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 causal association between 91 kinds of circulating inflammatory proteins and different subtypes of breast cancer(estrogen receptor-positive and-negative breast cancer)using a two-sample Mendelian randomization(MR)method.Methods Corresponding exposure and outcome data were extracted from the genome-wide association study database.The data were analyzed by two-sample MR with inverse-variance weighting(IVW)as the primary study method,and MR-Egger,weighted median,simple mode,and weighted mode were used to complement the results.The results were complemented by sensitivity analysis to verify the reliability of the data.Results The IVW results showed that SULT1A1(P=0.0007)was associated with an increased risk of total BC,whereas IL-5(P=0.0011)was associated with a decreased risk of total BC.SULT1A1(P=0.0011)and CX3CL1(P=0.0005)were associated with an increased risk of ER+BC,whereas beta-NGF(P=0.0001)was associated with an increased risk of ER-BC.Supplem-entary analysis methods validated that the findings were consistent in direction and magnitude.The results of the sensitivity analysis showed that the data were reliable and unbiased.Conclusion Using the MR method,this study confirms that SULT1A1 is a risk factor for overall breast cancer,whereas IL-5 is a protective factor for overall breast cancer.SULT1A1 and CX3CL1 are risk factors for estrogen receptor-positive breast cancer,and beta-NGF is a risk factor for estrogen receptor-negative breast cancer.

OBJECTIVE To screen and identify the differential substance bases of Pinellia ternate and its different concoctions,conduct network pharmacological analysis on the common and differential substance bases,and explore the relationship between the substance bases and the changes in the efficacy of Pinellia ternate before and after concoction based on the UPLC-Q-TOF-MS/MS and multivariate statistical analysis.METHODS The main substance bases of 42 batches of samples were examined by UPLC-Q-TOF-MS/MS,and the differential components were screened by orthogonal partial least squares discriminant analysis(OPLS-DA)with VIP>1.5,P<0.01 and FC>2 or<0.5 as the screening criteria.The targets were further retrieved from the TCMIP database,and their protein interactions were analysed by GO enrichment and KEGG enrichment to visualise the"herbal-component-target-pathway"map.RESULTS Compared with Pinellia ternate,Pinelliae Rhizoma Praeparatum has 14 different components,mainly glycyrrhetinic acid,glycyrrhizic acid and glycyrrhizin,etc.The components with reduced content were mainly amides.There were 18 differential constituents between raw and ginger,mainly nucleosides,flavonoids and amino acids.The content of guanosine,xanthine and tyrosine was reduced,while the content of adenosine monophosphate was increased.There were 18 differential components between raw and Pinelliae Rhizoma Praeparatum Cum Alumine,and the relative content of many components in Pinelliae Rhizoma Praeparatum Cum Alu-mine was reduced,such as sphingomyelin.Further,the TCMIP database was used to retrieve targets from the differential substance base,and protein interaction analysis was performed on the targets,resulting in 67 core targets for Pinellia ternate,45 core targets for Pinelliae Rhizoma Praeparatum,and 38 core targets for Pinelliae Rhizoma Praeparatum cum Zingibere Et Alumine.Finally,the meta-bolic pathways were analyzed by GO enrichment and KEGG enrichment.CONCLUSION The UPLC-Q-TOF-MS/MS method estab-lished in this experiment can better isolate and identify the chemical components in Pinellia ternate.Combined with multivariate statisti-cal analysis and network pharmacology,the material basis and potential mechanism of action of Pinellia ternate and its concoction prod-ucts can provide ideas for the study of the action targets and provide data support for the rational clinical application of Pinellia ternate and its concoction products.

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.

