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.

Objective:To investigate the application value of dual-layer detector spectral CT in the precise outlining of gross tumor volume (GTV) in lung cancer patients.Methods:Imaging data of 39 patients with pathologically confirmed lung cancer on dual-energy enhanced CT scans in Hebei Medical University Third Hospital were retrospectively analyzed. Among them, 13 patients were not complicated with lung atelectasis and 26 cases were complicated with lung atelectasis and 9 of them received positron emission computed tomography (PET-CT) scan. The virtual single-energy images of arterial and venous dual-phase 40 keV images were reconstructed with the spectral base images of Iqon dual-energy CT, and the GTV of the primary foci was outlined using the reconstructed images and conventional enhanced CT images. The GTV outlined by conventional enhanced CT image, 40 keV virtual monoenergetic (VM) CT image, 40 keV VM-iodine density (VM-ID) fusion image in the arterial phase, conventional enhanced CT image, 40 keV VM image and 40 keV VM-ID image in the venous phase and PET-CT image was defined as GTV ACT, GTV A40VM, GTV A40VMID, GTV VCT, GTV V40VM, GTV V40VMID and GTV PET-CT, respectively. The consistency of target area outlining was assessed by calculating the GTV volume, the Dice similarity coefficient (DSC), and the 95 th percentile of the Hausdorff distance (HD95). Pairwise comparison among groups was conducted by Friedman test and corrected by Bonferroni correction. Results:In GTV comparisons, the differences in GTV ACT, GTV VCT, GTV A40VM and GTV V40VM in patients without pulmonary atelectasis were not statistically significant ( χ2=1.89, P=0.595). The DSC and HD95 of GTV ACTvs. GTV A40VM were 0.96 and 3.00, and the DSC and HD95 of GTV VCTvs. GTV V40VM were 0.94 and 2.93, respectively. The differences in GTV ACT, GTV A40VM, GTV A40VMID, GTV VCT, GTV V40VM, GTV V40VMID and GTV PET-CT in patients complicated with pulmonary atelectasis were statistically significant (all P<0.001). Pairwise comparison of Bonferroni correction showed that there was no statistically significant difference in GTV A40VM, GTV A40VMID, GTV V40VM, GTV V40VMID and GTV PET-CT (all P=1.000), all of which were significantly smaller than those of GTV ACT and GTV VCT (both P=0.001), and there was no statistically significant difference between GTV ACT and GTV VCT (both P=1.000). Based on the tumor extent shown by PET-CT (standardized uptake value =2.5), DSC were slightly higher and HD95 were slightly lower than conventional enhanced CT of GTV A40VM, GTV V40VM, GTV A40VMID, GTV V40VMIDvs. GTV PET-CT, respectively. When the arterial phase sequences were compared with PET-CT, pairwise comparison of Bonferroni correction showed that the DSC and HD95 of GTV A40VMvs. GTV PET-CT and GTV ACTvs. GTV PET-CT were statistically significant (both P<0.01), and the differences were not statistically significant among the remaining groups (all P>0.05). When intravenous phase sequences were compared with PET-CT, pairwise comparison of Bonferroni correction revealed that the DSC and HD95 of GTV V40VMIDvs. GTV PET-CT and GTV VCTvs. GTV PET-CT were statistically significant (both P<0.01), and the differences were not statistically significant among the remaining groups (all P>0.05). Conclusions:The use of 40 keV VMI-ID fusion images to outline the target area of the primary tumor lesions is closer to that of PET-CT, which provides a novel option for the precise outlining of the target area of clinical radiotherapy.

