To conduct a theoretical research of industrial innovation ecosystem to solve the problems in the development of traditional Chinese medicine industry which stem from the lack of innovation motivation and the blockage of the construction of innovation ecosystem.

This paper analyzed the evolution of the system and the changes of the role of the innovation subject in the evolution, and put forward the effective strategic choice path, so as to promote the evolution of traditional Chinese medicine industry innovation ecosystem, and to provide references for improving the innovation and competitiveness of traditional Chinese medicine industry. On the basis of clarifying the composition and interaction mode of the innovation ecosystem of traditional Chinese medicine industry, this paper analyzed the changing characteristics of innovation subjects in the three stages of system innovation evolution 1.0, 2.0 and 3.0 in Huangjing (Polygonati Rhizoma) industry of Anhui Province. Innovation individuals led by scientific research, formed by innovation producers such as universities, research and development institutions and R&D enterprises, and changed into innovation groups formed by the service of intermediary institutions, financial institutions, government and other innovation disintegrators, and then changed into innovation community, facilitated by innovation consumers composed of large enterprises and the public.

The research showed that P.rhizoma industry innovation ecosystem in Anhui Province has gone through the 1.0 stage driven by technological innovation and the 2.0 stage guided by policies, but the 3.0 stage driven by market pull has not been completed. The obstacles to its evolution arised from the insufficient product innovation of innovative producers such as R&D-oriented enterprises and hospitals, the imperfect construction of information platforms for innovative decomposers such as intermediary agencies and sales enterprises, and the failure of industrial chain collaboration caused by the absence of innovative consumers such as manufacturing enterprises and growers.

The final formation of the industrial innovation ecosystem 3.0 can only be driven by R&D enterprises promoting product innovation, intermediary agencies improving information platforms, and manufacturing enterprises leading industrial chain collaboration.

To draw on the useful experience of the breakthrough therapy designation (BTD) system in the United States (US) to provide suggestions and references for improving the BTD system in China.

Through a comparative analysis of the implementation effects of the BTD systems in China and the US, the implementation effects and gaps of the BTD systems in the two countries were revealed.

The numbers of applications for BTD recognition in China and the US were generally on the rise, but the rates of BTD recognition and approval in China were significantly lower than those in the US, which may be related to the uneven quality of the applications and the lack of policy refinement. China's BTD drugs had a shorter pre-market clinical development time, but a longer review time, reflecting the difference in the strength of clinical trial guidance between the two countries' drug regulatory agencies. In terms of clinical trial design for antitumour drugs, China preferred single-arm, non-randomised design with objective remission rate as the primary endpoint; whereas the trial designs in the US were richer and more diverse. In addition, no BTD Chinese medicine has been approved for marketing. It is recommended that China's drug regulatory agencies learn from the US experience, formulate BTD review and management standards, strengthen the leading role of reviewers, set up interdisciplinary teams, strengthen the guidance of clinical trial development and improve the efficiency of research and development and review; at the same time, strengthen the supervision of BTD-recognised medicines after superimposed conditional approval for listing, and promote the declaration and approval of BTD traditional Chinese medicines. Pharmaceutical companies should strengthen the training of R&D teams on BTD regulations and skills, improve the quality of BTD drug applications, and promote the accelerated marketing of products to meet patients' clinical needs.

To construct the correlation model of "appearance characteristics-chemical components" of Crataegi Fructus by integrating appearance characteristics (diameter, thickness and total mass) and internal quality indicators (water content, extract, total ash and HPLC characteristic spectrum) to identify the key quality control indicators of Crataegi Fructus.

After measuring the indicators, principal component analysis (PCA), orthogonal partial least squares discriminant analysis (OPLS-DA), factor analysis (FA) and IQR variability analysis were used for data mining, and key indicators were determined by cross-validation of multiple methods.

PCA and OPLS-DA identified seven indicators, including water content, chlorogenic acid, cryptochlorogenic acid, et al. FA extracted cryptochlorogenic acid, hyperoside, and isoquercitrin. IQR analysis yielded 11 variability indicators. Overall, cryptochlorogenic acid and hyperoside were identified as core indicators across all three analytical methods.

The correlation model of "appearance characteristics-chemical composition" of Crataegi Fructus was established, and the key quality control indexes were determined as cryptochlorogenic acid and hyperoside, which provided a new research method for the standardization of quality of Chinese herbal slices.

To establish quantitative proton nuclear magnetic resonance (qHNMR) method to determine the contents of methyl benzenesulfonate, propyl benzenesulfonate, isopropyl benzenesulfonate, methyl p-toluenesulfonate, and isopropyl p-toluenesulfonate.

Proton nuclear magnetic resonance spectroscopy (qHNMR) spectra were collected by BRUKEANANCE NEO 600 MHz NMR spectrometer. The parameters were set up as follows: 30° pulse sequences, the relaxation delay time was 10 s, the number for scanning was 16, and the experiment temperature was controlled at 25 ℃, dimethyl terephthalate were used as internal standard, respectively. The quantitative study of benzenesulfonate ester compounds was carried out in CDCl₃-d as solvents.

