ObjectiveThis study aims to develop a prediction model for the compatibility of Chinese medicinal pairs based on Graph Convolutional Networks （GCN）， named HC-GCN. The model integrates the properties of herbs with modern pharmacological mechanisms to predict pairs with specific therapeutic effects. It serves as a demonstration by applying the model to predict and validate the efficacy of blood-activating herb pairs. MethodsThe training dataset for herb pair prediction was constructed by systematically collecting commonly used herb pairs along with their characteristic data， including Qi， flavor， meridian tropism， and target genes. Integrating traditional characteristics of herb with modern bioinformatics， we developed an efficacy-oriented herb pair compatibility prediction model （HC-GCN） using graph convolutional networks （GCN）. This model leverages machine learning to capture the complex relationships in herb pair compatibility， weighted by efficacy features. The performance of the HC-GCN model was evaluated using accuracy （ACC）， recall， precision， F1 score （F1）， and area under the ROC curve （AUC）. Its predictive effectiveness was then compared to five other machine learning models： eXtreme Gradient Boosting （XGBoost）， logistic regression （LR）， Naive Bayes， K-nearest neighbor （KNN）， and support vector machine （SVM）. ResultsUsing herb pairs with blood-activating effects as a demonstration， a prediction model was constructed based on a foundational dataset of 46 blood-activating herb pairs， incorporating their Qi， flavor， meridian tropism， and target gene characteristics. The HC-GCN model outperforms other commonly used machine learning models in key performance metrics， including ACC， recall， precision， F1 score， and AUC. Through the predictive analysis of the HC-GCN model， 60 herb pairs with blood-activating effects were successfully identified. Among of these potential herb pairs， 44 include at least one herb with blood-activating effects. ConclusionIn this study， we established an efficacy-oriented compatibility prediction model for herb pairs based on GCN by integrating the unique characteristics of traditional herbs with modern pharmacological mechanisms. This model demonstrated high predictive performance， offering a novel approach for the intelligent screening and optimization of traditional Chinese medicine prescriptions， as well as their clinical applications.

ObjectiveTo investigate the efficacy of ovarian tissue cryopreservation and autologous transplantation in preserving fertility and ovarian endocrine function in patients with cervical cancer. MethodsA 26-year-old patient with stage ⅡA1 cervical cancer underwent ovarian tissue harvesting and cryopreservation during cancer surgery. Following complete remission of the cancer， autologous ovarian tissue transplantation was performed. Follow-up monitoring included assessment of menopausal symptoms， hormone levels， and follicular development. ResultsSix months after transplantation， follicle-stimulating hormone levels decreased to 6.60 U/L， and estradiol levels increased from ＜10.00 ng/L to 89.00 ng/L. At 10 months after transplantation， ultrasound monitoring confirmed follicular development and physiological ovulation in the transplanted ovarian tissue. By 15 months after transplantation， follicle-stimulating hormone levels remained stable at 7.24 U/L， and estradiol levels further increased to 368.00 ng/L. Over 2 years after transplantation， the patient successfully gave birth to a healthy baby through assisted reproductive technology. ConclusionThe restoration of endocrine and ovulation functions in the transplanted cryopreserved ovarian tissue， followed by successful pregnancy， demonstrates the clinical success of ovarian tissue transplantation.

