1.Post‑transplant cyclophosphamide plus anti‑thymocyte globulin decreased serum IL‑6 levels when compared with post‑transplant cyclophosphamide alone after haploidentical hematopoietic stem cell transplantation
Jeong Suk KOH ; Myung‑Won LEE ; Thi Thuy Duong PHAM ; Bu Yeon HEO ; Suyoung CHOI ; Sang‑Woo LEE ; Wonhyoung SEO ; Sora KANG ; Seul Bi LEE ; Chul Hee KIM ; Hyewon RYU ; Hyuk Soo EUN ; Hyo‑Jin LEE ; Hwan‑Jung YUN ; Deog‑Yeon JO ; Ik‑Chan SONG
Blood Research 2025;60():5-
Background:
Post-transplantation cyclophosphamide (PTCy) and anti-thymocyte globulin (ATG) are common pro‑ phylactic strategies for graft-versus-host disease (GVHD) after haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Interleukin (IL)-6 is a surrogate marker for cytokine release syndrome (CRS) and acute GVHD.Method The clinical outcomes and complications of haplo-HSCT with PTCy plus ATG versus PTCy monotherapy were compared according to serum IL-6 levels at Chungnam National University Hospital (Daejeon, South Korea) from Jan‑ uary 2019 to February 2023.
Results:
Forty patients who underwent haplo-HSCT were analyzed. A significant difference in IL-6 levels was observed between the PTCy plus ATG and PTCy alone groups (7.47 ± 10.55 vs. 117.65 ± 127.67; p = 0.003). More patients in the PTCy plus ATG group had a CRS grade of 0 than in the PTCy alone group (p < 0.001). Serum IL-6 levels were associated with grades II–IV acute GVHD (r = 0.547, p < 0.001). The cumulative incidence (CI) of grades II–IV acute GVHD was significantly higher in the PTCy alone group (67.9% vs. 4.8%; p < 0.001). No significant difference in the CI for chronic GVHD was detected between the PTCy plus ATG and PTCy alone groups (72.1% vs. 82.0%; p = 0.730). The CI of 1-year non-relapse mortality was significantly higher in the PTCy alone group than in the PTCy plus ATG group (42.2% vs. 15.9%; p = 0.022). The 1-year overall survival (OS) was significantly better in the PTCy plus ATG group (75.9% vs. 35.3%; p = 0.011). The 1-year GVHD-free, relapse-free survival rate was 29.4% in the PTCy alone group and 54.0% in the PTCy plus ATG group (p = 0.038).
Conclusion
Serum IL-6 levels were higher in the PTCy alone group than in the PTCy plus ATG group. The addition of ATG before stem cell infusion affected IL-6 levels and reduced the incidences of CRS and grade II–IV acute GVHD in haplo-HSCT patients. This study suggests that PTCy plus ATG as GVHD prophylaxis in haplo-HSCT is beneficial in terms of clinical outcomes and complications of HSCT.
2.Post‑transplant cyclophosphamide plus anti‑thymocyte globulin decreased serum IL‑6 levels when compared with post‑transplant cyclophosphamide alone after haploidentical hematopoietic stem cell transplantation
Jeong Suk KOH ; Myung‑Won LEE ; Thi Thuy Duong PHAM ; Bu Yeon HEO ; Suyoung CHOI ; Sang‑Woo LEE ; Wonhyoung SEO ; Sora KANG ; Seul Bi LEE ; Chul Hee KIM ; Hyewon RYU ; Hyuk Soo EUN ; Hyo‑Jin LEE ; Hwan‑Jung YUN ; Deog‑Yeon JO ; Ik‑Chan SONG
Blood Research 2025;60():5-
Background:
Post-transplantation cyclophosphamide (PTCy) and anti-thymocyte globulin (ATG) are common pro‑ phylactic strategies for graft-versus-host disease (GVHD) after haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Interleukin (IL)-6 is a surrogate marker for cytokine release syndrome (CRS) and acute GVHD.Method The clinical outcomes and complications of haplo-HSCT with PTCy plus ATG versus PTCy monotherapy were compared according to serum IL-6 levels at Chungnam National University Hospital (Daejeon, South Korea) from Jan‑ uary 2019 to February 2023.
