Though all the marketed drugs of dipeptidyl peptidase IV inhibitors are structurally different, their inherent correlation is worthy of further investigation. Herein we rapidly discovered a novel DPP-IV inhibitor 8g (IC50 = 4.9 nmol.L-1) which exhibits as good activity and selectivity as the market drugs through scaffold hopping and drug splicing strategies based on alogliptin and linagliptin. This study demonstrated that the employment of classic medicinal chemistry strategy to the marketed drugs with specific target is an efficient approach to discover novel bioactive molecules.
Dipeptidyl-Peptidase IV Inhibitors ; chemical synthesis ; chemistry ; Drug Design ; Drug Discovery ; methods ; Humans ; Hypoglycemic Agents ; chemical synthesis ; chemistry ; Linagliptin ; chemical synthesis ; chemistry ; Molecular Structure ; Piperidines ; chemical synthesis ; chemistry ; Structure-Activity Relationship ; Uracil ; analogs & derivatives ; chemical synthesis ; chemistry

Abstract: Objective　To analyze the epidemiological characteristics of 151 cases of melioidosis and the drug resistance of Burkholderia pseudomallei (BP), in order to provide the basis for diagnosis, treatment and reasonable prevention of melioidosis. Methods　A total of 151 inpatients and outpatients from the Second Affiliated Hospital of Hainan Medical University from January 1, 2013 to August 31, 2022 were collected, and clinical specimens were submitted for examination to isolate and identify BP strains. The clinical data of 151cases of melioidosis and the drug resistance characteristics of pathogenic bacteria were retrospectively analyzed, and using SPSS26.0 software for statistical analysis. Results　Among 151 cases with BP infection, there were 138 males (91.4%) and 13 females (8.6%); the most patients were aged from 45-<60 years old, accounting for 74 cases (49.0%); melioidosis incidence was concentrated in October (19.2%), November (19.2%), August (9.9%) and July (8.6%), and; the number of confirmed cases showed an increasing trend and the time for confirmation was <10 d; Internal medicine system (31.1%), surgery system (26.5%) and intensive care department (20.5%) were the common departments for treating melioidosis; blood (49.0%), sputum (9.9%) and wound secretion (8.6%) were the main clinical specimens for detecting BP; pulmonary infection (68.2%), sepsis (35.1%) and local suppurative infection (23.8%) were the top clinical manifestations in patients with BP infection; the effective rate of treating melioidosis was 74.8%; abnormal liver function was a risk factor for the curative effect of melioidosis (χ2=5.010, P<0.05); the sensitivity rates of BP strains to sulfamethoxazole-trimethoprim (SXT), doxycycline (DOX), imipenem(IPM), ceftazidime (CAZ), amoxicillin/clavulanate (AMC) and tetracycline (TCY) were generally more than 90%, with sensitivities of 98.7%, 97.2%, 96.7%, 94.0%, 93.2% and 90.7%, respectively. Conclusions　It can be concluded that misdiagnosis or missed diagnosis of melioidosis is easy to occur, and the understanding of the epidemiological characteristics and risk factors in this area should be strengthened. The sensitivity of BP to commonly used antibiotics has shown a certain downward trend, clinical use should be standardized, and drug resistance monitoring should be strengthened to improve the efficacy of melioidosis treatment.

ObjectiveTo investigate the role of platelet-derived growth factor(PDGF) and its receptor in the development of hypertrophic scar. MethodsThe expression of PDGF and its receptor were detected in biopsy specimens of 9 pieces of normal skin, 7 pieces of granulation tissue of burn wound and 34 pieces of hypertrophic scar by immunohistochemical staining using specific polyclonal antibodies.ResultsPDGF and its receptor markedly increased in granulation tissue and hypertrophic scars, reaching the peak in the hypertrophic scars within 6 months and then decreased after the peak, whereas PDGF and its receptor expressed weakly in only a few normal skin specimens, and the differences were significant(P<0.05).ConclusionsThe increasing expression of PDGF and its receptor may be related to the development of hypertrophic scar.

OBJECTIVETo investigate the effect of HMME-PDT (Hematoporphyrin Monomethyl Ether-Photodynamic therapy) on Hyperplastic scar in the rabbit ear.

METHODSThe acute model of dermal Hyperplastic scar in the rabbit ear was established. 24 scars were randomly divided into 2 groups: the experimental group (n = 12) received HMME-PDT treatment, and the controlled group (n = 12) received no special treatment. Specimens were harvested from scars on postoperative 28 day. Scar hyper plasty and collagen fibers were observed by haematoxylin-eosin staining and Van-Gieson staining respectively. The microvessel density was calculated under microscope.

