1.AI-integrated IQPD framework of quality prediction and diagnostics in small-sample multi-unit pharmaceutical manufacturing: Advancing from experience-driven to data-driven manufacturing.
Kaiyi WANG ; Xinhai CHEN ; Nan LI ; Huimin FENG ; Xiaoyi LIU ; Yifei WANG ; Yanfei WU ; Yufeng GUO ; Shuoshuo XU ; Lu YAO ; Zhaohua ZHANG ; Jun JIA ; Zhishu TANG ; Zhisheng WU
Acta Pharmaceutica Sinica B 2025;15(8):4193-4209
The pharmaceutical industry faces challenges in quality digitization for complex multi-stage processes, especially in small-sample systems. Here, an intelligent quality prediction and diagnostic (IQPD) framework was developed and applied to Tong Ren Tang's Niuhuang Qingxin Pills, utilizing four years of data collected from four production units, covering the entire process from raw materials to finished products. In this framework, a novel path-enhanced double ensemble quality prediction model (PeDGAT) is proposed, which combines a graph attention network and path information to encode inter-unit long-range and sequential dependencies. Additionally, the double ensemble strategy enhances model stability in small samples. Compared to global traditional models, PeDGAT achieves state-of-the-art results, with an average improvement of 13.18% and 87.67% in prediction accuracy and stability on three indicators. Additionally, a more in-depth diagnostic model leveraging grey correlation analysis and expert knowledge reduces reliance on large samples, offering a panoramic view of attribute relationships across units and improving process transparency. Finally, the IQPD framework integrates into a Human-Cyber-Physical system, enabling faster decision-making and real-time quality adjustments for Tong Ren Tang's Niuhuang Qingxin Pills, a product with annual sales exceeding 100 million CNY. This facilitates the transition from experience-driven to data-driven manufacturing.
2.Effects of Ditan Yizhi Decoction on Mitochondrial Autophagy in Rats with Vascular Dementia Based on Wnt/β-catenin Signaling Pathway
Mengyu GU ; Lieqian SUN ; Jie YANG ; Kaiyi WANG ; Fan WU ; Chao YANG ; Li ZHENG ; Xiangzhong SHEN
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(5):127-133
Objective To observe the effects of Ditan Yizhi Decoction on Wnt/β-catenin signaling pathway and mitochondrial autophagy in vascular dementia(VD)rats.Methods Totally 70 male SD rats were randomly selected as the sham-operation group,with only the common carotid artery isolated and not ligated,and the rest of the rats were used to prepare a rat model of VD by the modified bilateral common carotid artery permanent ligature method.The successfully modeled rats were randomly divided into model group,donepezil group,agonist group and Ditan Yizhi Decoction low-,medium-and high-dosage groups and were given corresponding interventions for 4 weeks.Morris water maze experiment was used to assess the learning and memory ability of rats,HE staining and Nissl staining were used to observe the morphology of hippocampal tissue,transmission electron microscopy was used to observe the ultrastructure of hippocampal neuron,Western blot was used to detect the expressions of PINK1,Parkin,p62,Beclin-1,LC3BⅡ/Ⅰ,β-catenin,GSK-3β,p-GSK-3β protein.Results Compared with the sham-operation group,rats in the model group had a prolonged escape latency(P<0.01),a reduced number of crossing platforms(P<0.01);neuronal gaps in the CA1 area of the hippocampus were enlarged,with irregular cell morphology and blurred borders,neuronal solidification,Nissl bodies dissolution and fragmentation,reduced quantity,mitochondrial cristae disorder,and disruption of the structure of the bilayer membrane,with a greater number of autophagosomes in the surroundings;the expressions of PINK1,Parkin,Beclin-1,LC3BⅡ/I,β-catenin,p-GSK-3β/GSK-3β protein were significantly increased(P<0.01),and p62 protein expression was significantly decreased(P<0.01).Compared with the model group,the escape latency of rats in donepezil group,agonist group and Ditan Yizhi Decoction low-,medium-and high-dosage groups were significantly shortened(P<0.01),and the number of crossing platforms significantly increased(P<0.05,P<0.01);the number of neurons in the hippocampal CA1 region increased,with normal morphology and orderly arrangement,Nissl bodies were abundant,and transmission electron microscopy showed that mitochondrial morphology recovered,rupture decreased,and autophagosomes around mitochondria decreased,the protein expressions of PINK1,Parkin,Beclin-1,LC3BⅡ/Ⅰ,β-catenin and p-GSK-3β/GSK-3β in hippocampal tissue were significantly decreased(P<0.01),the protein expression of p62 significantly increased(P<0.05,P<0.01).Conclusion Ditan Yizhi Decoction can improve learning memory ability and neuronal morphology in VD rats,and its mechanism may be related to the activation of Wnt/β-catenin signaling pathway to inhibit mitophagy.
