mainly caused by excessive hyperplasia of intima along with the formation of fibrous plaques and lipid plaques. OCT and IVUS have typical finding in imaging that can assist in determining the cause of stent occlusion as well as the lesion's nature, thereby providing crucial guidance for subsequent clinical treatment and drug selection.
3.Salvianolic Acid B and Ginsenoside Rg1 Combination Attenuates Cerebral Edema Accompanying Glymphatic Modulation.
Lingxiao ZHANG ; Yanan SHAO ; Zhao FANG ; Siqi CHEN ; Yixuan WANG ; Han SHA ; Yuhan ZHANG ; Linlin WANG ; Yi JIN ; Hao CHEN ; Baohong JIANG
Neuroscience Bulletin 2025;41(11):1909-1923
Cerebral edema is characterized by fluid accumulation, and the glymphatic system (GS) plays a pivotal role in regulating fluid transport. Using the Tenecteplase system, magnesium salt of salvianolic acid B/ginsenoside Rg1 (SalB/Rg1) was injected intravenously into mice 4.5 h after middle cerebral artery occlusion and once every 24 h for the following 72 h. GS function was assessed by Evans blue imaging, near-infrared fluorescence region II (NIR-II) imaging, and magnetic resonance imaging (MRI). SalB/Rg1 had significant effects on reducing the infarct volume and hemorrhagic transformation score, improving neurobehavioral function, and protecting tissue structure, especially inhibiting cerebral edema. Meanwhile, the influx/efflux drainage of GS was enhanced by SalB/Rg1 according to NIR-II imaging and MRI. SalB/Rg1 inhibited matrix metalloproteinase-9 (MMP-9) activity, reduced cleaved β-dystroglycan (β-DG), and stabilized aquaporin-4 (AQP4) polarity, which was verified by colocalization with CD31. Our findings indicated that SalB/Rg1 treatment enhances GS function and attenuates cerebral edema, accompanying the regulation of the MMP9/β-DG/AQP4 pathway.
Animals
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Ginsenosides/administration & dosage*
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Brain Edema/etiology*
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Male
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Benzofurans/administration & dosage*
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Glymphatic System/diagnostic imaging*
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Mice
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Infarction, Middle Cerebral Artery/drug therapy*
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Aquaporin 4/metabolism*
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Disease Models, Animal
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Mice, Inbred C57BL
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Matrix Metalloproteinase 9/metabolism*
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Neuroprotective Agents/pharmacology*
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Depsides
4.Expert consensus on peri-implant keratinized mucosa augmentation at second-stage surgery.
Shiwen ZHANG ; Rui SHENG ; Zhen FAN ; Fang WANG ; Ping DI ; Junyu SHI ; Duohong ZOU ; Dehua LI ; Yufeng ZHANG ; Zhuofan CHEN ; Guoli YANG ; Wei GENG ; Lin WANG ; Jian ZHANG ; Yuanding HUANG ; Baohong ZHAO ; Chunbo TANG ; Dong WU ; Shulan XU ; Cheng YANG ; Yongbin MOU ; Jiacai HE ; Xingmei YANG ; Zhen TAN ; Xiaoxiao CAI ; Jiang CHEN ; Hongchang LAI ; Zuolin WANG ; Quan YUAN
International Journal of Oral Science 2025;17(1):51-51
Peri-implant keratinized mucosa (PIKM) augmentation refers to surgical procedures aimed at increasing the width of PIKM. Consensus reports emphasize the necessity of maintaining a minimum width of PIKM to ensure long-term peri-implant health. Currently, several surgical techniques have been validated for their effectiveness in increasing PIKM. However, the selection and application of PIKM augmentation methods may present challenges for dental practitioners due to heterogeneity in surgical techniques, variations in clinical scenarios, and anatomical differences. Therefore, clear guidelines and considerations for PIKM augmentation are needed. This expert consensus focuses on the commonly employed surgical techniques for PIKM augmentation and the factors influencing their selection at second-stage surgery. It aims to establish a standardized framework for assessing, planning, and executing PIKM augmentation procedures, with the goal of offering evidence-based guidance to enhance the predictability and success of PIKM augmentation.
