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 doseresponse relationship between the risk of elevated blood pressure and body mass index (BMI) in primary and secondary school students in Shibei District, Qingdao, so as to provide a reference for precise interventions of elevated blood pressure. Methods: Statistical analysis was conducted on the health examination data of 92 091 primary and secondary school students in Shibei District, Qingdao, in 2022. Overweight and obesity were assessed using the standards from the Screening for Overweight and Obesity among Schoolaged Children and Adolescents, and blood pressure levels were evaluated using the Reference of Screening for Elevated Blood Pressure among Children and Adolescents Aged 7-18 Years. The relationship between BMI and elevated blood pressure was examined using analysis of variance, Chisquare test, multifactorial Logistic regression, and a combination of restricted cubic spline after data cleaning. Results: Based on the standardized scores under different age and gender, BMI was classified into 5 categories. Compared with the group of BMIZ scores 0-<1, the risk of developing high blood pressure gradually decreased with BMIZ scores (OR=0.55, 0.53, P<0.05). Conversely, the risk of developing high blood pressure increased with increasing BMIZ scores (OR=1.90, 3.71, P<0.05). Stratified analyses showed that BMI was positively associated with elevated blood pressure by gender (male, female), age (aged 7-8, 9-11, 12-14, 15-16), and waisttohip ratio (≤0.83, >0.83) (OR=1.18, 1.19, 1.15, 1.22, 1.19, 1.18, 1.19, 1.18, P<0.01). There were multiplicative interactions between BMI and gender, between BMI and age, between BMI and waisttohip ratio (OR=1.53, 1.08, 2.31, P<0.01). Restricted cubic spline analysis showed that as BMI levels increased, the risk of developing elevated blood pressure showed a nonlinear increasing trend in both the 7yearold and the 10 to 16yearold (χ2=27.56, 10.69, 6.10, 27.26, 18.32, 25.71, 10.53, 6.14, P<0.05). Conclusions The risk of elevated blood pressure in primary and secondary school students increases with BMI, showing a nonlinear doseresponse relationship. The blood pressure should be monitored regularly, and comprehensive and effective measures should be implemented to control elevated blood pressure in children and adolescents.

BACKGROUND:With the increase of patients with cubital tunnel syndrome,ulnar groove plasty does not affect the normal anatomical structure and distribution of the ulnar nerve,which is one of the main surgical procedures for the treatment of cubital tunnel syndrome.3D printing combined with ulnar groove plasty can more accurately position the expansion depth and width of the ulnar groove to avoid some surgical complications. OBJECTIVE:To investigate the effect of 3D printing technology combined with ulnar groove plasty on nerve electrophysiology and prognosis in patients with cubital tunnel syndrome. METHODS:A total of 70 patients with moderate and severe cubital tunnel syndrome who were treated in Cangzhou Integrated Traditional Chinese and Western Medicine Hospital from March 2020 to March 2022 were selected as the study subjects.They were divided into two groups,with 35 cases in each group.The control group underwent traditional ulnar groove plasty.The observation group underwent 3D printing technology combined with ulnar groove plasty.The patients were followed up for 3 months.The clinical efficacy,latency,amplitude of compound muscle action potential of abductor pollicis brevis of the affected limb and ulnar nerve motor conduction velocity,grip strength on the affected side,pinch strength of the middle and thumb fingers,S-W monofilament of the little finger,two-point discrimination of the little finger,and Disabilities of the Arm,Shoulder and Hand Questionnaire score were compared between the two groups. RESULTS AND CONCLUSION:(1)Compared with the control group(74%),the excellent and good rate was significantly higher in the observation group(91%)(P<0.05).(2)Compared with pre-treatment,the latency of compound muscle action potential of abductor pollicis brevis of affected limb was significantly shorter and the wave amplitude and ulnar nerve motor conduction velocity were significantly higher in the two groups after treatment.The latency was significantly shorter and the wave amplitude and ulnar nerve motor conduction velocity were significantly higher in the observation group than those in the control group(P<0.05).(3)Compared with pre-treatment,the grip strength,middle finger and thumb pinch strength of the affected side,S-W monofilament of the little finger and two-point discrimination of the little finger were significantly decreased in the two groups after treatment.The grip strength,middle finger and thumb pinch strength on the affected side were greater,S-W monofilament of the little finger and two-point discrimination of the little finger were significantly smaller in the observation group than those in the control group(P<0.05).(4)Compared with pre-treatment,the Disabilities of the Arm,Shoulder and Hand Questionnaire scores of the two groups were significantly reduced after treatment,and the Disabilities of the Arm,Shoulder and Hand Questionnaire scores of the observation group were significantly lower than those of the control group(P<0.05).(5)It is concluded that 3D printing technology combined with ulnar groove plasty in the treatment of cubital tunnel syndrome can effectively improve its clinical efficacy,promote the neurophysiological recovery of patients,and enhance the function of fingers and upper limbs,which has high clinical application value.