Objective To investigate the protective effect of Schisandrin B on myocardial infarction in rats and its mechanism.Methods Fifty SD rats were randomly divided into sham group,model group,positive control group(10 mg·kg-1 captopril),experimental-L group(30 mg·kg-1 schisandrin B)and experimental-H(60 mg·kg-1 schisandrin B)group,with 10 rats in each group.Cardiac function related indexes were detected,serum myocardial injury markers and serum inflammatory factors were detected by the kit,myocardial apoptosis was detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling(TUNEL)method,and myocardial tissue related protein expression levels were detected by Western blot method.Results Left ventricular ejection fraction(LVEF)levels in sham group,model group,positive control group,experimental-L group and experimental-H group were(78.42±4.32)％,(41.65±2.94)％,(59.76±5.35)％,(49.13±3.92)％and(67.04±3.00)％;the contents of creatine kinase-MB(CK-MB)were(33.95±2.68),(100.51±3.92),(48.27±3.70),(70.34±2.93)and(49.13±3.67)U·mL-1;interleukin-1 β(IL-1 β)levels were(1.02±0.12),(3.02±0.20),(1.61±0.13),(2.33±0.26)and(1.34±0.14)ng·mL-1;TUNEL positive cell rates were(3.47±0.82)％,(31.79±3.68)％,(11.22±1.02)％,(19.74±1.42)％and(14.38±1.13)％;the expression levels of Nod-like receptor thermal protein domain associated protein 3(NLRP3)protein were 0.35±0.07,1.04±0.10,0.55±0.05,0.85±0.07 and 0.39±0.06;the protein levels of cysteine aspartic acid specific protease 1(caspase-1)were 0.34±0.05,1.05±0.10,0.50±0.06,0.72±0.05 and 0.46±0.03,respectively.The above indexes were compared between model group and sham group,the differences were statistically significant(all P＜0.05).The positive control group,experimental-L group and experimental-H group were compared with model group,the differences were statistically significant(all P＜0.05).The difference between experimental-H group and experimental-L group were statistically significant(all P＜0.05).Conclusion Schisandrin B can mediate inflammatory response and cardiomyocyte apoptosis,improve cardiac function,and protect rats with myocardial infarction,which is related to NLRP3 inflammatory pathway.

ObjectiveTo investigate the efficacy and safety of N-acetylcysteine （NAC） in the treatment of severe alcoholic hepatitis （SAH）， and to provide a basis for clinical medication for SAH. MethodsA prospective randomized controlled trial was conducted among 172 SAH patients with a Maddrey discriminant function score of >32 points who were recruited by The Fifth Medical Center of Chinese PLA General Hospital from June 2015 to June 2018， and these patients were divided into NAC group with 84 patients and control group with 86 patients. NAC （8 g/day， 28 days） was assessed in terms of its safety in SAH patients， its impact on 28-day biochemical parameters， and its role in improving 28- and 180-day survival rates. A further analysis was performed to investigate the effect of NAC on the 28- and 180-day survival rates of SAH patients with acute-on-chronic liver failure （ACLF-SAH patients） and those without acute-on-chronic liver failure （non-ACLF-SAH patients）. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. The Kaplan-Meier method was used to plot survival curves， and the Log-rank test was used for comparison of survival curves. Univariate and multivariate Cox proportional-hazards regression model analyses were used to investigate independent influencing factors. ResultsNo serious adverse events were observed during NAC treatment， suggesting that NAC had a good safety profile. Compared with the control group， NAC did not significantly improve the 28-day biochemical parameters （all P>0.05） and survival rate of SAH patients （P=0.081）， but it could improve the 180-day survival rate of SAH patients （67.4% vs 81.0%， χ²=4.280， P=0.039）. NAC did not improve the 28- and 180-day survival rates of ACLF-SAH patients （both P>0.05）； NAC did not improve the 28-day survival rate of non-ACLF-SAH patients （P>0.05）， but it could improve the 180-day survival rate of these patients （68.4% vs 88.9%， χ²=4.883， P=0.027）. The multivariate Cox regression survival analysis showed that NAC treatment （hazard ratio ［HR］=2.530， 95% confidence interval ［CI］： 1.334‍ ‍— 4.796， P=0.004，）， Maddrey discriminant function score （HR=3.852， 95%CI： 2.032 — 7.304， P<0.001）， and serum sodium level （HR=1.948， 95%CI： 1.079‍ ‍—‍ ‍3.517， P=0.027） were independent influencing factors for 180-day survival rate in SAH patients. ConclusionNAC has a good safety profile in the treatment of SAH and can improve the 180-day survival rate of SAH patients， and in particular， non-ACLF-SAH patients can benefit from NAC treatment in terms of middle- and long-term survival rates.