Results:
Forty patients who underwent haplo-HSCT were analyzed. A significant difference in IL-6 levels was observed between the PTCy plus ATG and PTCy alone groups (7.47 ± 10.55 vs. 117.65 ± 127.67; p = 0.003). More patients in the PTCy plus ATG group had a CRS grade of 0 than in the PTCy alone group (p < 0.001). Serum IL-6 levels were associated with grades II–IV acute GVHD (r = 0.547, p < 0.001). The cumulative incidence (CI) of grades II–IV acute GVHD was significantly higher in the PTCy alone group (67.9% vs. 4.8%; p < 0.001). No significant difference in the CI for chronic GVHD was detected between the PTCy plus ATG and PTCy alone groups (72.1% vs. 82.0%; p = 0.730). The CI of 1-year non-relapse mortality was significantly higher in the PTCy alone group than in the PTCy plus ATG group (42.2% vs. 15.9%; p = 0.022). The 1-year overall survival (OS) was significantly better in the PTCy plus ATG group (75.9% vs. 35.3%; p = 0.011). The 1-year GVHD-free, relapse-free survival rate was 29.4% in the PTCy alone group and 54.0% in the PTCy plus ATG group (p = 0.038).
Conclusion
Serum IL-6 levels were higher in the PTCy alone group than in the PTCy plus ATG group. The addition of ATG before stem cell infusion affected IL-6 levels and reduced the incidences of CRS and grade II–IV acute GVHD in haplo-HSCT patients. This study suggests that PTCy plus ATG as GVHD prophylaxis in haplo-HSCT is beneficial in terms of clinical outcomes and complications of HSCT.
3.Post‑transplant cyclophosphamide plus anti‑thymocyte globulin decreased serum IL‑6 levels when compared with post‑transplant cyclophosphamide alone after haploidentical hematopoietic stem cell transplantation
Jeong Suk KOH ; Myung‑Won LEE ; Thi Thuy Duong PHAM ; Bu Yeon HEO ; Suyoung CHOI ; Sang‑Woo LEE ; Wonhyoung SEO ; Sora KANG ; Seul Bi LEE ; Chul Hee KIM ; Hyewon RYU ; Hyuk Soo EUN ; Hyo‑Jin LEE ; Hwan‑Jung YUN ; Deog‑Yeon JO ; Ik‑Chan SONG
Blood Research 2025;60():5-
Background:
Post-transplantation cyclophosphamide (PTCy) and anti-thymocyte globulin (ATG) are common pro‑ phylactic strategies for graft-versus-host disease (GVHD) after haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Interleukin (IL)-6 is a surrogate marker for cytokine release syndrome (CRS) and acute GVHD.Method The clinical outcomes and complications of haplo-HSCT with PTCy plus ATG versus PTCy monotherapy were compared according to serum IL-6 levels at Chungnam National University Hospital (Daejeon, South Korea) from Jan‑ uary 2019 to February 2023.
Results:
Forty patients who underwent haplo-HSCT were analyzed. A significant difference in IL-6 levels was observed between the PTCy plus ATG and PTCy alone groups (7.47 ± 10.55 vs. 117.65 ± 127.67; p = 0.003). More patients in the PTCy plus ATG group had a CRS grade of 0 than in the PTCy alone group (p < 0.001). Serum IL-6 levels were associated with grades II–IV acute GVHD (r = 0.547, p < 0.001). The cumulative incidence (CI) of grades II–IV acute GVHD was significantly higher in the PTCy alone group (67.9% vs. 4.8%; p < 0.001). No significant difference in the CI for chronic GVHD was detected between the PTCy plus ATG and PTCy alone groups (72.1% vs. 82.0%; p = 0.730). The CI of 1-year non-relapse mortality was significantly higher in the PTCy alone group than in the PTCy plus ATG group (42.2% vs. 15.9%; p = 0.022). The 1-year overall survival (OS) was significantly better in the PTCy plus ATG group (75.9% vs. 35.3%; p = 0.011). The 1-year GVHD-free, relapse-free survival rate was 29.4% in the PTCy alone group and 54.0% in the PTCy plus ATG group (p = 0.038).
Conclusion
Serum IL-6 levels were higher in the PTCy alone group than in the PTCy plus ATG group. The addition of ATG before stem cell infusion affected IL-6 levels and reduced the incidences of CRS and grade II–IV acute GVHD in haplo-HSCT patients. This study suggests that PTCy plus ATG as GVHD prophylaxis in haplo-HSCT is beneficial in terms of clinical outcomes and complications of HSCT.
