ObjectiveTo observe the effects of Danggui Shaoyaosan on macrophage polarization and renal inflammation in db/db mice with diabetic kidney disease （DKD）， and to explore its renal protective effects and underlying mechanisms. MethodsEight db/m mice were assigned to the normal group， and forty db/db mice were randomly divided into a model group， low-， medium-， and high-dose Danggui Shaoyaosan groups （8.39， 16.77， 33.54 g·kg^-1）， and an irbesartan group （0.025 g·kg^-1）. All mice were administered treatment by gavage for 12 consecutive weeks. General conditions of the mice were observed during the intervention. At the end of the 12-week intervention， 24-h urine samples were collected using metabolic cages， after which the mice were anesthetized for sample collection. Blood was collected by enucleation and centrifuged to obtain serum for the determination of glycated serum protein （GSP）， serum creatinine （SCr）， blood urea nitrogen （BUN）， total cholesterol （TC）， and triglycerides （TG）. The urinary albumin-to-creatinine ratio （UACR） was measured. Renal pathological changes were observed using hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and Masson staining. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum tumor necrosis factor-α （TNF-α）， interleukin-10 （IL-10）， and monocyte chemoattractant protein-1 （MCP-1） levels. Immunofluorescence （IF） was performed to detect F4/80 expression in renal tissue， and immunohistochemistry （IHC） was used to assess CD206 expression. Real-time quantitative polymerase chain reaction （Real-time PCR） was employed to measure the mRNA expression of TNF-α， IL-10， inducible nitric oxide synthase （iNOS）， and arginase-1 （Arg-1）. Western blot analysis was used to detect the protein expression of iNOS， Arg-1， CD86， and CD206 in renal tissue. ResultsCompared with the normal group， the model group showed increased levels of GSP， UACR， SCr， BUN， TC， and TG， elevated levels of the inflammatory factor TNF-α and the chemokine MCP-1， and decreased IL-10 levels （P<0.01）. Pathological examination revealed glomerular hypertrophy， mesangial cell proliferation with marked mesangial expansion， inflammatory cell infiltration， vacuolar degeneration of renal tubular epithelial cells， prominent glycogen deposition， and increased collagen fiber deposition. In addition， relative F4/80 fluorescence intensity was enhanced， CD206 expression in the glomeruli and renal interstitium was reduced， and TNF-α and iNOS mRNA expression was increased. IL-10 and Arg-1 mRNA expression was decreased， iNOS and CD86 protein expression was increased， and Arg-1 and CD206 protein expression was decreased （P<0.05， P<0.01）. Compared with the model group， the Danggui Shaoyaosan groups and the irbesartan group showed decreased levels of GSP， UACR， SCr， BUN， TC， and TG， reduced serum TNF-α and MCP-1 levels， and increased IL-10 levels. Renal pathological damage was improved to varying degrees. Relative F4/80 fluorescence intensity was reduced， CD206 expression in the glomeruli and renal interstitium was increased， and TNF-α and iNOS mRNA expression was decreased. IL-10 and Arg-1 mRNA expression was increased， iNOS and CD86 protein expression was reduced， and Arg-1 and CD206 protein expression was increased （P<0.05， P<0.01）. ConclusionDanggui Shaoyaosan can improve renal function and alleviate renal pathological damage in db/db mice. Its mechanism may be related to inhibiting M1 pro-inflammatory macrophage polarization， promoting M2 anti-inflammatory macrophage polarization， reducing inflammatory responses， delaying the progression of renal fibrosis， improving renal pathological injury， and thereby exerting renal protective effects.

