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 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.

Aim To explore the role of the ten-eleven translocation 2(TET2)/ubiquinol-cytochrome C reductase hinge protein(UQCRH)axis in the inhibition of vascular smooth muscle cell(VSMC)apoptosis by fibroblast growth fac-tor-2(FGF-2).Methods Cultured VSMCs were divided into control group,FGF-2 group,and FGF-2+fibroblast growth factor receptor(FGFR)pan-inhibitor LY2874455 group.VSMCs overexpressing TET2(OETET2)or UQCRH(OEUQCRH)were divided into control group,FGF-2 group,and OETET2+FGF-2 or OEUQCRH+FGF-2 group.Ho-echst33342 and PI staining were used to detect cell apoptosis,CCK-8 assay was employed to measure cell proliferation,and Western blot was used to examine the expression levels of apoptosis-related proteins pro-Caspase-3,cleaved Caspase-3,Bax,Bcl-2,as well as TET2 and UQCRH.The NCBI and methprimer websites were utilized for predicting and analyzing CpG island sites in the UQCRH gene promoter.Results FGF-2 could inhibit VSMC apoptosis,promote proliferation,downregulate apoptosis-related proteins cleaved Caspase-3,Bax,TET2,and UQCRH expression,and upregulate anti-ap-optotic protein Bcl-2 expression(compared with control group,P＜0.05).However,it did not affect pro-Caspase-3 ex-pression(compared with control group,P＞0.05).LY2874455 could counteract the effects of FGF-2(compared with FGF-2 group,P＜0.05).Overexpression of TET2 or UQCRH could reverse the anti-apoptotic and pro-proliferative effects of FGF-2 on VSMC,with upregulation of apoptosis-related protein expression and downregulation of anti-apoptotic protein expression(compared with FGF-2 group,P＜0.05).The UQCRH gene promoter region contained three CpG islands.Overexpression of TET2 could upregulate UQCRH expression in VSMC treated with FGF-2(compared with FGF-2 group,P＜0.05).Conclusion FGF-2,by inhibiting TET2 expression and UQCRH expression,reduces VSMC apoptosis and promotes its proliferation.