Objective:To observe alterations in center retinal thickness (CRT) in patients diagnosed with central retinal artery occlusion (CRAO) before and after undergoing superselective arterial thrombolysis (IAT) treatment.Methods:A retrospective clinical study. From August 2022 to September 2023, 12 patients (12 eyes) diagnosed with CRAO and treated with IAT at the ophthalmology department of Shenzhen Second People's Hospital. Among these patients, there were 8 males (8 eyes) and 4 females (4 eyes), all experiencing unilateral onset. The mean age was (47.00±15.06) years. The mean duration from onset to thrombolysis was (30.00±30.42) h. All eyes underwent best corrected visual acuity (BCVA) and optical coherence tomography (OCT) assessments; additionally, 6 eyes underwent Fluorescein fundus angiography (FFA). BCVA assessments were conducted using a standard logarithmic chart and transformed into logarithm of the minimum angle of resolution (logMAR) values for statistical analysis. The OCT measured CRT at various locations around the macular fovea (M), including upper (S1, S3), lower (I1, I3), nasal (N1, N3), and temporal (T1, T3) areas at 1 mm and 3 mm distances from the fovea. CRT was defined as the vertical distance between the inner retinal boundary membrane and the inner interface of the retinal pigment epithelial layer. Pre- and post-IAT examinations were performed using the same equipment and methodologies within a 24-hour interval. Changes in CRT at different macular points were compared and observed, while arterial imaging time changes were assessed in 6 eyes that underwent FFA. Paired t-tests were utilized to analyze logMAR BCVA, CRT at different locations, and arterial imaging time pre- and post-treatment. Results:Prior to IAT treatment, the logMAR BCVA for the affected eye was 3.48±1.42, while the arterial imaging time for the 6 eyes undergoing FFA examination was (27.50±5.47) s. After 24 hours, the logMAR BCVA had improved to 2.35±1.59 for the affected eye, with 9 eyes showing varying degrees of BCVA improvement. The arterial imaging time was (24.17±7.28) s post-treatment. The differences in logMAR BCVA and arterial imaging time before and after treatment were found to be statistically significant ( t=2.489, 3.262; P<0.05). Additionally, the comparison of CRT at S3 ( t=2.871), I1 ( t=2.325), and T3 ( t=3.446) before and after treatment yielded statistically significant differences ( P<0.05). Conversely, the comparison of CRT at S1 ( t=1.879), I3 ( t=1.915), N1 ( t=2.001), N3 ( t=1.987), T1 ( t=2.180), and M ( t=-0.490) showed no statistically significant differences ( P>0.05). Conclusions:IAT treatment for CRAO has been shown to be effective in achieving therapeutic effects by reducing CRT in the macular area. However, the short-term improvement in retinal edema in the macular area is limited.

Objective To evaluate the effectiveness of internet-based decision aids(DA)in colorectal cancer screening.Methods Randomized controlled trials of efficacy of internet-based DA in colorectal cancer screening were searched by computer from CNKI,Wanfang Data,VIP,CBM,PubMed,the Cochrane Library,Embase and Web of Science.The retrieval period was from the establishment of the database to June 2023.Descriptive analysis was used to analyze the main contents and summarize their clinical application effects.Results A total of 12 literatures were included,including 6038 subjects,of which 3089 were in experimental group and 2949 were in control group.The results showed that the contents of internet-based DA mainly included basic information support,benefits and risks of colorectal cancer screening,and clarification of patients'personal values.It could help patients enhance screening willingness,improve informed decision-making ability,reduce decision-making conflicts,and promote the positive role of patients in decision-making.Patients have higher satisfaction with internet-based DA.Conclusion Internet-based DA has shown positive results in the application of colorectal cancer screening,and has unique advantages over the traditional paper version of the manual,but it still has certain limitations.In the future,we can learn from the relevant theoretical achievements of foreign decision-making assistance,research and develop a more comprehensive DA for colorectal cancer screening combined with China's national conditions.

Objective:To provide evidence-based recommendations for the prevention and management of lower limb ischemia in veno-arterial extracorporeal membrane oxygenation (VA-ECMO) patients during treatment according to search, evaluate, and summarize the best evidence on the prevention and management of lower limb ischemia in patients with VA-ECMO.Methods:Based on the PIPOST framework (population, intervention, professional, outcome, setting, and type of evidence), an evidence-based question was formulated. A systematic search was conducted according to the "6S" evidence pyramid model in both domestic and international databases, as well as professional association websites, for all evidence related to the prevention and management of lower limb ischemia in VA-ECMO patients (aged ≥18 years). The types of evidence included clinical decisions, guidelines, expert consensus, systematic reviews, evidence summaries, and original studies. The search was conducted from the construction of the databases to February 2024. Two researchers independently conducted a literature quality evaluation, extracted and summarized evidence from the studies that met the quality criteria.Results:A total of 13 articles were included, consisting of 3 clinical decisions, 3 guidelines, 3 expert consensus, 3 systematic reviews, and 1 randomized controlled trial. A total of 18 pieces of evidence in 7 dimensions were summarized, including risk factors of VA-ECMO lower limb ischemia, evaluation before catheterization, evaluation and monitoring during treatment, prevention of lower limb ischemia, treatment of lower limb ischemia, management of distal perfusion catheter (DPC), and monitoring after VA-ECMO weaning.Conclusion:This evidence summary provides evidence-based recommendations for the prevention and management of lower limb ischemia in VA-ECMO patients, aiming to assist clinical healthcare professionals in developing tailored strategies for the prevention and management of lower limb ischemia based on during VA-ECMO support.

