Abstract Oral cavity cancer is the sixth-leading cancer worldwide, which has become one of the important factors affecting oral health. The morbidity of oral squamous cell carcinoma(OSCC) accounts for nearly 80% of oral cavity cancer. The pathogenesis and prevention of OSCC have become a hot topic in this field. Previous studies have shown that bone morphogenetic proteins(BMPs) participated in the development, invasion and metastasis of gastric and bone cancers, thereby impacting the prognosis of the patients. Recent studies have found that BMPs also play a key role in the development, progression, metastasis, and invasion of OSCC, This review therefore summarizes the correlation and molecular mechanism between BMPs and the biological behavior of OSCC.

Infectious bone defect,one of the complex and refractory types of bone defects,is characterized by infec-tion,inflammation and subsequent bone tissue destruction.These conditions often lead to severe consequences such as limb necrosis,dysfunction or even amputation.The previous treatment method for infectious bone defect primarily involves thorough debridement and bone grafting after infection control with antibacterial drugs.Howev-er,this method carries drawbacks,including the possibility of drug resistance and systemic toxicity due to high-dose use of antimicrobial drugs.With advancements in modern medicine and in-depth research on biomaterials,va-rious novel antibacterial materials have been increasingly applied in the treatment of infectious bone defect,demon-strating promising outcomes.This paper reviews the applications and therapeutic efficacy of novel antibacterial ma-terials in treating infectious bone defect at home and abroad,aiming to provide references for clinical management.

Infectious bone defect,one of the complex and refractory types of bone defects,is characterized by infec-tion,inflammation and subsequent bone tissue destruction.These conditions often lead to severe consequences such as limb necrosis,dysfunction or even amputation.The previous treatment method for infectious bone defect primarily involves thorough debridement and bone grafting after infection control with antibacterial drugs.Howev-er,this method carries drawbacks,including the possibility of drug resistance and systemic toxicity due to high-dose use of antimicrobial drugs.With advancements in modern medicine and in-depth research on biomaterials,va-rious novel antibacterial materials have been increasingly applied in the treatment of infectious bone defect,demon-strating promising outcomes.This paper reviews the applications and therapeutic efficacy of novel antibacterial ma-terials in treating infectious bone defect at home and abroad,aiming to provide references for clinical management.

Immunoparalysis is the main cause of death in patients with intermediate and terminal sepsis. The correction of immunoparalysis is an important direction of sepsis treatment. In the pathological process of sepsis, a variety of factors contribute to the imbalanced secretion of cytokines, weakened function of antigen-presenting cells, apoptosis and depletion of lymphocytes, and ultimately lead to immunoparalysis, secondary infection, and even patient deaths. Cytokines such as GM-CSF, IFN-γ, IL-7, and IL-15, immune checkpoint-related therapies such as PD-1/PD-L1 antibodies, CTLA-4 antibodies, TIM-3 antibodies, and LAG-3 antibodies, and immunoreactive substances such as thymosin α1 and immunoglobulin might be beneficial to correct the immune paralysis of patients. the progress of immunotherapy to correct immune paralysis in sepsis were reviewed in this article.

Sepsis is life-threatening with complex pathogenesis. It is a big problem in the medical field. Clinically, antibiotics, hormones and mechanical ventilation are the main treatments. There is a lack of specific therapeutic drugs. The treatment effect is not good. In recent years, more and more progress has been made in the treatment of sepsis with traditional Chinese medicine. This article reviews the etiology, pathogenesis and treatment strategies of sepsis. It focuses on four therapies, including clearing away heat and detoxification, clearing the interior, activating blood circulation and removing blood stasis, and strengthening the foundation. We further discuss the advantages and disadvantages of traditional Chinese medicine in the treatment of sepsis, in order to provide reference for the clinical treatment of sepsis.

Motion sickness is a series of physiological responses in human being caused by abnormal movement stimulation. With the development of science and technology, a growing number of people choose to travel by high speed vehicles. Motion sickness happens more frequently. A large number of non-drug and drug intervention methods have been reported in the treatment of motion sickness. This article provides an overview on the research developments in the prevention and treatment of motion sickness in order to provide new ideas for drug research.