Objective:This study investigated the expression of C-X-C motif chemokine receptor 3 (CXCR3) on CD45RO? T cells in the peripheral blood of patients with Alzheimer′s disease (AD) and its association with clinical features.Methods:A total of 41 AD patients and 30 age-and sex-matched healthy controls (HCs) were recruited from the Department of Neurology at the Medical Division of PLA General Hospital between September 2022 and March 2024. Flow cytometry was used to quantify CXCR3 expression on CD45RO? T cell subsets in peripheral blood. Dementia severity in AD patients was assessed using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Spearman correlation analysis examined the relationship between CD45RO?CXCR3? T cell levels and cognitive function in the AD group. Receiver operating characteristic (ROC) curve analysis determined the predictive utility of CD45RO?CXCR3? T cells for AD, quantified by the area under the curve (AUC).Results:Compared to healthy controls, AD patients exhibited significantly elevated levels of CD8?CD45RO?CXCR3? T cells [17.8% (7.2%, 40.3%) vs. 8.2% (5.1%, 12.3%), Z=-2.59, P<0.05]. However, no significant differences were observed for CD4?CD45RO?CXCR3? T cells, CD4?CD45RO?CXCR3? T cells, or CD8?CD45RO?CXCR3? T cells ( P>0.05). Spearman correlation analysis revealed a negative correlation between CD8?CD45RO?CXCR3? T cell levels and cognitive scores (MMSE: r=-0.72, P<0.05; MoCA: r=-0.70, P<0.05). ROC analysis demonstrated an AUC of 0.81 for CD8?CD45RO?CXCR3? T cells in predicting AD, with a sensitivity of 59.0% and specificity of 93.3%. Conclusions:CXCR3 expression is significantly upregulated on CD8?CD45RO? T cells in AD patients, and its levels correlate with cognitive impairment severity. These findings suggest that CD8?CD45RO?CXCR3? T cells may serve as a potential biomarker for AD diagnosis and progression monitoring.

Objective:This study investigated the expression of C-X-C motif chemokine receptor 3 (CXCR3) on CD45RO? T cells in the peripheral blood of patients with Alzheimer′s disease (AD) and its association with clinical features.Methods:A total of 41 AD patients and 30 age-and sex-matched healthy controls (HCs) were recruited from the Department of Neurology at the Medical Division of PLA General Hospital between September 2022 and March 2024. Flow cytometry was used to quantify CXCR3 expression on CD45RO? T cell subsets in peripheral blood. Dementia severity in AD patients was assessed using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Spearman correlation analysis examined the relationship between CD45RO?CXCR3? T cell levels and cognitive function in the AD group. Receiver operating characteristic (ROC) curve analysis determined the predictive utility of CD45RO?CXCR3? T cells for AD, quantified by the area under the curve (AUC).Results:Compared to healthy controls, AD patients exhibited significantly elevated levels of CD8?CD45RO?CXCR3? T cells [17.8% (7.2%, 40.3%) vs. 8.2% (5.1%, 12.3%), Z=-2.59, P<0.05]. However, no significant differences were observed for CD4?CD45RO?CXCR3? T cells, CD4?CD45RO?CXCR3? T cells, or CD8?CD45RO?CXCR3? T cells ( P>0.05). Spearman correlation analysis revealed a negative correlation between CD8?CD45RO?CXCR3? T cell levels and cognitive scores (MMSE: r=-0.72, P<0.05; MoCA: r=-0.70, P<0.05). ROC analysis demonstrated an AUC of 0.81 for CD8?CD45RO?CXCR3? T cells in predicting AD, with a sensitivity of 59.0% and specificity of 93.3%. Conclusions:CXCR3 expression is significantly upregulated on CD8?CD45RO? T cells in AD patients, and its levels correlate with cognitive impairment severity. These findings suggest that CD8?CD45RO?CXCR3? T cells may serve as a potential biomarker for AD diagnosis and progression monitoring.

