ObjectiveTo investigate the mechanisms of Runmu Dihuang decoction （RMDHD） in treating perimenopausal dry eye with liver-kidney Yin deficiency syndrome based on the silent information regulator 3 （SIRT3）/hypoxia-inducible factor-1α （HIF-1α）/nuclear factor-κB （NF-κB） signaling pathway. MethodsSixty female Sprague-Dawley rats were randomly divided into six groups （n=10 per group）： Sham operation group， model group， sodium hyaluronate eye drop group， and low-， medium-， and high-dose RMDHD groups （5.625， 11.25， 22.50 g·kg^-1）. Except for the sham operation group， all rats underwent bilateral ovariectomy and were administered 0.1% benzalkonium chloride eye drops combined with long-term chronic irritation to establish a perimenopausal dry eye model with liver-kidney Yin deficiency syndrome. Drug administration began in the 11th week after modeling and continued for 21 days. General conditions， screen-grip test scores， tear secretion volume， tear film breakup time （TFBUT）， and corneal fluorescein staining were recorded. Serum levels of reactive oxygen species （ROS）， follicle-stimulating hormone （FSH）， estradiol （E₂）， and progesterone （PROG） were measured by enzyme-linked immunosorbent assay （ELISA）. Pathological changes in the lacrimal glands， corneas， and uteri were observed using hematoxylin-eosin （HE） staining. Protein expression levels of SIRT3， HIF-1α， phosphorylated NF-κB p65 （p-NF-κB p65）， and total NF-κB p65 in the lacrimal glands were detected by Western blot. The expression of inflammatory cytokines interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in the lacrimal glands was assessed by immunohistochemistry （IHC）. ResultsAfter model establishment， no significant differences were observed among the groups except the sham operation group. Compared with the sham operation group， the other groups exhibited slowed movement， dull responses， increased irritability， reduced body weight， elevated rectal temperature， decreased screen-grip test scores， reduced tear secretion， and significantly shortened TFBUT （P<0.05）. After treatment， compared with the model group， the sodium hyaluronate eye drop group and all RMDHD groups showed improved general conditions， significantly increased tear secretion （P<0.05）， prolonged TFBUT （P<0.05）， and elevated screen-grip test scores （P<0.05）. Serum ROS and FSH levels were significantly decreased， while E₂ and PROG levels were significantly increased （P<0.05）. Pathological damage to the cornea， lacrimal glands， and uterus was ameliorated. In addition， protein expression levels of SIRT3 and HIF-1α in the lacrimal glands were significantly upregulated （P<0.05）， whereas the expression of p-NF-κB p65， IL-1β， and TNF-α was significantly downregulated （P<0.05）. ConclusionRMDHD increases tear secretion and TFBUT， improves lacrimal gland and corneal injury， and alleviates dry eye symptoms in a perimenopausal dry eye rat model with liver-kidney Yin deficiency syndrome. The underlying mechanism may be related to regulation of the SIRT3/HIF-1α/NF-κB signaling pathway， inhibition of oxidative stress and inflammatory responses， and reduction of ocular surface tissue damage.

Background: The treatment landscape for melanoma, a particularly malignant skin cancer, is constrained by notable drug resistance and toxicity. β-Asarone, a natural compound from Acorus tatarinowii, has shown anticancer potential. Disruption of calcium homeostasis and mitochondrial dysfunction are key regulators of tumor cell survival and death. Objective: This research was conducted to investigate the impact of β-Asarone on B16F10 melanoma cells, focusing on its potential to induce apoptosis by modulating calcium signaling and mitochondrial function. Methods: Cell proliferation and apoptosis were evaluated using CCK-8, colony formation, EdU, and TUNEL assays. Intracellular calcium levels and mitochondrial membrane potential were measured using Fluo-4 AM, Rhod-2 AM, and JC-1 staining. Reactive oxygen species (ROS) generation and adenosine triphosphate (ATP) levels were assessed by fluorescent probes and ATP assay. Western blotting was utilized to detect apoptosis-related proteins, AMP-activated protein kinase (AMPK) pathway activation, and mitochondrial dynamics (OPA1, DRP1, FIS1). Results: Treatment with β-Asarone notably inhibited the proliferation of B16F10 cells while simultaneously inducing apoptosis. Fluorescent probe analysis revealed that β-Asarone triggered cytosolic and mitochondrial Ca 2+ overloaded in both the cytosol and mitochondria, accompanied by decreased mitochondrial membrane potential, elevated ROS levels, and reduced ATP production. Western blot analysis showed increased expression of DRP1 and FIS1, decreased OPA1, and enhanced AMPK phosphorylation, indicating that β-Asarone promotes mitochondrial fission through AMPK activation, likely driven by intracellular calcium imbalance. Conclusion This study demonstrates that β-Asarone induces apoptosis in B16F10 melanoma cells by triggering Ca 2+ overload and mitochondrial dysfunction.