4.Research progress on prevention and treatment of hepatocellular carcinoma with traditional Chinese medicine based on gut microbiota.
Rui REN ; Xing YANG ; Ping-Ping REN ; Qian BI ; Bing-Zhao DU ; Qing-Yan ZHANG ; Xue-Han WANG ; Zhong-Qi JIANG ; Jin-Xiao LIANG ; Ming-Yi SHAO
China Journal of Chinese Materia Medica 2025;50(15):4190-4200
Hepatocellular carcinoma(HCC), the third leading cause of cancer-related death worldwide, is characterized by high mortality and recurrence rates. Common treatments include hepatectomy, liver transplantation, ablation therapy, interventional therapy, radiotherapy, systemic therapy, and traditional Chinese medicine(TCM). While exhibiting specific advantages, these approaches are associated with varying degrees of adverse effects. To alleviate patients' suffering and burdens, it is crucial to explore additional treatments and elucidate the pathogenesis of HCC, laying a foundation for the development of new TCM-based drugs. With emerging research on gut microbiota, it has been revealed that microbiota plays a vital role in the development of HCC by influencing intestinal barrier function, microbial metabolites, and immune regulation. TCM, with its multi-component, multi-target, and multi-pathway characteristics, has been increasingly recognized as a vital therapeutic treatment for HCC, particularly in patients at intermediate or advanced stages, by prolonging survival and improving quality of life. Recent global studies demonstrate that TCM exerts anti-HCC effects by modulating gut microbiota, restoring intestinal barrier function, regulating microbial composition and its metabolites, suppressing inflammation, and enhancing immune responses, thereby inhibiting the malignant phenotype of HCC. This review aims to elucidate the mechanisms by which gut microbiota contributes to the development and progression of HCC and highlight the regulatory effects of TCM, addressing the current gap in systematic understanding of the "TCM-gut microbiota-HCC" axis. The findings provide theoretical support for integrating TCM with western medicine in HCC treatment and promote the transition from basic research to precision clinical therapy through microbiota-targeted drug development and TCM-based interventions.
Humans
;
Gastrointestinal Microbiome/drug effects*
;
Carcinoma, Hepatocellular/microbiology*
;
Liver Neoplasms/microbiology*
;
Drugs, Chinese Herbal/administration & dosage*
;
Animals
;
Medicine, Chinese Traditional
5.Clinical efficacy of open reduction and internal fixation with plates versus minimally invasive Kirschner wire fixation for osteoporotic Colles' fractures.
Jun-Wei ZHANG ; Jin-Yong HOU ; Zhao-Hui LI ; Zhen-Yuan MA ; Xiang GAO ; Hong-Zheng BI ; Ling-Ling CHEN ; Hai-Tao WANG ; Wei-Zhi NIE ; Yong-Zhong CHENG ; Xiao-Bing XI
China Journal of Orthopaedics and Traumatology 2025;38(1):18-24
OBJECTIVE:
To compare the short-term clinical efficacy and safety of closed reduction with Kirschner wire fixation versus open reduction with plate fixation for treating osteoporotic Colles' fractures in middle-aged and elderly patients.
METHODS:
Between January 2018 and January 2023, 119 patients with Colles fractures were retrospectively analyzed, including 39 males and 80 females, aged from 48 to 74 years old with an average of(60.58±6.71) years old. The time from injury to operation ranged 1 to 13 days with an average of (5.29±2.52) days. According to the surgical method, they were divided into Kirschner wire fixation group (Kirschner wire group) and plate internal fixation group (plate group). In Kirschner wire group, there were a total of 68 patients, comprising 21 males and 47 females. The average age was (61.15±6.24) years old, ranged from 49 to 74 years old. Among them, 41 cases involved the left side while 27 cases involved the right side. In the plate group, there were a total of 51 patients, including 18 males and 33 females. The average age was (59.78±5.71) years old ranged from 48 to 72 years old. Among them, there were 31 cases on the left side and 20 cases on the right side. The following parameters were recorded before and after the operation:operation time, intraoperative blood loss, hospitalization days, hospitalization expenses, postoperative complications, and radiographic parameters of distal radius (distal radius height, ulnar deviation angle, palmar tilt angle). The clinical efficacy was evaluated at 3 and 12 months after the operation using Gartland-Werley and disabilites of the arm shoulder and hand (DASH) scores.