Objective:To investigate the current status of endoscopic treatment for gastroesophageal varices in portal hypertension in China, and to provide supporting data and reference for the development of endoscopic treatment.Methods:In this study, initiated by the Liver Health Consortium in China (CHESS), a questionnaire was designed and distributed online to investigate the basic condition of endoscopic treatment for gastroesophageal varices in portal hypertension in 2022 in China. Questions included annual number and indication of endoscopic procedures, adherence to guideline for preventing esophagogastric variceal bleeding (EGVB), management and timing of emergent EGVB, management of gastric and isolated varices, and improvement of endoscopic treatment. Proportions of hospitals concerning therapeutic choices to all participant hospitals were calculated. Guideline adherence between secondary and tertiary hospitals were compared by using Chi-square test.Results:A total of 836 hospitals from 31 provinces (anotomous regions and municipalities) participated in the survey. According to the survey, the control of acute EGVB (49.3%, 412/836) and the prevention of recurrent bleeding (38.3%, 320/836) were major indications of endoscopic treatment. For primary [non-selective β-blocker (NSBB) or endoscopic therapies] and secondary prophylaxis (NSBB and endoscopic therapies) of EGVB, adherence to domestic guideline was 72.5% (606/836) and 39.2% (328/836), respectively. There were significant differences in the adherence between secondary and tertiary hospitals in primary prophylaxis of EGVB [71.0% (495/697) VS 79.9% (111/139), χ2=4.11, P=0.033] and secondary prophylaxis of EGVB [41.6% (290/697) VS 27.3% (38/139), χ2=9.31, P=0.002]. A total of 78.2% (654/836) hospitals preferred endoscopic therapies treating acute EGVB, and endoscopic therapy was more likely to be the first choice for treating acute EGVB in tertiary hospitals (82.6%, 576/697) than secondary hospitals [56.1% (78/139), χ2=46.33, P<0.001]. The optimal timing was usually within 12 hours (48.5%, 317/654) and 12-24 hours (36.9%, 241/654) after the bleeding. Regarding the management of gastroesophageal varices type 2 and isolated gastric varices type 1, most hospitals used cyanoacrylate injection in combination with sclerotherapy [48.2% (403/836) and 29.9% (250/836), respectively], but substantial proportions of hospitals preferred clip-assisted therapies [12.4% (104/836) and 26.4% (221/836), respectively]. Improving the skills of endoscopic doctors (84.2%, 704/836), and enhancing the precision of pre-procedure evaluation and quality of multidisciplinary team (78.9%, 660/836) were considered urgent needs in the development of endoscopic treatment. Conclusion:A variety of endoscopic treatments for gastroesophageal varices in portal hypertension are implemented nationwide. Participant hospitals are active to perform emergent endoscopy for acute EGVB, but are inadequate in following recommendations regarding primary and secondary prophylaxis of EGVB. Moreover, the selection of endoscopic procedures for gastric varices differs greatly among hospitals.

ObjectiveTo explore the efficacy-driving mechanism of Danhong injection （DHI） in the treatment of stable angina pectoris （SAP） based on the composition-activity relationship of target modules and clarify the pharmacological effects of DHI. MethodAccording to the angina frequency （AF） in the Seattle Angina Questionnaire （SAQ） that was obtained in the previous clinical trial， the patients before and after DHI treatment were grouped based on efficacy. The transcriptomic data of the patients before treatment and in the best efficacy group 30 days post-treatment were selected as the data source， and then weighted gene co-expression network analysis （WGCNA） was employed to construct the co-expression network. Relevant modules in the network were identified and associated with clinical features. In addition， the On-modules （Z value below 0） were identified by Zsummary. The topological indicators such as density， centrality， and clustering coefficient were adopted to explore the dynamics of DHI efficacy at the network level and module level， respectively. In addition， the driver genes were screened by the personalized network control （PNC） algorithm. Finally， rat H9C2 cells were used to establish the model of hypoxia/reoxygenation （H/R）， which was used to confirm the potential therapeutic target of DHI for SAP and provide a scientific basis for revealing the therapeutic mechanism of DHI. ResultWe identified 19 modules in the best efficacy group of DHI for SAP， and the comparison between day 0 and day 30 revealed 12 On-modules. The changes of network topological indicators at the network and module levels confirmed the correlation between the best efficacy of DHI treatment and topological dynamics. Finally， the driver genes， Klotho and fibroblast growth factor 22 （FGF22）， in DHI treatment of SAP were verified by the H9C2 cell model of H/R. ConclusionBased on clinical transcriptome data， this study determined the composition-activity relationship of target modules of DHI for SAP， which provided a scientific basis for deciphering the efficacy-driven mechanism of DHI for SAP.