Objective To investigate the correlation of triacylglycerol glucose(TyG)index,monocyte to high-density lipoprotein cholesterol ratio(MHR)with coronary artery disease and myocardial ischemia degree in coronary heart disease(CHD),and to analyze the two Predictive value of coronary artery disease and myocardial ischemia degree.Methods CHD patients from the 920th Hospital of the Chinese People's Liberation Army Joint Logistics Support Force from January 2019 to January 2022 were selected as the study group(n = 150),and healthy physical examination subjects from the same period were selected as the control group(n = 75).The TyG index and MHR of the two groups were compared and analyzed.The extent of coronary artery disease was evaluated based on the Gensini score,and the TyG index and MHR of patients with different coronary lesions and myocardial ischemia were compared,and their correlation with Gensini score and myocardial ischemia was analyzed.The predictive value of TyG index,MHR,and the combined detection of both for coronary lesions and myocardial ischemia was evaluated using receiver operating characteristic(ROC)curves and area under the curve(AUC).Results The TyG index and MHR of the study group were(4.12±0.35)and(0.26±0.08)×109,respectively,which were higher than those of the control group(4.94±0.55)and(0.43±0.12)×109,and the TyG index and MHR of severe coronary artery disease>moderate coronary artery disease>mild coronary artery disease,acute myocardial infarction TyG index,MHR>unstable angina pectoris>stable angina pectoris(P<0.05);TyG index and MHR were positively correlated with Gensini score(r = 0.621,0.635,P<0.05),and positively correlated with the severity of myocardial ischemia(r = 0.617,0.642,P<0.05).The AUC of TyG index and MHR for the joint identification of mild coronary artery disease and moderate coronary artery disease was 0.917,which was greater than the AUCs of 0.749 and 0.832 for the two conditions individually.The AUC of TyG index and MHR for the joint identification of mild to moderate coronary artery disease and severe coronary artery disease was 0.935,which was greater than the AUCs of 0.770 and 0.767 for the two conditions individually(P<0.05).The AUC of TyG index and MHR for the joint identification of stable angina pectoris and unstable angina pectoris was 0.922,which was greater than the AUCs of 0.812 and 0.824 for the two conditions individually.The AUC of TyG index and MHR for the joint identification of stable angina pectoris,unstable angina pectoris,and acute myocardial infarction was 0.913,which was greater than the AUCs of 0.708 and 0.714 for the two conditions individually(P<0.05).Conclusions TyG index and MHR are positively correlated with Gensini score and myocardial ischemia degree.The combined detection of the two has a higher application value in the evaluation of coronary artery disease and myocardial ischemia degree.

Objective:To investigate the relationship between the in vivo metabolic ratio (MR) of Aripiprazole (ARI) and CYP2D6 gene polymorphism in children with tic disorders (TD) and its effect on dose-exposure (DE), so as to promote precision drug use. Methods:In this study, a real-world observational study design was used to collect 81 children with TD who visited the Department of Neurology of Wuhan Children′s Hospital from January 2021 to January 2024, the concentration of the prototype drug and the main metabolite Dehydroaripiprazole (DARI), the detection data of CYP2D6 single nucleotide gene polymorphism (SNP) and clinical data were collected, and the relationship between the DARI/ARI metabolic ratio (MR) and CYP2D6 metabolic type was analyzed by the receiver operating characteristic (ROC) curve.A DE model between ARI dose and steady-state trough concentration was established by population modeling, and the effects of CYP2D6 metabolic type, MR and body weight on DE were analyzed.Goodness-of-fit diagram (GOF), visual predictive check (VPC) and prediction error analysis were used to verify the prediction performance of the DE model.Results:ROC analysis showed that there was a correlation between MR and CYP2D6 metabolic type, the MR sensitivity cut-point of CYP2D6 ultrafast metabolic (UM) patients was 0.399, and the cut-point of MR in intermediate metabolic (IM) patients was 0.252.Based on this, the patients were divided into three categories: MR TYPE Ⅰ: MR≥0.399, MR TYPE Ⅱ: 0.252