ObjectiveThe widespread adoption of portable fundus cameras for primary care and community screening is hindered by limitations in current autofocus(AF) technologies. Image-based methods relying on sharpness evaluation require iterative searches, resulting in slow convergence, while projection-based techniques are susceptible to optical artifacts and calibration errors. To address these challenges, this study introduces a novel AF system based on direct wavefront sensing, designed to deliver simultaneous high speed, high precision, and operational robustness within the compact form factor essential for portable ophthalmic devices. MethodsOur approach fundamentally reimagines the AF process by directly measuring the ocular wavefront aberration. We developed a custom portable fundus camera integrating a miniaturized Shack-Hartmann wavefront sensor (SHWS) into the optical path. An 850 nm laser diode projects a point source onto the retina via oblique illumination to minimize corneal reflections. Light scattered from this spot carries the eye’s refractive error through the imaging optics and is directed to the SHWS, positioned at a plane optically conjugate to the primary color CMOS imaging sensor. A microlens array within the SHWS samples the incident wavefront, generating a pattern of focal spots on a CCD. Real-time centroid analysis of these spots provides a map of local wavefront slopes. These measurements are processed through a singular value decomposition (SVD) algorithm to fit a Zernike polynomial basis set, enabling real-time reconstruction of the wavefront phase. The defocus component (S) is extracted from the second-order Zernike coefficients, providing a direct, quantitative measure of the refractive error in diopters. This value serves as a precise error signal in a closed-loop control system, which commands a voice-coil actuated focusing lens to its null position in a single, deterministic step, eliminating the need for iterative search algorithms. ResultsComprehensive evaluation demonstrated the system’s high performance. Testing on a calibrated model eye (OEMI-7) established a highly linear relationship between the computed defocus S and the focusing lens position across a ±20 Diopter (D) compensation range, achievable within a 5 mm mechanical travel. The system achieved a focusing precision of 0.08 D, corresponding to an 18-fold improvement over a conventional projection spot-size method tested under identical conditions. The total focus acquisition time, encompassing wavefront measurement, computation, and lens actuation, averaged under 0.5 s. Clinical validation with 25 human volunteers (50 eyes, refractive range -15 D to +10 D) confirmed practical efficacy. The wavefront-sensing AF succeeded in 92% of attempts with a mean time of 0.5 s, substantially outperforming a projection-based benchmark which achieved only a 32% success rate with an average time of 4.25 s. The system provided instantaneous directional guidance and maintained stability during minor ocular movements. Objective assessment of image quality, via amplitude contrast of retinal vasculature, showed consistent and significant enhancement following AF correction across the entire tested diopter range. ConclusionThis work successfully implements and validates a direct wavefront-sensing autofocus paradigm for portable fundus cameras. By directly quantifying and compensating for the optical defocus aberration, this method bypasses the fundamental limitations of image-processing and projection-based techniques, enabling rapid, precise, and deterministic diopter compensation. The developed system delivers an exceptional combination of a wide operational range (±20 D), high accuracy (0.08 D), fast convergence (0.5 s), and a compact physical footprint. This technology provides a practical and high-performance focusing solution capable of enhancing the reliability, throughput, and diagnostic utility of portable retinal imaging in large-scale screening applications. Future efforts will be directed towards system cost optimization and performance adaptation for diverse ocular conditions.

Background/Aims: Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy. Methods: We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues. Results: We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts. Conclusion Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.

Objective: To investigate the association between brain and muscle Arnt like protein 1( BMAL 1) gene and ambulatory blood pressure (ABP) parameters in college students, and to explore the influence of the interaction between the gene and weight status on the ABP levels, so as to provide reference for early prevention of chronic cardiovascular diseases related to hypertension. Methods: During September 2022 to June 2024, a total of 510 college students were recruited from a university in Changsha, China for on site questionnaire investigation, physical examination, ABP monitoring and genotyping testing. Multiple linear regression method was used to explore the association between the BMAL 1 gene and ABP indicators. An interaction term was included in the general linear model of multiple linear regression to analyze the interactive effects of BMAL 1 gene polymorphisms and weight status on ABP levels. Results: The prevalence of abnormal 24 hour blood pressure, abnormal daytime blood pressure, and abnormal nighttime blood pressure were 3.3%, 3.1%, and 3.9%, respectively. Multiple linear regression analysis showed that the BMAL 1/rs7950226 polymorphism was positively correlated with the 24 hour diastolic blood pressure(DBP) and the daytime DBP level after adjusting for gender, age, and body mass index( β =0.87,0.99, both P <0.05). Also, interaction between BMAL 1/ rs 11022775 and weight status on the nighttime DBP level ( P interaction =0.03) was found. The CC genotype carriers had significantly higher nighttime DBP level ( β =3.52, P <0.05) among overweight/obesity college students, but no differences in nocturnal DBP levels were observed between CC genotype carriers and TT+CT genotype carriers among college students with normal body weight( P > 0.05). Conclusions The rs 7950226 polymorphism is associated with 24 hours DBP and daytime DBP levels. Significant interaction between rs 11022775 with weight status on the nighttime DBP level is found among college students.

