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.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.
3.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.
4.Biomechanical Analysis and Optimization of Minimally Invasive Pelvic Internal Fixation
Minghu WU ; Zhaohua BAO ; Jiandong WANG ; Chun BI ; Guoying DENG
Journal of Medical Biomechanics 2022;37(2):E250-E255
Objective By comparing biomechanical properties of two-screw rod and three-screw rod for fixing pelvic fracture, the difference in mechanical effects of different screw rod fixation positions in pelvic minimally invasive surgery was studied.Methods The mechanical models of pelvis fixed by two-screw rod and three-screw rod were established, and biomechanical characteristics of the pelvis during standing on both legs, during single-legged standing on healthy side or affected side, as well as in sitting posture were compared and analyzed by finite element simulation, and the fixation effect of three-screw rod was verified by clinical experiments.Results Both fixation methods could restore mechanical transmission of the pelvis. But for three-screw rod fixation, the stress on both sides of the pelvis was more balanced, and the displacement of the whole body and fracture surface was also lower during single-legged standing.Conclusions The three-screw rod fixation has an excellent effect in stability, which is more beneficial for fracture recovery.
5.The clinical value of the logistic regression model with a combination of three-dimensional CT quantitative and qualitative parameters in predicting the invasiveness of pure ground glass nodules
Xuhong MIN ; Qilong SONG ; Yongqiang YU ; Biao SONG ; Bin WANG ; Yuan LI ; Zhaohua WANG ; Wu CHEN ; Xu WANG
Chinese Journal of Radiology 2021;55(1):34-39
Objective:To explore the value of the logistic regression model with three-dimensional CT quantitative parameters in combination with qualitative parameters in predicting the invasiveness of pure ground glass nodules (pGGN).Methods:The clinical data and image features of 191 patients (196 lesions) with pGGN on CT confirmed as lung adenocarcinoma by pathology from April 2019 to December 2019 in Anhui Chest Hospital were retrospectively analyzed. Totally, 196 lesions were divided into atypical adenomatous hyperplasia (AAH)+adenocarcinoma in situ (AIS)+minimally invasive adenocarcinoma (MIA) group ( n=128) and invasive adenocarcinoma (IAC) group ( n=68). CT quantitative parameters included the maximum diameter, volume, average CT value and quality of pGGN, and the qualitative parameters included the intrinsic vascular changes, abnormal air-bronchogram, lobulated signs, bubble-like sign, pleura-traction sign, and fuzzy tumor-lung interface sign. The Mann-Whitney U test was used to compare the quantitative parameters and the Pearson χ 2 test was used to compare the qualitative parameters between two groups. The independent predictors of IAC and predictive probability value were screened by univariate analysis in combination with multivariate logistic regression analysis. The ROC curves were drawn to compare the diagnostic probability of logistic regression prediction probability and each single parameter. Results:There were statistically significant differences in maximum diameter [0.92(0.77,1.14) cm vs. 1.41(1.12, 1.93) cm, Z=-7.366, P<0.001], volume[0.31(0.20, 0.53) cm 3 vs. 0.88(0.41, 2.00) cm 3, Z=-6.254, P<0.001], average CT value[-571.5(-637.2, -477.0) HU vs. -418.1(-532.4, -338.5) HU, Z=-5.882, P<0.001], quality[0.14(0.09, 0.25) g vs. 0.42(0.26, 1.21) g, Z=-7.438, P<0.001], intrinsic vascular changes(23 vs. 49, χ2=55.906, P<0.001), abnormal air-bronchogram(13 vs. 30, χ2=29.908, P<0.001) and pleura-traction sign(39 vs. 32, χ2=5.291, P=0.021) between the two groups. The logistic regression analysis showed that the maximum diameter, average CT value, intrinsic vascular changes and abnormal air-bronchogram were the independent risk factors of IAC, and the odds ratio value(95%CI) were 10.624(1.275-88.522), 1.004(1.000-1.008), 3.424(1.458-8.043) and 2.993(1.114-8.043), respectively. The ROC curve demonstrated that the area under the curve, sensitivity and specificity of the logistic regression model were 0.899, 0.912, and 0.711 respectively, which were better than separate analysis results from each single parameter. Conclusion:The logistic regression model with a combination of three-dimensional CT quantitative and qualitative parameters can predict the invasiveness of pGGN better.
