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.

Objective: To develop a modified calculation formula for renal tumor volume and tumor contact surface area (CSA) based on the modeling results of 3D Slicer software, and to create a webpage of the calculation formula for use. Methods: The general information and tumor anatomical data of 98 patients who underwent partial nephrectomy during Jan.2021 and Jul.2023 in the Second Affiliated Hospital of Xi'an Jiaotong University were retrospectively analyzed.The imaging data were input into 3D Slicer software in the form of Dicom files for tumor and ipsilateral kidney modeling to obtain tumor anatomical data.The relationship between tumor anatomical parameters and tumor volume and CSA was analyzed using multifactorial linear regression.The initial modified formulas (V2, C2) and the optimized modified formulas (V3, C3) for tumor volume over CSA were established, respectively, after insignificant variables were eliminated.The mean square error (MSE) and Akaike information criterion (AIC) of the modified and traditional formulas (V1, C1) were compared, and the formula with the smallest MSE and AIC was selected as the optimal tumor volume and CSA calculation formula.The median tumor volume and CSA obtained from 3D modeling were used as the cutoff values.The optimal formula and conventional formula were applied to calculate tumor volume and CSA for all patients, and risk stratification was performed for all patients based on these cutoff values, and the perioperative indicators of patients in the upper and lower groups were compared.Finally, an online calculation tool was developed based on HTML. Results: Based on multifactorial linear regression analysis, we obtained the modified tumor volume calculation formula: V=0.382abc+2.488a+2.372b－4.146c+1.948（V2）, V=0.469abc－4.586c+13.816（V3）; the modified tumor CSA calculation formula CSA=2.469a －2.262L －19.23a+6.206b+1.212c+18.017L+1.616h－3.97h －2.185h/h －0.388（C2）, CSA=2.376a －2.144L －20.157a+5.024b+1.128c+17.578L+2.525h－2.634（C3）.Both of the modified volume formula (MSE=151.298 vs. 127.807 vs. 104.106) and modified CSA formula (MSE=309.878 vs.23.556 vs.30.388) had smaller errors compared to the conventional formula.The modified volume calculation formula showed that bleeding was more and thermal ischemia time was longer in patients with larger tumor volumes than in patients with smaller tumor volumes (P<0.05); and the modified CSA calculation formula showed that bleeding was more, surgery and thermal ischemia time were longer in patients with high CSA than in patients with low CSA (P＜0.05).Finally, V3 and C3 are selected as the best calculation formula, and a web page (https://lizihao-bot.github.io/RCC-Calculate/) was established for easy use. Conclusion: This study combined data from a medical information technology platform with numerical modeling methods to provide a faster and more accurate method to calculate the renal tumor volume and CSA.Meanwhile, a webpage version of the tool was developed to enhance its practicability.

In recent years, with the continuous development and increasing maturity of interventional techniques, interventional treatment for congenital heart disease (CHD) has been progressively disseminated to county- and city-level hospitals in China. Concurrently, the standardized management of adult CHD (particularly patent foramen ovale) and the lifelong management of complex CHD are gaining increasing clinical attention, while the emergence of new techniques and products continuously advances the discipline. This article aims to review the new progress made in the field of interventional treatment for congenital heart disease in China during 2024. It specifically reviews and analyzes the following key aspects: (1) annual statistics on interventional closure procedures for CHD; (2) recent insights into patent foramen ovale closure; (3) advances in transcatheter pulmonary valve replacement; (4) interventional treatment and lifelong management strategies for complex CHD; (5) new interventional techniques for acquired heart disease; and (6) the application of artificial intelligence in CHD management. Through the synthesis and discussion of these topics, this article seeks to provide a detailed analysis of the current landscape of interventional treatment for CHD in China and project its future development trends.