Oral squamous cell carcinoma(OSCC)is a malignant tumor with a high mortality rate,which is characterized by late diag-nosis,high recurrence and metastasis rates,and poor prognosis.Cuproptosis,as a novel mode of cupric induced cell death,can inhibit the growth and proliferation of cancer cells by activating related pathways,which provides a new insight into the treatment of OSCC.This review aims to systematically introduce the mechanism of cuproptosis occurrence and development,as well as the research progress of cuproptosis in the prognosis of OSCC treatment.It provides new ideas and methods for clinical treatment.

Objective To investigate the correlation between rs712 and rs7973450 located at the 3'UTR region of the KRAS gene and the risk of cervical cancer(CC)and cervical intraepithelial neoplasia(CIN)in Chinese Han population in Yunnan province.Methods A total of 2405 individuals(461 subjects with CIN,961 subjects with CC and 983 healthy controls)were enrolled.The SNPs were genotyped used TaqMan assay and the correlation of these SNPs with CIN and CC was analyzed.Results The A allele of rs7973450 might be a protective factor for the occurrence of CIN(P = 0.004,OR= 0.651,95%CI 0.487～0.871)and CC(P = 7.00×10-4,OR= 0.667,95%CI 0.529～0.844).There was no significant difference in allelic and genotypic distribution of rs712 among CIN,CC and Control groups(P>0.017).The haplotype assay showed thatrs712A-rs7973450G was associated with increased risk of CIN(P = 4.00×10-4;OR= 1.714,95%CI 1.269～2.314)and CC(P = 3.84×10-5,OR= 1.667,95%CI 1.305～2.131).While haplotype rs712A-rs7973450A was associated with a lower risk of CC(P = 0.012,OR= 0.790,95%CI 0.658～0.950).Conclusion The A allele of rs7973450 in 3'UTR of KRAS gene might be the protective factor for the occurrence of CIN and CC in a Chinese Han population in Yunnan province.

AIM:To test and compare the perceptual eye position and fixation stability of adolescents with emmetropia and adolescents with low myopia, investigating the characteristics of the perceptual eye position and fixation stability of adolescents with low myopia.METHODS: Cross-sectional study. A total of 132 adolescents(264 eyes)who visited in the ophthalmology clinic of our hospital from April to December 2023 were randomly selected as the research subjects. Participants were categorized into normal control group(n=45, 90 eyes), simple low myopia group(n=45, 90 eyes)and low myopia with anisometropia group(n=42, 84 eyes)according to their refractive status and were underwent assessments for perceptual eye position and fixation stability.RESULTS: Compared with the normal control group, the static and dynamic horizontal perceptual eye position deviation of the simple low myopia group and the low myopia with anisometropia group were significantly increased(P<0.05). Compared with the simple low myopia group, the static and dynamic horizontal perceptual eye position deviation of the low myopia with anisometropia group were significantly increased(P<0.05). There was no significant difference in static and dynamic vertical perceptual eye position deviation among the three groups(P>0.05); compared with the normal control group, the horizontal and vertical fixation stability of the simple low myopia group and the low myopia with anisometropia group were significantly worse(all P<0.01), but there was no differences in the simple low myopia group and the low myopia with anisometropia group(P >0.05).CONCLUSION: Abnormalities are observed in perceptual eye position and fixation stability function in adolescents with low myopia compared with those adolescents with emmetropia, even at best corrected visual acuity. The occurrence of anisometropia could lead to an increased degree of horizontal perceptual eye position displacement.