ObjectiveTo investigate the mechanism of ferroptosis mediated by long-chain acyl-CoA synthetase 4 （ACSL4） signalling pathway in rats with coronary heart disease with blood stasis syndrome and the intervention effect of Xuefu Zhuyutang. MethodsSPF male SD rats were randomly divided into normal group， sham-operation group， model group， trimetazidine group （5.4 mg·kg^-1）， low-， medium-， and high-dose group （3.51， 7.02，14.04 g·kg^-1） of Xuefu Zhuyutang. The coronary artery left anterior descending ligation method was used to prepare a model of coronary heart disease with blood stasis syndrome， and continuous treatment for 7 d was conducted， while the sham-operation group was only threaded and not ligated. The general macroscopic symptoms of the rats were observed， and indicators such as electrocardiogram， echocardiography， and blood rheology were detected. The pathological morphology of myocardial tissue was observed by hematoxylin-eosin （HE） staining， and the changes in mitochondria in myocardial tissue were observed by transmission electron microscopy. The level of iron deposition in myocardial tissue was observed by Prussian blue staining. The levels of 12-hydroxyeicosatetraenoic acid （12-HETE） and 15-HETE were detected in serum by enzyme-linked immunosorbent assay. A biochemical colourimetric assay was used to detect the levels of Fe²⁺， lipid peroxidation （LPO）， glutathione （GSH）， and T-GSH/glutathione disulfide （GSSG） in myocardial tissue. DCFH-DA fluorescence quantitative assay was employed to detect the levels of reactive oxygen species （ROS）. Western blot and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was adopted to detect the protein and mRNA expressions of glutathione peroxidase 4 （GPX4）， ferritin heavy chain 1 （FTH1）， ACSL4， and ly-sophosphatidylcholine acyltransferase3 （LPCAT3） in myocardial tissue. ResultsCompared with those in the normal group， the rats in the model group were poor in general macroscopic symptoms. The electrocardiogram showed widened QRS wave amplitude and increased voltage， bow-back elevation of the ST segments， elevated T waves， J-point elevation， and accelerated heart rate. Echocardiography showed a significant reduction in left ventricular ejection fraction （LVEF） and left ventricular fraction shortening （LVFS） （P<0.01）. Blood rheology showed that the viscosity of the whole blood （low， medium， and high rate of shear） was significantly increased （P<0.01）. HE staining showed an abnormal structure of myocardial tissue. There was a large area of myocardial necrosis and inflammatory cell infiltration and a large number of connective tissue between myocardial fibers. Transmission electron microscopy showed that the mitochondria were severely atrophy or swelling. The cristae were reduced or even broken， and the matrix was flocculent or even vacuolated. Prussian blue staining showed that there were a large number of iron-containing particles， and the iron deposition was obvious. The content of 12-HETE and 15-HETE in the serum was significantly increased （P<0.01）. The content of Fe²⁺， LPO， and ROS in myocardial tissue was significantly increased （P<0.01）. The content of GSH was significantly decreased （P<0.01）， and T-GSH/GSSG was decreased （P<0.01）. The protein and mRNA expressions of GPX4 and FTH1 in myocardial tissue were both significantly decreased （P<0.05， P<0.01）， while those of ACSL4 and LPCAT3 increased significantly （P<0.01）. Compared with the model group， the general macroscopic symptoms and electrocardiogram results of rats in low-， medium- and high-dose groups of Xuefu Zhuyutang were alleviated， and the differences in LVEF/LVFS ratios were all significantly increased （P<0.05， P<0.01）. The differences in whole-blood viscosity （low， medium， and high rate of shear） were all significantly decreased （P<0.01）. The results of HE staining and transmission electron microscopy showed that the morphology， structure， and mitochondria of cardiomyocytes were improved. The content of 12-HETE and 15-HETE in serum was reduced to different degrees in low-， medium-， and high-dose groups of Xuefu Zhuyutang （P<0.05， P<0.01）. The content of Fe²⁺， LPO， and ROS was significantly reduced in the medium- and high-dose groups of Xuefu Zhuyutang （P<0.05， P<0.01）， and the content of GSH and T-GSH/GSSG was significantly increased （P<0.05， P<0.01）. The protein and mRNA expressions of GPX4 and FTH1 were significantly increased to varying degrees in the medium- and high-dose groups of Xuefu Zhuyutang （P<0.05， P<0.01）， and ACSL4 and LPCAT3 were decreased to different degrees in the low-， medium-， and high-dose groups of Xuefu Zhuyutang （P<0.05， P<0.01）. ConclusionXuefu Zhuyutang can regulate iron metabolism and anti-lipid oxidation reaction to mediate ferroptosis through the ACSL4 signalling pathway， thus exerting a protective effect on rats with coronary heart disease with blood stasis syndrome.