3.Effects of plasma exchange followed by double plasma molecular adsorption system on cytokines in patients with hepatitis B virus-related acute-on-chronic liver failure
Le ZHANG ; Kaiyi ZHANG ; Yushan LI ; Jiawei XIA ; Hanzhang SHEN ; Xiang LI
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2025;32(2):196-200
Objective To explore the significance of immunotherapy for patients with hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF)using plasma exchange(PE)followed by double plasma molecular adsorption system(DPMAS),as well as its impact on prognosis.Methods Patients who were admitted to the Third People's Hospital of Kunming from June 2019 to June 2023 and met the early and mid-stage diagnostic criteria for HBV-ACLF were selected as the research subjects,with a total of 120 cases.After admission,the patients were divided into the PE+DPMAS group(PD group,63 cases)and the PE group(57 cases)based on different treatment plans.The changes in liver function,coagulation function,cytokines,and model for end-stage liver disease(MELD)scores after treatment,as well as the clinical improvement rates,were observed in both groups.Results ① After treatment,the levels of serum total bilirubin(TBil)in the PD group were significantly lower than those in the PE group(μmol/L:163.4±53.3 vs.226.1±72.5,P<0.05),and the prothrombin activity(PTA)was significantly increased[(51.5±9.2)%vs.(41.1±7.7)%,P<0.05].②After treatment,the levels of interleukins(IL-2,IL-6,IL-8)and tumor necrosis factor-α(TNF-α)in both groups decreased compared to before treatment at 1,2,and 4 weeks,reaching the lowest levels at 4 weeks,the levels of IL-2,IL-6,IL-8,and TNF-α in the PD group were lower than those in the PE group[IL-2(ng/L):1.83(1.75)vs.2.04(1.85),IL-6(ng/L):11.31(5.07)vs.18.18(9.05),IL-8(ng/L):21.14(8.35)vs.29.09(12.41),TNF-α(ng/L):9.16(5.10)vs.14.12(7.27)].The levels of IL-10 decreased at 1 week and 2 weeks after treatment.In the PD group,IL-10 increased at 4 weeks after treatment.The differences compared to the baseline levels before treatment were statistically significant(P<0.05).At 4 weeks after treatment,the level of IL-10 in the PD group was significantly higher than that in the PE group[ng/L:24.72(11.56)vs.19.03(10.04),P<0.05].③ The clinical improvement rates in the PD group were significantly higher than those in the PE group at 2 weeks and 4 weeks after treatment[2 weeks after treatment:65.08%(41/63)vs.40.35%(23/57);4 weeks after treatment:84.13%(53/63)vs.54.39%(31/57),both P<0.05].④After 4 weeks of treatment,the MELD scores in both groups decreased significantly.Compared with the PE group,the MELD score in the PD group was significantly lower(14.87±3.45 vs.19.68±4.63,P<0.05).Conclusion Compared with PE alone,PE+DPMAS treatment for early and mid-stage ACLF patients can more effectively clear the large amount of inflammatory mediators released in the body,better regulate the balance between pro-inflammatory and anti-inflammatory cytokines in the patient's serum,thereby preventing or delaying the formation of systemic inflammatory response syndrome(SIRS)and multiple organ dysfunction syndrome(MODS).The clinical therapeutic effect is better,with a higher improvement rate,achieving the goal of reducing liver damage,improving patient survival rate,and thus improving prognosis.