Patients with inflammatory bowel disease (IBD) require long-term pharmacotherapy. Due to the wide variety of clinically available drugs, medication safety has become increasingly concerning. As an indispensable component of pharmaceutical formulations, drug excipients may induce various adverse reactions, including rash, allergic responses, and gastrointestinal discomfort, and may even lead to severe organic injury. However, they are often overlooked in clinical practice. Therefore, identifying and managing excipient-related adverse reactions is crucial for ensuring medication safety. To address this issue, this article systematically reviews common excipients in IBD therapeutics, the underlying mechanisms of excipient-induced adverse reactions, and corresponding management strategies, aiming to enhance clinicians' awareness of excipient-related issues, improve their ability to recognize and manage such reactions, and ultimately ensure patient safety.

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.

AIM: To analyze the changes in binocular visual function before and after small incision lenticule extraction(SMILE)in patients with different degrees of myopia.METHODS:A prospective non-randomized controlled study was conducted. A total of 94 patients(188 eyes)who visited the refractive outpatient department of the ophthalmology department of the General Hospital of the PLA from June 2022 to June 2023 and voluntarily chose SMILE were consecutively included. They were grouped according to the degree of myopia, including 24 cases(48 eyes)in the low myopia group(-3.00 D

OBJECTIIVE:The positive role of exercise intervention in the prevention and treatment of sarcopenia has received widespread attention,but the optimal exercise dose for elderly sarcopenic patients still needs to be further determined.The article explored the dose-effect relationship between various elements of exercise prescription and the improvement of muscle mass,muscle strength and physical function in community-dwelling elderly patients with sarcopenia,aiming to provide scientific support for the development of exercise prescription for community-dwelling elderly patients with sarcopenia.METHODS:Literature published from the inception to October 9,2024 in PubMed,EMBASE,Scopus,Web of Science,CNKI,WanFang,VIP,and CBMdisc databases was systematically searched.Meta-analysis was performed using RevMan 5.3 software.Standardized mean difference(SMD)and its 95％CI were used as effect statistics.RESULTS:(1)A total of 11 randomized controlled trials were included,with 348 in the trial group and 304 in the control group.(2)Meta-analysis results showed that exercise improved appendicular skeletal muscle mass index,grip strength,and walking speed in elderly patients with sarcopenia(SMDs 0.46,0.63,0.67,P＜0.05).(3)When the frequency of exercise was 2-3 days/week,appendicular skeletal muscle mass index(SMD=0.57,95％CI:0.28-0.86,P＜0.001),grip strength(SMD=0.70,95％CI:0.37-1.02,P＜0.001),and walking speed(SMD=0.69,95％CI:0.20-1.18,P=0.006)were effectively improved in elderly patients with sarcopenia.(4)When the duration of exercise was 25-60 minutes per session,appendicular skeletal muscle mass index(SMD=0.28,95％CI:0.07-0.50,P=0.01),grip strength(SMD=0.37,95％CI:0.16-0.59,P＜0.001),and walking speed(SMD=0.39,95％CI:0.06-0.73,P=0.02)were effectively improved in elderly patients with sarcopenia.(5)When the exercise intensity was moderate,appendicular skeletal muscle mass index(SMD=0.69,95％CI:0.35-1.03,P＜0.001),and grip strength(SMD=0.36,95％CI:0.09-0.64,P=0.009),and walking speed(SMD=0.91,95％CI:0.34-1.47,P=0.002)were effectively improved in elderly patients with sarcopenia.(6)When the dose of exercise cycle was 8-12 weeks,appendicular skeletal muscle mass index(SMD=0.42,95％CI:0.20-0.64,P＜0.001),grip strength(SMD=0.45,95％CI:0.26-0.64,P＜0.001),and walking speed(SMD=0.76,95％CI:0.27-1.25,P=0.002)were effectively improved in elderly patients with sarcopenia.CONCLUSION:Active,regular exercise can improve muscle health in older adults with sarcopenia.It is recommended that older patients with sarcopenia exercise at least 2 to 3 days per week,25 to 60 minutes each time,lasting for 8 to 12 weeks of moderate intensity exercise to improve muscle health.

