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.The influence of enhanced heel anti-gravity posture stability training on the spatiotemporal gait parameters of hemiplegic stroke survivors
Le XIAO ; Fangbo LIN ; Meiyun ZHOU ; Chao LIU ; Hua LIU ; Hao XIAO ; Zhaohua GU
Chinese Journal of Physical Medicine and Rehabilitation 2025;47(8):699-703
Objective:To observe the effect of intensified heel anti-gravity posture stability training on the gait of stroke survivors.Methods:Thirty-six hemiplegic stroke survivors were randomly divided into a control group and an experimental group, each of 18. Both groups received conventional rehabilitation treatment (including limb positioning, limb movement training and conventional walking training), while the experimental group was additionally provided with 30 minutes of intense heel anti-gravity posture stability training 5 days a week for 4 weeks. Before and after the treatment, the subjects′ walking speed, stride frequency, step length, peak knee flexion angle and peak hip flexion angle were documented using three-dimensional gait analysis with a movement training system.Results:The average walking speed, stride rate, step length, peak hip flexion and peak knee flexion of both groups had improved significantly after the treatments. But the average walking speed [(0.46±0.06)m/s], step length [(85.05±6.68)cm], peak hip flexion angle [(34.80±2.80)°] and peak knee flexion angle [(40.55±3.58)°] of the treatment group were significantly better than those of the control group.Conclusions:Intensified heel anti-gravity posture stability training can significantly improve the walking speed, step length, hip flexion and knee flexion of hemiplegic stroke survivors.
3.Decompression mechanism of symmetrically adduction of lumbar decompression induced resorption of herniated nucleus pulpous
Chunlin ZHANG ; Zhaohua HOU ; Xu YAN ; Yan JIANG ; Su FU ; Yongming NING ; Dongzhe LI ; Chao DONG ; Xiaokang LIU ; Yongkui WANG ; Zhengming CAO ; Tengyue YANG
Chinese Journal of Tissue Engineering Research 2025;29(9):1810-1819
BACKGROUND:Traditional surgery for lumbar disc herniation involves extensive excision of tissue surrounding the nerve for decompression and removal of protruding lumbar intervertebral discs,which poses various risks and complications such as nerve damage causing paralysis,lumbar instability,herniation recurrence,intervertebral space infection,and adjacent vertebral diseases. OBJECTIVE:To propose the symmetrically adduction of lumbar decompression induced resorption of herniated nucleus pulpous technique for lumbar spine symmetrically decompression,showing the induced resorption of herniated nucleus pulpous phenomenon and early clinical efficacy,and then analyze its decompression mechanism. METHODS:214 patients with lumbar disc herniation at Department of Orthopedics,First Affiliated Hospital of Zhengzhou University from March 2021 to May 2023 were enrolled in this study.Among them,81 patients received conservative treatment as the control group,and 133 patients received symmetrically adduction of lumbar decompression induced resorption of herniated nucleus pulpous treatment as the trial group.Before surgery,immediately after surgery(7-14 days),and early after surgery(over 1 year),MRI images were used to measure the volume changes of lumbar disc herniation.CT images were used to measure the posterior displacement distance of the lumbar spinous process ligament complex,as well as the width and height of the lateral recess.Japanese Orthopaedic Association scores were used to evaluate the patient's neurological function recovery. RESULTS AND CONCLUSION:(1)Control group:81 patients with lumbar disc herniation were treated conservatively,with a total of 171 herniated lumbar discs.The average follow-up time was(22.7±23.1)months.The first and second MRI measurements of 171 herniated lumbar discs showed herniated lumbar disc volumes of(551.6±257.9)mm3 and(792.2±330.4)mm3,respectively,with an average volume increase rate of(53.2±44.4)%,showing statistically significant differences(P<0.001).Out of 171 herniated lumbar discs,4 experienced natural shrinkage,with an absorption ratio of 2.3%(4/171)and an absorption rate of(24.5±9.9)%.(2)Trial group:133 patients with lumbar disc herniation had a total of 285 herniated lumbar discs.(1)Immediately after surgery:All patients were followed up immediately after surgery.229 out of 285 herniated lumbar discs experienced retraction,with an absorption ratio of 80.3%(229/285)and an average absorption rate of(21.5±20.9)%,with significant and complete absorption accounting for 6.5%.There were a total of 70 herniated lumbar discs in the upper lumbar spine,with an absorption ratio of 85.7%(60/70),an average absorption rate of(23.1±19.5)%,and a maximum absorption rate of 86.6%.There were 215 herniated lumbar discs in the lower lumbar spine,with an absorption ratio of 78.6%(169/215),an average absorption rate of(21.0±21.3)%,and a maximum absorption rate of 83.2%.Significant and complete absorption of the upper and lower lumbar vertebrae accounted for 5.7%and 6.5%,respectively,with no statistically significant difference(P>0.05).The average distance of posterior displacement of the spinous process ligament complex immediately after surgery was(5.2±2.8)mm.There were no significant differences in the width and height of the left and right lateral recess before and immediately after surgery(P>0.05).The Japanese Orthopaedic Association score immediately after surgery increased from(10.1±3.4)before surgery to(17.0±4.8),and the immediate effective rate after surgery reached 95.6%.