AIM: To investigate the abnormal conditions and change patterns of accommodative facility in patients with different refractive states before and after small incision lenticule extraction(SMILE)surgery.METHODS:A prospective clinical cohort study was conducted. A total of 59 patients(118 eyes)who underwent SMILE surgery and had visual function files established in our hospital from June to December 2023 were randomly selected, including 37 males and 22 females, aged 18-35 years(with an average age of 25.19±5.65 years). According to the preoperative spherical equivalent(SE), they were divided into two groups: the low-to-moderate myopia group(SE≥-6.00 DS)with 40 patients(80 eyes), and the high myopia group(SE<-6.00 DS)with 19 patients(38 eyes). The monocular and binocular accommodative facility before surgery and at 1 wk and 1 mo after surgery were compared, and the changes in accommodative facility before and after SMILE surgery in the two groups of patients were analyzed.RESULTS:All surgeries were completed successfully. In the low-to-moderate myopia group, 33 cases(66 eyes)completed the 1-month follow-up after surgery, with a loss to follow-up rate of 17.5%(7/40). In the high myopia group, 15 patients(30 eyes)completed the 1-month follow-up after surgery, with a loss to follow-up rate of 21.1%(4/19). After SMILE surgery, the uncorrected visual acuity and SE of both low-to-moderate myopia and high myopia were significantly improved(all P<0.05). The accommodative facility of the right eyes in all the patients at 1 mo after surgery was better than that before surgery and at 1 wk after surgery(P=0.002, 0.006), the accommodative facility of the left eyes was significantly increased at 1 mo after surgery than that at 1 wk after surgery(P=0.005), and the binocular accommodative facility at 1 mo after surgery was significantly increased compared with that before surgery(P<0.017). Furthermore, there were statistical significance in accommodative facility of the right eyes in the low-to-moderate group at 1 mo compared with that before surgery and at 1 wk after surgery(P=0.011, 0.004); it was significantly increased in the left eyes at 1 mo after surgery compared with that at 1 wk after surgery(P=0.001), and binocular accommodative facility at 1 mo after surgery was significantly better than that before surgery(P<0.001). Furthermore, there was no statistical significance in the right, left and binocular accommodative facility of patients in the high myopia group(all P>0.017).CONCLUSION: After SMILE surgery, the monocular accommodative facility shows a transient decrease and then exceeds the preoperative level at 1 mo after surgery, and the binocular accommodative facility gradually improves after surgery. SMILE surgery has a positive impact on the monocular and binocular accommodative facility in patients with low-to-moderate myopia, but has no significant impact on the accommodative facility in patients with high myopia. It is of clinical significance to strengthen the detection of monocular and binocular accommodative facility before and after SMILE surgery.

