In recent years, multi-modal combined anti-tumor has become an effective strategy for clinical tumor treatment. Photothermal therapy with its characteristics of minimally invasive, controllable, high efficiency, and strong specificity, can effectively make up for the toxic side effects and tumor resistance caused by traditional drug treatment. The research shows that the combination of photothermal therapy and chemotherapy has better synergistic antitumor effect. However, chemotherapeutic drugs and photothermal agents may have different pharmacokinetic behaviors in vivo, so it is difficult to ensure their effective transmission in tumor site, and the free form is easy to be metabolized and degraded in vivo. How to deliver the two therapeutic modes of drugs/photothermal reagents to tumor tissues in a specific, efficient and synchronous manner to achieve the best combined antitumor effect is an important problem to be solved in the combined antitumor application. The development of nano-drug delivery technology provides a new idea for the application of tumor treatment. In this paper, combined with the latest research progress in this field, the anti-tumor mechanism of photothermal therapy combined with chemotherapy, the advantages of nano drug delivery, the types and characteristics of commonly used nano materials and the principle of drug delivery are reviewed in order to provide a reference for the further development of multi-mode combined treatment of tumor.

An ethanol extract of Chloranthus henryi (Chloranthaceae) was subjected to various chromatographic procedures including silica gel column chromatography, MCI column chromatography, Sephadex LH-20 column chromatography, and preparative HPLC. Five purified sesquiterpenes analyzed by spectroscopic analyses (MS, IR, NMR) and single crystal X-ray diffraction were elucidated as (1S, 6S, 8R)-8-ethoxychlomultin C (1a), (1R, 6R, 8S)-8-ethoxychlomultin C (1b), (+)-phaeocaulin D (2), atractylenolide Ⅰ (3), and 8-β-ethoxyasterolid (4). Compounds 1a and 1b were a new pair of sesquiterpene enantiomers and compounds 2-4 were isolated from this plant for the first time. Compounds 1a, 1b, 2 and 3 increased cell viability in H₂O₂-treated PC12 cells from (43.41±1.59)% to (61.71±7.56)%, (66.05±5.61)%, (74.34±3.32)% and (69.58±5.02)% at 10 μmol·L^-1, respectively.

Polyketide synthase 13 (Pks13) performs a critical role in the final assembly step of mycolic acid synthesis in Mycobacterium tuberculosis. The inhibition of Pks13 can influence the biosynthesis of mycolic acid, which leads to Mycobacterium tuberculosis cell death. Researchers have discovered Pks13 inhibitors with five chemical scaffolds as antituberculosis agents. Herein, we summarize recent advances in the study of Pks13 inhibitors including the process of discovery, the mechanism of action and structure-activity relationships.

This paper mainly studied the effect of Xiyanping injection on the bacterial endotoxin lipopolysaccharide (LPS)-induced fever in rabbits, preliminarily investigated the mechanisms, and provided pharmacological basis for the clinical application. The rabbit model of endotoxin-induced fever was established by using LPS as the inducer; The changes of rectal temperature were measured; The levels of prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and phospholipaseA2 (PLA2) in the serum were measured; The levels of PGE2, cyclic adenosine monophosphate (cAMP), and arginine vasopressin (AVP) in cerebrospinal fluid as well as hypothalamus were detected. The animal welfare and experimental process are in accordance with the regulations of the Animal Ethics Committee of China Pharmaceutical University in this study. The results showed that Xiyanping injection (12.5, 25, and 50 mg·kg^-1) could significantly reduce LPS-upregulated body temperature of rabbits, and the duration of action could reach 5.5-8.5 h. At the doses of 25 and 50 mg·kg^-1, the antipyretic effect of Xiyanping injection was comparable to that of analgin injection (50 mg·kg^-1). Furthermore, Xiyanping injection and analgin injection both reduced the levels of PGE2, IL-1β, TNF-α, and PLA2 in the serum of febrile rabbits to the varying degrees. In addition, Xiyanping injection also down-regulated the levels of PGE2, cAMP, and AVP in the hypothalamus, and PGE2 and cAMP in the cerebrospinal fluid. The level of AVP in the cerebrospinal fluid was up-regulated. This study indicated that Xiyanping injection could significantly improve the endotoxin-induced fever in rabbits, and mechanisms were closely related to the regulation of the levels of PGE2, TNF-α, IL-1β, PLA2, cAMP, and AVP in serum, hypothalamus, and cerebrospinal fluid.