4.Exploration on the Effects of Ditan Yizhi Decoction Regulating Glucose Metabolism on Cognitive Impairment in Vascular Dementia Rats Based on ROS/Drp1 Axis
Mengyu GU ; Lieqian SUN ; Jie YANG ; Kaiyi WANG ; Fan WU ; Shujie XU ; Xing LAI ; Li ZHENG ; Xiangzhong SHEN ; Chao YANG
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(8):82-90
Objective To observe the effects of Ditan Yizhi Decoction on mitochondrial dynamics-mediated glucose metabolism in vascular dementia(VaD)rats based on the ROS/Drp1 axis;To explore its mechanism in treating VaD.Methods Ten male SD rats were randomly selected from 70 as the sham-operation group,and VaD models were prepared using the modified bilateral common carotid artery permanent ligation method for the remaining rats.The successfully modeled rats were randomly divided into model group,positive drug group(donepezil hydrochloride),inhibitor group(Mdivi-1)and Ditan Yizhi Decoction low-,medium-and high-dosage groups(12.86,25.725,51.45 g/kg),and intervened with corresponding method for 4 consecutive weeks.Morris water maze experiment was used to assess the learning memory ability of rats,HE and Nissl staining were used to observe the morphology of hippocampal tissue,transmission electron microscopy was used to observe the mitochondrial ultrastructure of hippocampal neurons,DHE fluorescent probe was used to detect the content of ROS in hippocampal neurons,Western blot was used to detect the expressions of Drp1,p-Drp1,Mfn2,Opa1,HK1,PKM2,GLUT1 and LDHA,the contents of serum IL-1β,IL-6 and TNF-α were detected by ELISA.Results Compared with the sham-operation group,rats in the model group had a prolonged escape latency(P<0.01)and a reduced number of crossing platforms(P<0.01);neuronal gaps in the CA1 region of the hippocampus were enlarged,with irregular cell morphology and blurred borders,neuronal consolidation,lysis and fragmentation of Nissl bodies and reduced number of Nissl bodies,swelling and deformation of mitochondria,disorganization of the cristae,and disruption of the bilayer membrane structure;the content of ROS in CA1 region of the hippocampus was elevated,the protein expressions of Mfn2 and Opa1 significantly decreased(P<0.01),the expressions of p-Drp1,HK1,PKM2,GLUT1,LDHA proteins significantly increased(P<0.01),and serum contents of IL-1β,IL-6 and TNF-α significantly increased(P<0.01).Compared with the model group,the escape latency was significantly shortened in Ditan Yizhi Decoction groups,positive drug group and inhibitor group(P<0.01),and the number of crossing platforms increased(P<0.05,P<0.01);the number of neurons in the hippocampal CA1 region increased,with normal morphology,orderly arrangement,abundant Nissl bodies,recovered mitochondrial morphology,and decreased rupture;the ROS content in hippocampal CA1 region decreased(P<0.01),while the expressions of Mfn2 and Opa1 proteins increased(P<0.01),the expressions of p-Drp1,HK1,PKM2,GLUT1 and LDHA proteins decreased(P<0.01),and the serum contents of IL-1β,IL-6 and TNF-α decreased(P<0.05).Conclusion Ditan Yizhi Decoction can improve cognitive impairment and neuronal morphology in VaD rats,and the mechanism maybe related to regulation of mitochondrial dynamics through the ROS/Drp1 axis,attenuating glycometabolic disorders,and reducing inflammatory response.
