AIM: To explore the factors influencing heart rate(HR)changes during small incision lenticule extraction(SMILE)surgery by monitoring HR trends at different time points of the procedure.METHODS: Prospective cohort study. A total of 69 patients who underwent SMILE surgery at the Laser Vision Correction Center of Xi'an No.1 Hospital from April to May 2024 were enrolled. Before the surgery, patients completed the State Anxiety Inventory(S-AI, questions 1-20)to assess their preoperative anxiety scores related to the next day's surgery. Baseline HR was recorded using medical pulse oximeter, and real-time HR was recorded during patient positioning, lenticule scanning, lenticule separation and extraction, and the application of postoperative eye drops.RESULTS: The HR during patient positioning was 83.61±13.87 bpm, which was significantly different from the baseline HR(77.52±10.88 bpm), HR during lenticule separation and extraction(75.54±12.52 bpm), and HR during postoperative eye drop application(76.65±10.54 bpm; all P<0.001). When stratified by median age, older patients(>26 years)had the HR during lenticule separation and extraction 76.27±9.93 bpm, which differed from the HR at positioning(84.82±14.10 bpm)and at lens scanning(82.76±13.72 bpm; all P<0.005). Stratified by gender, the HR of male patients at positioning was the highest(85.31±16.61 bpm), which differed significantly from the baseline HR(78.26±12.63 bpm), HR during lenticule separation and extraction(77.14±14.59 bpm), and HR during postoperative eye drop application(77.11±12.49 bpm; all P<0.005). There was no correlation between HR during positioning and preoperative anxiety scores(r=0.124, P=0.418).CONCLUSION: HR changes during SMILE surgery vary with different procedural stages, peaking during patient positioning and reaching the lowest point during lenticule separation and extraction. Older patients showed higher HR during positioning, and male patients exhibited higher HR during positioning.

In recent years, the rapid development of transportation and sports industries, coupled with the accelerated population aging in China, has led to a steady increase in the incidence of articular cartilage injuries, wear, and degenerative changes. Currently, the clinical treatment options for cartilage defects primarily include conservative therapies and surgical interventions, both of which have certain limitations. Cartilage tissue engineering (CTE), as a novel technology, provides an infinite prospect for cartilage regeneration and repair. Because of the abilities of scaffolds to mimic the natural cartilage structure, exhibit excellent biocompatibility and biomimetic mechanical properties, and promote cell adhesion and proliferation, scaffolds are considered effective delivery systems for growth factors, genes, and drugs. This review summarizes the clinical treatments for cartilage defects and their limitations, discusses the materials and preparation techniques of scaffolds used in CTE, with a particular focus on drug-loaded scaffold delivery systems in cartilage repair and regeneration, and offers a perspective on the future application of drug-loaded CTE. The aim is to provide theoretical guidance and new approaches for the repair of cartilage defects.
Tissue Engineering/methods* ; Humans ; Tissue Scaffolds ; Drug Delivery Systems/methods* ; Regeneration ; Cartilage, Articular/physiology* ; Animals ; Biocompatible Materials

Synthetic biology is a crucial tool for the development of the bio-industry and bio-economy, representing a significant aspect of new quality productive forces. As a core course for graduate students in bioengineering, Synthetic Biology plays a vital role in ensuring the supply of essential talents for the development of the bio-industry in the new era. To better serve regional economic development and provide high-level talents for China's progress in the bio-industry, we analyzed typical issues encountered in the past teaching activities, set up a multi-disciplinary teaching team, optimized the course contents, adjusted the teaching mode, and mobilized students' learning interest. With the application of scientific research project as the starting point, we guided students to think and discuss deeply through the simulation of application writing and project defense, which improved students' critical thinking and innovative thinking. With industrialization as a focus, we explored a new training model combining production, education, and research through the joint practice base of the university and enterprises introduced typical cases of biomanufacturing to encourage students to engage in scientific research. The teaching reform significantly enhances the comprehensive abilities and national sentiments of graduate students. This paper hopes to serve as a reference for colleagues engaged in teaching in this field.
Synthetic Biology/education* ; Teaching ; China ; Humans

