BACKGROUND: Neoadjuvant chemoradiotherapy followed by radical surgery has been a common practice for patients with locally advanced rectal cancer, but the response rate varies among patients. This study aimed to develop a ResNet-Vision Transformer based magnetic resonance imaging (MRI)-endoscopy fusion model to precisely predict treatment response and provide personalized treatment. METHODS: In this multicenter study, 366 eligible patients who had undergone neoadjuvant chemoradiotherapy followed by radical surgery at eight Chinese tertiary hospitals between January 2017 and June 2024 were recruited, with 2928 pretreatment colonic endoscopic images and 366 pelvic MRI images. An MRI-endoscopy fusion model was constructed based on the ResNet backbone and Transformer network using pretreatment MRI and endoscopic images. Treatment response was defined as good response or non-good response based on the tumor regression grade. The Delong test and the Hanley-McNeil test were utilized to compare prediction performance among different models and different subgroups, respectively. The predictive performance of the MRI-endoscopy fusion model was comprehensively validated in the test sets and was further compared to that of the single-modal MRI model and single-modal endoscopy model. RESULTS: The MRI-endoscopy fusion model demonstrated favorable prediction performance. In the internal validation set, the area under the curve (AUC) and accuracy were 0.852 (95% confidence interval [CI]: 0.744-0.940) and 0.737 (95% CI: 0.712-0.844), respectively. Moreover, the AUC and accuracy reached 0.769 (95% CI: 0.678-0.861) and 0.729 (95% CI: 0.628-0.821), respectively, in the external test set. In addition, the MRI-endoscopy fusion model outperformed the single-modal MRI model (AUC: 0.692 [95% CI: 0.609-0.783], accuracy: 0.659 [95% CI: 0.565-0.775]) and the single-modal endoscopy model (AUC: 0.720 [95% CI: 0.617-0.823], accuracy: 0.713 [95% CI: 0.612-0.809]) in the external test set. CONCLUSION The MRI-endoscopy fusion model based on ResNet-Vision Transformer achieved favorable performance in predicting treatment response to neoadjuvant chemoradiotherapy and holds tremendous potential for enabling personalized treatment regimens for locally advanced rectal cancer patients.
Humans ; Rectal Neoplasms/diagnostic imaging* ; Magnetic Resonance Imaging/methods* ; Male ; Female ; Middle Aged ; Neoadjuvant Therapy/methods* ; Aged ; Adult ; Chemoradiotherapy/methods* ; Endoscopy/methods* ; Treatment Outcome

The continuous emergence of SARS-CoV-2 variants as well as other potential future coronavirus has challenged the effectiveness of current COVID-19 vaccines. Therefore, there remains a need for alternative antivirals that target processes less susceptible to mutations, such as the formation of six-helix bundle (6-HB) during the viral fusion step of host cell entry. In this study, a novel high-throughput screening (HTS) assay employing a yeast-two-hybrid (Y2H) system was established to identify inhibitors of HR1/HR2 interaction. The compound IMB-9C, which achieved single-digit micromolar inhibition of SARS-CoV-2 and its Omicron variants with low cytotoxicity, was selected. IMB-9C effectively blocks the HR1/HR2 interaction in vitro and inhibits SARS-CoV-2-S-mediated cell-cell fusion. It binds to both HR1 and HR2 through non-covalent interaction and influences the secondary structure of HR1/HR2 complex. In addition, virtual docking and site-mutagenesis results suggest that amino acid residues A930, I931, K933, T941, and L945 are critical for IMB-9C binding to HR1. Collectively, in this study, we have developed a novel screening method for HR1/HR2 interaction inhibitors and identified IMB-9C as a potential antiviral small molecule against COVID-19 and its variants.