Using dimethyl terephthalate as internal standard, the contents of five benzenesulfonate ester compounds determined by qHNMR method were basically consistent with the results obtained by mass balance method.

The qHNMR method established in this study is simple, rapid, and accurate, and can be used for the determination of benzenesulfonate ester compounds, providing strong evidence data for the accurate assignment of the reference material.

To construct a lignin-based self-assembled nanodrug delivery system loaded with vancomycin and evaluate its in vitro antibacterial performance and biocompatibility.

Vancomycin-loaded lignin nanoparticles (NPs) were prepared via self-assembly. The particle size and morphology were characterized using dynamic light scattering (DLS) and transmission electron microscopy (TEM), while drug loading capacity, encapsulation efficiency, and release profile were determined by mass spectrometry. Staphylococcus aureus was used as a model strain to assess antibacterial activity via the microdilution broth method. The antibacterial mechanisms, including biofilm disruption and membrane damage, were investigated through colony counting, crystal violet staining, live/dead bacterial staining, and scanning electron microscopy (SEM). Biocompatibility was evaluated using the CCK-8 assay on HeLa cells.

Uniform lignin-vancomycin nanocomposites (~100 nm) were successfully prepared. The NPs exhibited pH-responsive drug release, with faster release under weakly acidic conditions (pH=5.5). Antibacterial tests demonstrated effective biofilm destruction and bacterial membrane disruption. CCK-8 assays confirmed excellent biocompatibility, supporting potential in vivo applications.

The lignin-based self-assembled nanocarrier efficiently loads and sustains vancomycin release, enhances antibacterial efficacy via membrane-targeting mechanisms, and shows favorable biosafety. This system provides a promising strategy for treating bacterial infections.

To develop multifunctional hydrogels with excellent antibacterial properties and biocompatibility for the treatment of bacterial infection wounds, which can rapidly heal wounds and relieve pain.

A three-dimensional porous composite hydrogel was prepared by using methacrylated gelatin and polyacrylamide as raw materials and loading copper sulfide particles and ibuprofen through photo-crosslinking. The hydrogel has good biocompatibility and antibacterial properties. The morphology and structure of the hydrogel were characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), X-ray diffractometer (XRD), etc. The swelling and degradation properties, mechanical properties and rheological properties of the drug-loaded PAAM/GelMA composite hydrogel were analyzed. Meanwhile, in vitro biological experiments were conducted to verify its excellent biocompatibility and explore its antibacterial properties.

The PG-CuS@Ib hydrogel displayed a high swelling performance (100%±5%), which can effectively absorb exudate. The antibacterial tests against Escherichia coli and Staphylococcus aureus showed that the inhibition rates were both over 99%. In the biocompatibility test, the survival rate of MC3T1-E1 cells was high, the cell morphology was spread out, and there was no obvious hemolysis (<5%).

The PG-CuS@Ib multifunctional composite hydrogel can meet the key requirements for wound healing. In general, the PG-CuS@Ib hydrogel has promising prospects as a wound dressing.

To analyze the occurrence pattern and clinical characteristics of liver injury related to cadonilimab, and provide a reference for formulating individualized medication regimens for patients.

The medical data of cancer patients who received cadonilimab treatment and developed liver injury in Hunan Cancer Hospital from January 2021 to December 2023 were collected. Information such as patients' personal information, disease information, medication information, liver injury status, and the outcomes of adverse reaction management were recorded in detail.

A total of 14 patients were included, with 11 males and 3 females, and the median age was 57 years. The primary disease was mainly lung cancer (57.14%). In terms of medication, 64.28% of the patients used cadonilimab according to the recommended dosage and administration method in the instruction manual, while 35.72% of the patients had off-label medication. A total of 11 patients were treated with combination therapy, and anlotinib combination therapy accounted for the highest proportion (45.45%), followed by lenvatinib (18.18%). The median occurrence time of cadonilimab-related liver injury was 65 days, and 71.43% of the patients developed it within 3 months after medication. Liver injury of grade 3 and above accounted for 60.00%. In terms of the type of liver injury, most patients (71.42%) showed hepatocellular injury type, and the median values of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) reached 324.0 U·L^-1 and 430.9 U·L^-1 respectively. The clinical manifestations were mainly fatigue (21.43%) and jaundice (7.14%). 71.43% of the patients improved after hormone and liver protection treatment, and 28.57% needed long-term follow-up and monitoring of liver function.

Cadonilimab-related liver injury mostly occurs in the early stage of medication, mainly in the form of hepatocellular injury, and the proportion of liver injury of grade 3 and above is relatively high. Combined medication (such as anlotinib) may increase the risk of liver injury. It is recommended to strengthen the monitoring of liver function in the initial stage of treatment, and the prognosis can be significantly improved after symptomatic treatment.

To explore and analyze the adverse drug events (ADEs) of rasagiline mesylate after its launch, in order to improve the safety and rationality of clinical medication.

Adverse event reports of rasagiline mesylate from May 2006 to September 2024 were searched and extracted from the FDA Adverse Event Reporting System (FAERS) in the United States and the Japanese Adverse Drug Event Report Database (JADER). The reporting odds ratio (ROR) and proportional reporting ratio (PRR) methods were used to process and analyze the data. Positive signals were screened and compared with the instructions to identify potential new drug adverse reactions.