As green, sustainable, and environmentally friendly material processing processes using biological cells or enzymes to achieve substance conversion, bioprocesses play an increasingly important role in biomanufacturing. It is difficult to optimize bioprocesses because of the complex relationship at multiple levels and multiple scales. The knowledge of mesoscale behaviors is the key to understanding the dynamics of bioprocesses and to sort out the complex relationships of parameter variations in the spatial-temporal domain. Mesoscale numerical simulation paves a way for understanding these phenomena, and the integration of artificial intelligence (AI) and mesoscale simulation offers new vitality into the optimization of bioprocesses. This article reviews the progress in mesoscale simulation and AI optimization of bioprocesses and discusses the possible development directions, aiming to promote the development of this field.
Artificial Intelligence ; Biotechnology/trends* ; Computer Simulation

Infectious diseases continue to pose a threat to global public health. Successive global shocks caused by emerging and re-emerging pathogens have continuously challenged existing surveillance systems, highlighting the urgent need to build efficient and precise pathogen surveillance networks. Pathogen genomic databases have been developed rapidly in recent two decades, significantly improving the molecular identification, evolutionary analysis, and transmission tracking of pathogens, and changing disease surveillance strategies and patterns. This paper summarizes the developmental history and current state of pathogen genomic databases, and discusses their applications in public health, including pathogen variation surveillance, emerging or suspected pathogen identification, and epidemiological tracing. Furthermore, this paper systematically analyzes the limitations and key challenges faced by current global health prevention and control system, and suggests the focus of the development of online pathogen databases to address existing shortcomings, ultimately improve global infectious disease surveillance and early warning

Since the global outbreak in 2022, the mpox epidemic has evolved from an African endemic to a public health emergency of international concern. The 2024 mpox outbreak in the Democratic Republic of the Congo caused by the Clade Ⅰb lineage is yet another wake-up call, with markedly higher prevalence and fatality rates observed among children under 15 years of age, thereby presenting new challenges for the children. Therefore, it is necessary to strengthen prevention and control, block mother-to-child transmission routes, and establish innovative models with active community participation to reduce the risk of mpox transmission. In the future, it is urgent to analyze molecular mechanisms underlying the mother-to-child transmission of the virus, develop targeted antiviral drugs, establish a pediatric critical disease scoring system, and incorporate mpox vaccines into the World Health Organization′s expanded programme on immunization.

Objective:To observe any effect of electroacupuncture on the urodynamics of rats modeling chronic urinary retention after a sacral cord injury (SCI), and to explore its regulatory effect on interstitial Cajal cells (ICCs) in the bladder and the mechanism.Methods:Seventy-five female Sprague-Dawley rats were randomly divided into a sham operation group, a model group, an electroacupuncture group, an inhibitor group, and an inhibitor plus electroacupuncture group, each of 15. On day 1 of the experiment the sacral spinal cord was completely transected at the level of the 3rd lumbar vertebra in all groups except the sham operation group. In that group the spinous processes and laminae of L 2-4 were exposed but not injured, and then sutured. On day 16, both the inhibitor group and the inhibitor plus electroacupuncture group were given intraperitoneal injections of imatinib mesylate, while the electroacupuncture group and the inhibitor plus electroacupuncture group began 14 consecutive days of electroacupuncture. After the intervention, urodynamic testing was performed on the rats in all five groups, and they were then sacrificed. Hematoxylin-eosin staining was used to observe any morphological changes in the bladder. Transmission electron microscopy was employed to assess the ultrastructure and quantity of ICCs in the bladder. And the gene and protein expression of c-Kit and stem cell factor (SCF) in bladder tissue were detected using polymerase chain reactions and western blotting. Western blotting was also applied to detect the relative expression of c-Kit phosphorylated proteins. Results:Compared with the sham group, the model and inhibitor groups showed significant differences in their urination rates, residual urine volumes, bladder volumes and compliance on the 30th day of the experiment. Compared with the model group, the rats who received electroacupuncture displayed more complete voiding, lower residual urine volume, greater bladder volume and better compliance. Compared with the electroacupuncture group, the urodynamic evaluation of the inhibitor plus electroacupuncture group indicated a significant decrease in urination rate, but a significant increase in residual urine volume, bladder volume and compliance. The SCI modeling had destroyed the morphology of the bladder detrusor muscle and the ultrastructure of the ICCs. And the number of Cajal interstitial cells and the relative expression of c-Kit, SCF, and p-c-Kit had decreased significantly. Compared with the model group, a significant improvement was observed in all urodynamic indicators, the morphology of the detrusor muscle, the ultrastructure and number of ICCs, and the relative expression of c-Kit, SCF, and p-c-Kit in the electroacupuncture groups. There were poorer urodynamic indicators, detrusor muscle morphology, ultrastructure and number of ICCs in the inhibitor plus electroacupuncture group compared with the group which received electroacupuncture alone, but there was a significant decrease in the relative expression of p-c-Kit.Conclusions:Electroacupuncture can improve the urodynamics of chronic urinary retention after sacral cord injury, at least in rats. The mechanism may be related to the benign regulation of ICCs through the bladder′s c-kit/SCF signal system.