6.Genome Warehouse: A Public Repository Housing Genome-scale Data
Chen MEILI ; Ma YINGKE ; Wu SONG ; Zheng XINCHANG ; Kang HONGEN ; Sang JIAN ; Xu XINGJIAN ; Hao LILI ; Li ZHAOHUA ; Gong ZHENG ; Xiao JINGFA ; Zhang ZHANG ; Zhao WENMING ; Bao YIMING
Genomics, Proteomics & Bioinformatics 2021;19(4):584-589
The Genome Warehouse (GWH) is a public repository housing genome assembly data for a wide range of species and delivering a series of web services for genome data submission, storage, release, and sharing. As one of the core resources in the National Genomics Data Center (NGDC), part of the China National Center for Bioinformation (CNCB;https://ngdc.cncb.ac.cn), GWH accepts both full and partial (chloroplast, mitochondrion, and plasmid) genome sequences with different assembly levels, as well as an update of existing genome assemblies. For each assembly, GWH collects detailed genome-related metadata of biological project, biological sample, and genome assembly, in addition to genome sequence and annotation. To archive high-quality genome sequences and annotations, GWH is equipped with a uniform and standardized procedure for quality control. Besides basic browse and search functionalities, all released genome sequences and annotations can be visualized with JBrowse. By May 21, 2021, GWH has received 19,124 direct submissions covering a diversity of 1108 species and has released 8772 of them. Collectively, GWH serves as an important resource for genome-scale data management and provides free and publicly accessible data to support research activities throughout the world. GWH is publicly accessible at https://ngdc.cncb.ac.cn/gwh.
7.Research status and hot spot analysis of user information behavior in online health communities in China
Guorui FAN ; Bote LUO ; Zhaohua DENG ; Xiang WU
Chinese Journal of Hospital Administration 2020;36(5):383-386
This paper analyzed the current situation and research hotspots of user information behavior in online health communities in China, a study of practical and theoretical significance for relevant scholars to learn the forefront of user behavior research in online health communities and better engage in related research. Thanks to literature review, this paper analyzed the research status of user information behavior in online health communities in China, and summarized the main research hotspots. Generally speaking, the research results of user behavior in online health communities in China were rich in volume, yet there remained a gap between China and foreign researches in the depth of research and the breadth of research objects.Future research should focus on making up for these deficiencies.
8.Treatment strategy of the scar uterus patients in assisted reproduction
Xiaoli WU ; Hong YU ; Man LUO ; Ling YANG ; Huizhen TANG ; Zhaohua LIU ; Huilian CHEN ; Nannan LI
Journal of Chinese Physician 2020;22(9):1332-1336
Objective:To investigate the effect of scar uterus on assisted reproduction treatment strategy.Methods:From January 1, 2017 to December 31, 2017, 109 cases of scar uterus group and 63 cases of vaginal delivery history group who underwent in vitro fertilization-embryo transfer (IVF-ET) assisted pregnancy fresh embryo transfer in our hospital were retrospectively analyzed. Results:⑴ There was no significant difference in the total amount of gonadotropin (Gn) and the total days of GN in patients <35 between scar uterus group and the vaginal delivery history group ( P>0.05), but there were significant differences in the number of oocytes, mature oocytes, two pronucleus (2PN) and excellent embryos between the scar uterus group and the vaginal delivery history group ( P<0.05). When the age was ≥35 years old, there was no significant difference in the total number of GN, the total days of GN, the number of oocytes obtained, the number of mature oocytes, the number of 2PN and the number of excellent embryos between the two groups ( P>0.05). ⑵ There were no statistically significant differences in clinical pregnancy rate and embryo implantation rate between the two groups of patients < 35 years old, no matter single embryo transplantation or double embryos transplantation. When transplant two embryos, the clinical pregnancy rate and embryo implantation rate in the scar uterus group were slightly lower than those in the vaginal delivery history group (57.57% vs 71.05% and 39.39% vs 47.37%, respectively), but with no significant difference ( P>0.05). There were no statistically significant differences in the clinical pregnancy rate and embryo implantation rate between single embryo transplantation and double embryo transplantation in patients≥35 years old ( P>0.05). ⑶ There were no statistically differences in biochemical pregnancy rate, early abortion rate, preterm birth rate and average newborn weight between the scar uterus group and the vaginal delivery history group ( P>0.05). Conclusions:Cesarean section may affect the ovarian function. For patients with previous cesarean section, early evaluation of ovarian function is recommended. Single embryo transfer does not reduce the outcome in IVF-ET. It is recommended to perform single embryo transfer for patients with scar uterus to reduce the risk during pregnancy of twin pregnancy.