Humans
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Consensus
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Dental Implants
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Mouth Mucosa/surgery*
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Keratins
5.Analysis on Clinical Characteristics and Medication Patterns of 2 999 Patients with Knee Osteoarthritis Treated with Wangbi Tablets Based on the Real World
Kuayue ZHANG ; Chao LI ; Zhuoyun WU ; Yawei DONG ; Yuzhi LIU ; Jiaming LIN ; Yuefeng CHEN ; Baohong MI ; Chunzhu GONG ; Fuhui LIN ; Weiheng CHEN
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(2):156-163
Objective To study the clinical characteristics and medication patterns of Wangbi Tablets in treating patients with knee osteoarthritis(KOA)in the real world and to analyze the advantages and specific features of Chinese patent medicines in treating advantage disease.Methods A prospective case registry study was conducted,registering 3 000 patients from 30 TCM and Western medicine hospitals across China from April 2019 to December 2021.Data on gender,age,BMI,Chinese medicine staging(CMS),K-L grading,medication duration,VAS score,medical history and combined medication were collected for descriptive analysis.Comparisons were made between different stages and between single-use and combined-use groups.The Apriori algorithm was used for association analysis of combined medications.Results A total of 2 999 patients were included,with 2 063 females(68.79%)and 936 males(31.21%).The average age was(56.89±8.90)years.The average BMI was(23.80±2.88)kg/m2.The proportion of patients in CMS I was 512(17.07%),with a VAS median score of 8,while the proportion of patients in CMS Ⅱ was 2 181(72.73%),with a VAS median score of 6.The proportion of patients in CMS Ⅲ was 306(10.20%),with a VAS median score of 3;316 cases(10.54%)were classified as K-L grade I,2 477 cases(82.59%)as grade Ⅱ,204 cases(6.80%)as grade Ⅲ,and 2 cases(0.07%)as grade Ⅳ.Medication analysis indicated that the single-use group(1507 cases,50.25%)was larger than the combined-use group(1 492 cases,49.75%).In terms of the number of drugs used in combination,one(39.01%)and two(38.14%)were the main types;in terms of medication types,combination therapy with Western medicine(62.27%)and simultaneous use of Western medicine and other Chinese materia medica(26.14%)were the main methods;the top three drugs with the highest frequency of combination use were glucosamine capsules,imrecoxib tablets and sodium hyaluronate injection.The top three drug combinations with the highest support were"Huoxue Zhishang Powder+imrecoxib tablets","glucosamine capsules+imrecoxib tablets"and"glucosamine capsules+sodium hyaluronate injection".Inter-group comparisons showed that the medication duration for Wangbi Tablets in CMS I was longer than in CMS Ⅱ and CMS Ⅲ(P<0.01).The proportion of patients on monotherapy in CMS I(62.11%)was higher than in CMS Ⅱ(46.54%)and CMS Ⅲ(56.86%)(P<0.001).Among patients in CMS I(16.41%)and CMS Ⅲ(21.24%),the highest proportion used one combined medication,whereas in CMS Ⅱ,the highest proportion was for those using two combined medications(20.50%).In all three groups,CMS I(19.53%),CMS Ⅱ(33.70%)and CMS Ⅲ(30.72%),the highest proportion of combined medications was Western medicine.Conclusion More than half of the patients treated KOA with Wangbi Tablets alone.Approximately one-fifth of the patients were in CMS I,with a median pain score of 8.The average duration of medication for patients in CMS I,CMS Ⅱ and CMS Ⅲ decreases,and there is no obvious pattern in the medication method at different stages;combination therapy is represented by"Huoxue Zhishang Powder+imrecoxib tablets"and"glucosamine capsules+imrecoxib tablets".
6.Yishen Shengyang formula ameliorates allergic rhinitis via Bach2-driven Treg cell regulation
Zhichao MA ; Chaohui ZHANG ; Yongjie YING ; Yilong WANG ; Qiaozhi JIN ; Wubing CHEN ; Baohong TAO
China Modern Doctor 2025;63(15):56-60
Objective To investigate the therapeutic effects and mechanisms of Yishen Shengyang formula in allergic rhinitis(AR)by regulating the transcription factor BTB and CNC homology 2(Bach2)to promote regulatory T cell(Treg cell)differentiation.Methods AR mouse models were established via ovalbumin(OVA)sensitization and randomly divided into control group,AR model group(AR group),Yishen Shengyang formula group and dexamethasone group.Nasal symptoms were evaluated using behavioral scores;Histopathological changes in nasal mucosa were observed via hematoxylin-eosin and periodic acid Schiff stain;Serum levels of OVA-specific immunoglobulin E(sIgE),interleukin-4(IL-4),and transforming growth factor-β(TGF-β)were measured by enzyme linked immunosorbent assay;Splenic Treg proportions were analyzed via flow cytometry;Bach2 protein expression was assessed by Western blot.Results Compared with control group,AR group mice showed significantly increased behavioral scores(P<0.05),goblet cell hyperplasia,inflammatory infiltration,elevated OVA-sIgE and IL-4 levels(P<0.05),reduced TGF-β(P<0.05),and decreased splenic Treg proportions and Bach2 expression(P<0.05).Yishen Shengyang formula treatment alleviated nasal symptoms(P<0.05),mitigated mucosal damage,decreased OVA-sIgE and IL-4,increased TGF-β(P<0.05),and upregulated Treg proportions and Bach2 expression(P<0.05),with efficacy comparable to dexamethasone.Conclusion Yishen Shengyang formula demonstrates potential therapeutic effects on allergic rhinitis by upregulating Bach2 expression and promoting Treg cell differentiation.This study provides a novel strategy and experimental basis for the traditional Chinese medicine treatment of AR.