Chronic heart failure(CHF)is a common end-stage manifestation of cardiovascular disease,and the"spleen-small intestine-heart"axis is its important mechanism.Current studies have shown that the"spleen"in TCM and mitochondria function are similar,and the physiological dysfunction of the"small intestine"is also closely related to intestinal bacterial dysbiosis,and the pathology of the spleen and the small intestine will be transmitted to the heart to accelerate the occurrence and development of CHF.Based on the relevant theory of spleen-small intestine-heart,this article described the correlation between abnormal mitochondrial energy metabolism and imbalance of intestinal flora and CHF from the aspects of the spleen,small intestine and heart,and believed that the essence of CHF is a pathological condition formed by mitochondrial energy metabolism crisis and intestinal microecological disorders,which could provide theoretical references for the TCM prevention and treatment of CHF.

Objectives:To investigate the relationship between QRS duration and its changes during hospitalization and long-term all-cause mortality in patients with chronic heart failure.Methods:A total of 3 580 patients who attended three tertiary hospitals in Shanxi Province(First Hospital of Shanxi Medical University,Shanxi Cardiovascular Hospital,Shanxi Bethune Hospital)and were diagnosed with chronic heart failure from March 2014 to November 2021,were enrolled in this study.QRS duration at admission and discharge were collected,and the changes in QRS duration during hospitalization(ΔQRS)and the ΔQRS ratio(ΔQRS/admission QRS duration×100% )were calculated.Patients were divided into three group according to tertiles of ΔQRS:the group with decreasing QRS duration(n=1 364),the group with stable QRS duration(n=1 248),and the group with progressing QRS duration(n=968).Telephone follow-up was conducted at months 1,3,6,12,and every 6 months thereafter after discharge till May 1,2023,long-term all-cause mortality was the primary endpoint.Survival curves were plotted using the Kaplan-Meier method,and comparisons between groups were made using the log-rank method.Cox proportional risk regression model was used for prognostic analysis,and restricted cubic spline curves were calculated to evaluate QRS duration-related variables during hospitalization and the risk of long-term all-cause mortality in patients with chronic heart failure.Results:The median follow-up was 71(56,92)months,and all-cause mortality occurred in 502(14.0% )patients.Long-term all-cause mortality was lower in the group with decreasing QRS duration and the group with stable QRS duration compared with the progressing QRS duration group(13.9% vs.10.7% vs.18.6%,χ2=28.607,P<0.001).Multifactorial Cox regression analysis showed that admission QRS duration(HR=1.005,95% CI:1.002-1.009,P=0.003)and higher ΔQRS ratio during hospitalization(HR=2.071,95% CI:1.247-3.440,P=0.005)were independent influencing factors of long-term all-cause mortality in chronic heart failure patients.Restricted cubic spline curves showed that when the admission QRS duration was>96.36 ms,the longer the QRS duration,the higher the risk of all-cause mortality;when the admission QRS duration fluctuated from 89.32-96.36 ms,the QRS duration was a protective factor for long-term all-cause mortality in patients with chronic heart failure;and when the ΔQRS ratio during hospitalization was≥3.40%,higher ΔQRS ratio was linked with increased risk of all-cause mortality.Conclusions:QRS duration and ΔQRS ratio during hospitalization are independent predictors of long-term all-cause mortality in patients with chronic heart failure.Admission QRS duration>96.36 ms and ΔQRS ratio during hospitalization≥3.40% are associated with increased risk of long-term all-cause mortality in patients with chronic heart failure.

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

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.