Human-animal interaction has a long-standing tradition dating back to ancient times. With the rapid advancements in intelligent chips, wearable devices, and machine algorithms, the intelligent interaction between animals and electronic technology, facilitated by electronic devices and systems for communication, perception, and control, has become a reality. These electronic devices aim to implement an animal-centric working mode to enhance human understanding of animals and promote the development of animal intelligence and creativity. This article takes medium-sized and large animals as research objects, with the goal of developing their ability enhancement, and introduces the concept of “intelligent animal augmentation system (IAAS)”. This concept is used to describe the characteristics of such devices and provides a comprehensive overview of existing animal and computer interface solutions. In general, IAAS can be divided into implantable and non-implantable types, each composed of interface platforms, perception and interpretation, control and instruction components. Through various levels of enhancement systems and architectural patterns, intelligent interaction between humans and animals can be realized. Although existing IAAS still lack a complete independent interaction system architecture, they hold great promise and development space in the future. Not only can they be applied as substitutes for cutting-edge devices and transportation equipment, but they are also expected to achieve cross-species information interaction through intelligent interconnection. Additionally, IAAS can promote bidirectional interaction between humans and animals, playing a significant role in advancing animal ethics and ecological protection. Furthermore, the development of interaction models based on animal subjects can provide insightful research experiences for the design of human-computer interaction systems, thereby contributing to the more efficient realization of the ambitious goal of human-machine integration.

Orodispersible films (oral dispersible films), a novel form of oral solid dosage forms, are widely used for patients with dysphagia and those with uncontrollable autonomic behavior. In this study, suvorexant orodispersible film was prepared by hot melt extrusion technology, and the disintegration time, mechanical properties, in vitro dissolution and pharmacokinetics were evaluated, compared with other orodispersible films and commercially available tablets Belsomra. All experiments were approved by the Committee on the Management and Use of Laboratory Animals of Academy of Military Medical Sciences (IACUC-DWZX-2024-504). The results showed that the dissolution rate of suvorexant orodispersible film was faster and the mechanical strength was better than that of other commercially available orodispersible film, which could meet the needs of storage and transportation. Differential scanning calorimetry and X-ray diffraction results showed that suvorexant was dispersed within the orodispersible film in an amorphous state. The in vitro dissolution of the film was observed to be four times faster than that of the commercial tablets, achieving complete dissolution within five minutes. Pharmacokinetic evaluations in Beagle dogs revealed that the self-formulated orodispersible film exhibited no significant differences in the area under the blood concentration-time curve when compared with Belsomra. However, the film showed a faster onset of action, with a peak time that was twice as rapid, and a maximum blood concentration that was twice as high as that of Belsomra. Leveraging hot melt extrusion technology, the suvorexant orodispersible film offers a straightforward, continuous production process with consistent quality. It serves as an excellent platform for the development of solvent-free film preparations tailored for patients with special needs.

The rheological properties of drug and carrier materials have a wide range of guiding significance for the formulation and process development of solid dispersions. In this study, the rheological properties of materials with different drug carrier ratios were systematically studied with suvorexant as the model drug and copovidone as the carrier material, which provided a sufficient basis for determining the formulation and process of solid dispersions. The optimal suvorexant-copovidone ratio obtained by oscillating temperature scanning was 1∶4. If the ratio is greater than 1∶ 4, the glass transformation temperature of the material will increase significantly, and the solubilization effect of the solid dispersion will show a downward trend. The results of oscillation temperature scanning and oscillation temperature sweep can show that when the extrusion temperature is greater than 150 ℃, the viscosity of the material is less than 10 000 Pa·s, and the melt can be extruded smoothly, and the best extrusion temperature of 160-180 ℃ can be obtained by combining the dissolution results. Finally, the dissolution of suvorexant tablets guided by rheological property studies in multiple media is similar to that of the commercially available tablets Belsomra. Therefore, rheological studies can screen and optimize the formulation and process of suvorexant solid dispersions at the mechanism level, which is of great significance to improve the success rate of R&D and shorten the R&D cycle of solid dispersions prepared by hot melt extrusion.