Aim To investigate the effect of hypobaric hypoxia on macrophage necroptosis and atherosclerotic plaque instability and explore the underlying mechanisms.Methods Mouse bone marrow-derived macrophages were i-solated and cultured,and divided into control group(21％oxygen concentration)and hypoxia group(3％oxygen concen-tration).After 48 hours,cell necroptosis was detected,and the expression of cell necroptosis related proteins was deter-mined by Western blot.Healthy male ApoE-/-mice were randomly divided into control group and hypobaric hypoxia group.After the intervention for 16 weeks,the plasma lipids and inflammatory cytokines were measured,the areas of ath-erosclerotic plaque and necrotic core were evaluated by HE staining.The content of plaque collagen was detected by Mas-son staining.The number of macrophages in the plaque and the expression of necrotic apoptosis related proteins were de-tected by immunohistochemical staining and Western blot.Results Hypoxia induced increased necrotic apoptosis of macrophages(P＜0.01),while necroptotic inhibitor necrostatin-1(Nec-1)reduced hypoxia induced cell death(P＜0.05);hypoxia leads to a decrease in the expression of adenosine deaminase acting on RNA 1(ADAR1)in macrophages(P＜0.01),and an increase in the expression of Z-DNA binding protein 1(ZBP1),phosphorylated receptor-interacting serine/threonine-protein kinase(p-RIPK3),and phosphorylated mixed lineage kinase domain-like protein(p-MLKL)(all P＜0.01).Compared with the control group,the plasma lipid levels of ApoE-/-mice in the hypobaric hypoxia group did not change significantly(P＞0.05),the plasma inflammatory cytokines(TNF-α,IL-1β,IL-6 and MCP-1)increased(all P＜0.05),the area of atherosclerotic plaque increased(P＜0.05),the area of plaque necrotic core increased,the content of plaque collagen decreased,the number of macrophages increased,the expression of ADAR1 decreased,and the expres-sion of ZBP1 and p-MLKL increased(all P＜0.01).Conclusion Hypobaric hypoxia causes the imbalance of A-DAR1/ZBP1 expression in macrophages,activates RIPK3/MLKL signaling pathway,promotes macrophage necroptosis,in-creases the area of plaque necrosis core,and leads to increase instability of atherosclerotic plaque.

Objective To evaluate the advantages of a real-time computer endoscopy-assisted system(EndoAngel)for colorectal lesions detection in colonoscopy.Methods 2 000 patients who underwent EndoAngel assisted colonoscopy and conventional colonoscopy were selected for the study in a single-center,self-controlled study.According to different examination methods,the patients were divided into artificial intelligence(AI)group and traditional colonoscopy group,each with 1 000 cases.The results were statistically analyzed and compared with the polyp detection rate and adenoma detection rate of the two groups using pathological diagnosis as the gold standard.Further subgroup analysis will be conducted based on the seniority of the operating physicians.Results AI group's polyp detection rate was higher(39.3％)than conventional colonoscopy group polyp detection rate(29.0％),with statistically significant difference(x2=23.59,P=0.000).Of these,the detection rates of hyperplastic polyps and adenomatous polyps were 19.1％and 25.2％,which were significantly higher than those of 12.4％and 20.8％in the conventional colonoscopy group,and the differences were statistically significant(x2=16.92,P=0.000;x2=5.46,P=0.019).Further subgroup analysis of the two groups by physician seniority,the polyp detection rate of AI low seniority group(36.6％)was higher than that of conventional colonoscopy low seniority group(20.40％),with a statistically significant difference(x2=32.20,P=0.000).Among them,the detection rates of hyperplastic polyp(17.8％)and adenomatous polyp(23.6％)in AI low seniority group were higher than those in the conventional colonoscopy low seniority group(12.8％vs 13.6％),and the differences were significant(x2=4.82,P=0.028;x2=16.51,P=0.000).There were no significant differences in adenomatous polyp detection rates between the two groups of senior physicians.Conclusion EndoAngel assisted system can improve the polyp detection rate of colonoscopy,especially for the effect of low seniority physicians is more significant.