(2)Early postoperative period:Among them,46 patients completed the early postoperative follow-up.There were 101 herniated lumbar discs,with an absorption ratio of 94%(95/101)and an average absorption rate of(36.9±23.7)%.Significant and complete absorption accounted for 30.6%,with a maximum absorption rate of 100%.Out of 101 herniated lumbar discs,3 remained unchanged in volume,with a volume invariance rate of 2.97%(3/101).Out of 101 herniated lumbar discs,3 had an increased volume of herniated lumbar discs,with an increase ratio of 2.97%(3/101)and an increase rate of(18.5±18.4)%.The Japanese Orthopaedic Association score increased from preoperative(9.3±5.1)to(23.5±4.0),with an excellent and good rate of 93.4%.(3)The early postoperative lumbar disc herniation absorption ratios of the control group and trial group were 2.3%and 85.9%,respectively,with statistically significant differences(P<0.001).(4)Complications:There were two cases of incision exudation and delayed healing in the trial group.After conservative treatment such as dressing change,no nerve injury or death occurred in the incision healing,and no cases underwent a second surgery.(5)It is concluded that symmetrically adduction of lumbar decompression induced resorption of herniated nucleus pulpous is a new method for treating lumbar disc herniation that can avoid extensive excision of the"ring"nerve and achieve satisfactory early clinical efficacy.It does not damage the lumbar facet joints or alter the basic anatomical structure of the lateral recess,fully preserves the herniated lumbar discs,and can induce significant or even complete induced resorption of herniated nucleus pulpous.Symmetrically adduction of lumbar decompression induced resorption of herniated nucleus pulpous provides a new basis and method for the clinical treatment of lumbar disc herniation.
4.Preliminary comparative analysis of cytokines related to blood and lipid metabolism and histopathological characteristics in SPF grade and GF grade golden hamsters
Yaxi GUO ; Zhaohua WANG ; Xiaopeng DU ; Kaihui LIU ; Hua ZHU
Acta Laboratorium Animalis Scientia Sinica 2025;33(6):858-865
Objective To compare the hematological parameters,biochemical profiles,histopathological characteristics,and cytokines associated with lipid metabolism in 8-weeks-old specific pathogen-free(SPF)grade and germ-free(GF)golden hamsters.Methods Twenty 8-weeks-old SPF grade and GF golden hamsters,with equal numbers of males and females,were utilized in this study.Serum cytokines associated with routine blood parameters,blood biochemistry,and lipid metabolism were quantified using automated hematology and biochemical analyzers,and enzyme-linked immunosorbent assay kits.The cecum,small intestine,lung,spleen,forestomach,and glandular stomach were examined by histopathology.Results We compared the result between SPF grade and GF golden hamsters at 8 weeks of age.Regarding hematological parameters,females showed significant differences(P<0.05)in white blood cell count,hemoglobin concentration,mean corpuscular hemoglobin(MCH),and mean platelet volume between the two groups,and highly significant differences(P<0.001)in MCH concentration(MCHC),platelet distribution width(PDW),and lymphocyte count(LYM).Males showed significant differences(P<0.05)in mean corpuscular volume,MCH,LYM,neutrophil count,basophil count,and basophil percentage,and highly significant differences(P<0.001)in MCHC,PDW,lymphocyte percentage,and neutrophil percentage.In terms of biochemical parameters,females showed significant differences(P<0.05)in low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol,fasting insulin(FINS),and glycosylated serum protein(GSP),and highly significant differences(P<0.001)in triglycerides(TG).Males showed significant differences(P<0.05)in GSP levels and highly significant differences(P<0.001)in total cholesterol,TG,LDL-C,FINS,and C-peptide levels.For serum cytokines related to lipid metabolism,females showed significant differences(P<0.05)in interleukin(IL)-10,adiponectin(ADP),and IL-6 levels,and highly significant differences(P<0.001)in high-sensitivity C-reactive protein(hs-CRP).Males showed significant differences(P<0.05)in hs-CRP levels and highly significant differences(P<0.001)in ADP and tumor necrosis factor-alpha levels.Hematoxylin/eosin staining showed that the cecal muscle layer was thinner and the number of crypts attached to the mucous membrane was reduced in GF compared with SPF grade golden hamsters.In addition,the ileocele was enlarged and the number of goblet cells was increased,the alveolar septum was widened,immune cells in the white pulp of the spleen were increased,and the blood content in the blood sinuses was increased.There was also thinning of the anterior gastric mucosa and the basophilic strength of the glandular gastric tube gland was weakened.Conclusions This study established the differences in routine blood parameters,blood biochemistry indicators,histopathological features,and cytokines associated with lipid metabolism between 8-weeks-old SPF grade and GF golden hamsters,to establish preliminary reference ranges.