Objective To investigate the effect of Xiao Chaihu Decoction and Xiangsha Liujunzi Decoction on the changes of gastric mucosal pathological score and gastrointestinal hormones in patients with chronic atrophic gastritis(CAG)of liver stagnation and spleen deficiency type.Methods A total of 156 cases of CAG patients with liver stagnation and spleen deficiency syndrome were randomly divided into a control group and an observation group,78 cases in each group.The control group was treated with conventional western medicine,and the observation group was treated with Xiao Chaihu Decoction and Xiangsha Liujunzi Decoction on the basis of treatment for the control group.The course of treatment covered four weeks.The changes in the scores of traditional Chinese medicine(TCM)symptoms such as epigastric distention and pain,poor appetite,loose stools,limb weakness,belching and acid regurgitation,gastric mucosal pathological scores and serum levels of gastrointestinal hormones of motilin(MTL)and gastrin(GAS)in the two groups were observed before and after treatment.The negative conversion rate of Helicobacter pylori(Hp)in the two groups was compared,and the clinical efficacy and safety of the two groups were evaluated.Results(1)After four weeks of treatment,the total effective rate of the observation group was 93.59％(73/78),which was significantly higher than 82.05％(64/78)of the control group,and the difference between the two groups was statistically significant(P＜0.05).(2)After treatment,the scores of TCM symptoms such as epigastric distention and pain,poor appetite,loose stool,limb weakness,belching and acid regurgitation in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the decrease in the observation group was significantly superior to that in the control group(P＜0.05).(3)After treatment,the pathological scores of gastric mucosa in the two groups were significantly decreased when compared with those before treatment(P＜0.05),and the decrease in the observation group was more significant than that in the control group(P＜0.01).(4)After four weeks of treatment,the negative conversion rate of Hp in the observation group was 91.03％(71/78),which was significantly higher than that in the control group(75.64％,59/78),and the difference between the two groups was statistically significant(P＜0.05).(5)After treatment,the level of serum GAS in the two groups was significantly decreased(P＜0.05)and the serum MTL level was significantly increased compared with that before treatment(P＜0.05);the decrease of serum GAS level and the increase of serum MTL level in the observation group were significantly superior to those in the control group(P＜0.05).(6)There were no obvious abnormalities in the routine test of blood,urine,stool,kidney function,and liver function,electrocardiograph and other safety indicators during the treatment of the two groups of patients,no adverse reactions such as dizziness,rash and chest distress occurred either,with high safety.Conclusion Xiao Chaihu Decoction combined with Xiangsha Liujunzi Decoction exerts a significant therapeutic effect on GAS of liver stagnation and spleen deficiency type,which can effectively relieve the clinical symptoms,improve the pathological changes of gastric mucosa and promote Hp negative conversion.The therapeutic mechanism may be related to the regulation of gastrointestinal hormone levels.

In recent years,a large amount of studies have confirmed that the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway plays a decisive role in the follicular atresia and apoptosis by regulating the inflammatory response,apoptosis and autophagy,and oxidative stress of ovarian cells as well as ovarian granular cell proliferation,which is a key pathway for the occurrence and development of premature ovarian failure(POF).Traditional Chinese medicine(TCM)has obvious advantages in the treatment of chronic complex diseases such as POF,and the regulation of PI3K/AKT signaling pathway is one of the mechanisms of the prevention and treatment of POF with Chinese herbal medicine.The intervention of POF with TCM can be achieved by inhibiting the inflammatory response,counteracting oxidative stress,inhibiting apoptosis and autophagy,and promoting granular cell proliferation in the occurrence and development of POF through the regulation of the PI3K/AKT signaling pathway.This article reviewed the role of PI3K/AKT signaling pathway and its upstream and downstream molecules in the pathogenesis of POF,and explored the mechanism of TCM in intervening POF through the PI3K/AKT signaling pathway,which will provide theoretical evidence for the basic research and new drug development for POF.

