Signal detection is a critical task in drug safety regulation. However, it inevitably generates irrelevant or false signals, posing challenges for resource allocation by marketing authorization holders. To reasonably assess these signals, different countries have established various principles for prioritizing the evaluation of risk signals. This study systematically compares these principles and finds that the U.S. Food and Drug Administration(FDA) focuses on practical issues, such as identifying drug confusion or drug interactions. However, China's Good Pharmacovigilance Practices and the European Medicines Agency(EMA) emphasize a comprehensive evaluation framework. The Council for International Organizations of Medical Sciences(CIOMS) emphasizes the consistency of multiple data sources, highlighting the reliability of signal evaluation. China practices a multidisciplinary approach combining traditional Chinese and western medicine, and the risk signals related to traditional Chinese medicine(TCM) have unique characteristics, including complex components, cumulative toxicity, specific theoretical foundations, and drug interactions. The different priorities in risk signal evaluation principles across countries suggest that China should strengthen clinical trial research, emphasize corroboration with evidence of multiple sources, and pay particular attention to the risks of drug interactions in the TCM regulatory science. Establishing the risk signal prioritization principles that align with the characteristics of TCM enables more precise and efficient scientific regulation of TCM.
Humans ; Medicine, Chinese Traditional/standards* ; China ; Drugs, Chinese Herbal/adverse effects* ; United States ; United States Food and Drug Administration

This paper aimed to investigate the therapeutic effect and mechanism of action of the Yiqi Fumai Formula(YQFM), a kind of traditional Chinese medicine(TCM), on mice with experimental heart failure based on the "heart-gut axis" theory. Based on the network pharmacology integrated with the group collaboration algorithm, the active ingredients were screened, a "component-target-disease" network was constructed, and the potential pathways regulated by the formula were predicted and analyzed. Next, the model of experimental heart failure was established by intraperitoneal injection of adriamycin at a single high dose(15 mg·kg~(-1)) in BALB/c mice. After intraperitoneal injection of YQFM(lyophilized) at 7.90, 15.80, and 31.55 mg·d~(-1) for 7 d, the protective effects of the formula on cardiac function were evaluated using indicators such as ultrasonic electrocardiography and myocardial injury markers. Combined with inflammatory factors in the cardiac and colorectal tissue, as well as targeted assays, the relevant indicators of potential pathways were verified. Meanwhile, 16S rDNA sequencing was performed on mouse fecal samples using the Illumina platform to detect changes in gut flora and analyze differential metabolic pathways. The results show that the administration of injectable YQFM(lyophilized) for 7 d significantly increased the left ventricular end-systolic internal diameter, fractional shortening, and ejection fraction of cardiac tissue of mice with experimental heart failure(P<0.05). Moreover, markers of myocardial injury were significantly decreased(P<0.05), indicating improved cardiac function, along with significantly suppressed inflammatory responses in cardiac and intestinal tissue(P<0.05). Additionally, the species of causative organisms was decreased, and the homeostasis of gut flora was improved, involving a modulatory effect on PI3K-Akt signaling pathway-related inflammation in cardiac and colorectal tissue. In conclusion, YQFM can affect the "heart-gut axis" immunity through the homeostasis of the gut flora, thereby exerting a therapeutic effect on heart failure. This finding provides a reference for the combination of TCM and western medicine to prevent and treat heart failure based on the "heart-gut axis" theory.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Heart Failure/microbiology* ; Mice ; Mice, Inbred BALB C ; Male ; Disease Models, Animal ; Gastrointestinal Microbiome/drug effects* ; Heart/physiopathology* ; Humans ; Signal Transduction/drug effects*