7.Analysis on Clinical Characteristics and Medication Patterns of 2 999 Patients with Knee Osteoarthritis Treated with Wangbi Tablets Based on the Real World
Kuayue ZHANG ; Chao LI ; Zhuoyun WU ; Yawei DONG ; Yuzhi LIU ; Jiaming LIN ; Yuefeng CHEN ; Baohong MI ; Chunzhu GONG ; Fuhui LIN ; Weiheng CHEN
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(2):156-163
Objective To study the clinical characteristics and medication patterns of Wangbi Tablets in treating patients with knee osteoarthritis(KOA)in the real world and to analyze the advantages and specific features of Chinese patent medicines in treating advantage disease.Methods A prospective case registry study was conducted,registering 3 000 patients from 30 TCM and Western medicine hospitals across China from April 2019 to December 2021.Data on gender,age,BMI,Chinese medicine staging(CMS),K-L grading,medication duration,VAS score,medical history and combined medication were collected for descriptive analysis.Comparisons were made between different stages and between single-use and combined-use groups.The Apriori algorithm was used for association analysis of combined medications.Results A total of 2 999 patients were included,with 2 063 females(68.79%)and 936 males(31.21%).The average age was(56.89±8.90)years.The average BMI was(23.80±2.88)kg/m2.The proportion of patients in CMS I was 512(17.07%),with a VAS median score of 8,while the proportion of patients in CMS Ⅱ was 2 181(72.73%),with a VAS median score of 6.The proportion of patients in CMS Ⅲ was 306(10.20%),with a VAS median score of 3;316 cases(10.54%)were classified as K-L grade I,2 477 cases(82.59%)as grade Ⅱ,204 cases(6.80%)as grade Ⅲ,and 2 cases(0.07%)as grade Ⅳ.Medication analysis indicated that the single-use group(1507 cases,50.25%)was larger than the combined-use group(1 492 cases,49.75%).In terms of the number of drugs used in combination,one(39.01%)and two(38.14%)were the main types;in terms of medication types,combination therapy with Western medicine(62.27%)and simultaneous use of Western medicine and other Chinese materia medica(26.14%)were the main methods;the top three drugs with the highest frequency of combination use were glucosamine capsules,imrecoxib tablets and sodium hyaluronate injection.The top three drug combinations with the highest support were"Huoxue Zhishang Powder+imrecoxib tablets","glucosamine capsules+imrecoxib tablets"and"glucosamine capsules+sodium hyaluronate injection".Inter-group comparisons showed that the medication duration for Wangbi Tablets in CMS I was longer than in CMS Ⅱ and CMS Ⅲ(P<0.01).The proportion of patients on monotherapy in CMS I(62.11%)was higher than in CMS Ⅱ(46.54%)and CMS Ⅲ(56.86%)(P<0.001).Among patients in CMS I(16.41%)and CMS Ⅲ(21.24%),the highest proportion used one combined medication,whereas in CMS Ⅱ,the highest proportion was for those using two combined medications(20.50%).In all three groups,CMS I(19.53%),CMS Ⅱ(33.70%)and CMS Ⅲ(30.72%),the highest proportion of combined medications was Western medicine.Conclusion More than half of the patients treated KOA with Wangbi Tablets alone.Approximately one-fifth of the patients were in CMS I,with a median pain score of 8.The average duration of medication for patients in CMS I,CMS Ⅱ and CMS Ⅲ decreases,and there is no obvious pattern in the medication method at different stages;combination therapy is represented by"Huoxue Zhishang Powder+imrecoxib tablets"and"glucosamine capsules+imrecoxib tablets".
