Objective:To explore the mechanism of hypertension inducing erectile dysfunction(ED)using transcriptomics and network pharmacology.Methods:We randomly divided 12 male rats with spontaneous hypertension(SHT)into an L-arginine(LA)group(n=6)and an SHT model control(MC)group(n=6),took another 6 Wistar Kyoto male rats as normal controls(NC),and treated the animals in the LA group by intraperitoneal injection of LA at 400 mg/kg and those in the latter two groups with physio-logical saline,once a day,all for 7 days.Then we observed the blood pressure and penile erection of the rats,and determined the ex-pressions of the cGMP/PKG signaling pathway-related proteins and mRNAs in different groups using ELISA,Western blot and RT-qPCR.Results:Transcriptomics combined with network pharmacology showed that the cGMP/PKG signaling pathway played a key role in hypertension-induced ED.In vivo animal experiments revealed a significantly lower frequency of penile erections in the MC than in the NC group(1.33±0.52 vs 2.67±0.51,P＜0.05).The protein expressions of eNOS,PKG and sGC were markedly de-creased in the model controls compared with those the normal controls(P＜0.05),but remarkably upregulated in the LA group com-pared with those in the MC group(P＜0.05).Conclusion:Hypertension decreases the expressions of eNOS,NO,sGC,cGMP and PKG proteins and the level of testosterone by inhibiting the cGMP/PKG signaling pathway,which consequently suppresses the relaxa-tion of the penile vascular smooth muscle and reduces erectile function.

OBJECTIVE: To investigate the effect and potential mechanism of dihydromyricetin (Dmy) on H9C2 cell proliferation, apoptosis, and autophagy. METHODS: H9C2 cells were randomly divided into 7 groups, namely control, model, EV (empty pCDH-CMV-MCS-EF1-CopGFP-T2A-Puro vector), IV (circHIPK3 interference), Dmy (50 µ mol/L), Dmy+IV, and Dmy+EV groups. Cell proliferation and apoptosis were detected by cell counting kit-8 assay and flow cytometry, respectivley. Western blot was used to evaluate the levels of light chain 3 II/I (LC3II/I), phospho-phosphoinositide 3-kinase (p-PI3K), protein kinase B (p-AKT), and phospho-mammalian target of rapamycin (p-mTOR). The level of circHIPK3 was determined using reverse transcriptase polymerase chain reaction. Electron microscopy was used to observe autophagosomes in H9C2 cells. RESULTS: Compared to H9C2 cells, the expression of circHIPK in H9C2 hypoxia model cells increased significantly (P<0.05). Compared to the control group, the cell apoptosis and autophagosomes increased, cell proliferation rate decreased significantly, and the expression of LC3 II/I significantly increased (all P<0.05). Compared to the model group, the rate of apoptosis and autophagosomes in IV, Dmy, and Dmy+IV group decreased, the cell proliferation rate increased, and the expression of LC3 II/I decreased significantly (all P<0.05). Compared to the control group, the expressions of p-PI3K, p-AKT, and p-mTOR in the model group significantly reduced (P<0.05), whereas after treatment with Dmy and sh-circHIPK3, the above situation was reversed (P<0.05). CONCLUSION Dmy plays a protective role in H9C2 cells by inhibiting circHIPK expression and cell apoptosis and autophagy, and the mechanism may be related to PI3K/AKT/mTOR pathway.
Proto-Oncogene Proteins c-akt/metabolism* ; Signal Transduction ; Phosphatidylinositol 3-Kinases/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; Apoptosis ; Autophagy