To evaluate the therapeutic effect of a modified Devine procedure with a subcutaneous sliding fixation method for the treatment of congenital concealed penis, we retrospectively selected 45 patients with congenital concealed penises who were admitted to General Hospital of Ningxia Medical University (Yinchuan, China) between September 2020 and November 2023. In all cases, the penis was observed to be short, and retracting the skin at the base revealed a normal penile body, which immediately returned to its original position upon release. All patients underwent the modified Devine procedure with subcutaneous sliding fixation and completed a 12-week postoperative follow-up. A statistically significant increase in penile length was observed postoperatively, with the median length increasing from 4.0 (interquartile range [IQR]: 3.5-4.8; 95% confidence interval [CI]: 3.9-4.4) cm to 8.0 (IQR: 7.8-8.0; 95% CI: 7.7-7.9) cm, with P < 0.001. The parents were satisfied with the outcomes, including increased penile length, improved hygiene, and enhanced esthetics. Except for mild foreskin edema in all cases, no complications (such as infections, skin necrosis, or penile retraction) were observed. The edema was resolved within 4 weeks after the operation. This study demonstrates that the modified Devine procedure utilizing the subcutaneous sliding fixation method yields excellent outcomes with minimal postoperative complications, reduced penile retraction, and high satisfaction rates among patients and their families.
Humans ; Male ; Penis/abnormalities* ; Retrospective Studies ; Urologic Surgical Procedures, Male/methods* ; Treatment Outcome ; Child ; Plastic Surgery Procedures/methods*

OBJECTIVE: To evaluate the efficacy and safety of denosumab in the treatment of prostate cancer with bone metastases. METHODS: Relevant studies were retrieved from PubMed, EMBASE, Cochrane, Web of Science, Sinomed , CNKI and Wanfang databases. The Cochrane risk-of-bias assessment tool was used to evaluate the quality of included studies, and relevant data were extracted. meta-analysis was performed using RevMan 5.4 and RStudio software, and forest plots were generated. RESULTS: Six randomized controlled trials (RCTs) were included. Compared with the control group, denosumab significantly reduced the risk of skeletal-related events (HR=0.78, 95% CI: 0.62-0.93). In terms of safety, denosumab did not increase the risk of total adverse events, severe adverse events and the adverse events higher than CTC grade 3. CONCLUSION Denosumab can delay the time to first skeletal-related event with good safety. However, due to the limitations of this study, further high-quality, large-sample, multicenter RCTs are needed to confirm these findings.
Humans ; Denosumab/therapeutic use* ; Bone Neoplasms/drug therapy* ; Prostatic Neoplasms/drug therapy* ; Male ; Randomized Controlled Trials as Topic ; Bone Density Conservation Agents/therapeutic use*

Coronavirus disease 2019 (COVID-19) is an acute infectious respiratory disease that has been prevalent since December 2019. Chinese medicine (CM) has demonstrated its unique advantages in the fight against COVID-19 in the areas of disease prevention, improvement of clinical symptoms, and control of disease progression. This review summarized the relevant material components of CM in the treatment of COVID-19 by searching the relevant literature and reports on CM in the treatment of COVID-19 and combining with the physiological and pathological characteristics of the novel coronavirus. On the basis of sorting out experimental methods in vivo and in vitro, the mechanism of herb action was further clarified in terms of inhibiting virus invasion and replication and improving related complications. The aim of the article is to explore the strengths and characteristics of CM in the treatment of COVID-19, and to provide a basis for the research and scientific, standardized treatment of COVID-19 with CM.
Humans ; Drugs, Chinese Herbal/pharmacology* ; COVID-19 Drug Treatment ; SARS-CoV-2/drug effects* ; COVID-19/therapy* ; Medicine, Chinese Traditional/methods* ; Antiviral Agents/pharmacology* ; Animals