8.Yishen Shengyang formula ameliorates allergic rhinitis via Bach2-driven Treg cell regulation
Zhichao MA ; Chaohui ZHANG ; Yongjie YING ; Yilong WANG ; Qiaozhi JIN ; Wubing CHEN ; Baohong TAO
China Modern Doctor 2025;63(15):56-60
Objective To investigate the therapeutic effects and mechanisms of Yishen Shengyang formula in allergic rhinitis(AR)by regulating the transcription factor BTB and CNC homology 2(Bach2)to promote regulatory T cell(Treg cell)differentiation.Methods AR mouse models were established via ovalbumin(OVA)sensitization and randomly divided into control group,AR model group(AR group),Yishen Shengyang formula group and dexamethasone group.Nasal symptoms were evaluated using behavioral scores;Histopathological changes in nasal mucosa were observed via hematoxylin-eosin and periodic acid Schiff stain;Serum levels of OVA-specific immunoglobulin E(sIgE),interleukin-4(IL-4),and transforming growth factor-β(TGF-β)were measured by enzyme linked immunosorbent assay;Splenic Treg proportions were analyzed via flow cytometry;Bach2 protein expression was assessed by Western blot.Results Compared with control group,AR group mice showed significantly increased behavioral scores(P<0.05),goblet cell hyperplasia,inflammatory infiltration,elevated OVA-sIgE and IL-4 levels(P<0.05),reduced TGF-β(P<0.05),and decreased splenic Treg proportions and Bach2 expression(P<0.05).Yishen Shengyang formula treatment alleviated nasal symptoms(P<0.05),mitigated mucosal damage,decreased OVA-sIgE and IL-4,increased TGF-β(P<0.05),and upregulated Treg proportions and Bach2 expression(P<0.05),with efficacy comparable to dexamethasone.Conclusion Yishen Shengyang formula demonstrates potential therapeutic effects on allergic rhinitis by upregulating Bach2 expression and promoting Treg cell differentiation.This study provides a novel strategy and experimental basis for the traditional Chinese medicine treatment of AR.
9.Reassessment of non-acute occlusion in intracranial flow diverter implantation: an animal experimental study based on optical coherence tomography, intravascular ultrasound, and pathological correlation
Zhuangzhuang WEI ; Qi TIAN ; Shuailong SHI ; Jie YANG ; Ji MA ; Zhen LI ; Haiqiang SANG ; Yi TANG ; Yuncai RAN ; Yong ZHANG ; Baohong WEN ; Shanshan XIE ; Jinjuan CHEN ; Enjie LIU ; Xinwei HAN ; Tengfei LI
Chinese Journal of Neurology 2025;58(6):607-614
Objective:To investigate and summarize the imaging and pathological features of non-acute occlusion following flow diverter (FD) implantation in animal models.Methods:Four experimental pigs (experimental group) that experienced non-acute occlusion (occlusion time exceeding 24 hours) within the FD stent implanted in the common carotid artery, and 19 pigs (control group) that did not experience stent occlusion during the same period were involved. Using an interventional approach under digital subtraction angiography (DSA), the 4 occluded FD lumens were mechanically opened. Optical coherence tomography (OCT), intravascular ultrasound (IVUS) and histopathological examinations were performed to evaluate the intraluminal composition and characteristics of the occlusive tissues. These findings were compared with non-occluded FD stents to summarize the imaging and pathological changes within the occluded FD lumen.Results:The occlusion times of the FD stents in the 4 experimental pigs were 16 weeks, 20 weeks, 20 weeks, and 24 weeks postoperatively. All occluded stents were successfully recanalized under DSA, with a technical success rate of 4/4. Among the 19 non-occluded FD stents, OCT and IVUS revealed uniform (16 stents) or non-uniform (3 stents) neointimal coverage of the stent struts, presenting as homogeneous high/slightly high signal intensity or medium echogenicity. Histopathological examination indicated that the neointima was primarily composed of smooth muscle cells and a small amount of fibrous connective tissues. In contrast, the 4 occluded FD stents demonstrated excessive neointimal proliferation and plaque formation, leading to luminal loss, as shown by OCT and IVUS. The occlusion tissues predominantly presented as homogeneous high signal intensity with weak attenuation (fibrous plaques) on OCT, with some regions showing blurred low signal intensity and strong attenuation (lipid plaques). IVUS presented homogeneous echogenicity (fibrous plaques) and hypoechogenic zones (lipid plaques). Histopathological examination showed that the occlusion tissues mainly consisted of smooth muscle cells, fibrous connective tissues, and lipids, accompanied by numerous foam cells and a minor presence of inflammatory cells.Conclusions:Histopathological examinations confirm that non-acute occlusion of FD is mainly caused by excessive hyperplasia of intima along with the formation of fibrous plaques and lipid plaques. OCT and IVUS have typical finding in imaging that can assist in determining the cause of stent occlusion as well as the lesion's nature, thereby providing crucial guidance for subsequent clinical treatment and drug selection.