Further evidence is needed to explore the impact of high-altitude environments on the neurologic function of neonates.Non-invasive techniques such as cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography can provide data on cerebral oxygenation and brain electrical activity.This study will conduct multiple cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography monitoring sessions at various time points within the first 3 days postpartum for healthy full-term neonates at different altitudes.The obtained data on cerebral oxygenation and brain electrical activity will be compared between different altitudes,and corresponding reference ranges will be established.The study involves 6 participating centers in the Chinese High Altitude Neonatal Medicine Alliance,with altitude gradients divided into 4 categories:800 m,1 900 m,2 400 m,and 3 500 m,with an anticipated sample size of 170 neonates per altitude gradient.This multicenter prospective cohort study aims to provide evidence supporting the impact of high-altitude environments on early brain function and metabolism in neonates.[Chinese Journal of Contemporary Pediatrics,2024,26(4):403-409]

Objective To construct a risk prediction model for healthcare-associated infection(HAI)in stroke pa-tients,accurately and effectively screen out potential high-risk groups,and formulate targeted preventive interven-tions to reduce the occurrence of infection.Methods Stroke patients in the"Henan Stroke Cohort"in 2019-2021 were selected as the study objects,and relevant clinical data were collected as the main analysis data for model con-struction and internal validation.The relevant data of stroke patients in three hospitals that had never participated in the cohort construction from January to September 2022 were randomly selected as a test set for external validation of the risk prediction model.The main analysis data were randomly divided into a training set and a test set,and a risk prediction model was constructed based on logistic regression,artificial neural network(ANN)algorithm,extreme gradient boosting algorithm and random forest algorithm,respectively.Multiple indicators were used to evaluate the prediction performance of the model,and the optimal model was externally validated based on the test set data.Results The infection rate of stroke patients was 20.6％in the main analysis data and 56.4％in the test set data.The accuracy of the risk prediction model based on logistic regression was 91.2％,the area under the re-ceiver operating characteristic(ROC)curve(AUC)was 0.938,the precision rate,recall rate,specificity,and the F1 score were 0.851,0.695,0.968,and 0.765,respectively.The accuracy rate,precision rate,specificity and AUC of the logistic risk prediction model and the ANN risk prediction model were all significantly better than other models,while the recall rate and F1 score of the logistic risk prediction model were slightly better than the ANN risk prediction model.The logistic risk prediction model had excellent prediction performance in external validation.Conclusion HAI risk prediction model of stroke patients based on logistic regression can better screen out high-risk stroke patients with infection risk,and can contribute to formulate targeted preventive interventions to reduce the occurrence of infection.

Objective The rabbit knee osteoarthritis(KOA)model was established by simple anterior cruciate ligament disruption.Methods The selected 40 adult white rabbits were randomly divided into two groups,blank group with 6 rabbits and model group with 34 rabbits.The rabbits in model group were given the disruption of anterior cruciate ligament of right knee joint.In the fourth,eighth and the twelfth weeks of modeling,different degrees of degenerative changes have been ob-served on the rabbits articular cartilages from both macroscopic and microscopic aspects.Results At 4,8 and 12 weeks after modeling,the articular cartilage of the rabbits in the model group showed degenerative changes in different degrees.At 8 and 12 weeks,the typical pathological manifestations of KOA in the middle and late stages were found in the infrapatellar fat pad and synovium,respectively.There were no changes in articular cartilage,infrapatellar fat pad and synovial membrane in the blank group at the same time.There were significant differences in the gross score between the model group and the blank group at 4 weeks[(1.300±0.674)vs 0.000],8 weeks[(2.400±0.516)vs 0.000]and 12 weeks[(3.583±0.668)vs 0.000](P＜0.05),the histopathological scores were significantly different,at 4 weeks[(2.900±0.567)vs 0.000],8 weeks[(7.500±1.178)vs(0.500±0.707)],12 weeks[(11.833±1.337)vs(1.500±0.707)],(P＜0.05).Conclusion The establishment of rabbit knee arthritis model by simply cutting the anterior cruciate ligament is simple and feasible,with good stability,high success rate,small trauma,short modeling cycle and less changes in animal physiological structure.The rabbit knee arthritis model es-tablished by simply cutting the anterior cruciate ligament has good modeling effect on different stages and grades of knee os-teoarthritis,and the postoperative infection and trauma can be controlled,which can meet the test requirements.

