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 extracorporeal shock wave assisted drug therapy on patients with temporomandibular joint disorder
Pengcheng WANG ; Chunhui CHEN ; Xi TONG ; Xinhai FU
STOMATOLOGY 2024;44(11):856-859
Objective To analyze the effect of extracorporeal shock wave assisted drug therapy on clinical outcomes of patients with temporomandibular disorders(TMD).Methods A total of 86 TMD patients in our hospital from September 2018 to September 2019 were included and divided into group A(n=43)and group B(n=43)by random number table method.Group A(n=43)received oral glucosamine hydrochloride tablets on the basis of conventional treatment;group B(n=43)received extracorporeal shock wave therapy on the basis of group A.The pain degree,maximum mouth opening,temporomandibular joint function,temporomandibular joint bounce times,life quality and occurrence of adverse reactions were compared between the two groups.Results Compared with that before treatment,the visual analogue scale(VAS)scores,maximum mouth opening,temporomandibular joint dysfunction index(DI),palpation index(PI),Fricton craniomandibular index(CMI)level,joint bounce times and oral health impact scale(OHIP-14)score of two groups were significantly improved(P<0.05),and all indexes in group B were significantly better than those in group A(P<0.05).There was no significant difference in the incidence of adverse reactions between the two groups(P>0.05).Conclusion Extracorporeal shock wave assisted drug therapy can effectively reduce joint bounce in TMD patients,relieve patients'pain,improve patients'life quality and temporomandibular joint function,and has good safety.
3.Historical evolution and clinical application of classical prescription Yigongsan
Na CHEN ; Jingxian GUO ; Yanqi CHU ; Leilei GONG ; Xinhai JIANG ; Xiao HU ; Lan ZHANG
China Pharmacy 2024;35(1):119-123
Yigongsan, derived from QIAN Yi’s Key to Therapeutics of Children’s Diseases in the Song Dynasty, is a classic pediatric prescription that is included in the Catalogue of Ancient Classic Prescriptions (the Second Batch of Pediatrics) released by the National Administration of Traditional Chinese Medicine in 2022. This paper verifies and analyzes the historical origin, composition, dosage, processing, decoction method and efficacy of Yigongsan by systematically combing ancient books and modern documents. As a result, Yigongsan is composed of five herbs: Panax ginseng, Poria cocos, Atractylodes macrocephala, Citrus reticulata and Glycyrrhiza uralensis, of which P. cocos should be peeled, A. macrocephala is fried with soil, G. uralensis is roasted with honey while P. ginseng and C. reticulata are raw products. According to the dosage of ancient and modern times, each medicinal herb must be ground into fine powder, 1.6 g for each, added with 300 mL of water, 5 pieces of Zingiber officinale, and 2 Ziziphus jujuba, decocted together to 210 mL, and taken before meals. In ancient books, Yigongsan is used to treat vomiting, diarrhea, spleen and stomach deficiency, chest and abdominal distension, and lack of appetite, etc. Modern research showed that Yigongsan could also be used in the diseases of immune system, respiratory system, blood system, etc., involving infantile anorexia, asthma, anemia, tumors and so on.
4.The relationship between inflammatory factor expression and cell apoptosis in gingival tissue of the subjects with diabetes associated periodontitis
Tielou CHEN ; Xinhai ZHANG ; Erli XU ; Dahai TANG ; Haijun ZHAO ; Yimin XU ; Xiaoli ZHANG ; Wei LUAN ; Jin LIU ; Jun CHEN ; Liting MA
Journal of Practical Stomatology 2017;33(4):518-521
Objective:To study the relationship between IL-1β and TNFα expression and cell apoptosis in gingival tissue of the subjects with diabetes associated periodontitis(DAP).Methods:20 cases of DAP(group DAP) and 20 cases of health controls(group H)were included.The cell apoptosis and the ultrastructural changes in gingival tissue were observed by Tunnel staining and transmission electron microscope (TEM).IL-1β and TNFα expression in gingival tissue were detected by immunohistochemical staining.SBI,GI,PD and AL of the subjects were measured.The relationship between the level of IL-1β,TNFα and the cell appotosis was analyzed.Results:Apoptosis was obvious in prickle cells and basal cells of gingival tissue of DAP group.The percentage of apoptosis cells of DAP group was significantly higher than that of group H(P<0.01).The expression of IL-1β and TNFα in group DAP was significant higher than that of group H (P<0.01),and the mainly positive expression cells were macrophages,plasmocytes and lymphocytes.Conclusion:IL-1β and TNFα play a role in cell apoptosis in the gingival tissue of the patients with DAP.