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Objective To establish the reference interval of urine Alzheimer-associated neuronal thread protein(AD7c-NTP)for healthy adults in Mianyang area using the indirect method.Methods The detection results of urine AD7c-NTP from 5 093 healthy in-dividuals were collected from the information management database of Medical Laboratory Department of Sichuan Science City Hospital from March 2017 to March 2022.Skewness-kurtosis and Kolmogorov-Smirnov tests were used to determine whether the data followed a normal distribution.After removing outliers using the Box Plots method,the enrolled subjects were grouped by gender and age.The Mann-Whitney U or Kruska-Wallis H tests were used to analyze the between-group differences of urine AD7c-NTP in healthy individu-als with different genders and ages.The adjacent age groups without statistically significant difference(P＞0.05)were combined,and the indirect method(non-parametric test method)was used to calculate the reference intervals for different gender and age groups.Results Skewness-kurtosis and Kolmogorov-Smirnov tests showed that the data followed a non-normal distribution.After removing 293 outliers using the Box Plots method,a total of 4 800 subjects,including 3 199 males and 1 601 females,were enrolled.The enrolled subjects were grouped by gender and age,and the non-parametric test method were used to establish the reference intervals of urine AD7c-NTP in healthy populations with different genders.The Mann-Whitney U test confirmed that urine AD7c-NTP levels existed gen-der differences(Z=14.09,P＜0.01),and the reference intervals for males and females were≤1.10 ng/mL and≤1.40 ng/mL,re-spectively.There were also statistical differences in urine AD7c-NTP levels among different age groups of the same gender.After combi-ning adjacent age groups without statistically significant difference(P＞0.05),the reference intervals of urine AD7c-NTP in healthy populations with different genders and ages were established by the non-parametric test method,which were≤1.00 ng/mL for male 20-39 years old group,≤1.10 ng/mL for male 40-79 years old group,≤1.60 ng/mL for male≥80 years old group,≤1.30 ng/mL for female 20-69 years old group,and≤1.60 ng/mL for female≥70 years old group,respectively.The established reference intervals of urine AD7c-NTP were further verified by healthy individuals,and the results met the standards.Conclusion The reference intervals of urine AD7c-NTP in healthy populations with different genders and ages in Mianyang area are established successfully using the indi-rect method,which may help to predict the risk of Alzheimer's disease in clinical practice and provide support for the diagnosis and treatment of the disease.

Objective:To investigate the therapeutic efficacy of programmed death-1(PD-1)inhibitors in combination with drug-eluting beads transcatheter arterial chemoembolization(DEB-TACE)and radiofrequency ablation(RFA), as well as their impact on the prognosis of older patients with primary hepatocellular carcinoma(HCC).Methods:In this prospective cohort study, 120 patients aged 65 years and older with HCC at stage Ⅱb-Ⅲb were randomly assigned to an observation group (n=60)and a control group (n=60)between January 2021 and January 2024.The control group received DEB-TACE followed by RFA, while the observation group received a PD-1 inhibitor in combination with DEB-TACE followed by RFA, with both interventions lasting for 12 weeks.The clinical efficacy of the treatments in both groups was assessed, and changes in serum tumor markers before and after treatment were compared between the two groups.Safety was evaluated, survival data were recorded during follow-up, and the effects of different therapeutic regimens on patient prognosis were analyzed.Results:The disease control rate(DCR)and objective response rate(ORR)in the observation group were 88.33% and 78.33%, respectively, which were higher than those in the control group (71.67% and 28.33%, χ2=5.208, 30.134, P=0.022, <0.001). After treatment, levels of serum tumor markers (alpha fetoprotein, carbohydrate antigen 125, vascular endothelial growth factor)decreased in both groups (all P<0.05), with levels in the observation group being lower than those in the control group (all P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups (all P>0.05). By the end of follow-up, which ranged from 2 to 33 months, there were 15 death cases in the observation group, resulting in a cumulative survival rate of 75.00%(45/60) and a mean survival of 25.95 months.In the control group, there were 25 death cases, with a cumulative survival rate of 58.33%(35/60)and a mean survival of 20.33 months.The results of the Kaplan-Meier function analysis were as follows: Log-rank χ2=5.747, P=0.017; Breslow χ2=3.124, P=0.077.The results of the multivariate Cox regression analysis indicated that PD-1 inhibitor combined with DEB-TACE sequential RFA was a protective factor against death in older patients with primary HCC( HR=0.680, 95% CI: 0.463-0.998, P=0.014). Conclusions:The curative effect and safety of PD-1 inhibitor combined with DEB-TACE and RFA are favorable in older patients with advanced HCC.

Objective: To evaluate the efficacy and safety of plasma exchange (PE) in thymoma-associated myasthenia gravis (MG), thereby to provide theoretical support for its application in the treatment of thymoma-associated MG. Methods: A total of 133 patients with thymoma-associated MG admitted from January 2018 to September 2024 were retrospectively analyzed. Patients were matched using propensity score to reduce selection bias, yielding 22 matched pairs for both PE group (n=22) and non-PE group (n=22). Patient characteristics including gender, age of disease onset, course of disease, history of thymoma resection, clinical absolute scores [clinical absolute scores (CAS) and clinical relative scores (CRS)], and synchronized immunotherapy regimen of the two groups were analyzed. The CAS scores before and after treatment were compared between the two groups, and the CRS was used to assess the treatment efficiency. Safety of the two treatment regimens were also compared. Continuous variables were compared using the t-test or ANOVA, while categorical data were compared by the chi-square test. Results: A total of 133 patients were included and divided into two groups according to whether they underwent plasma exchange treatment: the PE group (n=22) and the non-PE group (n=111). To exclude bias caused by large difference in the number of cases between the two groups, we performed propensity score matching. After matching, the number of cases in both groups was 22. There was no significant difference in baseline clinical characteristics between the two groups (P>0.05), including gender, age of onset, duration of disease course, history of thymectomy and baseline CAS score before treatment. Compared to the non-PE group, patients in the PE group showed more significant improvement in CAS score (5.09±1.95 vs 3.59±1.50, P<0.05) and a higher CRS score (75.00% vs 50.00%, P<0.001). Compared to the non-PE group, PE group had significantly longer ICU stay, longer hospital stay and higher hospitalization cost (P<0.05). There was no statistically significant difference in adverse events between the two groups during treatment (P>0.05). During long-term follow-up, both the PE and non-PE groups showed relatively low 1-, 3-, and 5-year recurrence rate, with no significant difference between the two groups (P>0.05). Conclusion: This study indicates that plasma exchange has clear value in the treatment of patients with thymoma-associated myasthenia gravis. It can not only significantly improve patients' muscle strength to alleviate motor dysfunction and enhance quality of life, but also does not significantly increase the incidence of adverse reactions. Therefore, it can be regarded as one of the preferred treatment options that achieve a "balance between efficacy and safety" for such patients, and provides an important basis for optimizing treatment strategies, improving prognosis, and promoting the application of subsequent treatment regimens.