This study investigated the characteristics of gut microbiota imbalance in patients with infectious diarrhea caused by various pathogenic infections,and the role of Bacteroides in maintaining homeostasis in the intestinal environment.The gut microbiota in patients with diarrhea caused by pathogenic infections,such as viral and bacterial infections,was determined through full-length 16S rRNA amplicon sequencing.Patients with diarrhea were grouped and analyzed according to the presence of single bacterial infection,single viral infection,mixed infection,or Clostridioides difficile infection.Bacteroides had the highest absolute number and relative abundance in the gut microbiota in healthy people,whereas patients with infectious diar-rhea showed lower relative abundance of Bacteroides at each phylum/order/family/genus taxonomic level.Alpha diversity anal-ysis indicated no significant differences among groups.NMDS and PCoA indicated formation of distinct clusters in the control group compared with the different infectious diarrhea groups.The diversity of the gut microbiota was higher in the control group than the infectious diarrhea groups.Patients with infec-tious diarrhea caused by different pathogens showed differing predominant gut microbiota.Bifidobacterium predominated in the single viral infection group,Streptococcus predominated in the single bacterial infection group,and Lachnoclostridium predominated in the mixed infection group.Escherichia and Klebsiella were the major gut microbiota in the C.difficile infection group.Meanwhile,the dominant gut microbiota in the healthy population was Bacteroides.COG function prediction revealed that the healthy control group formed a distinct cluster from the different infection groups.The functions of defense mechanisms,cell wall synthesis,protein modification,cellular differentiation,and replication and recombination were signifi-cantly diminished in all infectious diarrhea groups.In general,patients with infectious diarrhea caused by different pathogens showed dysbiosis,with diminished gut microbiota diversity and the emergence of related biomarkers.Our findings indicated that Bacteroides has a key role in maintaining the homeostasis of the human intestinal environment,thus providing new ideas for the subsequent treatment of infectious diarrhea and research in other fields.

Objective To evaluate the predictors of biochemical recurrence after laparoscopic radical prostatectomy.Methods The study cohort consisted of 416 consecutive prostatecancer patients who underwent radical prostatectomy in Zhongshan Hospital,Fudan University between Jan 2016 and Jun 2018.No patient received adjuvant therapy until documented biochemical recurrence.Biochemical recurrence-free survival(BCRFS)was estimated using the Kaplan-Meier method.Univariable and multivariable Cox proportional hazards regression models were utilized to determine variables predictive of biochemical recurrence.Results The median follow-up period was 174 weeks(inter quartile range 133-209 weeks).The overall biochemical recurrence rate was 21.39%(88/416).The time to biochemical recurrence was(51.11±47.71)weeks.Until the end of follow-up,the biochemical recurrence rates were 10%(1/10),6.12%(3/49),16.41%(43/262)and 43.16%(41/95)for low-risk,medium-risk,high-risk and locally advanced prostate cancer,respectively.On multivariable analysis,tumor invasion of the seminal vesicles(HR:2.119,95%CI:1.154-3.891,P=0.016);Seminal vesicle invasion(HR:1.824,95%CI:1.034-3.220,P=0.038),Gleason score≥8(HR:2.746,95%CI:1.268-5.943,P=0.010),prostate-specific antigen(PSA)=10-20 ng/mL(HR:4.240,95%CI:2.550-7.050,P<0.001);PSA>20 ng/mL(HR:6.341,95%CI:3.296-12.202,P<0.001)were the main predictors of biochemical recurrence.Conclusion Laparoscopic radical prostatectomy provides effective control of biochemical recurrence during the mid-term follow-up period.Tumor invasion of the seminal vesicles,seminal vesicle invasion,GS≥8,PSA=10-20 ng/mL,PSA>20 ng/mL were important predictors of biochemical recurrence after radical prostatectomy.