Mitochondrial dysfunction is a critical factor in the pathogenesis of Alzheimer's disease (AD). The mitochondrial contact site and cristae organizing system (MICOS) plays a pivotal role in shaping the inner mitochondrial membrane, forming cristae junctions and establishing interaction sites between the inner and outer mitochondrial membranes and thereby serving as a cornerstone of mitochondrial structure and function. In the past decade, MICOS abnormalities have been extensively linked to AD pathogenesis. In particular, dysregulated expression of MICOS subunits and mutations in MICOS-related genes have been identified in AD, often in association with hallmark pathological features such as amyloid-β plaque accumulation, neurofibrillary tangle formation, and neuronal apoptosis. Furthermore, MICOS subunits interact with several etiologically relevant proteins, significantly influencing AD progression. The intricate crosstalk between these proteins and MICOS subunits underscores the relevance of MICOS dysfunction in AD. Therapeutic strategies targeting MICOS subunits or their interacting proteins may offer novel approaches for AD treatment. In the present review, we introduce current understanding of MICOS structures and functions, highlight MICOS pathogenesis in AD, and summarize the available MICOS-targeting drugs potentially useful for AD.

Objective:To construct a virtual-real interactive system HE-01 for the treatment of microtia based on HoloLens and verify the feasibility of applying HE-01 in ear reconstruction.Methods:Six volunteers (3 males and 3 females, average age: 20.5 years old) and six patients with microtia(3 males and 3 females, average age: 7.6 years old) were recruited from Plastic Surgery Hospital of Chinese Academy of Medical Sciences from August to September 2021. The Mimics Research 21.0 software and 3-matic research software were used to construct a virtual three-dimensional auricle model. Based on HoloLens and occlusal splint navigation marker device, the virtual-real interactive system HE-01 for the treatment of microtia was constructed. The registration accuracy, tracking delay and display effect of different colors (red, green, blue and skin color) of HE-01 were evaluated through repeated experiments of volunteers. The operation process was defined through repeated experiments of patients and the feasibility of applying HE-01 in auricular reconstruction was verified.Results:HE-01 was built successfully and the operation flow was clear. The experiment of six volunteers (12 ears) showed a high registration accuracy (average error rate 2.3%-2.4%, less than 2.7% of the bilateral auricle size difference of normal people), low tracking delay (six volunteers were all less than 0.1 s), and best green and red display effect of virtual auricle guide under different angles (-60°, -30°, 0°, 30°, 60°). Experiments of patients with microtia showed that HE-01 could be applied to auricular reconstruction, and there were no obvious complications in wearing the navigation marker device, which had repeatability and stability.Conclusion:This study has completed the conceptual design of augmented-reality assisted auricular reconstruction based on navigation device, CT data and HoloLens. HE-01 has good registration accuracy, tracking speed and display effect, laying a good foundation for further software development and clinical transformation.

More than 70%of tumor patients require radiotherapy.Medical electron linear accelerators are important high-end radiotherapy equipment for tumor radiotherapy.With the application of artificial intelligence technology in medical electron linear accelerator,radiotherapy has evolved from ordinary radiotherapy to today's intelligent radiotherapy.This study introduces the development history,working principles and system composition of medical electron linear accelerators.It outlines the key technologies for improving the performance of medical linear electron accelerators,including beam control,multi-leaf collimator,guiding technology and dose evaluation.It also looks forward to the development trend of major radiotherapy technologies,such as biological guided radiotherapy,FLASH radiotherapy and intelligent radiotherapy,which provides references for the development of medical electron linear accelerators.