5.Causal relationship between immune cells and knee osteoarthritis:a two-sample bi-directional Mendelian randomization analysis
Guangtao WU ; Gang QIN ; Kaiyi HE ; Yidong FAN ; Weicai LI ; Baogang ZHU ; Ying CAO
Chinese Journal of Tissue Engineering Research 2025;29(5):1081-1090
BACKGROUND:Knee osteoarthritis(KOA)is a common chronic inflammatory disease that causes damage to joint cartilage and surrounding tissues.Immune cells play an important role in the immune-inflammatory response in knee osteoarthritis,but the specific mechanisms involved are still not fully understood. OBJECTIVE:To evaluate the potential causal relationship between 731 immune cell phenotypes and the risk of knee osteoarthritis using Mendelian randomization. METHODS:Summary statistics of genome-wide association studies(GWAS)for 731 immune cell phenotypes(from GCST0001391 to GCST0002121)obtained from the GWAS catalog and GWAS data for knee osteoarthritis from the IEUGWAS database(ebi-a-GCST007090)were used.Inverse variance-weighted method,MR-Egger regression,weighted median method,weighted mode method,and simple mode method were employed to investigate the causal relationship between immune cells and knee osteoarthritis.Sensitivity analyses were conducted to assess the reliability of the Mendelian randomization results.Reverse Mendelian randomization analysis was also performed using the same methods. RESULTS AND CONCLUSION:The forward MR analysis indicated significant causal relationships(FDR<0.20)between knee osteoarthritis and four immune cell phenotypes,namely CD27 on CD24+CD27+in B cells(OR=1.026,P=0.000 26,Pfdr=0.18),CD33 on CD33dim HLA DR-in myeloid cells(OR=1.014,P=0.000 50,Pfdr=0.18),and CD45RA+CD28-CD8br%CD8br in Treg cells(OR=1.001,P=0.000 78,Pfdr=0.18),and PDL-1 on monocytes in mononuclear cells(OR=0.952,P=0.000 98,Pfdr=0.18).These immune cell phenotypes showed direct positive or negative causal associations with the risk of knee osteoarthritis.Reverse Mendelian randomization analysis revealed no significant causal relationships(FDR<0.20)between knee osteoarthritis as exposure and any of the 731 immune cell phenotypes.The results of sensitivity analysis show that the P-values of the Cochran's Q test and the MR-Egger regression method for bidirectional Mendelian randomization were both greater than 0.05,indicating that there is no significant heterogeneity and pleiotropy in the causal effect analysis between immune cell phenotypes and knee osteoarthritis.To conclude,there may be four potential causal relationships between immune cell phenotypes,such as CD27 on CD24+CD27+cells,CD33 on CD33dim HLA DR-cells,CD45RA+CD28-CD8br%CD8br cells,and PDL-1 on monocytes,and knee osteoarthritis.These findings provide valuable clues for studying the biological mechanisms of knee osteoarthritis and exploring early prevention and treatment strategies.They also offer new directions for the development of intervention drugs.
6.Investigation and verification of a radiation worker with monitored personal doses exceeding the investigation level
Pin GAO ; Kaiyi WANG ; Yanqiu DING ; Xiaorui WANG ; Peize TANG ; Jingyu LI ; Wen GUO
Chinese Journal of Radiological Health 2025;34(6):841-845
Objective To identify the reasons why the monitored personal doses of radiation worker A in an institution exceeded the investigation level in 2023 and 2024, and remind workers to wear personal dosimeters in a standardized manner in scenarios such as work and business trips to ensure the authenticity and reliability of the monitoring data. Methods A thermoluminescence measurement system was used to read the personal dosimeters worn by radiation workers. Investigations were carried out on personnel whose doses exceeded the investigation level described in the “Specifications for individual monitoring of occupational external exposure” (GBZ 128—2019). The reasons for doses exceeding the investigation level were analyzed using additional dosimeters and conducting on-site experiments. Results In 2023 and 2024, radiation worker A recorded a total of 5 personal dose equivalents exceeding the investigation level (1.23 mSv) over a total of 8 monitoring cycles (each lasting 90 days). Following one cycle where the dose exceeded the investigation level, two additional dosimeters (each for a 30-day cycle) were issued to worker A, revealing readings below the investigation level for the 30-day monitoring cycle (0.41 mSv). The reading for the dosimeter was 2-3 μSv per time when passing through an X-ray security scanner, and approximately 2.10 mSv per time when passing through a computed tomography security scanner. Conclusion Within a 90-day monitoring cycle, a single exposure of a personal dosimeter to a computed tomography security scanner can result in a dose exceeding the investigation level. Radiation workers should avoid placing dosimeters in backpacks or suitcases that pass through computed tomography security scanners during business trips, so as to reduce the impact of security scanner irradiation on personal dose monitoring.