RESULTSCompared with the controlled group, HMME-PDT treatment in the experimental group reduced scar formation, decreased the microvessel density and prevented excess collagen deposition at the wound site.

CONCLUSIONSHMME-PDT may play a role in inhibiting hyperplastic scar in rabbit ear.

Animals ; Cicatrix, Hypertrophic ; pathology ; therapy ; Ear ; pathology ; Female ; Hematoporphyrins ; pharmacology ; Male ; Photochemotherapy ; Rabbits

Objective: To explore the factors affecting the prognosis of patients with hepatocellular carcinoma (HCC) combined with portal vein tumor thrombosis (PVTT), and to analyze the clinical value of transcatheter arterial chemoembolization (TACE) combined with iodine-125 seed implantation in such patients. Methods: A retrospective analysis of 53 patients with HCC combined with PVTT was performed. In the study group, 32 cases were treated with TACE combined with iodine-125 seed implantation, and 21 cases in the control group were treated with TACE combined with sorafenib. Survival analysis was carried out on eight factors such as gender, age, Child-Pugh classification, alpha fetoprotein level, portal vein tumor thrombosis (PVTT) type, forms of liver tumor, extra-hepatic metastasis and treatment modalities. The efficacy of TACE combined with iodine-125 seed implantation and TACE combined with sorafenib was further compared. The χ ² test was used to evaluate the efficacy of the two groups. A single factor survival analysis was calculated by Kaplan-Meier estimator and multifactor survival analysis by Cox proportional hazards model. Results: All 53 patients were successfully treated. The median tumor progression time (mTTP) and median overall survival (mOS) were 8 months and 11 months, respectively. The disease control rate (DCR) of the study group for PVTT was 93.8%, which was significantly higher than that of the control group (61.9%, χ ² = 6.448, P = 0.011). The difference was statistically significant; the objective remission rate of the study group for PVTT was 75.0%. Significantly higher than 9.5% in the control group, P < 0.05, the difference was statistically significant; the DCR of the primary tumor in the study group was 50.0%, which was lower than the 70.0% of the PVTT in the control group, P = 0.231, the difference was not statistically significant. The progression of primary HCC lesions in patients with multivariate survival analysis: Child-Pugh grade A patients were compared to grade B [Hazard ratio (HR) = 0.236, P = 0.003]; no extra-hepatic metastasis (HR = 0.258, P = 0.002); and TACE combined with iodine-125 seed implantation group compared with TACE combined sorafenib group (HR = 0.372, P = 0.002), the differences were statistically significant. Multivariate survival analysis of patients with overall survival: AFP < 400 ng/mL vs. AFP≥400 ng/mL (HR = 0.389, P = 0.030); Child-Pugh grade A vs. B (HR = 0.263, P = 0.006); and no extra-hepatic metastasis (HR = 0.306, P = 0.006), the differences were statistically significant. Conclusion TACE combined with iodine-125 seed implantation for the treatment of HCC with PVTT can effectively control the progression of PVTT and intrahepatic lesions and improve the prognosis of patients.

Objective To explore the willingness of care and related influencing factors among caregivers of those 'left at hometown' children under 7 years in Chinese rural areas.Methods Questionnaires were used to survey caregivers (n=7585) who were identified by multi-stage stratified cluster sampling. Multi-factor ordinal logistic regression analysis was used to screen the influencing factors on the willingness of care among them. Results The percentage on 3.5% respectively in the group with single parent while 19.5%, 71.4% and 9.1% respectively in the group of both parents having left home. Data from the multi-factor ordinal logistic regression analysis showed that factors including the age of the caregiver, annual per capita income for caregivers'families, social connections and the length of children' s mother being absent, amount of fees for living provided by parent/parents, and the child' s age and lifestyle, being the only child or not, and the age of the child when the parent/parents left the residence etc, were related to the willingness of care of the givers. Conclusion Willingness of care calls for attention and urgent improvement.Influencing factors and measures need to be taken when necessary.

Objective To study the method of emergency blood collection during a long-distance voyage to ensure blood transfusion treatment.Methods Ten voluntary blood donors were recruited, a base unit of blood was collected and preserved.Reactions of the blood donors were observed, and the blood quality was tested.Results The success rate of blood collection was 90% and the qualification rate was 100%.Conclusion Emergency blood collection during a long-distance voyage is feasible,which can help ensure blood supply in peace time or war time.