5.Preliminary comparative analysis of cytokines related to blood and lipid metabolism and histopathological characteristics in SPF grade and GF grade golden hamsters
Yaxi GUO ; Zhaohua WANG ; Xiaopeng DU ; Kaihui LIU ; Hua ZHU
Acta Laboratorium Animalis Scientia Sinica 2025;33(6):858-865
Objective To compare the hematological parameters,biochemical profiles,histopathological characteristics,and cytokines associated with lipid metabolism in 8-weeks-old specific pathogen-free(SPF)grade and germ-free(GF)golden hamsters.Methods Twenty 8-weeks-old SPF grade and GF golden hamsters,with equal numbers of males and females,were utilized in this study.Serum cytokines associated with routine blood parameters,blood biochemistry,and lipid metabolism were quantified using automated hematology and biochemical analyzers,and enzyme-linked immunosorbent assay kits.The cecum,small intestine,lung,spleen,forestomach,and glandular stomach were examined by histopathology.Results We compared the result between SPF grade and GF golden hamsters at 8 weeks of age.Regarding hematological parameters,females showed significant differences(P<0.05)in white blood cell count,hemoglobin concentration,mean corpuscular hemoglobin(MCH),and mean platelet volume between the two groups,and highly significant differences(P<0.001)in MCH concentration(MCHC),platelet distribution width(PDW),and lymphocyte count(LYM).Males showed significant differences(P<0.05)in mean corpuscular volume,MCH,LYM,neutrophil count,basophil count,and basophil percentage,and highly significant differences(P<0.001)in MCHC,PDW,lymphocyte percentage,and neutrophil percentage.In terms of biochemical parameters,females showed significant differences(P<0.05)in low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol,fasting insulin(FINS),and glycosylated serum protein(GSP),and highly significant differences(P<0.001)in triglycerides(TG).Males showed significant differences(P<0.05)in GSP levels and highly significant differences(P<0.001)in total cholesterol,TG,LDL-C,FINS,and C-peptide levels.For serum cytokines related to lipid metabolism,females showed significant differences(P<0.05)in interleukin(IL)-10,adiponectin(ADP),and IL-6 levels,and highly significant differences(P<0.001)in high-sensitivity C-reactive protein(hs-CRP).Males showed significant differences(P<0.05)in hs-CRP levels and highly significant differences(P<0.001)in ADP and tumor necrosis factor-alpha levels.Hematoxylin/eosin staining showed that the cecal muscle layer was thinner and the number of crypts attached to the mucous membrane was reduced in GF compared with SPF grade golden hamsters.In addition,the ileocele was enlarged and the number of goblet cells was increased,the alveolar septum was widened,immune cells in the white pulp of the spleen were increased,and the blood content in the blood sinuses was increased.There was also thinning of the anterior gastric mucosa and the basophilic strength of the glandular gastric tube gland was weakened.Conclusions This study established the differences in routine blood parameters,blood biochemistry indicators,histopathological features,and cytokines associated with lipid metabolism between 8-weeks-old SPF grade and GF golden hamsters,to establish preliminary reference ranges.