7.Clinical efficacy of vertebral"Collapse"lesion resection surgery for treating thoracolumbar spinal metastases
Shuang LI ; Kai ZHU ; Kaiyi WANG
Chinese Journal of Spine and Spinal Cord 2025;35(2):127-134
Objectives:To explore the clinical efficacy and the postoperative recurrence rate of the vertebral"Collapse"lesion resection for treating thoracolumbar spinal metastases compared to separation surgery.Methods:A retrospective study was conducted on 78 patients with thoracolumbar spinal metastases treated at Tianjin University General Hospital from December 2018 to December 2022.There were 42 males(53.8%)and 36 females(46.2%),with a mean age of 61.9±10.6 years(range 34-76 years).The patients were divided into separation surgery group(21 cases)and"Collapse"resection group(57 cases).Two to three weeks after surgery,radiotherapy,chemotherapy or targeted drugs were given according to the type of primary tumor after wound healing.The data on operative time,intraoperative blood loss,drainage volume,Frankel classification for spinal cord injury,and visual analogue scale(VAS)scores for pain preoperatively,7d after operation and at final follow-up,as well as local recurrence rates and perioperative complications were collected.Results:The operative time and intraoperative blood loss in the"Collapse"resection group(328.7±89.2min,782.5±89.2mL)were significantly higher than those in the separation surgery group(243.2±89.2min,585.7±89.2mL)(P<0.05).There was no statistically significant difference in postoperative drainage volume between the two groups("Collapse"resection group 698.2±230.2mL vs separation surgery group 674.7±180.7mL)(P>0.05).During follow-up,all the patients in the separation surgery group received stereotactic radiotherapy postoperatively;While 10 patients(21.2%)in the"Collapse"resection group underwent radiotherapy,and the remaining 47(78.8%)patients received targeted,immunological,or chemotherapy as part of comprehensive treatment.The recurrence rate in the separation surgery group was approximately 9.5%(2/21).Among the patients who received"Collapse"resection plus radiotherapy,there was 1 local recurrence,resulting in a recurrence rate of 10%(1/10),while the patients who didn't receive radiotherapy experienced 3 local recurrences,with a recurrence rate of 6.4%(3/47).The overall recurrence rate for patients in the"Collapse"resection group was 7.0%(4/57).There was no statistically significant difference in recurrence rates between the two surgical procedures(P=0.708).In the separation surgery group,postoperative complications included one case of wound infection,one case of wound dehiscence two months after postoperative radiotherapy,and one case of epidural hematoma causing compression.In the group of"Collapse"resection,complications included one case of cerebrospinal fluid leakage with secondary infection and one case of superficial wound infection.VAS scores on 7d postoperatively significantly decreased compared to preoperative scores in both groups(P<0.05),and there were significant differences in VAS scores at final follow-up compared to preoperative scores(P<0.05).No statistical difference in VAS scores was observed between the two groups on 7d postoperatively and at final follow-up(P>0.05).Except for 5 Frankel A-D grade patients with no significant improvement in neurological function,the remaining 73 patients showed no deterioration in neurological function,with varying degrees of recovery of at least 1 grade,yielding an improvement rate of 93.6%(73/78).Conclusions:The vertebral"Collapse"resection for thoracolumbar spinal tumors does not require postoperative radiotherapy,as the tumor recurrence rate is comparable to that of patients treated with separation surgery followed by radiotherapy.
8.Clinical efficacy of vertebral"Collapse"lesion resection surgery for treating thoracolumbar spinal metastases
Shuang LI ; Kai ZHU ; Kaiyi WANG
Chinese Journal of Spine and Spinal Cord 2025;35(2):127-134
Objectives:To explore the clinical efficacy and the postoperative recurrence rate of the vertebral"Collapse"lesion resection for treating thoracolumbar spinal metastases compared to separation surgery.Methods:A retrospective study was conducted on 78 patients with thoracolumbar spinal metastases treated at Tianjin University General Hospital from December 2018 to December 2022.There were 42 males(53.8%)and 36 females(46.2%),with a mean age of 61.9±10.6 years(range 34-76 years).The patients were divided into separation surgery group(21 cases)and"Collapse"resection group(57 cases).Two to three weeks after surgery,radiotherapy,chemotherapy or targeted drugs were given according to the type of primary tumor after wound healing.The data on operative time,intraoperative blood loss,drainage volume,Frankel classification for spinal cord injury,and visual analogue scale(VAS)scores for pain preoperatively,7d after operation and at final follow-up,as well as local recurrence rates and perioperative complications were collected.Results:The operative time and intraoperative blood loss in the"Collapse"resection group(328.7±89.2min,782.5±89.2mL)were significantly higher than those in the separation surgery group(243.2±89.2min,585.7±89.2mL)(P<0.05).There was no statistically significant