Objective:To explore the changes in entero-insular axis function and its role in mice with severe burns.Methods:This study was an experimental study. Ninety C57BL/6J male mice aged 8-10 weeks were divided into sham injury group and burn group (with 45 mice in each group) according to the random number table. A full-thickness scald (hereinafter referred to as burn) wound of 30% of the total body surface area was created on the back of mice in burn group, and the mice in sham injury group were simulated to cause a sham injury. Twenty-four hours after injury, the fasting blood glucose was measured ( n=12), followed by intraperitoneal glucose tolerance test and oral glucose tolerance test; the curve of blood glucose concentration changes over time was plotted, and the area under the curve was calculated ( n=6); the blood was taken from the heart before intraperitoneal injection or gavage of glucose solution and at 30, 60, and 120 minutes after intraperitoneal injection or gavage of glucose solution for measuring the plasma insulin and glucagon like peptide-1 (GLP-1) levels using enzyme-linked immunosorbent assay (ELISA), with a sample number of 3; the ileal tissue was taken from 3 mice in each group for detecting the GLP-1 expression and apoptosis levels of intestinal L cells by immunofluorescence staining and TdT-mediated dUTP nick-end labeling staining; the pancreatic islets were collected from 6 mice in each group for glucose-stimulated insulin secretion experiments. After incubation with low glucose (2.8 mmol/L glucose) and high glucose (16.7 mmol/L glucose), the supernatant was taken and the insulin level was detected using ELISA. Thirty-six C57BL/6J male mice aged 8-10 weeks were divided into sham injury group, burn group, and burn+exendin-4 (Ex-4) group (with 12 mice in each group) according to the random number table. The mice in sham injury group and burn group were subjected to the same corresponding treatment as before. The mice in burn+Ex-4 group were injured in the same way as the burn group mice followed by treatment with GLP-1 receptor agonist Ex-4. Twenty-four hours after injury, mouse pancreatic islets were collected, the protein expressions of heavy-chain binding protein (BIP), protein kinase R-like endoplasmic reticulum kinase (PERK), phosphorylated PERK (p-PERK), eukaryotic translation initiation factor 2α (eIF2α), phosphorylated eIF2α (p-eIF2α), and CCAAT/enhancer-binding protein homologous protein (CHOP) were detected using Western blotting, and the p-PERK/PERK and p-eIF2α/eIF2α ratios were calculated ( n=3), the apoptosis rate of pancreatic islet cells was detected using flow cytometry ( n=3), the glucose stimulated insulin secretion experiment was conducted as before to detect insulin levels in the supernatant ( n=6). Results:Twenty-four hours after injury, the fasting blood glucose of mice in burn group was (7.3±1.0) mmol/L, which was significantly higher than (5.1±0.6) mmol/L in sham injury group ( t=6.36, P<0.05). Twenty-four hours after injury, in the intraperitoneal glucose tolerance test and oral glucose tolerance test, the areas under the curve of blood glucose concentration changes over time of mice in burn group were significantly larger than those in sham injury group (with t values of 4.32 and 6.03, respectively, P<0.05); compared with those in sham injury group, the plasma insulin levels of mice before intraperitoneal injection of glucose solution and the plasma GLP-1 levels of mice before intraperitoneal injection or gavage of glucose solution in burn group were significantly decreased ( P<0.05), and the plasma levels of insulin of mice at 30, 60, and 120 minutes after intraperitoneal injection or gavage of glucose solution, as well as the plasma levels of GLP-1 of mice at 30 and 60 minutes after gavage of glucose solution were significantly decreased in burn group ( P<0.05). Twenty-four hours after injury, compared with those in sham injury group, the GLP-1 expression level of intestinal L cells of mice in burn group was significantly decreased ( t=7.74, P<0.05), and the apoptosis level was significantly increased ( t=14.28, P<0.05). Twenty-four hours after injury, the insulin level in the supernatant of mice pancreatic islet incubated with high glucose in burn group was (8.5±0.4) ng/mg, which was significantly lower than (15.7±0.3) ng/mg in sham injury group ( t=18.68, P<0.05). Twenty-four hours after injury, compared with those in sham injury group, the protein expression levels of BIP, p-PERK/PERK, p-eIF2α/eIF2α, and CHOP in the pancreatic islets of mice in burn group were significantly increased ( P<0.05); compared with those in burn group, the protein expression levels of BIP, p-PERK/PERK, p-eIF2α/eIF2α, and CHOP in the pancreatic islets of mice in burn+Ex-4 group were significantly decreased ( P<0.05). Twenty-four hours after injury, the apoptosis rate of pancreatic islet cells of mice in burn group was (32.0±3.0)%, which was significantly higher than (10.3±2.5)% in sham injury group ( P<0.05); the apoptosis rate of pancreatic islet cells of mice in burn+Ex-4 group was (20.0±3.6)%, which was significantly lower than that in burn group ( P<0.05). Twenty-four hours after injury, the insulin level in the supernatant of mice pancreatic islet incubated with high glucose in burn group was significantly lower than that in sham injury group ( P<0.05), while the insulin level in the supernatant of mice pancreatic islet incubated with high glucose in burn+Ex-4 group was significantly higher than that in burn group ( P<0.05). Conclusions:After severe burns, the mice display dysfunction of the entero-insular axis, increased apoptosis of intestinal L cells, decreased synthesis and secretion of GLP-1, endoplasmic reticulum stress and increased apoptosis in pancreatic islet cells and a decrease in glucose-stimulated insulin secretion. The GLP-1 receptor agonist Ex-4 can protect the function of pancreatic islet cells of mice with severe burns, reducing the apoptosis level of pancreatic islet cells and promoting insulin secretion possibly via the alleviation of endoplasmic reticulum stress.

[Purpose]To analyze the trends of incidence and mortality of gastric cancer in Changle District of Fuzhou City,Fujian Province during 1991-2020.[Methods]The incidence and mor-tality data of gastric cancer from 1991 to 2020 were collected from cancer registries in Changle District.The crude incidence/mortality rates and age-standardized incidence/mortality rates by Chi-nese standard population(ASIRC/ASMRC)of gastric cancer were calculated.The change trends of gastric cancer incidence and mortality were analyzed by the Joinpoint linear regression model,and the annual percentage change(APC)and the average annual percentage change(AAPC)were cal-culated.[Results]From 1991 to 2020,the crude incidence of gastric cancer in Changle District was 62.28/105,the ASIRC was 55.71/105,the ASIRC decreased from 100.94/105 in 1991 to 26.45/105 in 2020 with an AAPC of-4.34％(P＜0.01).The crude mortality rate of gastric cancer was 50.58/105,the ASMRC was 44.35/105,the ASMRC decreased from 93.07/105 in 1991 to 20.03/105 in 2020 with an AAPC of-4.71％(P＜0.01).From 1991 to 2020,the incidence of gastric cancer in Changle District decreased in age groups of 0～44,45～54,55～64,65～74 and older than 75 years old,with the most significant decrease in the 45～54 age group.The mortality decreased in age group of 0～44,45～54,55～64 and 65～74 with the most significant decrease in 45～54 age group;there was no significant change in 75 and above age group.From 1991 to 2020,the median age of gastric cancer onset and death was delayed by 7 years and 13 years,respectively.[Conclusion]The incidence and mortality of gastric cancer had been considerably decreased during 1991-2000,indicating the success of prevention and control in Changle District;but they are still at a high level,so further targeted prevention and control measures are needed.