Screening carbonyl reductases with the ability to catalyze the reduction of complex carbonyl compounds is of great significance for the biosynthesis of R-tolvaptan(R-TVP). In this study, the target carbonyl reductase in the crude enzyme extract of rabbit liver was separated, purified, and identified by ammonium sulfate precipitation, gel-filtration chromatography, ion exchange chromatography, affinity chromatography, and protein mass spectrometry. With the rabbit liver genome as the template, the gene encoding the carbonyl reductase rlsr5 was amplified by PCR and the recombinant strain was successfully constructed. After RLSR5 was purified by affinity chromatography, its enzymatic properties were characterized. The results indicated that the gene sequence of rlsr5 was 972 bp, encoding a protein with a molecular weight of 40 kDa. RLSR5 was a dimeric protein, and each monomer was composed of a (α/β)₈-barrel structure. RLSR5 could asymmetrically reduce 7-chloro-1-[2-methyl-4-[(2- methylbenzoyl)amino]benzoyl]-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine (prochiral ketone, PK) to synthesize R-TVP. The specific activity of the enzyme was 36.64 U/mg, and the optical purity of the product was 99%. This enzyme showcased the optimal performance at pH 6.0 and 30 °C. It was independent of metal ions, with the activity enhanced by Mn²⁺. This study lays a foundation for the biosynthesis of tolvaptan of optical grade.
Animals ; Rabbits ; Alcohol Oxidoreductases/biosynthesis* ; Recombinant Proteins/metabolism* ; Escherichia coli/metabolism* ; Liver/enzymology*

Objective:To analyze the risk factors for central lymph node metastasis (CLNM) in patients with papillary thyroid cancer (PTC) aged 55 years and above, and to construct a predictive model with columnar graph.Methods:This retrospective study included 406 PTC patients aged 55 and above, treated at the First Affiliated Hospital of Zhengzhou University from Nov. 2019 to Feb. 2022. Data on demographic characteristics, disease features, and laboratory test results were collected. Univariate and multivariate logistic regression analyses were used to identify risk factors for CLNM and develop a clinical prediction model and nomogram.Results:The study involved 406 patients, divided into a modeling group (285 patients) and a validation group (121 patients). The predictive model identified independent risk factors for CLNM. In the modeling group, the model demonstrated a ROC AUC of 0.769, with 82.6% sensitivity, 63.0% specificity, and 67.7% accuracy. The validation group showed 66.7% sensitivity, 74.5% specificity, and 72.7% accuracy, with an AUC of 0.760. Hosmer-Lemeshow tests indicated good fit in both groups. Decision curve analysis confirmed the model's clinical decision-making value, showing better performance than traditional strategies and good generalizability and reliability.Conclusions:Sex, maximum tumor diameter, bilateral involvement of thyroid lobes, clinically evident cervical lymph nodes, and local invasion are independent predictive factors for CLNM in patients over 55 with papillary thyroid carcinoma (PTC). A clinical risk stratification nomogram model based on these risk factors demonstrates good predictive performance.

Objective:This article analyzed the current situation, similarities and differences and main problems of the registration and management systems of innovative medical devices in China and the United States.Methods:This article summarized the requirements and policies for the registration management of innovative medical devices in China and the United States, as well as the development and differences of the registration of innovative medical devices in China and the United States, and the main problems in the registration management of innovative medical devices in China.Results:At present, the development level of medical device industry in China and the United States was different, facing different development problems, and there were differences in the access standards and management methods of innovative medical devices. The registration management system established for innovative medical devices in China was gradually improving, and to a certain extent, it had promoted the enthusiasm of innovative product research and development and registration applications, but there were also problems such as unclear innovation evaluation scales, insufficient early intervention of review resources, and insufficient utilization of post-marketing data.Conclusions:Drawing on the beneficial experience of breakthrough device registration management in the United States, we will improve the registration management system for innovative products and shorten the review and approval cycle by clarifying the identification criteria for innovative medical devices, promoting the placement of review resources in the R&D stage, and further strengthening the use of post-marketing data and regulatory scientific research.