RESULTS:
The patients in both groups were followed up for a duration from 12 to 19 months with an average of(13.32±2.02) months. The Kirschner wire group exhibited significantly shorter operation time compared to the plate group 27.91(13.00, 42.00) min vs 67.52(29.72, 105.32) min, Z=-8.74, P=0.00. Intraoperative blood loss was also significantly lower in the Kirschner wire group than in the plate group 3.24(1.08, 5.40) ml vs 21.91(17.38, 26.44) ml, Z=-9.31, P=0.00. Furthermore, patients in the Kirschner wire group had a shorter length of hospital stay compared to those in the plate group (8.38±2.63) days vs (11.40±2.78) days, t=-3.12, P=0.00. Additionally, hospitalization cost was significantly lower in the Kirschner wire group than in the plate group 10 111.29(6 738.98, 13 483.60) yuan vs 15 871.11(11 690.40, 20 051.82) yuan, Z=-5.62, P=0.00. The incidence of complications was 2 cases in the Kirschner wire group and 1 case in the plate group, with no statistically significant difference(P>0.05). At 3 months postoprative, the radial height of the Kirschner wire group was found to be significantly smaller than that of the plate group, with measurements of (11.45±1.69) mm and (12.11±1.78) mm respectively (t=-2.06, P=0.04). However, there were no statistically significant differences observed in ulnar deviation angle and palmar tilt angle between the two groups (P>0.05). The DASH score and Gartland-Werley score in the Kirschner group were significantly higher than those in the plate group at 3 months post-operation (19.10±9.89) vs (13.47±3.51), t=4.34, P=0.00;(11.15±3.61) vs (6.41±2.75), t=8.13, P=0.00). However, there was no significant difference between the two groups at 12 months post-operation (P>0.05).
CONCLUSION
Compared to plate internal fixation, closed reduction with Kirschner wire support fixation yields a slightly inferior recovery of radial height;however, there is no significant disparity in the functional score of the affected limb at 12 months post-operation. Nonetheless, this technique offers advantages such as shorter operation time, reduced intraoperative blood loss, decreased hospitalization duration, and lower cost.
Humans
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Female
;
Male
;
Middle Aged
;
Aged
;
Fracture Fixation, Internal/instrumentation*
;
Bone Wires
;
Bone Plates
;
Retrospective Studies
;
Colles' Fracture/surgery*
;
Minimally Invasive Surgical Procedures/methods*
;
Open Fracture Reduction/methods*
;
Osteoporotic Fractures/surgery*
6.Clinical characteristics and survival analysis of pediatric Hodgkin lymphoma: a multicenter study.
Ying LIN ; Li-Li PAN ; Shao-Hua LE ; Jian LI ; Bi-Yun GUO ; Yu ZHU ; Kai-Zhi WENG ; Jin-Hong LUO ; Gao-Yuan SUN ; Yong-Zhi ZHENG
Chinese Journal of Contemporary Pediatrics 2025;27(6):668-674
OBJECTIVES:
To investigate the clinicopathological characteristics and prognostic factors of pediatric Hodgkin lymphoma (HL).
METHODS:
A retrospective analysis was conducted on the clinical data of children with newly diagnosed HL from January 2011 to December 2023 at four hospitals: Fujian Medical University Union Hospital, Fujian Medical University Zhangzhou Hospital, First Affiliated Hospital of Xiamen University, and Fujian Children's Hospital. Patients were categorized into low-risk (R1), intermediate-risk (R2), and high-risk (R3) groups based on HL staging and pre-treatment risk factors. The patients received ABVD regimen or Chinese Pediatric HL-2013 regimen chemotherapy. Early treatment response and long-term efficacy were assessed, and prognostic factors were analyzed using the Cox proportional hazards regression model.
RESULTS:
The overall complete response (CR) rates after 2 and 4 cycles of chemotherapy were 42% and 68%, respectively. Compared with the ABVD regimen group, patients treated with the HL-2013 regimen in the R1 group showed significantly higher CR rates after both 2 and 4 cycles (P<0.05). However, no statistically significant differences in CR rates were observed between the two regimens in the R2 and R3 groups (P>0.05). The 5-year event-free survival (EFS) rate, overall survival rate, and freedom from treatment failure rate were 83%±4%, 97%±2%, and 88%±4%, respectively. Cox analysis indicated that the presence of a large tumor mass at diagnosis and failure to achieve CR after 4 cycles of chemotherapy were independent risk factors for lower EFS rates (P<0.05).