Objective:To examine the impact of varied surgical treatment strategies on the prognosis of patients with initial resectable gastric cancer liver metastases (IR-GCLM).Methods:This is a retrospective cohort study. Employing a retrospective cohort design, the study selected clinicopathological data from the national multi-center retrospective cohort study database, focusing on 282 patients with IR-GCLM who underwent surgical intervention between January 2010 and December 2019. There were 231 males and 51 males, aging ( M(IQR)) 61 (14) years (range: 27 to 80 years). These patients were stratified into radical and palliative treatment groups based on treatment decisions. Survival curves were generated using the Kaplan-Meier method and distinctions in survival rates were assessed using the Log-rank test. The Cox risk regression model evaluated HR for various factors, controlling for confounders through multivariate analysis to comprehensively evaluate the influence of surgery on the prognosis of IR-GCLM patients. A restricted cubic spline Cox proportional hazard model assessed and delineated intricate associations between measured variables and prognosis. At the same time, the X-tile served as an auxiliary tool to identify critical thresholds in the survival analysis for IR-GCLM patients. Subgroup analysis was then conducted to identify potential beneficiary populations in different surgical treatments. Results:(1) The radical group comprised 118 patients, all undergoing R0 resection or local physical therapy of primary and metastatic lesions. The palliative group comprised 164 patients, with 52 cases undergoing palliative resections for gastric primary tumors and liver metastases, 56 cases undergoing radical resections for gastric primary tumors only, 45 cases undergoing palliative resections for gastric primary tumors, and 11 cases receiving palliative treatments for liver metastases. A statistically significant distinction was observed between the groups regarding the site and the number of liver metastases (both P<0.05). (2) The median overall survival (OS) of the 282 patients was 22.7 months (95% CI: 17.8 to 27.6 months), with 1-year and 3-year OS rates were 65.4% and 35.6%, respectively. The 1-year OS rates for patients in the radical surgical group and palliative surgical group were 68.3% and 63.1%, while the corresponding 3-year OS rates were 42.2% and 29.9%, respectively. A comparison of OS between the two groups showed no statistically significant difference ( P=0.254). Further analysis indicated that patients undergoing palliative gastric cancer resection alone had a significantly worse prognosis compared to other surgical options ( HR=1.98, 95% CI: 1.21 to 3.24, P=0.006). (3) The size of the primary gastric tumor significantly influenced the patients′ prognosis ( HR=2.01, 95% CI: 1.45 to 2.79, P<0.01), with HR showing a progressively increasing trend as tumor size increased. (4) Subgroup analysis indicates that radical treatment may be more effective compared to palliative treatment in the following specific cases: well/moderately differentiated tumors ( HR=2.84, 95% CI 1.49 to 5.41, P=0.001), and patients with liver metastases located in the left lobe of the liver ( HR=2.06, 95% CI 1.19 to 3.57, P=0.010). Conclusions:In patients with IR-GCLM, radical surgery did not produce a significant improvement in the overall prognosis compared to palliative surgery. However, within specific patient subgroups (well/moderately differentiated tumors, and patients with liver metastases located in the left lobe of the liver), radical treatment can significantly improve prognosis compared to palliative approaches.

Objective:To construct a virtual-real interactive system HE-01 for the treatment of microtia based on HoloLens and verify the feasibility of applying HE-01 in ear reconstruction.Methods:Six volunteers (3 males and 3 females, average age: 20.5 years old) and six patients with microtia(3 males and 3 females, average age: 7.6 years old) were recruited from Plastic Surgery Hospital of Chinese Academy of Medical Sciences from August to September 2021. The Mimics Research 21.0 software and 3-matic research software were used to construct a virtual three-dimensional auricle model. Based on HoloLens and occlusal splint navigation marker device, the virtual-real interactive system HE-01 for the treatment of microtia was constructed. The registration accuracy, tracking delay and display effect of different colors (red, green, blue and skin color) of HE-01 were evaluated through repeated experiments of volunteers. The operation process was defined through repeated experiments of patients and the feasibility of applying HE-01 in auricular reconstruction was verified.Results:HE-01 was built successfully and the operation flow was clear. The experiment of six volunteers (12 ears) showed a high registration accuracy (average error rate 2.3%-2.4%, less than 2.7% of the bilateral auricle size difference of normal people), low tracking delay (six volunteers were all less than 0.1 s), and best green and red display effect of virtual auricle guide under different angles (-60°, -30°, 0°, 30°, 60°). Experiments of patients with microtia showed that HE-01 could be applied to auricular reconstruction, and there were no obvious complications in wearing the navigation marker device, which had repeatability and stability.Conclusion:This study has completed the conceptual design of augmented-reality assisted auricular reconstruction based on navigation device, CT data and HoloLens. HE-01 has good registration accuracy, tracking speed and display effect, laying a good foundation for further software development and clinical transformation.