In traditional clinical teaching of impacted tooth extraction, there are problems including limited observation fields for students, insufficient doctor-patient communication training, inadequate clinical thinking development, and low levels of clinical participation. Based on the core elements of visualizing jaw structure with perspective, formulating clinical strategy, immersing in clinical participation, and cultivating the spirit of caregiving, we developed a virtual reality simulation teaching platform for the clinical decision analysis of impacted tooth extraction. The virtual simulation-based platform can create three different impacted tooth scenarios in 3D, which demonstrates the process of clinical decision analysis of impacted tooth extraction through virtuality-reality interaction, allowing students to immerse in the discovery, analysis, and resolution of the medical and humanistic problems in the process of impacted tooth extraction. The questionnaire survey showed that 81.36% (48/59) of the students believed that the software could improve their clinical thinking ability; 76.27% (45/59) of the students believed that it could help them master the basic process of impacted tooth extraction; and 62.71% (37/59) of the students believed that it could improve their skills of impacted tooth extraction. By providing immersive learning experience, constructive teaching design, and multi-dimensional teaching evaluation, the software achieved the goals of cultivating students' clinical thinking ability and professional literacy in oral and maxillofacial surgery.

Objective:To investigate the enrollment scale and distribution of Master's Degree in Pediatrics programs in China, and to provide a reference for promoting pediatric education and disciplinary development.Methods:Data on colleges and universities authorized to award Master's Degree in Pediatrics in 2023 were collected, sorted, and analyzed for the number, structure, distribution, and enrollment scale and direction of these institutions using descriptive statistics.Results:Among the 117 clinical medicine academic master's degree programs in China, 72 enroll pediatric academic master's degree candidates, with an enrollment of 260 students. Among the 120 master's degree programs in clinical medicine, 104 enroll professional master's degree candidates, enrolling 1 195 students. Enrollment is mainly concentrated in East China, "non-double first-class" colleges and universities, medical colleges and universities with subject level B, and enrollment is carried out in the direction of secondary disciplines.Conclusions:The number of colleges and universities authorized to award Master's Degree in Pediatrics was small, and the distribution of these colleges and universities was unbalanced. The enrollment scale was small and the orientation of Professional Master's Degree was not reasonable. Some colleges and universities were authorized to award Master's Degree in Pediatrics, but did not enroll any students. It is suggested to increase the number of colleges and universities authorized to award Master's Degree in Pediatrics and strengthen the staffing of pediatric departments. The aim is to expand the enrollment scale of candidates for Master's Degree in Pediatrics, improving the differential training of candidates for Academic Master's Degree and Professional Master's Degree, and attach importance to the construction of pediatrics.

Objective To provide alternative delivery methods of novel oral antitumor drugs for patients with dysphagia.Methods The retrieval range was determined according to the"Guidelines for Clinical Application of Novel Antitumor Drugs(2022 edition)".By consulting the instructions and searching databases such as PubMed,Micromedex,UpToDate,etc.,the preparation,stability,storage,and related clinical information of temporary liquid drug formulations were obtained.Results Seventy novel oral anticancer drugs were included in the literature search.Thirty-three drugs had relevant literature or data supporting alternative administration methods,only eight had information on alternative administration in the instructions,and the level of evidence for other drugs varied.Conclusion The evidence levels were low for most temporary liquid formulations,and medical teams should fully consider the advantages and disadvantages of using these products outside the instructions and use them with caution.