6.The influence of enhanced heel anti-gravity posture stability training on the spatiotemporal gait parameters of hemiplegic stroke survivors
Le XIAO ; Fangbo LIN ; Meiyun ZHOU ; Chao LIU ; Hua LIU ; Hao XIAO ; Zhaohua GU
Chinese Journal of Physical Medicine and Rehabilitation 2025;47(8):699-703
Objective:To observe the effect of intensified heel anti-gravity posture stability training on the gait of stroke survivors.Methods:Thirty-six hemiplegic stroke survivors were randomly divided into a control group and an experimental group, each of 18. Both groups received conventional rehabilitation treatment (including limb positioning, limb movement training and conventional walking training), while the experimental group was additionally provided with 30 minutes of intense heel anti-gravity posture stability training 5 days a week for 4 weeks. Before and after the treatment, the subjects′ walking speed, stride frequency, step length, peak knee flexion angle and peak hip flexion angle were documented using three-dimensional gait analysis with a movement training system.Results:The average walking speed, stride rate, step length, peak hip flexion and peak knee flexion of both groups had improved significantly after the treatments. But the average walking speed [(0.46±0.06)m/s], step length [(85.05±6.68)cm], peak hip flexion angle [(34.80±2.80)°] and peak knee flexion angle [(40.55±3.58)°] of the treatment group were significantly better than those of the control group.Conclusions:Intensified heel anti-gravity posture stability training can significantly improve the walking speed, step length, hip flexion and knee flexion of hemiplegic stroke survivors.
7.Establishment of sterile golden hamster model
Yaxi GUO ; Xiaopeng DU ; Kaihui LIU ; Zhaohua WANG ; Hua ZHU
Chinese Journal of Comparative Medicine 2024;34(8):87-93
Objective A sterile golden hamster model was established by cesarean section purification.Methods SPF-grade donor female golden hamsters were selected,and males and females were mated 1∶1 and separated after mating.The cage time of the surrogate mothers was 1 week earlier than that of the donor mothers.Parturient golden hamsters underwent hysterectomy on a sterilized workbench,and the uteruses were transferred into isolation kits and stripped.To obtain sterile milk for milk replacement,sterile ICR mice and sterile SD rats were used.After successful separation,the hamsters were transferred to isolation kits to prepare for feeding.The sterility status of the feeding isolation kits was tested monthly.Results Three caesarean sections were performed,but the first and second lactations failed.The third milk replacement was successful,and 18 young hamsters were obtained with survival rates of 88%and 66%after weaning.All hamsters were quality tested by GB/T 14926.41-2001.Conclusions Using a cesarean section purification technique and sterile ICR mice and SD rats for microbial-free milk replacement,a sterile golden hamster model was obtained.
8.Study on the decision-making mechanism of the party branch of university affiliated hospital partici-pating in clinical business department
Ying ZHANG ; Shuyun WANG ; Junna CUI ; Zhaohua LIU ; Zhaoquan HUANG
Modern Hospital 2024;24(9):1343-1346,1349
As the key of colleges and universities and medical career,the affiliated hospital's clinical department is the core of its development.In the new era,strengthening the mechanism of party branch participating in the decision-making of clin-ical departments is an inevitable requirement for implementing the party's leadership and strengthening hospital management.The Party branch of the affiliated hospital of the university has the"dual"attribute,through the establishment of the"core group"of the party branch to participate in decision-making in the clinical business department,the establishment of an efficient decision-making platform,the construction mechanism of supporting rules of procedure and supervision measures to realize its function,the in-depth analysis of management challenges and the improvement of countermeasures,in order to create a new way and a new mechanism of the party branch decision-making,and promote the deep integration of party building and business.
9.Study on risk factors for coma in patients with hypoglycemia
Quanhong LIN ; Yaowei XU ; Yuzhuo LI ; Lebai LIU ; Shifan TANG ; Xiaowan LIN ; Zhaohua XIN
Chinese Journal of Emergency Medicine 2024;33(9):1273-1280