OBJECTIVES: To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application. Methods and. RESULTS: Recommendations were formulated based on literature review and expert group discussion, and consensus was reached following expert consultation. The consensus recommendations are comprehensive, covering the entire treatment procedures from preoperative assessment and preparation, surgical operation process, postoperative management and traditional Chinese medicine treatment to individualized treatment planning. The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain, reduced the use of opioid drugs, and significantly improved the quality of life and enhanced immune function of the patients. Postoperative follow-up suggested good treatment tolerance among the patients without serious complications. CONCLUSIONS The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy. The combined treatment has a high clinical value with a good safety profile for management of cancer pain.
Humans ; Medicine, Chinese Traditional ; Cancer Pain/therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Drug Delivery Systems ; Pain Management/methods* ; China

OBJECTIVE: To develop a quality consistency evaluation strategy for traditional Chinese medicine (TCM) granules using sugar free Yangwei Granules as a model drug, and demonstrate the effectiveness of the developed method. METHODS: The strategy integrates several methods including, HPLC fingerprint and physical fingerprint methods analyze the similarity in chemical and physical properties of the TCM granule samples. Near-infrared (NIR) spectroscopy with principal components cluster analysis method is used to monitor normal operating conditions (NOC) samples accurately and to identify different types of abnormal operating conditions (AOC) samples, particularly those that deviate from the normal range. RESULTS: The combined use of HPLC fingerprint and physical fingerprint provides insights into the chemical and physical properties of the samples. NIR spectroscopy, combined with principal components cluster analysis, achieves high accuracy in monitoring NOC samples and identifying AOC samples without misjudgment. The approach proves useful as a complementary method in cases where HPLC fingerprint and physical fingerprint alone lack sufficient resolution. CONCLUSION This study establishes the feasibility and utility of the integrated approach for assessing the quality consistency of TCM granules. The strategy shows a high degree of generalization and holds significant importance for enhancing the quality control processes of TCM granules.

OBJECTIVE: Gastric cancer (GC) is one of the most common malignancies seen in clinic and requires novel treatment options. Morin is a natural flavonoid extracted from the flower stalk of a highly valuable medicinal plant Prunella vulgaris L., which exhibits an anti-cancer effect in multiple types of tumors. However, the therapeutic effect and underlying mechanism of morin in treating GC remains elusive. The study aims to explore the therapeutic effect and underlying molecular mechanisms of morin in GC. METHODS: For in vitro experiments, the proliferation inhibition of morin was measured by cell counting kit-8 assay and colony formation assay in human GC cell line MKN45, human gastric adenocarcinoma cell line AGS, and human gastric epithelial cell line GES-1; for apoptosis analysis, microscopic photography, Western blotting, ubiquitination analysis, quantitative polymerase chain reaction analysis, flow cytometry, and RNA interference technology were employed. For in vivo studies, immunohistochemistry, biomedical analysis, and Western blotting were used to assess the efficacy and safety of morin in a xenograft mouse model of GC. RESULTS: Morin significantly inhibited the proliferation of GC cells MKN45 and AGS in a dose- and time-dependent manner, but did not inhibit human gastric epithelial cells GES-1. Only the caspase inhibitor Z-VAD-FMK was able to significantly reverse the inhibition of proliferation by morin in both GC cells, suggesting that apoptosis was the main type of cell death during the treatment. Morin induced intrinsic apoptosis in a dose-dependent manner in GC cells, which mainly relied on B cell leukemia/lymphoma 2 (BCL-2) associated agonist of cell death (BAD) but not phorbol-12-myristate-13-acetate-induced protein 1. The upregulation of BAD by morin was due to blocking the ubiquitination degradation of BAD, rather than the transcription regulation and the phosphorylation of BAD. Furthermore, the combination of morin and BCL-2 inhibitor navitoclax (also known as ABT-737) produced a synergistic inhibitory effect in GC cells through amplifying apoptotic signals. In addition, morin treatment significantly suppressed the growth of GC in vivo by upregulating BAD and the subsequent activation of its downstream apoptosis pathway. CONCLUSION Morin suppressed GC by inducing apoptosis, which was mainly due to blocking the ubiquitination-based degradation of the pro-apoptotic protein BAD. The combination of morin and the BCL-2 inhibitor ABT-737 synergistically amplified apoptotic signals in GC cells, which may overcome the drug resistance of the BCL-2 inhibitor. These findings indicated that morin was a potent and promising agent for GC treatment. Please cite this article as: Wang Y, Sun XY, Ma FQ, Ren MM, Zhao RH, Qin MM, Zhu XH, Xu Y, Cao ND, Chen YY, Dong TG, Pan YF, Zhao AG. Morin inhibits ubiquitination degradation of BCL-2 associated agonist of cell death and synergizes with BCL-2 inhibitor in gastric cancer cells. J Integr Med. 2025; 23(3): 320-332.
Humans ; Flavonoids/therapeutic use* ; Stomach Neoplasms/pathology* ; Animals ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Cell Line, Tumor ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Ubiquitination/drug effects* ; Mice ; Drug Synergism ; Mice, Inbred BALB C ; Mice, Nude ; Xenograft Model Antitumor Assays ; Flavones