difference in postoperative drainage volume between the two groups("Collapse"resection group 698.2±230.2mL vs separation surgery group 674.7±180.7mL)(P>0.05).During follow-up,all the patients in the separation surgery group received stereotactic radiotherapy postoperatively;While 10 patients(21.2%)in the"Collapse"resection group underwent radiotherapy,and the remaining 47(78.8%)patients received targeted,immunological,or chemotherapy as part of comprehensive treatment.The recurrence rate in the separation surgery group was approximately 9.5%(2/21).Among the patients who received"Collapse"resection plus radiotherapy,there was 1 local recurrence,resulting in a recurrence rate of 10%(1/10),while the patients who didn't receive radiotherapy experienced 3 local recurrences,with a recurrence rate of 6.4%(3/47).The overall recurrence rate for patients in the"Collapse"resection group was 7.0%(4/57).There was no statistically significant difference in recurrence rates between the two surgical procedures(P=0.708).In the separation surgery group,postoperative complications included one case of wound infection,one case of wound dehiscence two months after postoperative radiotherapy,and one case of epidural hematoma causing compression.In the group of"Collapse"resection,complications included one case of cerebrospinal fluid leakage with secondary infection and one case of superficial wound infection.VAS scores on 7d postoperatively significantly decreased compared to preoperative scores in both groups(P<0.05),and there were significant differences in VAS scores at final follow-up compared to preoperative scores(P<0.05).No statistical difference in VAS scores was observed between the two groups on 7d postoperatively and at final follow-up(P>0.05).Except for 5 Frankel A-D grade patients with no significant improvement in neurological function,the remaining 73 patients showed no deterioration in neurological function,with varying degrees of recovery of at least 1 grade,yielding an improvement rate of 93.6%(73/78).Conclusions:The vertebral"Collapse"resection for thoracolumbar spinal tumors does not require postoperative radiotherapy,as the tumor recurrence rate is comparable to that of patients treated with separation surgery followed by radiotherapy.
9.Effects of Ditan Yizhi Decoction on Mitochondrial Autophagy in Rats with Vascular Dementia Based on Wnt/β-catenin Signaling Pathway
Mengyu GU ; Lieqian SUN ; Jie YANG ; Kaiyi WANG ; Fan WU ; Chao YANG ; Li ZHENG ; Xiangzhong SHEN
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(5):127-133
Objective To observe the effects of Ditan Yizhi Decoction on Wnt/β-catenin signaling pathway and mitochondrial autophagy in vascular dementia(VD)rats.Methods Totally 70 male SD rats were randomly selected as the sham-operation group,with only the common carotid artery isolated and not ligated,and the rest of the rats were used to prepare a rat model of VD by the modified bilateral common carotid artery permanent ligature method.The successfully modeled rats were randomly divided into model group,donepezil group,agonist group and Ditan Yizhi Decoction low-,medium-and high-dosage groups and were given corresponding interventions for 4 weeks.Morris water maze experiment was used to assess the learning and memory ability of rats,HE staining and Nissl staining were used to observe the morphology of hippocampal tissue,transmission electron microscopy was used to observe the ultrastructure of hippocampal neuron,Western blot was used to detect the expressions of PINK1,Parkin,p62,Beclin-1,LC3BⅡ/Ⅰ,β-catenin,GSK-3β,p-GSK-3β protein.Results Compared with the sham-operation group,rats in the model group had a prolonged escape latency(P<0.01),a reduced number of crossing platforms(P<0.01);neuronal gaps in the CA1 area of the hippocampus were enlarged,with irregular cell morphology and blurred borders,neuronal solidification,Nissl bodies dissolution and fragmentation,reduced quantity,mitochondrial cristae disorder,and disruption of the structure of the bilayer membrane,with a greater number of autophagosomes in the surroundings;the expressions of PINK1,Parkin,Beclin-1,LC3BⅡ/I,β-catenin,p-GSK-3β/GSK-3β protein were significantly increased(P<0.01),and p62 protein expression was significantly decreased(P<0.01).Compared with the model group,the escape latency of rats in donepezil group,agonist group and Ditan Yizhi Decoction low-,medium-and high-dosage groups were significantly shortened(P<0.01),and the number of crossing platforms significantly increased(P<0.05,P<0.01);the number of neurons in the hippocampal CA1 region increased,with normal morphology and orderly arrangement,Nissl bodies were abundant,and transmission electron microscopy showed that mitochondrial morphology recovered,rupture decreased,and autophagosomes around mitochondria decreased,the protein expressions of PINK1,Parkin,Beclin-1,LC3BⅡ/Ⅰ,β-catenin and p-GSK-3β/GSK-3β in hippocampal tissue were significantly decreased(P<0.01),the protein expression of p62 significantly increased(P<0.05,P<0.01).Conclusion Ditan Yizhi Decoction can improve learning memory ability and neuronal morphology in VD rats,and its mechanism may be related to the activation of Wnt/β-catenin signaling pathway to inhibit mitophagy.