Objective:To investigate the application value of dual-layer detector spectral CT in the precise outlining of gross tumor volume (GTV) in lung cancer patients.Methods:Imaging data of 39 patients with pathologically confirmed lung cancer on dual-energy enhanced CT scans in Hebei Medical University Third Hospital were retrospectively analyzed. Among them, 13 patients were not complicated with lung atelectasis and 26 cases were complicated with lung atelectasis and 9 of them received positron emission computed tomography (PET-CT) scan. The virtual single-energy images of arterial and venous dual-phase 40 keV images were reconstructed with the spectral base images of Iqon dual-energy CT, and the GTV of the primary foci was outlined using the reconstructed images and conventional enhanced CT images. The GTV outlined by conventional enhanced CT image, 40 keV virtual monoenergetic (VM) CT image, 40 keV VM-iodine density (VM-ID) fusion image in the arterial phase, conventional enhanced CT image, 40 keV VM image and 40 keV VM-ID image in the venous phase and PET-CT image was defined as GTV ACT, GTV A40VM, GTV A40VMID, GTV VCT, GTV V40VM, GTV V40VMID and GTV PET-CT, respectively. The consistency of target area outlining was assessed by calculating the GTV volume, the Dice similarity coefficient (DSC), and the 95 th percentile of the Hausdorff distance (HD95). Pairwise comparison among groups was conducted by Friedman test and corrected by Bonferroni correction. Results:In GTV comparisons, the differences in GTV ACT, GTV VCT, GTV A40VM and GTV V40VM in patients without pulmonary atelectasis were not statistically significant ( χ2=1.89, P=0.595). The DSC and HD95 of GTV ACTvs. GTV A40VM were 0.96 and 3.00, and the DSC and HD95 of GTV VCTvs. GTV V40VM were 0.94 and 2.93, respectively. The differences in GTV ACT, GTV A40VM, GTV A40VMID, GTV VCT, GTV V40VM, GTV V40VMID and GTV PET-CT in patients complicated with pulmonary atelectasis were statistically significant (all P<0.001). Pairwise comparison of Bonferroni correction showed that there was no statistically significant difference in GTV A40VM, GTV A40VMID, GTV V40VM, GTV V40VMID and GTV PET-CT (all P=1.000), all of which were significantly smaller than those of GTV ACT and GTV VCT (both P=0.001), and there was no statistically significant difference between GTV ACT and GTV VCT (both P=1.000). Based on the tumor extent shown by PET-CT (standardized uptake value =2.5), DSC were slightly higher and HD95 were slightly lower than conventional enhanced CT of GTV A40VM, GTV V40VM, GTV A40VMID, GTV V40VMIDvs. GTV PET-CT, respectively. When the arterial phase sequences were compared with PET-CT, pairwise comparison of Bonferroni correction showed that the DSC and HD95 of GTV A40VMvs. GTV PET-CT and GTV ACTvs. GTV PET-CT were statistically significant (both P<0.01), and the differences were not statistically significant among the remaining groups (all P>0.05). When intravenous phase sequences were compared with PET-CT, pairwise comparison of Bonferroni correction revealed that the DSC and HD95 of GTV V40VMIDvs. GTV PET-CT and GTV VCTvs. GTV PET-CT were statistically significant (both P<0.01), and the differences were not statistically significant among the remaining groups (all P>0.05). Conclusions:The use of 40 keV VMI-ID fusion images to outline the target area of the primary tumor lesions is closer to that of PET-CT, which provides a novel option for the precise outlining of the target area of clinical radiotherapy.

Objective To introduce a partially nested design based on the characteristics of TCM in treating the same disease with different treatments and syndrome differentiation and treatment.Methods Partially nested design was used for standardized treatment of complex interventions.The TCM group was divided into multiple subsets according to"syndrome type-treatment method-prescription"(with nested structure),while the control group was treated with standardized Western medicine(without nested structure);taking a case study of"different treatments for the same disease"data for ulcerative colitis,this design type was applied and analyzed using a multi-level model.Results The partially nested design was consistent with the feature of TCM of"different treatments for the same disease"and met the methodological requirements for evidence-based evaluation.Multilevel models allowed analyses with this type of data.Conclusion The use of partially nested design enables the evaluation of the comprehensive effectiveness of"different treatments for the same disease",which can provide a methodological reference for the assessment of clinical effectiveness of TCM.

Objective:To evaluate the effect of the impaction of posterior wall on the prognosis following open reduction and internal fixation for fractures of acetabular posterior wall.Methods:A retrospective study was conducted to analyze the data from the 83 patients with fracture of acetabular posterior wall who had been consecutively treated by open reduction and internal fixation at Department of Orthopaedics and Traumatology, Beijing Jishuitan Hospital from January 2017 to December 2020. The patients were divided into 2 groups based on involvement of posterior wall impaction. In the impaction group of 33 cases, there were 26 males and 7 females with an age of (47.4±11.6) years; in the non-impaction group of 50 cases, there were 43 males and 7 females with an age of (41.3±12.0) years. The quality of postoperative fracture reduction, the function of the affected hip at the last follow-up, and the complication rate during follow-up were compared between the 2 groups. Multifactorial binary logistic regression and age subgroups were used to analyze the effects of posterior wall impaction on functional outcomes.Results:The age, rate of associated injuries in other body parts, and rate of posterior wall comminution in the impaction group were significantly higher than those in the non-impaction group ( P<0.05), but there was no statistically significant difference in other general data of patients between the 2 groups ( P>0.05). All patients were followed up for (44.5±13.3) months after surgery. The rate of anatomical reduction in the non-impaction group (96.0%, 48/50) was significantly higher than that in the impaction group (57.6%, 19/33) ( P<0.05), and the good and excellent rate by the modified Merle d'Aubigné & Postel scale at the last follow-up in the non-impaction group (84.0%, 42/50) was significantly higher than that in the impaction group (51.5%, 17/33) ( P<0.05). There was no significant difference in the incidence of complications between the 2 groups ( P>0.05). After adjusting for age and gender, the difference in hip function was still significantly different between the 2 groups ( OR=0.23, 95% CI: 0.06 to 0.79, P=0.020). The effect of posterior wall impaction on functional outcomes was statistically significant in patients aged ≥50 years ( P=0.008), whereas the difference was not statistically significant in patients aged <50 years ( P=0.194). Conclusions:Compared with non-impaction ones, acetabular fractures of posterior wall impaction tend to lead to poorer quality of reduction, which in turn affects the postoperative recovery of hip joint function. The impact of impaction fractures on functional recovery is more significant in patients aged 50 years and above.