Pharmacological activity and drug likeness depend in principle upon the microscopic structure and macroscopic properties of drugs, which reside in their molecular structures. By means of medicinal chemistry the evolution of an active compound to a novel drug (NME) essentially makes the two pillars coexistence in one chemical structure, which either could merge as an intrinsic structure or connect from external fragments to each other with covalent bonds. Since the new millennium the advance in biology provides several knowledge and technologies, for example humanized monoclonal antibody, proteasome-ubiquitin system, allosteric modulation, natural macromolecules, structural biology, etc., for innovation of novel medicines. Taking several examples on marketed drugs or drug candidates in clinical trials, this article tries to concisely illustrate R & D conception of biology-driven drug design.

To establish a method for the determination of polymer impurities in ceftazidime raw materials and preparations, a ceftazidime degradation solution containing polymer impurities was prepared by forced polymerization. Polymer impurities in the degradation solution were separated and identified by high performance gel chromatography and the column switching-LC-MSⁿ method. A new RP-HPLC method for ceftazidime polymer was established and validated with a Phenomenex Gemini-C18 column using a mobile phase gradient elution of 0.02 mol·L^-1 phosphate buffer, methanol and acetonitrile. The results showed that when using this high performance gel chromatography method some small molecular weight impurities were co-eluted with the polymers, resulting in a poor specificity and poor quantitative accuracy. But when using the RP-HPLC method, four polymer impurities were detected in the 25-45 min time range with good specificity, sensitivity and robustness, including two ceftazidime dimers, trimers, and derivatives. Therefore, the described RP-HPLC method is suitable for the quality control of polymer impurities in ceftazidime, and ceftazidime degradation solution can be used as suitable solution for analysis of ceftazidime polymers.

This study systematically investigated the therapeutic effects of chemotherapy-induced mucositis (CIM) by cryptotanshinone (CTS) in mice. CIM mice were prepared by intraperitoneal injection of 5-fluorouracil (5-FU) and irinotecan for 4 days. A pseudo-sterile mouse model was established by intragastric administration of mixed antibiotics (metronidazole, vancomycin, and penicillin). The body weight, disease activity index (DAI), and defecation of mice were daily monitored. The animal welfare and experimental procedures followed the rules of the Animal Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences. We determined the contents of inflammatory factors, total cholesterol (TC), triglyceride (TG), and lipase activity in serum or colonic mucosa of CIM mice. We also studied the composition and relative abundance of fecal flora. The correlation of the relative abundance of fecal microbiota and environmental factors was further analyzed. CTS significantly decreased DAI and reduced the content of interleukin 6 (IL-6), interleukin 11 (IL-11), myeloperoxidase (MPO), and diamine oxidase (DAO) in the serum of CIM mice. CTS effectively increased the content of TG while reduced TC and lipase activity in serum. Results showed the incidence of CIM in pseudoaseptic model group was significantly reduced. Meanwhile, there was no significant difference in the contents of inflammatory factors and TG/TC ratio between pseudoaseptic model group and normal control group. There was a significant difference in the diversity and composition of fecal microbiota among groups. In addition, CTS restored the composition of fecal microbiota close to normal and significantly increased the abundance of g_norank_f_Muribaculaceae. Especially, g_Ruminiclostridium and g_norank_f_Muribaculaceae exhibited a significant positive correlation to TG but a negative correlation to DAO, MPO, IL-6, lipase, and TC. Cryptotanshinone significantly increased the abundance of g_norank_f_Muribaculaceae and g_ruminococcaceae_UCG-014 in fecal microbiota of CIM mice. In conclusion, we reported CTS effectively alleviated intestinal mucositis in mice induced by 5-fluorouracil and irinotecan by regulating fecal microbiota, inflammatory factors, and serum lipid.