Objective To investigate the protective effect of Linggui Zhugan Decoction on myocardial injury in diabetic rats;To explore its molecular mechanism.Methods The diabetes myocardial injury rat model was established by intraperitoneal high fat diet combined with injection of streptozotocin.Successfully modeled rats were randomly divided into model group,simvastatin group(5 mg/kg)and Linggui Zhugan Decoction low-and high-dosage group(3.75,7.5 g/kg).Normal rats were set as blank group,and each medication group was intervened with corresponding drugs.Fasting and random blood glucose were monitored using a glucometer,the left ventricular ejection fraction(LVEF)was measured,serum contents of total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),superoxide dismutase(SOD)and malondialdehyde(MDA)were detected by biochemical kits,the contents of cardiac troponin I(cTnI)and creatine kinase-MB(CK-MB)were detected by ELISA,the myocardial morphology and fibrosis were observed by HE and Masson staining,the positive expression of PDCD4 was detected by immunohistochemistry,the mRNA expressions of miR-21,PDCD4,PTEN and p53 were detected by RT-qPCR,and the protein expressions of PDCD4,PTEN and p53 were detected by Western blot.Results Compared with the blank group,fasting blood glucose and random blood glucose significantly increased at different time points in the model group(P<0.05,P<0.01),LVEF significantly decreased(P<0.01),the contents of serum TC,TG,LDL-C,HDL-C,MDA,cTnI,CK-MB significantly increased(P<0.05,P<0.01),and the content of SOD significantly decreased(P<0.01);the inflammatory cells infiltration and fibrosis injury in myocardial tissue were significantly aggravated(P<0.01),the expression of miR-21 in myocardial tissue significantly decreased,and the mRNA and protein expressions of PDCD4,PTEN,p53 significantly increased(P<0.05,P<0.01).Compared with the model group,fasting blood glucose significantly decreased in simvastatin group and Linggui Zhugan Decoction high-dosage group(P<0.05),LVEF significantly increased(P<0.01),the contents of serum TC,TG,LDL-C,HDL-C,MDA,cTnI and CK-MB significantly decreased(P<0.05,P<0.01),the content of SOD significantly increased(P<0.05,P<0.01);the inflammatory cells infiltration and fibrosis injury in myocardial tissue were significantly improved(P<0.01),the expression of miR-21 in myocardial tissue significantly increased,and the mRNA and protein expressions of PDCD4,PTEN,p53 significantly decreased(P<0.05,P<0.01).Conclusion Linggui Zhugan Decoction may inhibit the expressions of PDCD4,PTEN and p53 by increasing miR-21,thereby alleviating myocardial injury in diabetic rats.