OBJECTIVE To observe the effect of Qiai(Artemisia argyi Levl.et Van.var.argyi cv.Qiai)essential oil on the healing of infected skin wounds and explore its mechanism.METHODS 30 Kunming mice were randomly divided into five equal groups:blank control group,substrate group,positive control group(3 mL·kg-1 Mupirocin ointment),low-dose group(each patch containing 7.3 mg of Qiai essential oil),and high-dose group(each patch containing 57.6 mg of Qiai essential oil).After anesthe-sia,a 10 mm full-thickness circular skin wound was created on the back of each mouse.Following hemostasis,100 μL of Staphylococ-cus aureus bacterial solution(1.5×108 CFU·mL-1)was applied to the wound.The wounds in each group were treated in the afore-mentioned manner,the dressing was changed daily,and the healing of the skin wound was observed.On the 12th day post-surgery,the mice were euthanized and the skin around the wounds was collected for HE and Masson staining to observe pathological features;qPCR and Western blotting were used to detect the expression of genes related to wound healing(Col1a1,Col3a1,Fn1,VEGFA),in-flammatory factors(IL-1β,IL-6,TNF-α),and the PI3K/Akt signaling pathway in the wound skin tissue.Further,in NIH-3T3 mouse embryonic fibroblasts,the potential impact of Artemisia argyi volatile oil on PI3K/Akt signaling pathway activity was investigated using the PI3K inhibitor PI-103.RESULTS Animal experiments have shown that compared to the blank control group,the relative wound area in both the low-dose and high-dose groups significantly decreased;the infiltration of inflammatory cells in the wound tis-sues reduced,while the expression of collagen fibers increased;qPCR showed that,compared to the blank control group,the expres-sion of VEGFA,Col3a1,and Col1a1 in the low-dose and high-dose groups significantly increased,while the expression of inflamma-tory factors IL-1β and TNF-α decreased;further Western blotting revealed that compared to the blank control group,both the phos-phorylated PI3K/total PI3K ratio and the phosphorylated Akt/total Akt ratio in the low-dose and high-dose groups significantly in-creased in a dose-dependent manner.Cellular experimental results also confirmed that the volatile oil from Artemisia argyi exerts a reg-ulatory effect on the PI3K/Akt signaling pathway in NIH-3T3 cells.CONCLUSION The essential oil of Qiai can promote wound healing,with its mechanism possibly involving the activation of the PI3K/Akt signaling pathway,suppression of inflammatory factor ex-pression,and promotion of collagen expression.