10.Real-World Study on the Clinical Efficacy of Different Medication Regimens of Wangbi Tablet (尪痹片) in the Treatment of Knee Osteoarthritis
Kuayue ZHANG ; Chao LI ; Zhuoyun WU ; Yawei DONG ; Zelu ZHENG ; Yuzhi LIU ; Jun ZHOU ; Jiaming LIN ; Yuefeng CHEN ; Baohong MI ; Weiheng CHEN
Journal of Traditional Chinese Medicine 2024;65(22):2316-2325
ObjectiveTo investigate the differences in clinical efficacy of different medication regimens of Wangbi Tablets (尪痹片) for knee osteoarthritis (KOA) in a real-world setting, providing a basis for rational clinical use of Wangbi Tablets. MethodsA prospective registry study was conducted, involving 2,999 KOA patients registered in 30 hospitals nationwide from January 26th, 2019, to December 17th, 2021. Based on the use of Wangbi Tablets during the observation period, patients were divided into a monotherapy group (1,507 cases) and a combination therapy group (1,492 cases), and the combination group can be further divided into Wangbi Tablets plus Chinese medicine (CM), Wangbi Tablets plus western medicine (WM), and Wangbi Tablets plus Chinese and western medicine (CM+WM) subgroups. The baseline data of patients in the monotherapy group and the combination group were compared, including age, gender, body weight, medication time, clinical stage, K-L grade, and others. Efficacy indicators included the Visual Analog Scale (VAS) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and EuroQol five-dimensional (EQ-5D) health index, which were evaluated before and after 4-, 8- and 12-week treatment, and the difference before and after treatment was calculated after 4, 8 and 12 weeks of treatment. The difference between the baseline and 12 weeks of treatment of all the above indicators was used as the dependent variables, and gender, age, body mass index (BMI), course of disease, K-L grade, and clinical stage were used as independent variables, when multiple linear regression was taken to explore the influencing factors of the efficacy. At the same time, the occurrence of major symptoms (including morning stiffness, joint swelling, soreness of waist and knees, fear of wind, and fear of cold) was counted, and the disappearance of symptoms at each time point was counted after 4, 8, and 12 weeks of treatment. ResultsAt baseline, there were no statistically significant differences in gender and age distribution between the monotherapy and combination therapy groups (P>0.05); the proportion of patients in the acute stage and recovery stage was higher in the monotherapy group than in the combination therapy group, while the proportion in the remission stage was lower (P<0.05); the VAS score was higher in the monotherapy group, and the EQ-5D index was lower (P<0.01), with no statistically significant difference in total WOMAC score between the two groups (P>0.05). Compared to those measured before treatment and at previous timepoint, the VAS score and WOMAC total score significantly decreased in both groups, while EQ-5D value increased (P<0.05). The difference in VAS score between baseline and after 12-week treatment was higher in the monotherapy group than the combination group, while the differences in WOMAC total score and EQ-5D value between baseline and after 4-, 8- and 12-week treatment were higher in the combination group (P<0.05). Multiple linear regression showed that VAS score before treatment had greatest impact on pain improvement (P<0.01), and compared to Wangbi Tablets monotherapy, the combination of Wangbi tablets with WM or CM had larger associations with pain improvement (P<0.05); and Wangbi Tablets had better efficacy when the course of treatment was >28 days (P<0.01). Wangbi Tablets plus WM had a better effect on improving the overall function of the knee joint than Wangbi Tablets alone (P<0.01); and the efficacy of Wangbi Tablets with a course of treatment >28 days was better (P<0.05). The improvement of quality of life of patients in the attack and remission stages was more obvious than that in the recovery stage (P<0.01); Wangbi Tablets plus WM or CM had a better effect on improving quality of life than Wangbi Tablets alone (P<0.05). Before treatment, the proportion of patients with morning stiffness, soreness of waist and knees, fear of wind and chills in the monotherapy group was higher than that in the combination group (P<0.01). The proportion of main symptoms in both groups decreased after 4, 8 and 12 weeks of treatment (P<0.05). After 4 weeks of treatment, the disappearance rate of each main symptom in the combination group was higher than that in the monotherapy group, and after 12 weeks of treatment, the disappearance rate of fear of wind in the monotherapy group was higher than that in the combination group, while the disappearance rate of joint swelling and soreness of waist and knees was lower (P<0.05). ConclusionWangbi Tablets, whether used alone or in combination with other medications, is effective throughout the course of KOA, with greater benefits in improving joint function and quality of life during the acute and remission stages compared to the recovery stage. Combination therapy had a faster onset of effect, but began to converge with monotherapy after 8 weeks. The best efficacy was observed with the combination of Wangbi Tablets with WM, followed by combination with CM.

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