Objective: To provide a new solution for the digital design of nasal prostheses, this study explores the three-dimensional (3D) facial morphology completion method for external nasal defects based on the non-rigid registration process of 3D face template. Methods: A total of 20 male patients with tooth defect and dentition defect who visited the Department of Prosthodontics, Peking University School and Hospital of Stomatology from June to December 2022 were selected, age 18-45 years old. The original 3D facial data of patients were collected, and the 3D facial data of the external nose defect was constructed in Geomagic Wrap 2021 software. Using the structured 3D face template data constructed in the previous research of the research group, the 3D face template was deformed and registered to the 3D facial data of external nose defect (based on the morphology of non-defective area) by non-rigid registration algorithm (MeshMonk program), and the personalized deformed data of the 3D face template was obtained, as the complemented facial 3D data. Based on the defect boundary of the 3D facial data of the external nose defect, the complemented external nose 3D data can be cut out from the complemented facial 3D data. Then the nasofacial angle and nasolabial angle of the complemented facial 3D data and the original 3D facial data was compared and analyzed, the ratio between the nose length and mid-face height, nose width and medial canthal distance of the complemented facial 3D data was measured, the edge fit between the edge curve of the complemented external nose 3D data and the defect edge curve of the 3D facial data of external nose defect was evaluated, and the morphological difference of the nose between the complemented external nose 3D data and the original 3D facial data was analyzed. Results: There was no significant statistically difference (t=-0.23, P=0.823; Z=-1.72, P=0.086) in the nasofacial angle (28.2°±2.9°, 28.4°±3.5° respectively) and nasolabial angle [95.4°(19.2°), 99.9°(9.5°) respectively] between the 20 original 3D facial data and the complemented facial 3D data. The value of the ratio of nose length to mid-face height in the complemented facial 3D data was 0.63±0.03, and the value of the ratio of nose width to medial canthal distance was 1.07±0.08. The curve deviation (root mean square value) between the edge curve of the complemented external nose 3D data and the defect edge curve of the 3D facial data of external nose defect was (0.37±0.09) mm, the maximum deviation was (1.14±0.32) mm, and the proportion of the curve deviation value within±1 mm was (97±3)%. The distance of corresponding nose landmarks between the complemented facial 3D data and the original 3D facial data were respectively, Nasion: [1.52(1.92)] mm; Pronasale: (3.27±1.21) mm; Subnasale: (1.99±1.09) mm; Right Alare: (2.64±1.34) mm; Left Alare: (2.42± 1.38) mm. Conclusions: The method of 3D facial morphology completion of external nose defect proposed in this study has good feasibility. The constructed complemented external nose 3D data has good facial coordination and edge fit, and the morphology is close to the nose morphology of the original 3D facial data.

The pharmaceutical manufacturing model is gradually changing from intermittent manufacturing to continuous manufacturing and intelligent manufacturing. This paper briefly reviewed the supervision and research progress in continuous pharmaceutical manufacturing in China and abroad and described the definition and advantages of continuous pharmaceutical manufacturing. The continuous manufacturing of traditional Chinese medicine(TCM) at the current stage was summarized in the following three terms: the enhancement of the continuity of intermittent manufacturing operations, the integration of continuous equipment to improve physical continuity between units, and the application of advanced process control strategies to improve process continuity. To achieve continuous manufacturing of TCM, the corresponding key technologies, such as material property characterization, process modeling and simulation, process analysis technology, and system integration, were analyzed from the process and equipment, respectively. It was proposed that the continuous manufacturing equipment system should have the characteristics of high speed, high response, and high reliability, "three high(H~3)" for short. Considering the characteristics and current situation of TCM manufacturing, based on the two dimensions of product quality control and production efficiency, a maturity assessment model for continuous manufacturing of TCM, consisting of operation continuity, equipment continuity, process continuity, and quality control continuity, was proposed to provide references for the application of continuous manufacturing technology for TCM. The implementation of continuous manufacturing or the application of key continuous manufacturing technologies in TCM can help to systematically integrate advanced pharmaceutical technology elements and promote the uniformity of TCM quality and the improvement of production efficiency.
Medicine, Chinese Traditional ; Reproducibility of Results ; China ; Quality Control ; Pharmaceutical Preparations

Since the implementation of drug registration in China, the classification of Chinese medicine has greatly met the needs of public health and effectively guided the transformation, inheritance, and innovation of research achievements on traditional Chinese medicine(TCM). In the past 30 years, the development of new Chinese medicine has followed the registration transformation model of " one prescription for single drug". This model refers to the R&D and registration system of modern drugs, and approximates to the " law-abiding" medication method in TCM clinic, while it rarely reflects the sequential therapy of syndrome differentiation and comprehensive treatment with multiple measures. In 2017, Opinions on Deepening the Reform of Review and Approval System and Encouraging the Innovation of Drugs and Medical Devices released by the General Office of the CPC Central Committee and the General Office of the State Council pointed out that it is necessary to " establish and improve the registration and technical evaluation system in line with the characteristics of Chinese medicine, and handle the relationship between the traditional advantages of Chinese medicine and the requirements of modern drug research". Therefore, based on the development law and characteristics of TCM, clinical thinking should be highlighted in the current technical requirements and registration system of research and development of Chinese medicine. Based on the current situation of registration supervision of Chinese medicine and the modern drug research in China, the present study analyzed limitations and deficiency of " one prescription for single drug" in the research and development of Chinese medicine. Additionally, a new type of " series prescriptions" was proposed, which was consistent with clinical thinking and clinical reality. This study is expected to contribute to the independent innovation and high-quality development of the TCM industry.
China ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Prescriptions ; Public Health