An assay was established for detection of toxigenic Clostridioides difficile by combining microfluidic chip analysis with immunochromatography,and its performance was evaluated and compared with those of the Xpert C.difficile/Epi and VIDAS CD AB tests.Primer pairs were designed according to the tcdB and tpi genes in C.difficile.The specificity,limit of detection,reproducibility,and stability were evaluated.A total of 215 stool samples from patients with diarrhea were collected and tested in parallel with the Xpert C.difficile/Epi,VIDAS CDAB,and our assay.C.difficile was isolated from samples,and the tcdB gene was identified when discrepant results were obtained from the three above assays.Our assay showed no cross-reaction with other diarrhea-associated pathogens.Its reproducibility was 100％in testing of two standard plasmids containing tcdB and tpi genes at two concentrations(105 and 102 copies/μL).Two standard plasmids were detected after the PCR and immunochromatography reagents had been stored for 3,6,9,and 12 months,and all the results were posi-tive.The limit of detection was 10 copies/μL for toxigenic C.difficile.Testing of 33 samples positive for C.difficile with our assay(33/215,15.3％)yielded findings statistically coherent with those of the Xpert C.difficile/Epi test(kappa value=0.965).The sensitivity,specificity,positive predictive value,and negative predictive value of our assay,with respect to Xpert C.difficile/Epi as the standard,were 94.3％,100.0％,100.0％,and 98.9％;these values were significantly higher than those of VIDAS CDAB(60.0％,98.9％,91.3％,and 92.7％)(Kappa=0.714,OR=157.50,95％CI:62.03-847.28,P=0.013).In conclusion,our newly developed assay is specific,stable,and reproducible,and may be used for rapid and accu-rate detection of toxigenic C.difficile.The assay could be used for C.difficile infection screening in outpatient and emergen-cy,community medical service center,and epidemiological settings.

Objective To establish the reference interval of urine Alzheimer-associated neuronal thread protein(AD7c-NTP)for healthy adults in Mianyang area using the indirect method.Methods The detection results of urine AD7c-NTP from 5 093 healthy in-dividuals were collected from the information management database of Medical Laboratory Department of Sichuan Science City Hospital from March 2017 to March 2022.Skewness-kurtosis and Kolmogorov-Smirnov tests were used to determine whether the data followed a normal distribution.After removing outliers using the Box Plots method,the enrolled subjects were grouped by gender and age.The Mann-Whitney U or Kruska-Wallis H tests were used to analyze the between-group differences of urine AD7c-NTP in healthy individu-als with different genders and ages.The adjacent age groups without statistically significant difference(P＞0.05)were combined,and the indirect method(non-parametric test method)was used to calculate the reference intervals for different gender and age groups.Results Skewness-kurtosis and Kolmogorov-Smirnov tests showed that the data followed a non-normal distribution.After removing 293 outliers using the Box Plots method,a total of 4 800 subjects,including 3 199 males and 1 601 females,were enrolled.The enrolled subjects were grouped by gender and age,and the non-parametric test method were used to establish the reference intervals of urine AD7c-NTP in healthy populations with different genders.The Mann-Whitney U test confirmed that urine AD7c-NTP levels existed gen-der differences(Z=14.09,P＜0.01),and the reference intervals for males and females were≤1.10 ng/mL and≤1.40 ng/mL,re-spectively.There were also statistical differences in urine AD7c-NTP levels among different age groups of the same gender.After combi-ning adjacent age groups without statistically significant difference(P＞0.05),the reference intervals of urine AD7c-NTP in healthy populations with different genders and ages were established by the non-parametric test method,which were≤1.00 ng/mL for male 20-39 years old group,≤1.10 ng/mL for male 40-79 years old group,≤1.60 ng/mL for male≥80 years old group,≤1.30 ng/mL for female 20-69 years old group,and≤1.60 ng/mL for female≥70 years old group,respectively.The established reference intervals of urine AD7c-NTP were further verified by healthy individuals,and the results met the standards.Conclusion The reference intervals of urine AD7c-NTP in healthy populations with different genders and ages in Mianyang area are established successfully using the indi-rect method,which may help to predict the risk of Alzheimer's disease in clinical practice and provide support for the diagnosis and treatment of the disease.