ObjectiveTo explore the ethical issues and coping strategies in the diagnosis and treatment of 46, XY disorders of sex development （46, XY DSD） under a multidisciplinary team （MDT） model， and to deepen the understanding of relevant ethical issues while accumulating experience. MethodsA retrospective collection was conducted on the data of children with 46, XY disorders of sex development under a single-center MDT model from January 2017 to December 2024， and the ethical issues involved in the diagnosis and treatment process were analyzed. ResultsA total of 24 MDT discussion documents involving 20 children were collected， including 17 with female social gender and 3 with male social gender. The age ranged from 0.5 to 15.8 years， with children under 8 years accounting for 75%. The ethical issues primarily involved how to ensure adequate informed consent， whether surgery was necessary and its timing， and whether gender selection is reasonable and its timing. Among the 10 children raised as females who completed the gender role psychological scale assessment， 5 demonstrated masculine tendencies， all of whom had pathogenic genetic variants. Furthermore， only 1 patient changed the social gender to male. ConclusionThe diagnosis and treatment of 46, XY DSD is relatively complex， requiring multidisciplinary collaboration. This process involves numerous ethical issues and necessitates adhering to medical ethical principles. Ensuring adequate informed consent is crucial， especially for younger children. The surgery and its timing selection must adhere to the principles of beneficence， non-maleficence， and leaving room for the future. Gender selection constitutes a focus and challenge in diagnosis and treatment. Psychological scales and genetic etiologies are conducive to judgments regarding gender selection， yet multiple factors in the real world may interfere with the gender selection.

Objective:To analyze the characteristics of obstructive sleep apnea（OSA）in children with Prader-Willi syndrome (PWS),and to improve the understanding of OSA during rapid eye movement sleep.Methods:The clinical data of 13 children with PWS aged 2-14 years admitted to Shenzhen Children's Hospital from June 2017 to June 2024 were retrospectively collected as the PWS group,and 12 children with snoring caused by adenoids,tonsil hypertrophy and/or obesity were selected as the control group.The gender,age,body mass index (BMI),obstructive apnea index (OAI),oxygen desaturation index (ODI),obstructive sleep apnea hypopnea index (OAHI),rapid eye movement period OAHI(OAHIrem),non-rapid eye movement period OAHI(OAHInrem) and OAHIrem/total sleep period OAHI ratio were compared between the two groups.Multivariate linear regression was used to assess the association between PWS and OAHIrem.Results:Among the 13 children in PWS group,there were 7 males and 6 females,with an average age of (7.63±4.05) years and an average BMI of (23.06±6.12) kg/m2.Among the 12 children in control group,there were 10 males and 2 females,with an average age of (7.28±3.92) years and an average BMI of (22.41±5.68) kg/m2.There were no statistically significant differences in age,gender,and BMI between the two groups ( P>0.05).All 13 children (100%) with PWS had OSA,with 8 cases (61.53%) of mild OSA and 5 cases (38.46%) of moderate to severe OSA.OAI and ODI in PWS group were significantly higher than those in control group ( P<0.05).OAHI and OAHInrem in PWS group were higher than those in control group,but the difference was not statistically significant ( P>0.05).OAHIrem and OAHIrem/ total sleep OAHI ratio were significantly higher than those in the control group,with statistical significance ( P<0.05).Multivariate linear regression analysis showed that PWS was significantly correlated with OAHIrem/ total sleep OAH ratio (square root) ( P=0.008). Conclusion:Children with PWS have a high incidence of OSA,with a high proportion of moderate to severe OSA.They are prone to OSA with hypoxemia during rapid eye movement sleep.It is recommended that respiratory monitoring of children with PWS during rapid eye movement sleep should be strengthened,and individualized treatment plan should be formulated according to the type and severity of OSA.