BACKGROUND:Trauma-induced coagulopathy(TIC)due to serious injuries significantly leads to increased mortality and morbidity among elderly patients.However,the risk factors of TIC are not well elucidated.This study aimed to explore the risk factors of TIC in elderly patients who have major trauma. METHODS:In this retrospective study,the risk factors for TIC in elderly trauma patients at a single trauma center were investigated between January 2015 and September 2020.The demographic information including gender,age,trauma parts,injury severity,use of blood products,use of vasopressors,need of emergency surgery,duration of mechanical ventilation,length of stay in the intensive care unit(ICU)and hospital,and clinical outcomes were extracted from electric medical records.Multivariate logistic regression analysis was performed to differentiate risk factors,and the performance of the model was evaluated using receiver operating characteristics(ROC)curves. RESULTS:Among the 371 elderly trauma patients,248(66.8%)were male,with the age of 72.5±6.8 years,median injury severity score(ISS)of 24(IQR:17-29),and Glasgow coma score(GCS)of 14(IQR:7-15).Of these patients,129(34.8%)were diagnosed with TIC,whereas 242(65.2%)were diagnosed with non-TIC.The severity scores such as ISS(25[20-34]vs.21[16-29],P<0.001)and shock index(SI),(0.90±0.66 vs.0.58±0.18,P<0.001)was significantly higher in the TIC group than in the non-TIC group.Serum calcium levels(1.97±0.19 mmol/L vs.2.15±0.16 mmol/L,P<0.001),fibrinogen levels(1.7±0.8 g/L vs.2.8±0.9 g/L,P<0.001),and base excess(BE,-4.9±4.6 mmol/L vs.-1.2±3.1 mmol/L,P<0.001)were significantly lower in the TIC group than in the non-TIC group.Multivariate logistic regression analysis revealed that ISS>16(OR:3.404,95%CI:1.471-7.880;P=0.004),SI>1(OR:5.641,95%CI:1.700-18.719;P=0.005),low BE(OR:0.868,95%CI:0.760-0.991;P=0.037),hypocalcemia(OR:0.060,95%CI:0.009-0.392;P=0.003),and hypofibrinogenemia(OR:0.266,95%CI:0.168-0.419;P<0.001)were independent risk factors for TIC in elderly trauma patients.The AUC of the prediction model included all these risk factors was 0.887(95%CI:0.851-0.923)with a sensitivity and specificity of 83.6%and 82.6%,respectively. CONCLUSION:Higher ISS(more than 16),higher SI(more than 1),acidosis,hypocalcemia,and hypofibrinogenemia emerged as independent risk factors for TIC in elderly trauma patients.

BACKGROUND:Trauma-induced coagulopathy(TIC)due to serious injuries significantly leads to increased mortality and morbidity among elderly patients.However,the risk factors of TIC are not well elucidated.This study aimed to explore the risk factors of TIC in elderly patients who have major trauma. METHODS:In this retrospective study,the risk factors for TIC in elderly trauma patients at a single trauma center were investigated between January 2015 and September 2020.The demographic information including gender,age,trauma parts,injury severity,use of blood products,use of vasopressors,need of emergency surgery,duration of mechanical ventilation,length of stay in the intensive care unit(ICU)and hospital,and clinical outcomes were extracted from electric medical records.Multivariate logistic regression analysis was performed to differentiate risk factors,and the performance of the model was evaluated using receiver operating characteristics(ROC)curves. RESULTS:Among the 371 elderly trauma patients,248(66.8%)were male,with the age of 72.5±6.8 years,median injury severity score(ISS)of 24(IQR:17-29),and Glasgow coma score(GCS)of 14(IQR:7-15).Of these patients,129(34.8%)were diagnosed with TIC,whereas 242(65.2%)were diagnosed with non-TIC.The severity scores such as ISS(25[20-34]vs.21[16-29],P<0.001)and shock index(SI),(0.90±0.66 vs.0.58±0.18,P<0.001)was significantly higher in the TIC group than in the non-TIC group.Serum calcium levels(1.97±0.19 mmol/L vs.2.15±0.16 mmol/L,P<0.001),fibrinogen levels(1.7±0.8 g/L vs.2.8±0.9 g/L,P<0.001),and base excess(BE,-4.9±4.6 mmol/L vs.-1.2±3.1 mmol/L,P<0.001)were significantly lower in the TIC group than in the non-TIC group.Multivariate logistic regression analysis revealed that ISS>16(OR:3.404,95%CI:1.471-7.880;P=0.004),SI>1(OR:5.641,95%CI:1.700-18.719;P=0.005),low BE(OR:0.868,95%CI:0.760-0.991;P=0.037),hypocalcemia(OR:0.060,95%CI:0.009-0.392;P=0.003),and hypofibrinogenemia(OR:0.266,95%CI:0.168-0.419;P<0.001)were independent risk factors for TIC in elderly trauma patients.The AUC of the prediction model included all these risk factors was 0.887(95%CI:0.851-0.923)with a sensitivity and specificity of 83.6%and 82.6%,respectively. CONCLUSION:Higher ISS(more than 16),higher SI(more than 1),acidosis,hypocalcemia,and hypofibrinogenemia emerged as independent risk factors for TIC in elderly trauma patients.