A total of 7 303 and 1 263 ADE reports with rasagiline mesylate as the primary suspected drug were screened from the two databases, respectively, and 122 and 45 positive signals were obtained, involving 16 and 10 SOCs. There were slightly more female patients than male patients who experience adverse events, with the highest proportion being elderly patients (aged ≥65 years). Most cases experienced adverse reactions within one month after medication. The top three reported ADE signals in the FAERS database were falls, tremors, and dizziness, while the top three correlated ADE signals were sexual abnormalities (ROR=266.23, PRR=266.08), sudden sleep (ROR=167.63, PRR=166.97), and cerebral hypoperfusion (ROR=129.75, PRR=129.62). The top three ADE signals reported in the JADER database were hallucinations, visual hallucinations, and falls. The top three ADE signals with high correlation were orthostatic hypotension (ROR=226.93, PRR=216.91), blood pressure fluctuations (ROR=212.31, PRR=208.63), and sudden sleep (ROR=181.89, PRR=179.6). It mainly involved various neurological diseases, mental illnesses, various injuries, poisoning and operational complications, vascular and lymphatic diseases, etc. Forty-seven ADEs not included in the instruction manual were identified, including safety warning signals such as infectious aspiration pneumonia, cerebral infarction, rapid eye movement sleep behavior disorder, aortic dissection, etc.

When using rasagiline mesylate in clinical practice, in addition to paying attention to the ADEs already mentioned in the instructions, it is also necessary to pay attention to new suspected ADEs, and take intervention measures when necessary to ensure the safe and effective use of the drug for patients.

To systematically compare the effects of soybean oil-medium chain triglycerides-olive oil-fish oil (SMOF) and medium/long chain triglycerides (MCT/LCT) on parenteral nutrition-associated liver disease (PNALD) in neonates, thus to provide evidence-based guidance for clinical practice.

A comprehensive search was conducted in databases including CNKI, Wanfang, VIP, CBM, PubMed, Embase, Cochrane Library, and Web of Science, covering studies published from inception to December 30, 2024. Randomized controlled trials (RCTs) involving neonates receiving parenteral nutrition for ≥7 d were included. Eligible studies were assessed for quality, and data were extracted for analysis using R4.3.3 and Stata 14.

Seven RCTs involving 963 neonates were included. Compared to the MCT/LCT group, the SMOF group showed significantly lower levels of alanine aminotransferase (ALT) (SMD=-0.73, 95%CI: -1.34 to -0.12, P=0.018 7) and gamma-glutamyl transferase (GGT) (SMD=-0.89, 95%CI: -1.33 to -0.45, P<0.000 1), while aspartate aminotransferase and alkaline phosphatase levels were comparable between groups. In terms of bilirubin, the SMOF group had lower direct bilirubin levels (SMD=-0.61, 95%CI=-0.88 to -0.34, P<0.000 1), but no significant difference was observed in total bilirubin. Regarding lipid metabolism, triglyceride levels were lower in the SMOF group (SMD=-2.89, 95%CI: -3.80 to -1.97, P<0.000 1), whereas total bile acid levels were similar. The incidence of cholestasis was significantly reduced in the SMOF group (OR=0.54, 95%CI: 0.36 to 0.84, P=0.005 4). Additionally, SMOF did not increase the risk of sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia, or other severe adverse events compared to MCT/LCT, and there was no significant difference in mortality between the two groups.

Compared to MCT/LCT, SMOF improves PN-associated liver disease in neonates with a better safety profile.

To identify and analyze post-marketing adverse drug event (ADE) signals associated with pralsetinib and selpercatinib, compare their respective adverse event profiles, and provide a more comprehensive evidence base to support clinical decision-making in drug selection.

ADE reports for pralsetinib and selpercatinib were extracted from the U.S. FDA Adverse Event Reporting System (FAERS) database from April 2020 to December 2024. Disproportionality analysis was conducted using the reporting odds ratio (ROR) method.

The analysis revealed significant differences in the adverse event profiles of the two drugs. For instance, in the affected system, although the system organ class (SOC) distribution for the top three adverse events was similar between the two drugs, pratinib was associated with a higher frequency of risk signals in gastrointestinal disorders, respiratory/thoracic/mediastinal disorders, and nervous system disorders. In contrast, cepratinib exhibited a greater incidence of adverse reactions related to hepatobiliary disorders, skin and subcutaneous tissue disorders, and other system-specific effects compared to pratinib. Notably, even within the same SOC, the specific adverse reactions differed between the two drugs. For instance, in regard to cardiovascular toxicity, pralsetinib was linked to elevated myocardial necrosis markers, whereas selpercatinib was more frequently associated with QT interval prolongation. These distinctions highlight the need for drug-specific monitoring in clinical practice.

While pralsetinib and selpercatinib share some overlapping adverse effects, their risk profiles exhibit distinct patterns. Individualized drug selection, guided by patient-specific factors and the unique toxicity profiles of each agent, is essential to optimize therapeutic outcomes.