Objective To analyze the influence of shaping on the bending strength of bone plates and the influence of different locking nail distributions on plate force to provide biomechanical references for shaping plates and selecting different locking nail distributions.Methods Finite element simulation analysis of the four-point bending strength of a plate was performed according to the YY/T 0342-2020 standard.Theoretical analysis and finite element simulation method were used to analyze the force on prosthesis models with different lock-nail distributions.Results At 30° bending,the 3.7 mm-thick plate had 28%higher equivalent plastic strain than the 2.7 mm-thick plate.The 3.7 and 2.7 mm-thick plates had ultimate bending angles of 55° and 67°,respectively.The crease had little impact on the plate stress.The four-point bending strength and equivalent bending stiffness of the unshapeed structure were 2.64 N·m and 1.12 N·m2,respectively.The four-point bending strength and equivalent bending stiffness with the crease were 2.63 N·m and 1.10 N·m2,respectively.After forward and backward bending,the four-point bending strength of the plate decreased from 2.64 to 2.45 N·m by approximately 7.72%,and the equivalent bending stiffness decreased from 1.12 to 0.98 N·m2 by approximately 12%.The impact was obvious.After implantation of tamponade screws,the four-point bending strength of the single-hole plate improved significantly from 2.64 to 3.15 N·m,by approximately 19.32%and the equivalent bending stiffness increased from 1.12 to 1.14 N·m2,by approximately 2.1%.At least two locking holes were reserved on both sides of the fracture line.Not inserting the locking screw reduced the stress by approximately 50%compared with the full insertion of the locking screw.During 15-week postoperative walking without bone callus formation,the material stress of TC4 reached 852.7 MPa and yielding occurred.Conclusions In a clinical scenario where larger shaping is required,it is not suitable for plates with larger thicknesses and plate fractures are more likely to occur after large-thickness shaping.This can guide the clinical selection of plates with appropriate thickness based on the shaping angle,and tamponade screws can be implanted in extreme cases.Fixing locking screws clinically is recommended;however,a method of fixing the locking screws with full screws is not recommended.The biomechanical effect is best when two locking holes at both ends of the fracture line are maintained without fixing the locking screws.

AIM:To investigate the potential impact of mitoNEET[mitochondrial protein containing Asn-Glu-Glu-Thr(NEET)sequence]on mitochondrial metabolism in brown adipocytes,and to elucidate its underlying mecha-nism.METHODS:An in vitro model of primary mouse brown adipocytes was established.Western blot were utilized to detect relevant proteins,and iron ion and ATP content was measured using kits.Mitochondrial membrane potential and re-active oxygen species(ROS)were assessed by fluorescence microscopy and flow cytometry.RESULTS:The expression of the ferroptosis-related protein ACSL4 increased by 1.13 times in ferroptosis inducer erastin treatment group,whereas the expression of SLC7A11 and GPX4 decreased by 27.33%and 25.33%,respectively,compared with control group(P<0.05).The expression of Nrf1,PGC-1α,MFN2 and UCP1 proteins,related to mitochondrial energy metabolism,de-creased by 20.98%,15.17%,15.03%and 34.22%,respectively(P<0.05).Additionally,the mitoNEET protein con-tent was significantly reduced by 42.14%(P<0.05).The iron ion content in erastin group was substantially increased by 1.80 times compared with control group.However,a notable decrease in ATP content of 14.95%was seen(P<0.05).The results obtained from fluorescence microscopy and flow cytometry demonstrated a significant decrease in the mitochon-drial membrane potential of brown adipocytes in erastin group,with reductions of 52.18%and 61.31%(P<0.05),re-spectively.A substantial increase in mitochondrial ROS content of 80.97%was seen(P<0.05).Western blot analysis of overexpressed stable strains revealed a significant elevation in mitoNEET levels in brown adipocytes following lentivirus transfection,exhibiting an increase of 11.19 times(P<0.05),thus confirming successful transfection.The LV-mitoNEET group exhibited a significant decrease of 37.95%in the expression of ferroptosis-related protein ACSL4 in brown adipose cells compared with control group.Additionally,there was a notable increase of 77.82%and 66.3%in the expression of SLC7A11 and GPX4,respectively(P<0.05).Up-regulation was observed in the expression of MFN2(79.06%),PGC-1α(72.89%),Nrf1(40.14%),and UCP1(31.68%)(P<0.05).The test results demonstrated that the LV-mitoNEET group experienced a reduction of 43.5%in iron ion content compared with control group while exhibiting an increase of 33.5%in ATP content(P<0.05).The results obtained from fluorescence microscopy and flow cytometry demonstrated that mitoNEET overexpression led to a significant increase in the mitochondrial membrane potential of erastin-induced brown adipocytes,with increments of 17.61%and 96.05%,respectively.Additionally,mitoNEET overexpression effec-tively reduced the production of mitochondrial ROS by 24.48%(P<0.05).CONCLUSION:Our findings suggest that mitoNEET overexpression can effectively inhibit the disruption of mitochondrial energy metabolism caused by ferroptosis-induced death of brown adipocytes.