CONCLUSIONS
Pediatric HL generally has a favorable prognosis. The presence of a large tumor mass at diagnosis and failure to achieve CR after 4 cycles of chemotherapy indicate poor prognosis.
Humans
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Hodgkin Disease/pathology*
;
Male
;
Child
;
Female
;
Adolescent
;
Retrospective Studies
;
Child, Preschool
;
Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
;
Prognosis
;
Proportional Hazards Models
;
Survival Analysis
;
Infant
7.Clinical efficacy of robot-assisted single-position OLIF with lateral plate combined with posterior unilateral fixation for single-segment lumbar spinal stenosis.
Yuekun FANG ; Zhilin YANG ; Haotian LI ; Weizhou WANG ; Hangchuang BI ; Bing WANG ; Junjie DONG ; Jin YANG ; Zhiqiang GONG ; Lingqiang CHEN
Journal of Central South University(Medical Sciences) 2025;50(1):119-129
OBJECTIVES:
Oblique lateral interbody fusion (OLIF) has become a well-established treatment for lumbar spinal stenosis (LSS) due to its advantages of being minimally invasive, effective, and associated with fewer complications. However, relying solely on lateral fixation provides limited strength and uneven load distribution. Conventional posterior bilateral fixation after OLIF typically requires intraoperative repositioning, increases fluoroscopy frequency, and involves extensive dissection of posterior muscles and soft tissues, resulting in greater trauma, blood loss, and risks of dural tear, nerve root injury, and persistent postoperative low back pain. This study aims to compare the clinical efficacy of robot-assisted single-position OLIF with lateral plating and posterior unilateral fixation, OLIF with lateral fixation alone, and OLIF combined with posterior bilateral fixation for treating single-segment LSS, and to explore how to enhance fixation stability, reduce trauma, and achieve precise minimally invasive outcomes without changing patient positioning.
METHODS:
A retrospective analysis was conducted on the clinical data from patients treated for single-segment LSS between January 2020 and June 2023 at the First Affiliated Hospital of Kunming Medical University. Patients were divided into 3 groups: Robot group (robot-assisted single-position OLIF with lateral plate and posterior unilateral fixation, 33 cases), lateral group (OLIF with lateral fixation alone, 52 cases), and combined group (OLIF with posterior bilateral fixation, 45 cases). Surgical time, intraoperative blood loss, fluoroscopy frequency, hospital stay, pedicle screw placement accuracy, and complication rates were recorded. Pain visual analogue scale (VAS) scores and Oswestry disability index (ODI) scores were assessed preoperatively, postoperatively, and at the final follow-up. Radiological evaluations (X-ray, computed tomography, and magnetic resonance imaging) measured interbody disc height (IDH), intervertebral foraminal height (IFH), and cross-sectional area (CSA) of the dural sac. Differences between pre- and postoperative imaging indices were statistically analyzed, and complication rates, fusion rates, and cage subsidence rates were recorded.
RESULTS:
All patients exhibited good positioning of internal fixation devices and cages, with significant symptom relief and no cases of spinal cord injury or symptom worsening. The follow-up time was (15.2±3.6) months. The operation time of the robot group was (70.62±8.99) min, which was longer than that of the lateral group (45.90±6.09) min and shorter than that of the combined group (110.12±8.44) min. The intraoperative blood loss of the robot group was (44.27±6.87) mL, which was more than that of the lateral group (33.58±9.73) mL and less than that of the combined group (79.19±10.35) mL. The number of intraoperative fluoroscopy times of the robot group was (9.49±2.25), which was comparable to that of the lateral group (7.45±2.02) but less than that of the combined group (12.24±4.25). The hospital stay of the robot group was (9.28±2.10) days, which was longer than that of the lateral group (7.95±1.91) days and shorter than that of the combined group (12.49±5.07) days. The screw placement accuracy of the robot group was 98.48%, which was higher than that of the combined group (90.55%). Postoperative and final follow-up VAS and ODI scores were significantly lower than preoperative scores in all 3 groups (all P<0.05), and there were no significant differences in preoperative VAS and ODI scores among the groups (all P>0.05). Radiologically, IDH, IFH, and CSA at the surgical segment were significantly increased postoperatively and at final follow-up compared to preoperatively and at final follow-up compared to preoperative values (all P<0.05), with no significant differences among the groups postoperatively (all P>0.05). Internal fixation remained stable during the follow-up period, and all cages achieved fusion at final follow-up. The intervertebral fusion rate of the robot-assisted group was 93.40%, which was similar to that of the combined group (95.56%) and higher than that of the lateral approach group (90.34%). The complication rate of the robot-assisted group was 6.1%, which was comparable to that of the combined group (8.9%) and lower than that of the lateral approach group (15.4%) (P<0.05). No cases of fixation loosening or breakage were observed throughout the follow-up period.