As one of the major sources of infection, viruses could infect all organisms including bacteria, plants, animals, and humans. Infectious diseases caused by viruses pose a great threat and damage to human health and economic activities all over the world. Adaptor-associated protein kinase 1 (AAK1) is a member of the Ark1/Prk1 family of serine/threonine kinases and a specific key kinase regulating the phosphorylation of AP-2 protein μ2 subunit T156. In the past, AAK1 has been regarded as a feasible biological target for the treatment of nerve pain. Recently, scientists have found that inhibiting AAK1 can regulate endocytosis and inhibit virus invasion into cells. Therefore, AAK1 could be the potential target of anti-virus therapy. This paper reviews the research progress of small molecule AAK1 inhibitors in the field of antiviral, analyzes the future research directions and challenges, and provides new ideas for the development of antiviral drugs targeting AAK1.

PURPOSE: Low-velocity penetrating brain injury (LVPBI) caused by foreign bodies can pose life-threatening emergencies. Their complexity and lack of validated classification data have prevented standardization of clinical management. We aimed to compare the trans-base and trans-vault phenotypes of LVPBI to help provide guidance for clinical decision-making of such injury type. METHODS: A retrospective study on LVPBI patients managed at our institution from November 2013 to March 2020 was conducted. We included LVPBI patients admitted for the first time for surgery, and excluded those with multiple injuries, gunshot wounds, pregnancy, severe blunt head trauma, etc. Patients were categorized into trans-base and trans-vault LVPBI groups based on the penetration pathway. Discharged patients were followed up by outpatient visit or telephone. The data were entered into the Electronic Medical Record system by clinicians, and subsequently derived by researchers. The demography and injury characteristics, treatment protocols, complications, and outcomes were analyzed and compared between the two groups. A t-test was used for analysis of normally distributed data, and a Mann-Whitney U test for non-parametric data. A generalized linear model was further established to determine whether the factors length of stay and performance scale score were influenced by each factor. RESULTS: A total of 27 LVPBI patients were included in this analysis, comprised of 13 (48.1%) trans-base cases and 14 (51.9%) trans-vault cases. Statistical analyses suggested that trans-base LVPBI was correlated with deeper wounds; while the trans-vault phenotype was correlated with injury by metal foreign bodies. There was no difference in Glasgow Coma Scale score and the risk of intracranial hemorrhage between the two groups. Surgical approaches in the trans-base LVPBI group included subfrontal (n = 5, 38.5%), subtemporal (n = 5, 38.5%), lateral fissure (n = 2, 15.4%), and distal lateral (n = 1, 7.7%). All patients in the trans-vault group underwent a brain convex approach using the foreign body as reference (n = 14, 100%). Moreover, the two groups differed in application prerequisites for intracranial pressure monitoring and vessel-related treatment. Trans-base LVPBI was associated with higher rates of cranial nerve and major vessel injuries; in contrast, trans-vault LVPBI was associated with lower functional outcome scores. CONCLUSION Our findings suggest that trans-base and trans-vault LVPBIs differ in terms of characteristics, treatment, and outcomes. Further understanding of these differences may help guide clinical decisions and contribute to a better management of LVPBIs.

BACKGROUND: Computed tomography images are easy to misjudge because of their complexity, especially images of solitary pulmonary nodules, of which diagnosis as benign or malignant is extremely important in lung cancer treatment. Therefore, there is an urgent need for a more effective strategy in lung cancer diagnosis. In our study, we aimed to externally validate and revise the Mayo model, and a new model was established. METHODS: A total of 1450 patients from three centers with solitary pulmonary nodules who underwent surgery were included in the study and were divided into training, internal validation, and external validation sets (n = 849, 365, and 236, respectively). External verification and recalibration of the Mayo model and establishment of new logistic regression model were performed on the training set. Overall performance of each model was evaluated using area under receiver operating characteristic curve (AUC). Finally, the model validation was completed on the validation data set. RESULTS: The AUC of the Mayo model on the training set was 0.653 (95% confidence interval [CI]: 0.613-0.694). After re-estimation of the coefficients of all covariates included in the original Mayo model, the revised Mayo model achieved an AUC of 0.671 (95% CI: 0.635-0.706). We then developed a new model that achieved a higher AUC of 0.891 (95% CI: 0.865-0.917). It had an AUC of 0.888 (95% CI: 0.842-0.934) on the internal validation set, which was significantly higher than that of the revised Mayo model (AUC: 0.577, 95% CI: 0.509-0.646) and the Mayo model (AUC: 0.609, 95% CI, 0.544-0.675) (P < 0.001). The AUC of the new model was 0.876 (95% CI: 0.831-0.920) on the external verification set, which was higher than the corresponding value of the Mayo model (AUC: 0.705, 95% CI: 0.639-0.772) and revised Mayo model (AUC: 0.706, 95% CI: 0.640-0.772) (P < 0.001). Then the prediction model was presented as a nomogram, which is easier to generalize. CONCLUSIONS After external verification and recalibration of the Mayo model, the results show that they are not suitable for the prediction of malignant pulmonary nodules in the Chinese population. Therefore, a new model was established by a backward stepwise process. The new model was constructed to rapidly discriminate benign from malignant pulmonary nodules, which could achieve accurate diagnosis of potential patients with lung cancer.
Humans ; Lung ; Lung Neoplasms/diagnostic imaging* ; Multiple Pulmonary Nodules ; Risk Assessment ; Solitary Pulmonary Nodule/diagnostic imaging* ; Tomography, X-Ray Computed