Objective Based on the framework of"quantitative analysis of supporting policies",this study focuses on the formulation and implementation of supporting policies for pharmaceutical science and technology innovative enterprises in China,so as to provide a certain reference for the implementation and improvement of policies for pharmaceutical science and technology innovative enterprises in China.Methods This study used Roy Rothwell and Walter Zegveld's innovative policy tools as the basis for analysis,and combined with the dimension of policy type,the policy was quantitatively analyzed.Results A total of 47 effective policy documents were selected,including 22 issued by the state and 25 issued by Beijing municipal government.A total of 104 policy instruments were included through the dismantling of policy provisions.Specifically,environment-based policy tools accounted for the highest proportion(60.58%),while demand-based and supply-based policy tools were relatively few.From the perspective of policy types,there were more planning policy documents(25 articles),while there were relatively few specific implementation policies(22 articles).Conclusion It is necessary to focus on optimizing the formulation stage of support policies and improving the use of supply-oriented and demand-oriented policy tools to better meet the needs of pharmaceutical science and technology innovative enterprises.

Objective To assess the impact of DRG-based payment on inpatient costs for a single disease in a tertiary traditional Chinese medicine hospital.Methods This study focused on the inpatient information of patients with the DRG group FM19(percutaneous coronary artery stenting)in the cardiology department of a tertiary traditional Chinese medicine hospital from January 2020 to December 2021.We utilized Stata 15 statistical software and applied interrupted time series models and differ-ence-in-differences methods to evaluate the cost changes before and after DRG-based payment.Results After the implementa-tion of DRG-based payment,the annual average total cost for the FM19 group decreased by 26 503.62 yuan(P＜0.001),and the annual average cost of consumables decreased by 23 937.32 yuan(P＜0.001).The overall costs of traditional Chinese medi-cine and herbal treatments in the FM19 group significantly decreased(P＜0.05).For patients with angina,total costs,consum-able costs,and medication costs showed an overall decreasing trend;however,for patients with myocardial infarction,the reduc-tion in medication costs was not significant,while total costs and consumable costs decreased significantly.Conclusion The im-plementation of DRG-based payment for this disease type has shown significant cost control effects,with a notable decrease in the costs of traditional Chinese medicine treatments.Tertiary traditional Chinese medicine hospitals should proactively prepare to re-spond to and adapt to payment reforms.

Objective To analyze the medical services by Beijing Hospital of Traditional Chinese Medicine(TCM)and provide references for TCM hospitals to promote Internet-based medical services.Methods The data of Internet-based diagnosis and treatment,including registration,service volume,patient-doctor information,and payment items were collected from the Bei-jing Hospital of TCM from January 1,2022,to February 2023 for descriptive analysis.Results The cases of online video diag-nosis and treatment totaled 44 186,while graphic and textual consultations reached 3 231 times/person,with the registration can-cellation rates of 28.3％and 13.0％,respectively.In video diagnosis and treatment,doctors holding the professional title of As-sociate Senior Doctor or higher accounted for 66％of the total number of doctors providing online services,and they completed 75.4％of the total service volume.The service volume in the fields of psychology,dermatology,oncology,gastroenterology,re-spiratory,pediatrics,gynecology,and nephrology was higher.The number of patients taking Chinese herbal medicine was signifi-cantly higher than those taking western medicine and traditional Chinese patent medicines.Conclusion Online diagnosis and treatment partially meets patients'online medical needs but lacks TCM characteristics and integration with offline services.Therefore,more online TCM hospitals should be developed by strengthening popularization and education,optimizing functions and services,applying data in-depth,and developing high-quality online specialized clinics.

