Objective To prepare flumazenil sublingual tablets and study its bioavailability. Methods Flumazenil sublingual tablets were prepared by compressing flumazenil inclusion compound with hydroxypropyl-β-cyclodextrin as the inclusion material. In a double-cycle crossover trial, twelve beagle dogs were randomly divided into two groups, one group receiving flumazenil sublingual tablets and the other receiving flumazenil injections. LC-MS method was developed and validated to determine flumazenil plasma concentration. The pharmacokinetic parameters and bioavailability were calculated using WinNonlin pharmacokinetic software. Results In the pharmacokinetic study, AUC_last of flumazenil injection and sublingual tablet was （8.41±2.15） and （8.86±2.83） h·ng·ml⁻¹, respectively; C_max was （10.96±2.62） and （6.36±2.14） ng/ml, respectively; t_max was （0.18±0.05） and （0.58±0.24） h, respectively. The bioavailability of flumazenil sublingual tablet was 52.68%. Conclusion Clathrates were used to prepare flumazenil sublingual tablets to achieve safe and efficient delivery. LC-MS method was established for the determination of flumazenil plasma concentration, and the advantages were simple, accurate and sensitive.

Sprays have gained significant attention and widespread use due to their numerous advantages, including rapid action, safety, and convenience. They are widely used in various fields such as dermatology, respiratory disease treatment, wound repair, and central nervous system targeted drug delivery. With the in-depth research of new drugs and modern pharmaceutics, the development ideas of sprays are more diverse, and the application scenarios are increasingly extensive. In this review the clinical application status of sprays and the latest research progress were summarized. Then the quality control parameters were briefly introduced，which provided reference for the research and development of sprays.

Objective To construct methoxy polyethylene glycol (mPEG) modified gold nanoparticles (AuNPs) loaded with doxorubicin (DOX) AuNPs-mPEG@DOX in order to reduce the toxicity and side effects of DOX. Methods AuNPs-mPEG@DOX was prepared and characterized by Z-Average, Zeta potential and UV-Vis spectroscopy. The impact of thiol-linked DOX (HS-DOX) at various dosage concentrations on the drug adsorption rate and drug loading of AuNPs-mPEG@DOX was investigated. Furthermore, a HPLC method was developed to accurately determine the content of unadsorbed HS-DOX in AuNPs-mPEG@DOX. The specificity, linearity, precision, stability and average recovery of this method were thoroughly investigated. The cytotoxic effect of AuNPs-mPEG@DOX on MCF-10A and MCF-7 cells was evaluated using a CCK-8 assay. Results AuNPs-mPEG@DOX was successfully prepared with Z-Average of (46.12±0.49) nm, Zeta potential of (18.60±1.51) nm and the maximum absorption wavelength of 530 nm. An efficient HPLC method for the detection of unadsorbed HS-DOX in AuNPs-mPEG@DOX was devised. The optimal dosage concentration of HS-DOX for AuNPs-mPEG@DOX was determined to be 11.18 μg/ml, resulting in a drug adsorption rate of (9.21±2.88)% and a drug loading rate of (2.01±0.62)%. Cytotoxicity experiments demonstrated that AuNPs-mPEG@DOX significantly reduced the toxic and side effects of DOX on normal breast cells. Additionally, AuNPs-mPEG@DOX and free DOX exhibited comparable cytotoxic effects on breast tumor cells when DOX concentration was equal to or greater than 4.75 μmol/L. Conclusion AuNPs-mPEG@DOX effectively reduce the toxicity of DOX, providing a reference for future research on reducing the toxicity of AuNPs-linked drugs.