The excipient processing is an essential part of traditional Chinese medicine processing, and understanding its scientific connotations is a critical scientific issue that urgently needs resolution. Building upon a foundation where the composition of traditional Chinese medicine substances is fundamentally clear, this paper applies the techniques and methods of chemoinformatics to the study of the excipient processing mechanism. Relevant information on traditional Chinese medicines processed with four kinds of excipients (wine, vinegar, salt and honey) was collected, including properties, taste, meridian tropism, chemical components, etc. Molecular descritors and skeletons corresponding to each chemical component were calculated using chemoinformatics to characterize the properties and structural features of the components. Characteristic components associated with the four excipients (wine, vinegar, salt and honey) were explored through multivariate statistical analysis and Murcko skeleton analysis. Further analysis, taking honey-processed Astragali Radix as an example, the focus was on the impact of the processing excipient honey on the solubility and permeability of its characteristic pharmacologically active components (isoflavones). It was discovered that the excipient honey can increase their solubility and permeability, emphasizing that the impact of processing excipients on the pharmacological classification properties is a key breakthrough in elucidating the mechanism of excipient processing. In summary, this study analyzed the characteristic components associated with the processing excipients "wine, vinegar, salt and honey" based on their composition characteristics, providing data support for the research on the mechanism of excipient processing from a biopharmaceutical perspective.

The breakage pattern of unit particles during the production of oral solid dosage forms (OSD) is closely related to the quality of intermediate or final products. To accurately characterize the particles and study the evolution law of particle breakage, the Bonding model of the discrete element method (DEM) was used to investigate the breakage patterns of model parameters, particle shape and process conditions (loading mode and loading rate) on the dynamic breakage, force-time curve, breakage rate, maximum breakage size ratio and fracture strength of particles. The results showed that the particle breakage force was positively correlated with normal strength and bonded disk scale, negatively correlated with normal stiffness per unit area and tangential stiffness per unit area, and weakly correlated with tangential strength. The particle breakage rate was negatively correlated with the aspect ratio of the particles, and the maximum breakage size ratio was positively correlated with the aspect ratio of the particles; among the three loading modes, the breakage rate of compression breakage model was the largest, the breakage rate of shear breakage model was the second largest, and the breakage rate of wear breakage model was the smallest; the maximum breakage size ratio was positively correlated with the loading rate, the loading mode and the loading rate had no mutual influence on particle breakage rate, but had mutual influence on the maximum breakage size ratio. The research results will provide a theoretical basis for the shift of OSD from batch manufacturing to advanced manufacturing.