CONCLUSIONS
Robot-assisted single-position OLIF with lateral plate combined with posterior unilateral fixation effectively achieves indirect decompression and excellent spinal stability without the need for intraoperative repositioning. It provides high pedicle screw accuracy, reduces intraoperative blood loss, fluoroscopy times, and complication rates, offering a fully minimally invasive new treatment option for single-segment LSS.
Humans
;
Spinal Stenosis/surgery*
;
Robotic Surgical Procedures/methods*
;
Lumbar Vertebrae/surgery*
;
Spinal Fusion/instrumentation*
;
Male
;
Female
;
Retrospective Studies
;
Middle Aged
;
Aged
;
Treatment Outcome
;
Bone Plates
;
Minimally Invasive Surgical Procedures/methods*
;
Adult
8.Effect of Rhei Radix et Rhizoma and Eupolyphaga Steleophaga on liver protection mechanism based on pharmacokinetics and metabonomics.
Gang FENG ; Jianli BI ; Wenfang JIN ; Qi WANG ; Zhaokui DAN ; Baolei FAN
Chinese Herbal Medicines 2024;16(1):121-131
OBJECTIVE:
Based on metabonomics technology of high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) and hydrogen nuclear magnetic resonance spectroscopy (1H NMR), the pharmacokinetic characteristics and therapeutic mechanism of Rhei Radix et Rhizoma (RhRR, Dahuang in Chinese), Eupolyphaga Steleophaga (EuS, Tubiechong in Chinese) combined with RhRR acting on acute liver injury were explored.
METHODS:
Models of acute liver injury were established, and the pharmacokinetic methods of five components of RhRR-EuS in rats were found by HPLC-MS/MS. The liver tissues of different groups of mice were analyzed by 1H NMR spectroscopy combined with multivariate statistical analysis to investigate the metabolomics of RhRR-EuS and RhRR.
RESULTS:
Pharmacokinetic results showed there were different levels of bimodal phenomenon in different groups, and the absorption of free anthraquinone in RhRR increased after compatibility with EuS. In addition, the pathological state of acute liver injury in rats can selectively promote the absorption of emodin, chrysophanol, physcion and aloe emodin. Through 15 differential metabolites in the liver tissue of acute liver injury mice, it was revealed that RhRR-EuS and RhRR could protect the liver injury by regulating the metabolism of glutamine and glutamic acid, alanine, aspartic acid and glutamic acid, and phosphoinositide. However, the regulation of RhRR was weaker than that of RhRR-EuS.
CONCLUSION
For the first time, we studied the pharmacokinetics and metabolomics differences of RhRR-EuS and RhRR in rats and mice with acute liver injury, in order to provide theoretical reference for clinical treatment of liver disease by DHZCP.