Objective:To investigate the clinical characteristics and prognosis of fetuses with HNF1B gene variants. Methods:Fifty-two fetuses with HNF1B gene variants diagnosed by chromosomal copy number variation sequencing and/or whole exome sequencing at the First Affiliated Hospital of Zhengzhou University from January 2018 to June 2024 were retrospectively enrolled in this study, including 47 cases of 17q12 microdeletion and five cases of HNF1B point mutations. Prenatal ultrasound features, pregnancy outcomes, and postnatal manifestations were summarized and analyzed using descriptive statistics. Results:The prenatal ultrasound features of the 52 fetuses included enhanced renal parenchymal echo in 43 cases (82.7%), renal cysts in 15 cases (28.8%), enlarged kidney volume in 14 cases (26.9%), and pyelectasis in 13 cases (25.0%). Parental verification was completed for 35 cases, with 71.4% (25/35) being de novo mutations and 28.6% (10/35) inherited from either parent. Apart from eight cases with unknown pregnancy outcome (six cases were lost to follow-up, two cases refused to be followed up), the other 44 cases were successfully followed up, among which 68.2% (30/44) terminated the pregnancies and 31.8% (14/44) continued, resulting in live births. Prenatal ultrasound indicated renal abnormalities in all 14 live births, while postnatal follow-up showed seven cases with normal kidneys, one with reduced bilateral renal cysts, one with alleviated bilateral pyelectasis, four with unimproved renal structural abnormalities, and one who did not undergo a re-examination. Conclusion:The rate of renal abnormalities diagnosed by prenatal ultrasound in fetuses with HNF1B gene variants is high, and most of the pregnancies are terminated, although the renal sturctural abnormalities may improve after birth.

Objective:To investigate the clinical characteristics and genetic etiology of fetal Dandy-Walker spectrum (DWS) anomalies.Methods:This retrospective cohort study analyzed 28 fetuses with ultrasonographically confirmed DWS (ten classic Dandy-Walker malformations and 18 Dandy-Walker variants) at the First Affiliated Hospital, Zhengzhou University from January 2019 to June 2024. All cases underwent systematic ultrasonographic evaluation. Genetic analyses included chromosomal karyotyping alone ( n=4) or combined with copy number variation sequencing (CNV-seq) ( n=10). Descriptive statistics and Chi-square tests (or Fisher's exact test) with Bonferroni correction were applied. Results:(1) Among 28 fetuses, seven (25.0%) had isolated DWS and 21 (75.0%) non-isolated DWS. Central nervous system anomalies were most common (53.6%, 15/28). (2) Karyotyping identified abnormalities in four cases (4/14), including two triploidies, one case of mosaicism for a derivative chromosome der(1;10), and one 17p deletion. CNV-seq detected anomalies in six cases (25.0%, 6/24), four of which were missed by karyotyping: 3q23 deletion (encompassing ZIC1/ ZIC4), 13q11 duplication, and other critical variants. (3) Combined testing yielded a higher detection rate (28.6%, 8/28) than karyotyping alone (4/14, χ2=4.62, P=0.032) or CNV-seq alone (25.0%, 6/24, χ2=4.83, P=0.028) ( P=0.048 and 0.044 after Bonferroni correction). Conclusions:DWS demonstrates significant genetic heterogeneity, primarily involving chromosomal numerical anomalies (e.g., triploidy) and copy number variations (e.g., 3q23 deletion). Combined karyotyping and CNV-seq improves detection rates of genetic abnormalities.