Objective To provide relevant suggestions for ethical considerations in clinical research by searching literature related to ethics in clinical research using the visualization analysis software CiteSpace,and to analyze and compare the current research status of clinical research ethics at home and abroad.Methods The papers on the application of medical ethics in clinical trials from the core collection of CNKI and Web of Science databases were collected and the bibliometric software CiteSpace was used to draw a knowledge map of domestic and foreign literature.The research hotspots and development trends of medical ethics in clinical trials were analyzed.Results In terms of the process of informed consent,risk minimization,fair selection,and protection on the rights and interests of vulnerable groups,the focus of medical ethics research in China were basically consistent with foreign literature.The difference was that foreign research focused more on ethical education,the quality of life of research participants,and ethical counseling.Otherwise,domestic research focused more on the quality management of clinical trials and the specificity of traditional Chinese medicine research,with research on vulnerable groups mostly focused on children.Conclusion Chinese researchers should strengthen multi-dimensional research on medical ethics in China,and gradually expand their view from ethical review points and management research to applied research solved clinical problems and the specificity of research participants,and increasing the number and dimensions of research.

Objective To provide relevant suggestions for ethical considerations in clinical research by searching literature related to ethics in clinical research using the visualization analysis software CiteSpace,and to analyze and compare the current research status of clinical research ethics at home and abroad.Methods The papers on the application of medical ethics in clinical trials from the core collection of CNKI and Web of Science databases were collected and the bibliometric software CiteSpace was used to draw a knowledge map of domestic and foreign literature.The research hotspots and development trends of medical ethics in clinical trials were analyzed.Results In terms of the process of informed consent,risk minimization,fair selection,and protection on the rights and interests of vulnerable groups,the focus of medical ethics research in China were basically consistent with foreign literature.The difference was that foreign research focused more on ethical education,the quality of life of research participants,and ethical counseling.Otherwise,domestic research focused more on the quality management of clinical trials and the specificity of traditional Chinese medicine research,with research on vulnerable groups mostly focused on children.Conclusion Chinese researchers should strengthen multi-dimensional research on medical ethics in China,and gradually expand their view from ethical review points and management research to applied research solved clinical problems and the specificity of research participants,and increasing the number and dimensions of research.

Objective:To analyze the characteristics of obstructive sleep apnea（OSA）in children with Prader-Willi syndrome (PWS),and to improve the understanding of OSA during rapid eye movement sleep.Methods:The clinical data of 13 children with PWS aged 2-14 years admitted to Shenzhen Children's Hospital from June 2017 to June 2024 were retrospectively collected as the PWS group,and 12 children with snoring caused by adenoids,tonsil hypertrophy and/or obesity were selected as the control group.The gender,age,body mass index (BMI),obstructive apnea index (OAI),oxygen desaturation index (ODI),obstructive sleep apnea hypopnea index (OAHI),rapid eye movement period OAHI(OAHIrem),non-rapid eye movement period OAHI(OAHInrem) and OAHIrem/total sleep period OAHI ratio were compared between the two groups.Multivariate linear regression was used to assess the association between PWS and OAHIrem.Results:Among the 13 children in PWS group,there were 7 males and 6 females,with an average age of (7.63±4.05) years and an average BMI of (23.06±6.12) kg/m2.Among the 12 children in control group,there were 10 males and 2 females,with an average age of (7.28±3.92) years and an average BMI of (22.41±5.68) kg/m2.There were no statistically significant differences in age,gender,and BMI between the two groups ( P>0.05).All 13 children (100%) with PWS had OSA,with 8 cases (61.53%) of mild OSA and 5 cases (38.46%) of moderate to severe OSA.OAI and ODI in PWS group were significantly higher than those in control group ( P<0.05).OAHI and OAHInrem in PWS group were higher than those in control group,but the difference was not statistically significant ( P>0.05).OAHIrem and OAHIrem/ total sleep OAHI ratio were significantly higher than those in the control group,with statistical significance ( P<0.05).Multivariate linear regression analysis showed that PWS was significantly correlated with OAHIrem/ total sleep OAH ratio (square root) ( P=0.008). Conclusion:Children with PWS have a high incidence of OSA,with a high proportion of moderate to severe OSA.They are prone to OSA with hypoxemia during rapid eye movement sleep.It is recommended that respiratory monitoring of children with PWS during rapid eye movement sleep should be strengthened,and individualized treatment plan should be formulated according to the type and severity of OSA.