Objective:To investigate the incidence and risk factors of coma in patients with hypoglycemia (≤3.9 mmol/L).Methods:A retrospective study was conducted. Patients aged 20 years and older with blood glucose levels ≤3.9 mmol/L, and measured by emergency physicians from January 2020 to December 2022 were collected. Baseline patient data, clinical values collected on-site, and treatment outcomes were analyzed. The Glasgow Coma Scale (GCS) was used to determine if patients were comatose, with GCS ≤8 classified as the coma group and GCS >8 as the non-coma group. Further analysis was conducted on the resuscitated coma group to identify factors affecting patient recovery. Patients were divided into eight age groups, seven time periods within 24 h, and six blood glucose level groups to calculate the incidence of coma. A multivariate logistic regression model was constructed to analyze independent risk factors for coma in hypoglycemic patients.Results:A total of 754 patients with blood glucose levels ≤3.9 mmol/L were collected, with 425 cases of coma and 329 non-coma cases, resulting in a coma probability of 56.37% (95% CI: 52.82%-59.91%). Patients in the coma group were older ( P<0.001) and had a higher prevalence of diabetes compared to the non-coma group (82.12% vs. 67.78%, P<0.001). The age of all patients was (73.05±15.20) years, with the 61-90 years age groups being the most prone to hypoglycemia and coma. In terms of time distribution, the high-incidence periods for hypoglycemia and coma were 0-6 o’clock, 6-9 o’clock, and 14-18 o’clock. The primary causes of hypoglycemia included reduced energy intake after insulin injection (12.07%), improper use of insulin (6.37%), and reduced energy intake (6.23%), with 71.09% of cases having unknown causes. Additionally, 18.44% of patients used insulin before the onset of hypoglycemia, with a higher proportion in the coma group compared to the non-coma group (22.12% vs. 13.68%, P=0.003). The initial blood glucose level of all patients was (2.13±0.85) mmol/L, with lower levels observed in the coma group compared to the non-coma group ( P<0.001). The probabilities of coma occurrence corresponding to blood glucose levels were: 1.1-1.5 mmol/L (72.97%), 1.6-2.0 mmol/L (68.90%), 2.1-2.5 mmol/L (54.10%), 2.6-3.0 mmol/L (38.20%), 3.1-3.5 mmol/L (37.50%), and 3.6-3.9 mmol/L (19.40%). Multivariate logistic regression analysis indicated that age ( OR=1.021, 95% CI: 1.010-1.033, P<0.001), insulin use before onset ( OR=1.948, 95% CI: 1.142-3.323, P=0.014), and blood glucose concentration ( OR=0.426, 95% CI: 0.347-0.522, P<0.001) were independent predictors of coma in hypoglycemic patients. The investigation revealed that after intravenous injection of 50% glucose solution, 215 of 425 coma patients regained consciousness (50.58%), and the recovery time was (18.43±9.09) min. Patients in the recovery group were younger and had lower initial blood glucose levels compared to the non-recovery group (both P<0.05), while recovery group re-measured blood glucose levels were higher than those in the non-recovery group ( P=0.002). Conclusions:The probability of coma in hypoglycemic patients was high, with insulin use being a common trigger. Proper use of insulin is essential to prevent hypoglycemia and coma.
10.Gene mutation characteristics of clinical stage ⅠA lung adenocarcinoma and their relations with patients′ long-term prognosis
Li ZHANG ; Mengwen LIU ; Lin LI ; Shuang ZHAO ; Lihong WU ; Zhaohua YIN ; Meng LI ; Yanning GAO ; Ning WU
Chinese Journal of Oncology 2024;46(8):755-763
Objective:To explore the gene mutation characteristics and the relationship between gene mutations and long-term prognosis in clinical stage ⅠA lung adenocarcinoma patients.Methods:A retrospective analysis was conducted on 63 clinical stage ⅠA lung adenocarcinoma patients who underwent surgical resection at the Cancer Hospital of the Chinese Academy of Medical Sciences from January 2007 to October 2012, with documented postoperative recurrence or metastasis, as well as those who had a follow-up duration of 10 years or more without recurrence or metastasis. Whole exome sequencing (WES) technology was used to analyze the gene mutation profiles in tumor tissues and univariate and multivariate Cox regression analysis were used to clarify the influencing factors for patient prognosis.Results:After long term follow-up, 13 out of the 63 patients (21%) experienced recurrence or metastasis. WES technology analysis revealed that the most common tumor related gene mutations occurred in epidermal growth factor receptor (EGFR), with a mutation rate of 65.1% (41/63), followed by tumor protein p53 (TP53), fatatypical cadherin 1 (FAT1), low density lipoprotein receptor-related protein 1B (LRP1B), mechanistic target of rapamycin (MTOR), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma (PIK3CG), and SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4 (SMARCA4), with mutation rates of 30.2% (19/63), 20.6% (13/63), 15.9% (10/63), 15.9% (10/63), 15.9% (10/63), and 15.9% (10/63), respectively. Multivariate Cox regression analysis showed that PIK3CG mutations ( HR=21.52, 95% CI: 3.19-145.01),smoothened (SMO) mutations ( HR=35.28, 95% CI: 3.12-398.39), catenin beta 1 (CTNNB1) mutations ( HR=332.86, 95% CI: 15.76-7 029.05), colony stimulating factor 1 receptor (CSF1R) mutations ( HR=8 109.60, 95% CI: 114.19-575 955.17), and v-Raf murine sarcoma viral oncogene homolog B (BRAF) mutations ( HR=23.65, 95% CI: 1.86-300.43) were independent risk factors affecting the prognosis of clinical stage ⅠA lung adenocarcinoma patients. Conclusions:PIK3CG, SMO, CTNNB1, CSF1R, BRAF gene mutations are closely related to long-term recurrence or metastasis in clinical stage ⅠA lung adenocarcinoma. Patients with these gene mutations should be given closer clinical attention.

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