Objective To understand the trends and characteristics of clinical trials on cancer pain medications in recent years,and to provide a reference basis for the development and clinical research of cancer pain medications.Methods Relevant information on clinical trials of cancer pain medications from 1987 to 2022 was retrieved from the ClinicalTrials.gov database,and a descriptive analysis was conducted from the perspectives of trial types,registration dates,reporting regions,cancer pain type,and cancer pain medications.Results A total of 376 clinical trials were selected,Among them,the number of investigator-initiated trials(IIT)was greater than that of industry-sponsored trials(IST).North America had the highest total number of projects,IIT and IST projects.The total number of trials and IST projects increased first and then decreased,while the number of IIT trials steadily increased.There was relatively higher amount nof research focused on chronic cancer pain,breakthrough cancer pain,and severe cancer pain.The highest proportion of subjects studied were opioids,with fentanyl being particularly prominent among them.Conclusion Clinical trials of cancer pain medications have played an important role in advancing cancer pain medication,but there is a need to further strengthen IST research on novel cancer pain medications and conduct more IIT studies to better optimize cancer pain treatment outcomes.

Objective To establish a detection method for the determination of tetrodotoxin (TTX) in sustained-release microspheres. Methods The HPLC separation of tetrodotoxin was performed on an Agilent ZORBAX SB-C₁₈ column (4.6mm×150mm,5 μm) with acetonitrile, 8mmol/L sodium heptane sulfonate containing 0.005% TFA (5:95) (pH 4.0) as the mobile phase. The flow rate was 1.0 ml/min. The UV detection wavelength was 200 nm and the column temperature was 30 °C. Results The method had good specificity and linearity of TTX in the concentration range of 1−20 μg/ml. The intra-day precision, inter-day precision, stability and repeatability of the method were good, and the average recoveries were found between 98.0% and 102.0%. Conclusion This study established an HPLC method which was suitable for the determination of tetrodotoxin sustained-release microspheres. The method is accurate and reliable within the applicable range, with strong specificity, which could lead to quantitative detection.

Tetrodotoxin (TTX) is a neurotoxin found in puffer fish and other marine organisms. It has been used as an inhibitor of voltage-gated sodium channels (VGSCs), which could selectively bind to the α-subunit on the outer vestibule of VGSCs, preventing sodium ions from entering the channel, resulting in pharmacological activities. As a typical sodium channel blocker, TTX shows a significant analgesic effect. TTX could selectively block Na⁺ channels without affecting other ion channels, therefore it could reduce the probability of adverse reactions caused by commonly used antiarrhythmic drugs. In addition, TTX has a significant role in detoxification and prevention of renal failure, so TTX has great potential as a medicine. The structure and physicochemical properties, mechanism of action, pharmacological activities and preparations of tetrodotoxin have been reviewed in this paper, so as to provide a general support for the evaluation of its druggability and application in the field of pharmacy.

Tumor-associated macrophages (TAMs), one of the dominating constituents of tumor microenvironment, are important contributors to cancer progression and treatment resistance. Therefore, regulation of TAMs polarization from M2 phenotype towards M1 phenotype has emerged as a new strategy for tumor immunotherapy. Herein, we successfully initiated antitumor immunotherapy by inhibiting TAMs M2 polarization via autophagy intervention with polyethylene glycol-conjugated gold nanoparticles (PEG-AuNPs). PEG-AuNPs suppressed TAMs M2 polarization in both in vitro and in vivo models, elicited antitumor immunotherapy and inhibited subcutaneous tumor growth in mice. As demonstrated by the mRFP-GFP-LC3 assay and analyzing the autophagy-related proteins (LC3, beclin1 and P62), PEG-AuNPs induced autophagic flux inhibition in TAMs, which is attributed to the PEG-AuNPs induced lysosome alkalization and membrane permeabilization. Besides, TAMs were prone to polarize towards M2 phenotype following autophagy activation, whereas inhibition of autophagic flux could reduce the M2 polarization of TAMs. Our results revealed a mechanism underlying PEG-AuNPs induced antitumor immunotherapy, where PEG-AuNPs reduce TAMs M2 polarization via induction of lysosome dysfunction and autophagic flux inhibition. This study elucidated the biological effects of nanomaterials on TAMs polarization and provided insight into harnessing the intrinsic immunomodulation capacity of nanomaterials for effective cancer treatment.