Objective: To analyze the risk factors and clinical characteristics as well as long-term prognosis of young patients (aged 18-35 years) with acute ST-segment elevation myocardial infarction (STEMI). Methods: In this retrospective study, from January 2007 to December 2017, STEMI patients who were hospitalized in Beijing Anzhen Hospital, Capital Medical University and younger than 45 years old were collected. Patients were divided to the 18-35 years old group and 36-44 years old group. The basic information of patients, clinical laboratory results, surgical information and discharge diagnosis of enrolled patients were extracted from the electronic medical record system. Subgroup analysis on STEMI patients aged 18 to 35 years was performed to compare the clinical features and outcome of patients with normal coronary angiography or stenotic coronary angiography. Results: 496 patients (20.3%) were between 18 and 35 years old, 480 cases (96.8%) were men, and 371 cases (74.8%) were smokers. The proportion of hypertension and diabetes was lower, but percent of obese (122 cases (43.3%)), level of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), uric acid and homocysteine ​​(Hcy) were significantly higher in patients aged 18 to 35 years compared with STEMI patients aged 36 to 44 years (all P<0.05). In the 18-35 years old group, there were 53 patients (10.7%) with normal coronary angiography and 443 patients (89.3%) with stenosis. The age, proportion of hypertension and diabetes, TC, LDL-C, and triglyceride (TG) levels were lower in the normal coronary angiography group than those in the coronary artery stenosis group (all P<0.05). The main coronary artery lesions were single vessel lesions (263 cases (59.4%)), and the main culprit vessels were left anterior descending artery lesions (238 cases (53.7%)). The follow-up time was 7.0 (4.0, 10.0) years, cardiovascular events were reported in 62 patients (18.9%), of which 14 patients (3.2%) died. The survival rate of patients without cardiovascular events in normal coronary angiography group was higher than that in stenosis group (P=0.029). Multivariate Cox regression analysis showed that diabetes (HR=2.713, 95%CI 1.479-4.976, P=0.001) and dyslipidemia (HR=2.819, 95%CI 1.564-5.079, P=0.001) were independent risk factors for recurrence of cardiovascular events in adult STEMI patients aged 18 to 35 years. Conclusions: STEMI patients aged 18 to 35 years were featured by male sex, obese and smokers. The proportion of hypertension and diabetes was low, while the levels of LDL-C, uric acid and Hcy were high in these patients. Coronary artery stenosis was common, and the stenosis was more likely to occur in the left anterior descending branch. Patients with normal coronary angiography had a better prognosis than those with stenosis. Diabetes and hyperlipidemia increased the risk of recurrent cardiovascular events.
Adolescent ; Adult ; Anterior Wall Myocardial Infarction ; Coronary Angiography ; Humans ; Male ; Middle Aged ; Percutaneous Coronary Intervention ; Prognosis ; Retrospective Studies ; Risk Factors ; ST Elevation Myocardial Infarction/diagnostic imaging* ; Young Adult

Lower respiratory tract infection (LRTI) induced by respiratory syncytial virus (RSV) is an important cause of hospitalization for infants. Compared with adults, infants are more likely to cause serious respiratory diseases after RSV infection due to the specific immature airway structure and immune system. The balance of immune resistance and immune tolerance of the host is critical to effective virus clearance and disease control. This paper reviews the relationship between RSV infection and respiratory diseases in infancy, the influence factors of the high pathogenicity of RSV infection in early life, as well as the research progress of anti-RSV therapy, and expands the specific molecular events regulating immune resistance and immune tolerance. We expect to present new ideas for the prevention and treatment of RSV-related respiratory diseases in clinical practice.
Humans ; Infant ; Respiration Disorders ; Respiratory Syncytial Virus Infections ; Respiratory Syncytial Viruses ; Respiratory Tract Infections