5. The role of soft tissue transplantation in the reconstruction of gingival papilla
Chinese Journal of Stomatology 2017;52(2):86-90
Black triangle caused by gingival papilla loss is an ordinary clinical problem. Gingival recession and alveolar bone absorption in the area of gingival papilla lead to the increase of the vertical distance from the adjacent contact point to the alveolar ridge. Periodontal soft tissue grafts play a certain role in the gingival papilla reconstruction. This paper reviewed the effects of soft tissue grafts on the reconstruction of gingival papilla loss through following several aspects, summary of gingival papilla loss, gum soft tissue reconstruction, biological and chemical factors influencing gingival papilla reconstruction. The role of coronally advanced flap surgery, semilunar coronal repositioned flap surgery, subepithelial connective tissue graft, pedicle flap graft, envelop flap graft and tunnel technique were evaluated.
6.Comparative research on fluorescent quantitation PCR method and gene chips typing method in testing sensitivity of human papilloma virus
Xuegan YAO ; Xinhai LIU ; Meicai CHEN
International Journal of Laboratory Medicine 2014;(5):536-537
Objective To compare the sensitivity of the fluorescent quantitation PCR method (fluorescence quantitative method for short)and the gene chips typing method (gene chips method for short)in testing human papilloma virus(HPV) .Methods 305 outpatients in the gynecological clinic of the hospital from February 2010 to February 2013 were selected as the research subject . Then the cervical exfoliated cells were collected and detected HPV by the fluorescence quantitative method and the gene chips meth-od respectively .Those cases with inconsistent results were confirmed by the PCR sequencing method .305 cases were performed the liquid based cytology test .Results The sensitivity of the fluorescence quantitative method in detecting HPV was 33 .8% and which of the gene chips method was 37 .6% .The two methods had a higher conformance .The HPV infection rate was increased with the increase of cervical exfoliated cell atypia .Conclusion The fluorescence quantitative method and the gene chips method have a higher conformance .The sensitivity of the gene chips method is higher .The severity degree of cervical cytological change is positively cor-related with the HPV infection .
7.Prediction of blood tacrolimus concentration in liver transplantation recipients by artificial neural network.
Xiao-Hua FU ; Yi-Fang YE ; Mei-Juan LUO ; Xiao-Dan HONG ; Xiao-Lu CHEN ; Qiu-Yan YAO ; Ying-Ci RONG ; Bin REN
Acta Pharmaceutica Sinica 2012;47(9):1134-1140
This study is to establish an artificial neural network (ANN) for predicting blood tacrolimus concentration in liver transplantation recipients. Tacrolimus concentration samples (176 samples) from 37 Chinese liver transplantation recipients were collected. ANN established after network parameters were optimized by using momentum method combined with genetic algorithm. Furthermore, the performance of ANN was compared with that of multiple linear regression (MLR). When using accumulated dose of 4 days before therapeutic drug monitoring (TDM) of tacrolimus concentration as input factor, mean prediction error and mean absolute prediction error of ANN were 0.02 +/- 2.40 ng x mL(-1) and 1.93 +/- 1.37 ng x mL(-1), respectively. The absolute prediction error of 84.6% of testing data sets was less than 3.0 ng x mL(-1). Accuracy and precision of ANN are superior to those of MLR. The correlation, accuracy and precision of ANN are good enough to predict blood tacrolimus concentration.
Adult
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Aged
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Drug Monitoring
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methods
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Female
;
Humans
;
Immunosuppressive Agents
;
blood
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Linear Models
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Liver Transplantation
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Male
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Middle Aged
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Neural Networks (Computer)
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Tacrolimus
;
blood
8.Study of perioral force exerted on the teeth in preadolescent children with anterior crossbite.