9.IC4R-2.0:Rice Genome Reannotation Using Massive RNA-seq Data
Sang JIAN ; Zou DONG ; Wang ZHENNAN ; Wang FAN ; Zhang YUANSHENG ; Xia LIN ; Li ZHAOHUA ; Ma LINA ; Li MENGWEI ; Xu BINGXIANG ; Liu XIAONAN ; Wu SHUANGYANG ; Liu LIN ; Niu GUANGYI ; Li MAN ; Luo YINGFENG ; Hu SONGNIAN ; Hao LILI ; Zhang ZHANG
Genomics, Proteomics & Bioinformatics 2020;18(2):161-172
Genome reannotation aims for complete and accurate characterization of gene models and thus is of critical significance for in-depth exploration of gene function. Although the availability of massive RNA-seq data provides great opportunities for gene model refinement, few efforts have been made to adopt these precious data in rice genome reannotation. Here we reannotate the rice (Oryza sativa L. ssp. japonica) genome based on integration of large-scale RNA-seq data and release a new annotation system IC4R-2.0. In general, IC4R-2.0 significantly improves the completeness of gene structure, identifies a number of novel genes, and integrates a variety of functional annota-tions. Furthermore, long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) are system-atically characterized in the rice genome. Performance evaluation shows that compared to previous annotation systems, IC4R-2.0 achieves higher integrity and quality, primarily attributable to mas-sive RNA-seq data applied in genome annotation. Consequently, we incorporate the improvedannotations into the Information Commons for Rice (IC4R), a database integrating multiple omics data of rice, and accordingly update IC4R by providing more user-friendly web interfaces and implementing a series of practical online tools. Together, the updated IC4R, which is equipped with the improved annotations, bears great promise for comparative and functional genomic studies in rice and other monocotyledonous species. The IC4R-2.0 annotation system and related resources are freely accessible at http://ic4r.org/.
10.Applicationvalueof3DLAVAdynamiccontrastMRinBuddGChiarisyndrome
Xiao WANG ; Jing WU ; Zhaohua WANG ; Xuemei ZHAO ; Yinfeng QIAN ; Yongqiang YU
Journal of Practical Radiology 2019;35(5):763-766
Objective Toinvestigatetheapplicationvalueofthreedimensionalliveraccelerationvolumeacquisition(3D LAVA) multiphasedynamiccontrastenhancedMRIinBudd-Chiarisyndrome(BCS).Methods Aretrospectiveanalysiswasperformedforthe clinicaldataof49patientswithBCSwhounderwent3DLAVA multiphasedynamiccontrastenhanced MRIandwereconfirmedby DSA.Theappearanceofinferiorvenacava,hepaticvein,accessoryhepaticvein(AHV)andcollateralcirculationonbothDSAand3D LAVA wereobserved.BCStypeandAHVnumberswereanalyzedusingtheχ2test.3DLAVAandDSAinthemeasurementofthe mean diameter of A H V were compared by Student’s t test.The Kappa statistics was calculated to quantify the consistency between thetwomethodsinthedetectionofAHV.Results Amongthe49patients,therewasnosignificantdifferencebetweenMRIandDSA inBCSclassification (P=0.694).MRIandDSAshowedstatisticalsignificances(P<0.01)inthenumberofAHVandthemeancaliber of the A H V respectively.T he Kappa coefficient (K=0.621 ) de m onstrated good consistency for the tw o m ethods in detecting the numberofAHV.3DLAVAshowedmoreadvantagesincollateralcirculationthanDSA.Conclusion 3DLAVA mayaccuratelydetect hepaticvein,inferiorvenacava,AHV,andextrahepaticcollateralcirculationinBCSandcanhelptoevaluatethepatient’sconditionas wellastoselectthealternativemodalityininterventionaltherapy.

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