Objective To compare the differences in the anti-tumor growth effects of organisms with different injections of CT26 tumor cell RNA loaded into nanoliposomes. Methods The extracted tumor RNA was loaded into nanoliposomes to prepare tumor RNA nanoliposome vaccines, and the related properties of nanoliposome vaccines were investigated. The particle size of nanoliposome vaccines was （120.0±12.1）nm and zeta potential was （3.39±0.56）mV. Tumor RNA nanoliposome vaccines were injected into different parts of the mice to test and analyze the influence of different injections on the growth of colon cancer transplanted tumors in mice. Results Tumor RNA nanoliposome vaccines were used to inject tumor-transplanted mice in different ways. Compared with underarm injection, intraperitoneal injection enhanced the organism's anti-tumor immune response and inhibited the growth of transplanted tumors more effectively. The H&E staining of important organs in mice was compared and no obvious organic lesions were found in the organs. Conclusion Intraperitoneal injections of nanoliposome loaded with tumor RNA can enhance the body's anti-tumor immune response more effectively than underarm injections.

Objective To study the effect of flumazenil on hypnotic mice induced by diazepam and zolpidem ,and to eval-uate the possibility of flumazenil oral administration .Methods First ,Kunming mice were injected intraperitoneally with nor-mal saline and sodium pentobarbital (S + W) ,diazepam and pentobarbital sodium (D + W) ,zolpidem and pentobarbital sodi-um (Z + W) .The hypnotic effect of diazepam and zolpidem on prolonging the sleep time of pentobarbital sodium would be ver-ified by (D + W) group and (Z + W) group .Then the mice were injected intraperitoneally with flumazenil .The sleep time was used as the evaluation index to evaluate the effect of flumazenil against hypnosis . Finally , the oral administration of flumazenil was observed against hypnosis ,which was evaluated by using sleep time as an index .Results Compared with the control group (S+W) ,the diazepam group (D+W) and the zolpidem group (Z+W) significantly prolonged the sleep time in-duced by pentobarbital sodium (P<0 .001 ,P<0 .05);After Intraperitoneal injection of flumazenil ,compared with the diazepam group (D+W) and the zolpidem group (Z+W) ,the sleep time of the diazepam group [F(ip)+D+W] and the zolpidem group [F(ip)+Z+W] were significantly shorter (P<0 .001 ,P<0 .05);After oral administration of flumazenil ,the sleep time of the diazepam group [F(ig)+ D+ W] and the zolpidem group [F(ig)+ Z+ W] were also significantly shorter (P< 0 .001 ,P<0.05) .Conclusion Flumazenil ,whether intraperitoneal injection or intragastric administration ,could antagonize the hypnotic effect of diazepam and zolpidem .It was proved that oral administration of flumazenil had the same effect compared with intrap-eritoneal injection of flumazenil ,which provided the possibility of preparation of oral administration of flumazenil .

Objective: To analyze the clinical characteristics of allergic reactions in patients with colorectal cancer after routine premed-ication with dexamethasone (5 mg) before chemotherapy with an oxaliplatin-containing regimen and to provide a reference for reduc-ing the risk of oxaliplatin allergy. Methods: Retrospective analysis of 242 patients with colorectal cancer who received chemotherapy with an oxaliplatin-containing regimen at the Changzhou Cancer Hospital of Soochow University from January 2014 to October 2017 was performed, and the incidence of allergic reactions was calculated. The associations between multiple factors and allergic reactions were then assessed using univariate analysis. The independent factors of allergic reactions were assessed using multivariate Logistic analysis, and the treatment outcome of oxaliplatin rechallenge in allergic patients was discussed. Results: A total of 242 patients were studied. They received routine premedication with dexamethasone (5 mg) before chemotherapy with an oxaliplatin-containing regi-men. Twelve (4.9%) patients had type I allergic reactions, with a median onset time of 6 (5.5-10.5) cycles and a median cumulative dose of 895 (716.5-1 075.0) mg. Multivariate analysis identified undergoing an oxaliplatin-free interval as an independent risk factor (P=0.04). Rechallenging patients with prophylactic agents was successful in 1 (33.3%) of 3 patients who completed their treatment. Conclusions: Routine low-dose dexamethasone premedication before oxaliplatin administration is safe and exhibited a lower inci-dence of hypersensitivity reactions than that reported in literature. An oxaliplatin-free interval may increase the risk of hypersensitivity reactions. Caution should be exercised while rechallenging allergic patients with oxaliplatin.