Objective To investigate the correlation between maternal serum folic acid(FA),monocyte chemoattractant protein-1(MCP-1),progesterone-induced blocking factor(PIBF)levels and embryonic development cessation in early pregnancy.Methods From December 2021 to December 2023,98 pregnant women with embryonic development cessation in early pregnancy admitted to the Second Hospital of Jingzhou were regarded as the cessation group,and 50 normal early pregnancy pregnant women who underwent pregnancy examinations during the same period were as the control group.General clinical data was collected and analyzed.Enzyme-linked immunosorbent assay(ELISA)was applied to detect serum levels of FA,MCP-1 and PIBF.Multivariate logistic regression was applied to analyze the influencing factors of early pregnancy embryo cessation of development.Receiver operating characteristic(ROC)curve was plotted to analyze the predictive value of serum FA,MCP-1,and PIBF for early embryonic development cessation in pregnancy.Pearson method was applied to analyze the correlation between serum FA,MCP-1,PIBF,progesterone(PROG),estradiol(E2)and β-human chorionic gonadotropin(β-HCG).Results Compared with the control group,the serum FA(9.51±1.21 nmol/L vs 11.32±1.56 nmol/L)and PIBF(295.46±30.22 ng/ml vs 342.14±36.97 ng/ml)levels in the cessation group were greatly reduced,while the serum MCP-1(1.02±0.15 mg/ml vs 0.82±0.11 mg/ml)level was greatly increased,and the differences were statistically significant(t=7.785,8.347,8.229,all P＜0.001).There were great statistical differences in the history of embryonic development cessation(75.64%vs 25.36%),PROG(13.32±1.81 ng/ml vs 23.65±2.74 ng/ml),E2(221.34±25.69 pmol/L vs 298.65±31.64 pmol/L),and β-HCG levels(5 323.62±536.85U/L vs 8 562.31±924.55 U/L)between the two groups(t/χ2=6.548～27.428,all P<0.05).Pregnant women's history of embryonic development cessation and elevated level of MCP-1 were risk factors for embryonic development cessation in early pregnancy(Wald χ2=4.239,4.613,all P<0.05),while elevated levels of β-HCG,FA and PIBF were protective factors for embryonic development cessation in early pregnancy(Wald χ2=4.476,4.423,5.974,all P<0.05).The AUC of FA,MCP-1,PIBF,and their combination in predicting early embryonic development cessation in pregnancy was 0.811,0.805,0.816 and 0.908,respectively.The combined prediction was greatly better than that of individual diagnosis of FA MCP-1,and PIBF(Z=2.749,2.381,1.993,all P<0.05).FA and PIBF were positively correlated with PROG,E2 and β-HCG(r=0.433～0.512,all P<0.05),while MCP-1 was negatively correlated with PROG,E2 and β-HCG(r=-0.432,-0.487,-0.458,all P<0.05).Conclusion The serum levels of FA and PIBF in pregnant women with embryonic development cessation in early pregnancy decrease,while the level of MCP-1 increases.These three factors are all influencing factors for embryonic development cessation in pregnant women,and have certain auxiliary predictive value for embryonic development cessation in early pregnancy.