10.Effects of plasma exchange followed by double plasma molecular adsorption system on cytokines in patients with hepatitis B virus-related acute-on-chronic liver failure
Le ZHANG ; Kaiyi ZHANG ; Yushan LI ; Jiawei XIA ; Hanzhang SHEN ; Xiang LI
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2025;32(2):196-200
Objective To explore the significance of immunotherapy for patients with hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF)using plasma exchange(PE)followed by double plasma molecular adsorption system(DPMAS),as well as its impact on prognosis.Methods Patients who were admitted to the Third People's Hospital of Kunming from June 2019 to June 2023 and met the early and mid-stage diagnostic criteria for HBV-ACLF were selected as the research subjects,with a total of 120 cases.After admission,the patients were divided into the PE+DPMAS group(PD group,63 cases)and the PE group(57 cases)based on different treatment plans.The changes in liver function,coagulation function,cytokines,and model for end-stage liver disease(MELD)scores after treatment,as well as the clinical improvement rates,were observed in both groups.Results ① After treatment,the levels of serum total bilirubin(TBil)in the PD group were significantly lower than those in the PE group(μmol/L:163.4±53.3 vs.226.1±72.5,P<0.05),and the prothrombin activity(PTA)was significantly increased[(51.5±9.2)%vs.(41.1±7.7)%,P<0.05].②After treatment,the levels of interleukins(IL-2,IL-6,IL-8)and tumor necrosis factor-α(TNF-α)in both groups decreased compared to before treatment at 1,2,and 4 weeks,reaching the lowest levels at 4 weeks,the levels of IL-2,IL-6,IL-8,and TNF-α in the PD group were lower than those in the PE group[IL-2(ng/L):1.83(1.75)vs.2.04(1.85),IL-6(ng/L):11.31(5.07)vs.18.18(9.05),IL-8(ng/L):21.14(8.35)vs.29.09(12.41),TNF-α(ng/L):9.16(5.10)vs.14.12(7.27)].The levels of IL-10 decreased at 1 week and 2 weeks after treatment.In the PD group,IL-10 increased at 4 weeks after treatment.The differences compared to the baseline levels before treatment were statistically significant(P<0.05).At 4 weeks after treatment,the level of IL-10 in the PD group was significantly higher than that in the PE group[ng/L:24.72(11.56)vs.19.03(10.04),P<0.05].③ The clinical improvement rates in the PD group were significantly higher than those in the PE group at 2 weeks and 4 weeks after treatment[2 weeks after treatment:65.08%(41/63)vs.40.35%(23/57);4 weeks after treatment:84.13%(53/63)vs.54.39%(31/57),both P<0.05].④After 4 weeks of treatment,the MELD scores in both groups decreased significantly.Compared with the PE group,the MELD score in the PD group was significantly lower(14.87±3.45 vs.19.68±4.63,P<0.05).Conclusion Compared with PE alone,PE+DPMAS treatment for early and mid-stage ACLF patients can more effectively clear the large amount of inflammatory mediators released in the body,better regulate the balance between pro-inflammatory and anti-inflammatory cytokines in the patient's serum,thereby preventing or delaying the formation of systemic inflammatory response syndrome(SIRS)and multiple organ dysfunction syndrome(MODS).The clinical therapeutic effect is better,with a higher improvement rate,achieving the goal of reducing liver damage,improving patient survival rate,and thus improving prognosis.

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