Plant natural products have a wide range of pharmacological properties, not only can they be used as plant dietary supplements to meet the nutritional needs of the human body in the accelerated pace of life, but also occupy an important position in the research and development of therapeutic drugs for the treatment of tumors, inflammation and other diseases, and have been widely accepted by the public due to their good safety. However, despite the above advantages of plant natural products, limiting factors such as low solubility, poor stability, lack of targeting, high toxicity and side effects, and unacceptable odor have greatly impeded their conversion to clinical applications. Therefore, the development of new avenues for the application of new natural products has become an urgent problem to be solved at present. In recent years, with the continuous development of research, various strategies have been developed to improve the bioavailability of natural products. Among them, nanocarrier delivery system is one of the most attractive strategies at present. In past studies, a large number of nanomaterials (organic, inorganic, etc.) have been developed to encapsulate plant-derived natural products for their efficient delivery to specific organs and cells. Up to now, nanotechnology has not only been limited to pharmaceutical applications, but is also competing in the fields of nanofood processing technology and nanoemulsions. Among the various nanocarriers, liposomes are the largest nanocarriers with the largest market share at present. Liposomes are bilayer nanovesicles synthesized from amphiphilic substances, which have advantages such as high drug loading capacity and stability. Attractively, the flexible surface of liposomes can be modified with various functional elements. Functionalized modification of liposomes with different functional elements such as antibodies, nucleic acids, peptides, and stimuli-responsive moieties can bring out the excellent drug delivery function of liposomes to a greater extent. For example, the modification of functional elements with targeting function such as nucleic acids and antibodies on the surface of liposomes can deliver natural products to the target location and improve the bioavailability of drugs; the modification of stimulus-responsive groups such as photosensitizers, magnetic nanoparticles, pH-responsive groups, and temperature sensitizers on the surface of liposomes can achieve controlled release of drugs, localized targeting, and synergistic thermotherapy. In addition to the above properties, by using functionalized liposomes to encapsulate natural products with irritating properties can also effectively mask the irritating properties of natural products, improve public acceptance, and increase the possibility of application of irritating natural products. There are various strategies for modifying liposomes with functional elements, and the properties of functionalized liposomes constructed by different construction strategies differ. The commonly used construction strategies for functionalized liposomes include covalent modification and non-covalent modification. These two types of construction strategies have their own advantages and disadvantages. Covalent modification has better stability than non-covalent modification, but its operation is cumbersome. With the above background, this review focuses on the three typical problems faced by plant natural products at present, and summarizes the specific applications of functionalized liposomes in them. In addition, this paper summarizes the construction strategies for building different types of functionalized liposomes. Finally, this paper will also review the opportunities and challenges faced by functionalized liposomes to enter clinical therapy, and explore the opportunities to overcome these problems, with a view to better realizing the precise control of plant nanomedicines, and providing ideas and inspirations for researchers in related fields as well as relevant industrial staff.

Objective To understand the current status of emergency vaccination of hemorrhagic fever with renal syndrome (HFRS) vaccine in Jingzhou, serological monitoring and the incidence of vaccinated population, and to evaluate the protective effect of emergency vaccination of HFRS vaccine on the control of HFRS epidemic in the city. Methods From 2018 to 2020, HFRS vaccination was carried out in Jianli City, Honghu City, Jiangling County, Gongan County and some townships in Shashi City, Jingzhou City, focusing on people aged 30-59 years old. The incidence of HFRS, vaccination history of cases and HFRS vaccination data of Jingzhou City were collected and analyzed by descriptive epidemiological methods. The sera of those who had not been vaccinated with HFRS vaccine (non-vaccinated group) and those who had been vaccinated with HFRS vaccine (vaccinated group) were collected for IgG antibody detection, and the serum IgG was detected by ELISA method. The correlation between the change in the number of cases in townships where people were vaccinated (comparison between 2017-2018 and 2020) and the vaccination rate before 2019 was analyzed. Results A total of 446 900 doses of HFRS vaccine were vaccinated from 2018 to 2020, covering 22 townships in 5 counties and cities, accounting for 17.19% (22/128) of the total number of townships in the city. A total of 120 953 people completed 3 doses of vaccination, accounting for 11.30% of the total population and 23.77% of the population aged 30-59 in the vaccinated township. The positive rate of IgG in the unvaccinated group in Jingzhou was 9.91% (85/858). The positive rate of IgG in the vaccination group was 40.96% (34/83). The positive rates of IgG in the 1-dose group, 2- dose group, and 3-dose group were 0 (0/2), 18.18% (6/33), and 58.33% (28/48), respectively. From 2017 to 2020, a total of 16 cases had been vaccinated with HFRS before the onset of the disease, and 81.25% (13/16) received 2 doses or less of HFRS vaccine. The changes in the number of cases was negatively correlated with the vaccination rate of the whole population in townships where people were vaccinated (r_s=-0.58, P=0.011). The changes in the number of cases was negatively correlated with the vaccination rate of people aged 30-59 years in townships where people were vaccinated (r_s=-0.46, P=0.055). Conclusion The HFRS vaccination before 2019 has played a certain protective effect on the vaccinated population. However, the inoculation rate of HFRS vaccine in Jingzhou City is still low, and the protective effect on the whole population has not yet appeared.