Xinhai ZHANG ; Guoqin LIN ; Haijun ZHAO ; Jun CHEN ; Qingfu ZHANG ; Tielou CHEN
Journal of Biomedical Engineering 2011;28(1):76-80
30 preadolescent children with anterior crossbite were selected for the present study. Among them 15 were male and 15 children were female. Their age ranged from 8 to 12 years. The mean age was 10. 8 years. Their perioral forces were measured in the areas as following: the labial and lingual sides of mandibular and maxillar central incisors, the first premolars and molars of both sides. After analysis of the results, some conclusions were drawn as the following, the distribution of the perioral force of bilateral arch was symmetric, and there were no significant differences between genders. The values of the perioral force in the premolar and molar area were the largest. When the children were in their nature head position, the perioral force values of labial side were larger than those on the lingual side. On the lingual side of mandibular incisors negative values were found. The perioral force correlated with malocclusion. The position of the teeth decides the value of the perioral force. It has been well concluded that the forces exerted on the teeth were not the only factor that influenced teeth position. There are also other factors influencing the teeth poison. This needs further study.
Bite Force
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Child
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Dental Stress Analysis
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methods
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Female
;
Humans
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Lip
;
physiopathology
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Male
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Malocclusion, Angle Class I
;
physiopathology
9.Medical image automatic adjusting window and segmentation.
Zhenhuan ZHOU ; Siping CHEN ; Duchun TAO ; Xinhai CHEN
Journal of Biomedical Engineering 2005;22(2):331-334
Image guided surgical navigation system is the most advanced surgical apparatus, which develops most rapidly and has great application prospects in neurosurgery, orthopaedics, E.N.T. department etc. In current surgical navigation systems, windowing, segmenting and registration of medical images all depend on manual operation, and automation of image processing is urgently needed. This paper proposes the algorithm which realizes very well automatic windowing and segmentation of medical images: first, we analyze a lot of MRI and CT images and propose corresponding windowing algorithm according to their common features of intensity distribution. Experiments show that the effects of windowing of most MRI and CT images are optimized. Second, we propose the seed growing algorithm based on intensity connectivity,which can segment tumor and its boundary exactly by simply clicking the mouse, and control dynamically the results in real time. If computer memory permits, the algorithm can segment 3D images directly. Tests show that this function is able to shorten the time of surgical planning, lower the complexity, and improve the efficiency in navigation surgery.
Algorithms
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Brain Diseases
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diagnosis
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surgery
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Humans
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Image Enhancement
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methods
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Image Interpretation, Computer-Assisted
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instrumentation
;
methods
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Image Processing, Computer-Assisted
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Imaging, Three-Dimensional
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instrumentation
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Magnetic Resonance Imaging
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Neurosurgical Procedures
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Surgery, Computer-Assisted
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methods
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Tomography, X-Ray Computed
10.Immunohistochemical study of the synaptophysin in hirschsprung’s disease
Xinhai CUI ; Yuli CHEN ; Lei ZHANG ; Tangshan ZHANG
Chinese Journal of Current Advances in General Surgery 2004;0(06):-
Objective:To study the neuromuscular junction of the colon in patients with Hirschsprung’s disease by immunohistochemical methods.Methods:The distribution of the neuromuscular junction in the muscle layers of bowel from 10 normal controls and 20 Hirschsprung’s disease patients was studied by synaptophysin immunohistochemistry.Antimouse synaptophysin serum was used for visualization of neuromuscular junction.Results:In the colon of the control cases,synaptophysin-immunoreactivity was widely distributed in the circular muscle layer.In the dilated colon with Hirschsprung’s disease cases,synaptophysin-immunoreactivity was moderately distributed within normal ganglion cell and scarcely in constricted segment within degenerated ganglion cell.In contrast to the high degree of synaptophysin-immunoreactivity in the controls and dilated colon,the synaptophysin-immunoreactivity in the constricted segment were nil in the circular muscle layer.Conclutions:Dense synaptophysin-immunoreactivity nerve endings were prominent in the circular muscle layer in the control and there was almost no synaptophysin imm-unoreactivity activity in the circular muscle layer in the constricted segment.The circular muscle layer from the constricted segment is confirmed to be a region with poor innervation including extrinsic and intrinsic nerve. Based on the Cannon’s Law of Denervation,the muscles that are supplied by these nerves shorten and tighten,resulting in muscle spasm and stiffness.The constricted segment which was denervated,is incapable of transmitting normal propulsive peristaltic waves and therefore acts as a physiologic obstruction.

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