Anti-seizure medications (ASMs) are the main therapy for epilepsy.There are many kinds of ASMs with complex mechanism of action, so it is difficult for pharmacists to examine prescriptions.This paper put forward some suggestions on the indications, dosage forms/routes of administration, appropriateness of usage and dosage, combined medication and drug interaction, long-term prescription review, individual differences in pathophysiology of children, and drug selection when complicated with common epilepsy, for the reference of doctors and pharmacists.

Smart manufacturing still remains critical challenges for pharmaceutical manufacturing. Here, an original data-driven engineering framework was proposed to tackle the challenges. Firstly, from sporadic indicators to five kinds of systematic quality characteristics, nearly 2,000,000 real-world data points were successively characterized from Ginkgo Folium tablet manufacturing. Then, from simplex to the multivariate system, the digital process capability diagnosis strategy was proposed by multivariate C_pk integrated Bootstrap-t. The C_pk of Ginkgo Folium extracts, granules, and tablets were discovered, which was 0.59, 0.42, and 0.78, respectively, indicating a relatively weak process capability, especially in granulating. Furthermore, the quality traceability was discovered from unit to end-to-end analysis, which decreased from 2.17 to 1.73. This further proved that attention should be paid to granulating to improve the quality characteristic. In conclusion, this paper provided a data-driven engineering strategy empowering industrial innovation to face the challenge of smart pharmaceutical manufacturing.

Oligoasthenospermia is the primary cause of infertility. However, there are still enormous challenges in the screening of critical candidates and targets of oligoasthenospermia owing to its complex mechanism. In this study, stem cell factor (SCF), c-kit, and transient receptor potential vanilloid 1 (TRPV1) biosensors were successfully established and applied to studying apoptosis and autophagy mechanisms. Interestingly, the detection limit reached 2.787 × 10^-15 g/L, and the quantitative limit reached 1.0 × 10^-13 g/L. Furthermore, biosensors were used to investigate the interplay between autophagy and apoptosis. Schisandrin A is an excellent candidate to form a system with c-kit similar to SCF/c-kit with a detection constant (K_D) of 5.701 × 10^-11 mol/L, whereas it had no affinity for SCF. In addition, it also inhibited autophagy in oligoasthenospermia through antagonizing TRPV1 with a K_D of up to 4.181 × 10^-10 mol/L. In addition, in vivo and in vitro experiments were highly consistent with the biosensor. In summary, high-potency schisandrin A and two potential targets were identified, through which schisandrin A could reverse the apoptosis caused by excessive autophagy during oligoasthenospermia. Our study provides promising insights into the discovery of effective compounds and potential targets via a well-established in vitro-in vivo strategy.

China has classified the Corona Virus Disease 2019(COVID-19) as a statutory category B infectious disease and managed it according to Category B since January 8, 2023.In view that Omicron variant is currently the main epidemic strain in China, in order to guide the treatment of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) infection in children with the times, refer to the Diagnosis and Treatment Protocol for Novel Coronavirus Infection (Trial 10 th Edition), Expert Consensus on Diagnosis, Treatment and Prevention of Novel Coronavirus Infection in Children (Fourth Edition) and the Diagnosis and Treatment Strategy for Pediatric Related Viral Infections.The Expert Consensus on the Diagnosis, Treatment and Prevention of Novel Coronavirus Infection in Children (Fifth Edition) has been formulated and updated accordingly on related etiology, epidemiology, pathogenic mechanism, clinical manifestations, auxiliary examination, diagnosis and treatment, and added key points for the treatment of COVID-19 related encephalopathy, fulminating myocarditis and other serious complications for clinical reference.

OBJECTIVE Epileptic networks are char-acterized as two states,seizures or more prolonged inter-ictal periods.However,cellular mechanisms underlying the contribution of interictal periods to ictal events remain unclear.METHODS Here,we present the procedure for labeling seizure-activated and interictal-activated neuro-nal ensembles in mouse hippocampal kindling model using an enhanced-synaptic-activity-responsive element.This technique is combined with genetically encoded effectors to characterize and manipulate neuronal ensembles recruited by focal seizures(FS-Ens)and interictal periods(IP-Ens)in piriform cortex,a region that plays a key role in seizure generation.RESULTS Ca2+ activities and histo-logical evidence reveal a disjointed correlation between the two ensembles during FS dynamics.Optogenetic acti-vation of FS-Ens promotes further seizure development,while IP-Ens protects against it.Interestingly,both ensem-bles are functionally involved in generalized seizures(GS)due to circuit rearrangement.IP-Ens bidirectionally modulates FS but not GS by controlling coherence with hippocampus.CONCLUSION This study indicates that the interictal state may represent a seizure-preventing environment,and the interictal-activated ensemble may serve as a potential therapeutic target for epilepsy.