Objective:To investigate the effects of ultrasound-guided serratus anterior plane block (SAPB) on hemodynamics in children with microtia undergoing auricular reconstruction.Methods:This research was a prospective randomized control study. Patients were prospectively recruited from March 2022 to July 2022 at the Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Children with microtia undergoing auricular reconstruction with costal cartilage were randomly included in either a SAPB-pre group(SAPB pre-rib harvest group) or a SAPB-post group(SAPB post-rib harvest group). Both groups of children were anesthetized with combined intravenous and inhalation anesthesia. Anesthesia maintenance was provided with i. v. propofol 4-6 mg·kg -1·h -1 and remifentanil 0.1-0.3 μg·kg -1·min -1, sevoflurane at 1% concentration, and a flow rate of 2.5 L/min. During the operation, bispectral index(BIS) was maintained between 40-60, and alterations in mean arterial pressure (MAP) and heart rate (HR) were <20%, compared to the basic values. During the operation, 1% sevoflurane was inhaled to maintain anesthesia. The fluctuation of BIS, MAP, and HR was adjusted by the intraoperative infusion of remifentanil and propofol. Ultrasound-guided SAPB in the SAPB-pre group was performed by an anesthesiologist after tracheal intubation of general anesthesia. In the SAPB-post group, ultrasound-guided SAPB was performed by the same anesthesiologist before the tracheal catheter was removed at the end of the operation, and the concentration of ropivacaine was 0.25% (3 mg/kg). MAP, HR, and BIS were recorded at each time point of admission, pre-rib harvest, during-rib harvest, post-rib harvest, anesthesia extubation, leaving the room. The consumptions of propofol and remifentanil during the operation were also recorded. Continuous data were presented as Mean±SD. Non-repeated measurement parametric variables were compared using the independent samples t-test. Repeated measurement parametric variables were assessed using repeated measures analysis of variance. The same data at varying time points were compared using Dunnett- t test of multiple comparison procedures. Categorical data were compared using the Chi-square test. Results:Sixty children were randomized to SAPB-pre group and SAPB-post group and 30 in each group. The data of gender (boy 22/ girl 8 vs. boy 23/ girl 7), age[(8.03±1.07)years vs. (8.33±1.16)years], body mass index [(17.46±2.79)kg/m 2 vs. (17.23±2.11)kg/m 2], operation time[(185.33±16.29)min vs. (190.00±16.50)min] and length of costocartilage[(23.13±1.46)cm vs. (23.63±1.27)cm] between the two groups showed no significant differences ( P>0.05). There was no significant difference in MAP, HR and BIS values at the time of pre-rib harvest, during-rib harvest, and post-rib harvest in the SAPB-pre group ( P>0.05). In the SAPB-post group, the fluctuations of MAP, HR and BIS values at the time of pre-rib harvest, during-rib harvest and post-rib harvest were obvious ( P<0.01). The consumptions of propofol and remifentanil during the operation in the SAPB-pre group were significantly less than that in the SAPB-post group[(555.67±150.90)mg vs. (788.50±191.02)mg, P<0.01; (745.33±183.56)μg vs. (1 080.00±247.26)μg, P<0.01]. Conclusion:Ultrasound-guided serratus anterior plane block can stabilize the hemodynamics during auricular reconstruction using costal cartilage and reduce the consumption of general anesthetic.

The prevalence of osteoporosis， osteoarthritis， gouty arthritis， rheumatoid arthritis， and intervertebral disc degeneration is increasing year by year with the growing number of elderly people， and the common clinical manifestations of these diseases include severe pain in different areas， which seriously affects the daily life of the patients. Therefore， how to relieve the pain and reduce the prevalence of bone and joint diseases and improve the quality of life of the patients is a hot spot in the medical field. Studies have confirmed that NOD-like receptor family， pyrin domain-containing protein 3 （NLRP3） inflammasomes， as pattern recognition receptors， are involved in the inflammation， chondrocyte proliferation， osteoblast and osteoclast differentiation， intervertebral disc cell inflammation and scorching， extracellular matrix degradation and apoptosis， mitochondrial dysfunction， endoplasmic reticulum stress， and reactive oxygen species damage， demonstrating close link with the development of bone and joint diseases. Chinese medicine has a long history and demonstrates remarkable therapeutic effects in the treatment of bone and joint diseases. It can mitigate the pathological changes of bone and joint diseases by inhibiting NLRP3 inflammasomes to alleviate the pain， playing a role in preventing and treating these diseases. Therefore， this paper briefly describes the relationship between NLRP3 inflammasomes and the development of bone and joint diseases by reviewing the latest research progress at home and abroad. We summarize the latest studies about the active components， extracts， and compound prescriptions of Chinese medicines in the treatment of bone and joint diseases via regulating NLRP3 inflammasomes. This review is expected to offer new insights into the in-depth research on the pathogenesis and drug treatment of bone and joint diseases and provide a basis for the clinical application of Chinese medicine in the prevention and treatment of such diseases.