9.Review of evaluation and influencing factors of oral drug absorption fraction
Ping ZHANG ; Fu-lin BI ; Jin YANG
Acta Pharmaceutica Sinica 2024;59(1):84-93
Fraction absorbed (Fa) is an important parameter to describe the absorption level of oral drugs, and an important basis for the development and optimization of the formulation process. Because it is easily confused with the concept of absolute bioavailability, it has not received enough attention from the industry. There are many complex factors affecting Fa. There are three time-related factors that directly affect the extent of Fa: the release time, the absorption time, and the residence time. The relationship between these three time-related factors determines the extent of Fa. Generally, we are more concerned about the apparent factors that affect the extent of Fa, including independent variables and covariates; The independent variables include administered dose, route, dosage form, etc. The covariates are divided into internal and external factors, and external factors include food factors, drug interactions,
10.Mechanism of Cangxitongbi Capsules in Mediating Chondrocyte Pyroptosis in Knee Osteoarthritis via Regulating p38 MAPK/NLRP3/Caspase-1 Pathway
Zhimeng ZHANG ; Daotong YUAN ; Ximin JIN ; Rui GONG ; Zhenlong SONG ; Yongkui ZHANG ; Xiaole WANG ; Rongxiu BI ; Wenpeng XIE
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(22):61-68
ObjectiveTo explore the mechanism of Cangxi Tongbi capsules (CXTB) in regulating the p38 mitogen-activated protein kinase (p38 MAPK)/NOD-like receptor protein 3 (NLRP3)/cysteine protease-1 (Caspase-1) signaling pathway to inhibit pyroptosis of cartilage cells in knee osteoarthritis (KOA). MethodSixty male SD rats were randomly divided into a sham operation group, a model group, low, medium, and high dose CXTB groups, and a positive control group, with 10 rats per group. The modified Hulth method was employed to establish a rat model of KOA. According to their respective assignments, rats were administered CXTB (0.25, 0.5, 1.0 g·kg-1) and Celecoxib (24 mg·kg-1) by gavage. The sham operation and model groups were given an equivalent volume of physiological saline. Treatment was performed once daily for 28 days. Micro-computed tomography (Micro-CT) was used to assess bone volume/total volume (BV/TV) and trabecular separation (Tb.Sp). Joint degeneration was evaluated through hematoxylin-eosin (HE) staining, safranin-fast green (SO) staining, and Osteoarthritis Research Society International (OARSI) scoring. Western blot analysis was conducted to measure the expression levels of p38 MAPK, phosphorylated p38 MAPK (p-p38 MAPK), NLRP3, Caspase-1, and gasdermin D (GSDMD) proteins. Real-time PCR was used to assess mRNA expression levels of p38 MAPK, NLRP3, Caspase-1, and GSDMD genes. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum concentrations of inflammatory cytokines including tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-18 (IL-18). After knee replacement surgery, cartilage tissue was analyzed using Western blot to assess the protein expression levels of p38 MAPK, p-p38 MAPK, NLRP3, Caspase-1, and GSDMD, and Real-time PCR was used to evaluate gene expression levels of p38 MAPK, NLRP3, Caspase-1, and GSDMD. ResultMicro-CT analysis revealed significant narrowing of the joint space and increased bone spur formation in KOA rats compared with the sham operation group, with a decrease in BV/TV ratio and an increase in Tb.Sp value (P<0.01). Serum levels of TNF-α, IL-1β, and IL-18 were elevated (P<0.01). The protein expression levels of p-p38 MAPK, NLRP3, Caspase-1, and GSDMD in cartilage were significantly increased (P<0.01), and the mRNA expression levels of p38 MAPK, NLRP3, Caspase-1, and GSDMD were also enhanced (P<0.01). Significant differences in protein expression of p-p38 MAPK, NLRP3, Caspase-1, and GSDMD were observed between normal and diseased cartilage tissues after knee replacement surgery (P<0.05), and the gene expression of p38 MAPK, NLRP3, Caspase-1, and GSDMD were also significantly different (P<0.01). HE and SO staining showed roughened joint surfaces, reduced cartilage thickness, and disordered cellular arrangement in KOA rats. OARSI scores were significantly higher (P<0.01). Compared with the model group, treatment with low, medium, and high concentrations of CXTB resulted in increased BV/TV ratios and decreased Tb.Sp values in the knee joints of rats (P<0.01). HE and SO staining indicated a trend towards smoother joint surfaces and reduced OARSI scores (P<0.01). The protein expression levels of p-p38 MAPK, NLRP3, Caspase-1, and GSDMD were notably decreased (P<0.05), as were the mRNA expression levels of p38 MAPK, NLRP3, Caspase-1, and GSDMD (P<0.01). Additionally, serum concentrations of TNF-α, IL-1β, and IL-18 were significantly reduced (P<0.01). ConclusionCXTB intervention may alleviate knee joint degeneration in KOA rats and inhibit the expression of inflammatory factors and pyroptosis of cartilage cells, thereby protecting cartilage. The underlying mechanism may involve modulation of the p38 MAPK/NLRP3/Caspase-1 signaling pathway.

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