Objective:To explore the value of droplet digital PCR (ddPCR) and next-generation sequencing (NGS) technology in the pathogenetic diagnosis of sepsis patients, and to provide a reference basis for the early diagnosis of sepsis.Methods:A retrospective analysis was used to collect the clinical data of 53 patients with suspected sepsis admitted to the intensive care unit (ICU) of the Second Affiliated Hospital of Xi'an Jiaotong University from February to August 2023, and the blood was collected for blood culture, ddPCR and NGS detection simultaneously.Results:After excluding viral infections, the blood culture positive rate was 18.87%(10/53), the ddPCR positive rate was 47.17% (25/53), and the NGS positive rate was 41.51%(22/53). When using the ddPCR detection range as a reference, the ddPCR positivity rate was 98.11% (52/53), while the NGS positivity rate was 84.91%(45/53). There was a statistically significant difference in the positivity rate between the two groups ( P<0.05). Using blood culture as a reference, the sensitivity (60.00% vs 70.00%) and specificity (65.11% vs 69.77%) of ddPCR and NGS were in good agreement. In terms of pathogen detection, NGS had a wider detection range than ddPCR (34 species vs 21 species), and the difference was statistically significant (χ 2=55.000, P<0.001). In terms of time-consumption, blood culture took 66.93 h on average, while ddPCR was faster than NGS (about 4 h vs 20 h ). In terms of antimicrobial resistance (AMR) gene detection, five resistant strains were detected by both ddPCR and NGS, ddPCR detected two AMR genes, namely blaKPC and mecA, while NGS detected five AMR genes. Among them, except for blaKPC which was detected outside the target range in ddPCR, the other four AMR genes were also detected by ddPCR. Conclusions:Compared with blood culture, ddPCR and NGS have good application value in the etiological diagnosis of sepsis. Specifically, ddPCR has a higher detection rate of pathogens and takes less time. On the other hand, NGS has a wider detection range, especially for the discovery of some rare bacteria or pathogens that are difficult to be cultured routinely.

Objective:To deeply analyze the epidemiological characteristics and changing trends of intestinal infectious diseases in China, and provide scientific evidence for the prevention and control of intestinal infectious diseases.Methods:The incidence data of notifiable intestinal infectious diseases in China from 2013 to 2022 were collected from China Disease Prevention and Control Information System. Descriptive statistical method was used to analyze the distributions of intestinal infectious diseases in China, and the annual change rate and seasonal index were calculated.Results:During 2013-2022, intestinal infectious diseases were reported nationwide, with the cases accounting for 43.50% of all notifiable infectious disease cases. The average reported incidence rate was 224.50/100 000, showing a decreasing trend year by year (average annual percent change=-6.45%, t=-2.76, P=0.025). The top 5 intestinal infectious diseases were hand foot and mouth disease (HFMD) (130.40/100 000), other infectious diarrhea (80.18/100 000), dysentery (7.45/100 000), acute hemorrhagic conjunctivitis (2.49/100 000) and viral hepatitis E (1.92/100 000). The incidences of dysentery, HFMD, typhoid fever/paratyphoid fever, viral hepatitis A and acute hemorrhagic conjunctivitis all showed decreasing trends year by year (all P<0.05), while the incidences of hepatitis E and other infectious diarrhea showed no significant changes with year (both P>0.05). The incidence of intestinal infectious diseases was high during May to October, with the peak in June. The incidence rate of intestinal infectious diseases was significantly higher in men than in women (all P<0.05). The HFMD, other infectious diarrhea and dysentery cases were mainly children aged 0-5 years, while the cholera, hepatitis A, hepatitis E, typhoid fever/paratyphoid fever and acute hemorrhagic conjunctivitis cases were mainly farmers aged ≥20 years. The annual reported incidence rate of intestinal infectious diseases was higher in southern provinces (283.66/100 000) than in northern provinces (142.63/100 000), and the annual reported incidence rate of intestinal infectious diseases was higher in coastal provinces (279.52/100 000) than in inland provinces (181.78/100 000), the differences were all significant (both P<0.001). Conclusions:During 2013-2022, the incidence of intestinal infectious diseases decreased significantly in China, with HFMD and other infectious diarrhea as the main diseases. Strengthened surveillance for intestinal infectious diseases should be carried out in key groups, such as children living scatteredly and farmers, and targeted prevention and control measures should be taken according to the epidemiological characteristics of different diseases to effectively reduce the incidence of intestinal infectious diseases.

In the general population, obesity (high BMI) is often considered as an important risk factor for many diseases and premature death. However, in patients with a certain disease, the risk of death in people with obesity was lower than that in people with normal weight. This abnormal correlation has caused widespread discussion, and different explanations have been given by physiology and epidemiology. Based on causal inference theory, this study used directed acyclic graphs to introduce the collision bias (also called collision-stratification bias). Through example demonstrations, this study explored whether and why the abnormal correlation between obesity and higher survival rates in patients with hyperglycemia exists. Finally, it was concluded that this abnormal correlation among patients with a certain disease (e.g., hyperglycemia in the current analysis) was partly or even totally caused by collider bias.