The qualitative and quantitative analysis on traditional Chinese medicine and formula components can be made by chemical and instrumental analysis methods. Of both, the instrumental analysis methods play a dominant role, including HPLC, HPLC-MS, HPLC-NMR, GC, GC-MS, biochemical and biological effect. But because traditional Chinese medicines and formula have complicated components, chemical methods are so unspecific that they shall be used less or with caution. While instrumental analysis methods are so specific that they are appropriate for analyzing complicated single component. The analysis techniques for multiple components of traditional Chinese medicines and formula focus on fingerprints, but all of these analysis techniques are limited by the pre-requisite of separation and the lack of general-purpose detectors and therefore being hard to realize the determination of all components of traditional Chinese medicines and formula. In the natural world, however, organisms identify native and alien components through specificity and non-specificity of clusters decided by antigens and antibodies. For example, components of traditional Chinese medicines are directly or indirectly synthesized into antigens and injected into animals, in order to generate specific antibodies and then collect cross reaction information of these components to specific antibodies. As for components without cross reaction, their contents shall be directly read out on the basis of the inhibition rate curve of competitive reaction for specificity of antigens and antibodies. Besides, a cross inhibition rate matrix shall be established first, and them a multiple regression linear equation between cross component concentration or concentration logarithm and inhibition rate by labeling the immunity competitive reaction between antibodies and haptens of traditional Chinese medicine and compound components, and then solved to obtain concentration of each component. The two results are combined to establish the synthetic immunity chip method for traditional Chinese medicine and formula components.
Animals ; Chemistry, Pharmaceutical ; Drugs, Chinese Herbal ; chemistry ; High-Throughput Screening Assays ; methods ; Humans ; Immunohistochemistry ; methods ; Vaccines, Synthetic ; chemistry

Injections for traditional Chinese medicine have over 60 years of history of development and application. In recent years, however, their adverse reactions have been reported one after another. Consequently, studies on screening sensitinogens (sensibiligens) from injections for traditional Chinese medicine have drawn people's attention and become a tough problem all over the world. This essay analyzes the current state of studies on screening techniques of sensitinogens in injections for traditional Chinese medicine according their mechanism of immunotoxicity, and then proposes to adopt the synthetic immunoassay combining immunity bottle chip, immunity cover chip and immunity chromatographic fingerprint to screen sensitinogens from injections for traditional Chinese medicine, in order to build a safety evaluation barrier for development and clinical application of injections for traditional Chinese medicine.
Drug Hypersensitivity ; immunology ; Drugs, Chinese Herbal ; administration & dosage ; adverse effects ; chemistry ; toxicity ; Humans ; Medicine, Chinese Traditional ; methods

OBJECTIVETo observe the histopathological changes of a novel small-caliber vascular graft after implantation in canine theca interna under scanning electron microscope.

METHODA 3 cm segment of the vascular graft (diameter of 4 mm) was implanted in an end-to-end fashion to bridge the severed carotid artery in 19 healthy dogs. Color Doppler sonography was performed 2 weeks after the operation to observe the patency rate of artificial blood vessel. At 1, 8, 12 and 24 week postimplantation, the arteries (4, 4, 6 and 5, respectively) were collected for optical and scanning electron microscopies after angiography to observe the patency of the arteries.

RESULTSOf the total of 19 arteries, occlusion occurred in 1 at 12 weeks and 1 at 24 weeks. Optical and electron microscopies showed that 1 week after implantation, slight fibroplasias and formation of red thrombus could be seen at the vascular anastomosis without endothelial cell lining. At 8 weeks, the host tissue grew into the lumen of the graft through the pores to form uniform neointima consisting of plenty of collagen fibers, but still without endothelial cells. At 12 weeks, discontinuous endothelial cells were seen to grow on the surface of the neointima. In the middle segment of the vascular graft, immature endothelial cells were found to grow in clusters. The structure of the neointima was loose in comparison with that at the anastomosis, with occasional inflammation cells. Twenty-four weeks after grafting, endothelial cells grew over the entire inner wall of the patent graft, and the surface of the neointima at the anastomosis was lined with continuous endothelial cells.

CONCLUSIONThe vascular graft can be useful for reconstruction of canine carotid artery defect and achieves good endothelialization 24 weeks after implantation.

Animals ; Blood Vessel Prosthesis ; Blood Vessel Prosthesis Implantation ; methods ; Carotid Arteries ; diagnostic imaging ; physiology ; surgery ; Collagen ; metabolism ; Dogs ; Endothelial Cells ; cytology ; metabolism ; ultrastructure ; Microscopy, Electron, Scanning ; Models, Animal ; Time Factors ; Tunica Intima ; cytology ; metabolism ; ultrastructure ; Ultrasonography, Doppler, Color ; Vascular Patency