Objective To establish an assay method for diphenhydramine hydrochloride and caffeine in rat plasma by UPLC-MS/MS for pharmacokinetic study. Methods The chromatographic separation was performed on an ACE 3 C₁₈-PFP (3.0 mm×150 mm, 3 μm) by isocratic elution with the mobile phase of water containing 0.1% formic acid and acetonitrile (62:38, V/V). MS condition was optimized in the positive ion detection mode by multiple reaction monitoring (MRM), along with the Agilent JetStream electrospray source interface (AJS-ESI). The precursors to the product ion transitions were 256.2→167.0 (m/z) for diphenhydramine hydrochloride, 262.0→167.0 (m/z) for the internal standard (IS) diphenhydramine-D6, 195.0→138.0 (m/z) for caffeine and 204.0→116.2 (m/z) for the IS caffeine-D9. Results The calibration curve was linear in the range of 1-1×10³ ng/ml for diphenhydramine hydrochloride in rat plasma (r=0.999 6), and in the range of 15-1.5×10⁵ ng/ml for caffeine in rat plasma, (r=0.999 9). The intra-day and inter-day precision and accuracy were good (RSD<10%, RE<±10%). Pharmacokinetic studies showed that metabolic characteristics of diphenhydramine hydrochloride 10-30 mg/kg and caffeine 24-72 mg/kg were linear after intragastric administration. The two components were metabolized in rats with gender difference, the c_max and the AUC of diphenhydramine hydrochloride and caffeine were greater in female than those in males. Conclusion This method is accurate, rapid and sensitive. It can be used for the determination of diphenhydramine hydrochloride and caffeine in rat plasma collected for pharmacokinetic study. The results of pharmacokinetic studies in rats provide reliable data support for the clinical application of the compound preparation.

Objective:To study the effects of diphenhydramine and caffeine compound on motion sickness.Methods:Sixty Sprague Dawley (SD) rats were randomly divided into six groups with ten rats in each group, namely, blank control group, model control group, diphenhydramine group (2.25 mg/kg), compound (diphenhydramine and caffeine) low-dose group [(1.13+ 2.70) mg/kg], compound medium-dose group [(2.25+ 5.40) mg/kg], and compound high-dose group [(4.50+ 10.80) mg/kg]. The mental states of rats were observed. The motion sickness (MS) scores and saccharin water intake were evaluated. Thirty Beagle dogs were randomly divided into five groups with six dogs in each group, namely, model control group, diphenhydramine group (0.67 mg/kg), compound (diphenhydramine and caffeine) low-dose group [(0.33+ 0.80) mg/kg], compound medium-dose group [(0.67+ 1.60) mg/kg], and compound high-dose group [(1.34+ 3.20) mg/kg]. The latent periods of salivation and vomiting after rotational stimulation were observed and recorded.Results:The rats in the compound medium-dose group and the compound high-dose group did not manifest somnolence while the rats in other groups receiving diphenhydramine did. After rotational stimulation, the MS scores of the rats in the model group were higher than those of the rats in the compound groups, and the MS scores in the compound groups showed a dose-dependent decreasing trend. Before rotational stimulation, there were no significant difference in the saccharin water intake among the rats of all the groups. After rotational stimulation, the saccharin water intake in the model group was more significantly reduced than that of the blank control group ( P<0.01). Compared with the model group, the saccharin water intakes in diphenhydramine group and compound groups were significantly increased ( P<0.05), and the increase were dose-dependent. Before drug administration, all the Beagle dogs were susceptible to rotational stimulation with early salivation and vomiting. After drug administration, the latent periods of salivation and vomiting were all considerably extended ( P<0.05), and the extension of the latent periods in the compound groups was dose-dependent. Conclusion:The diphenhydramine and caffeine compound has protective effects against motion sickness, and the adverse reactions of inhibition in central nervous system are mild.

Objective:To study the effects of diphenhydramine and caffeine compound on motion sickness.Methods:Sixty Sprague Dawley (SD) rats were randomly divided into six groups with ten rats in each group, namely, blank control group, model control group, diphenhydramine group (2.25 mg/kg), compound (diphenhydramine and caffeine) low-dose group [(1.13+ 2.70) mg/kg], compound medium-dose group [(2.25+ 5.40) mg/kg], and compound high-dose group [(4.50+ 10.80) mg/kg]. The mental states of rats were observed. The motion sickness (MS) scores and saccharin water intake were evaluated. Thirty Beagle dogs were randomly divided into five groups with six dogs in each group, namely, model control group, diphenhydramine group (0.67 mg/kg), compound (diphenhydramine and caffeine) low-dose group [(0.33+ 0.80) mg/kg], compound medium-dose group [(0.67+ 1.60) mg/kg], and compound high-dose group [(1.34+ 3.20) mg/kg]. The latent periods of salivation and vomiting after rotational stimulation were observed and recorded.Results:The rats in the compound medium-dose group and the compound high-dose group did not manifest somnolence while the rats in other groups receiving diphenhydramine did. After rotational stimulation, the MS scores of the rats in the model group were higher than those of the rats in the compound groups, and the MS scores in the compound groups showed a dose-dependent decreasing trend. Before rotational stimulation, there were no significant difference in the saccharin water intake among the rats of all the groups. After rotational stimulation, the saccharin water intake in the model group was more significantly reduced than that of the blank control group ( P<0.01). Compared with the model group, the saccharin water intakes in diphenhydramine group and compound groups were significantly increased ( P<0.05), and the increase were dose-dependent. Before drug administration, all the Beagle dogs were susceptible to rotational stimulation with early salivation and vomiting. After drug administration, the latent periods of salivation and vomiting were all considerably extended ( P<0.05), and the extension of the latent periods in the compound groups was dose-dependent. Conclusion:The diphenhydramine and caffeine compound has protective effects against motion sickness, and the adverse reactions of inhibition in central nervous system are mild.