Cerasomes with different shapes were constructed to investigate the effect of the nanocarriers' shape on the cellular uptake and transmembrane capacity. Cerasome-forming lipid (CFL) was synthesized via halogenation, nucleophilic addition and acylation reaction and detected by mass spectrometry and nuclear magnetic resonance spectroscopy. CFL and short chain 1, 2-dihexanoyl-sn-glycero-3-phosphocholine (DHPC) were employed to prepare organic-inorganic hybrid bicelles in discal shapes (nanodisc) by the thin-film hydration method, and CFL was also used to prepare spherical cerasomes (nanosphere). The particle size and zeta potential of nanocarriers were measured by dynamic light scattering analysis, and the morphology was observed by transmission electron microscopy. With human colon cancer cell line Caco-2 as the model, the effect of the shape of nanocarriers on cellular uptake and transmembrane capacity was investigated qualitatively by confocal laser scanning microscope (CLSM), and the transmembrane capacity was analyzed quantitatively by high performance liquid chromatography (HPLC). The results showed that nanosphere and nanodisc had similar particle diameters around 110 nm and similar zeta potential around -25 mV, with regular morphology under transmission electron microscope. The cellular uptake rate of nanodisc was significantly higher than that of nanosphere in 20 minutes. Further research on Caco-2 cell monolayer demonstrated that nanodisc with faster uptake had less accumulation in the monolayer, which means it had a higher transmembrane rate on Caco-2 cell monolayer and the transmembrane capacity of the nanodisc was better than that of nanosphere within 2 h. These results suggest that rational design of the shape of nanocarriers is expected to regulate nano-bio interactions, promote the transmembrane transport of nanocarriers, and improve the drug absorption.

The aim of the present study was to determine the metabolic changes and possible toxic mechanisms of ketamine-associated bladder toxicity. Twenty-four male Sprague-Dawley (SD) rats were randomly allocated into a control group, a low-dose group and a high-dose group. The behavior of these rats was observed every day. In addition, the weight, 2 h urinary frequency and organ coefficient of the bladder were measured. Serum IL-6 and TNF-α levels were measured using an enzyme-linked immunosorbent assay (ELISA). Urinary metabolites were analyzed using gas chromatography-mass spectrometry (GC-MS). This research was approved by the Ethics Committee of the Animal Experiment Center of Southwest Medical University (No. 201901-98). After 12 weeks of administration, the frequency of 2 h urination and the bladder mass index were significantly different in the low-dose and high-dose groups compared with the control group. Serum IL-6 and TNF-α levels were higher than those of the control group (P < 0.05). Bladder HE staining showed that long-term administration of ketamine could induce cystitis. The concentrations of the three common differential metabolites, including 3-aminoisobutyric acid, citric acid and uric acid in the low-dose and the high-dose groups were increased compared with those in the control group. This study indicates that 3-aminoisobutyric acid, citric acid and uric acid and their related metabolic pathways may be closely related to ketamine-associated bladder toxicity.

Pazufloxacin eardrops are a topical quinolone agent for the treatment of outer ear infection. The present study evaluated the pharmacokinetics and topical distribution of pazufloxacin eardrops by a sensitive LC-MS/MS method for determining pazufloxacin in plasma and otorrhea. Plasma and otorrhea samples were extracted by acetonitrile-induced protein precipitation and were subjected to liquid chromatography-tandem mass spectrometric analysis with an electrospray ionization interface. The samples were separated on an HSS T₃ column (50 mm×2.1 mm, 1.8 μm). To avoid the matrix effect, gradient elution was performed with the mobile phase consisting of methanol and 1 mmol·L^-1 ammonium acetate aqueous solution (0.1% formic acid). The ion transitions for pazufloxacin and pazufloxacin-d₄ were m/z 319.1→281.2 and m/z 323.1→285.2, respectively, under the multiple reaction monitoring (MRM) mode. The method was linear in the range of 0.010 0-8.00 ng·mL^-1 for pazufloxacin in plasma and 0.500-1 000 ng·mg^-1 in otorrhea. The intra- and inter-day accuracy and precision for pazufloxacin in plasma and in otorrhea met acceptable criteria. The clinical trial was approved by the Society of Ethics and conducted in Nanjing First Hospital and Jiangsu Province Hospital. The validated methods were used in a systemic and topical pharmacokinetic study of 0.1% pazufloxacin eardrops in 3 patients with chronic suppurative otitis media.