Based our previous work, twelve purine derivatives were designed and synthesized as dual modulators of GPR119 and DPP-4by conjugating the GPR119 activating and DPP-4 inhibiting fragments with the position 6 and 9 of purine core via an approach of merged pharmacophores. Compound 11, bearing 2-fluoro-4-methylsulphonyl anilide and cyanopyrrolidine moieties, exhibited the most potent GPR119 agonistic activities (EC₅₀ = 0.33 μmol·L^-1, IA = 71.1%) and DPP-4 inhibitory (58.4% inhibition at 10 μmol·L^-1, 21.2% inhibition at 1 μmol·L^-1) activities in the in vitro antidiabetic study. Subsequently, we performed studies on structure activity relationships and molecular docking to guide the further drug design.

OBJECTIVE: To delineate the onset and recurrence characteristics of noncardiogenic ischemic stroke patients in China. METHODS: A prospective, multicenter and registry study was carried out in 2,558 patients at 7 representative clinical sub-centers during November 3, 2016 to February 17, 2019. A questionnaire was used to collect information of patients regarding CM syndromes and constitutions and associated risk factors. Additionally, stroke recurrence was defined as a primary outcome indicator. RESULTS: A total of 327 (12.78 %) patients endured recurrence events, 1,681 (65.72%) were men, and the average age was 63.33 ± 9.45 years. Totally 1,741 (68.06%) patients suffered first-ever ischemic stroke, 1,772 (69.27%) patients reported to have hypertension, and 1,640 (64.11%) of them reported dyslipidemia, 1,595 (62.35%) patients exhibited small-artery occlusion by The Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. Specifically, 1,271 (49.69%) patients were considered as qi-deficient constitution, and 1,227 (47.97%) patients were determined as stagnant blood constitution. There were 1,303 (50.94%) patients diagnosed as blood stasis syndrome, 1,280 (50.04%) patients exhibited phlegm and dampness syndrome and 1,012 (39.56%) patients demonstrated qi deficiency syndrome. And 1,033 (40.38%) patients declared intracranial artery stenosis, and 478 (18.69%) patients reported carotid artery stenosis. The plaque in 1,508 (41.36%) patients were of mixed. Particularly, 41.09% of them demonstrated abnormal levels of glycated hemoglobin levels. CONCLUSIONS Recurrence in minor and small-artery stroke cannot be ignored. Hypertension, dyslipidemia, abnormal HbA1c, intracranial artery stenosis and carotid plaque were more common in stroke patients. Particularly, phlegm-dampness and blood stasis syndromes, as well as qi deficiency and blood stasis constitutions, were still the main manifestations of stroke. (Trial registration at ClinicalTrials.gov No. NCT03174535).
Aged ; Constriction, Pathologic ; Female ; Hospitals ; Humans ; Hypertension ; Ischemic Stroke ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Prospective Studies ; Stroke/epidemiology* ; Syndrome

Objective: To summarize the application of temporalis muscle flap in the salvage nasopharyngectomy for advanced recurrent nasopharyngeal carcinoma (rNPC), and to provide guidance for the repair of extensive skull base defects in salvage rNPC. Methods: A total of 54 patients with the application of temporalis muscle flap in the salvage nasopharyngectomy for advanced rNPC were retrospectively analyzed, including 42 males and 12 females, aging from 29 to 71 years. There were 36 patients with rT3 and 18 patients with rT4. The surgical methods of temporalis muscle flap repair were summarized. The general situation, survival time and postoperative complications of patients were recorded, and the advantages and disadvantages of temporalis muscle flap were discussed. Results: The temporal muscle flap could completely cover the defect area of nasopharynx and skull base, without the need for other autologous repair materials. The follow-up period was 2 to 28 months. The survival rate of temporalis flap was 98.1% (53/54). The 1-year overall survival rate was 84.5% while 1-year progression-free survival rate was 49.0%. None of the patients had facial nerve injury. Three patients (5.6%) had necrosis of the cranial membrane required surgical intervention and four patients (7.4%) required a chonoplasty due to severe chonostril stenosis or chonostril atresia. Eleven cases (20.4%) had mouth opening restriction, chewing weakness, dysphagia and other eating difficulties. Conclusions: Temporalis muscle flap is an alternative flap for the salvage nasopharyngectomy for advanced rNPC. Temporal muscle flap shows high survival rate and wide coverage, but the surgeon should apprehend the possible complications and reduce the occurrence of them.
Humans ; Male ; Female ; Nasopharyngeal Carcinoma ; Retrospective Studies ; Surgical Flaps ; Nasopharyngeal Neoplasms/pathology* ; Muscles/pathology*

OBJECTIVE: To investigate the current status of antibiotic use for very and extremely low birth weight (VLBW/ELBW) infants in neonatal intensive care units (NICUs) of Hunan Province. METHODS: The use of antibiotics was investigated in multiple level 3 NICUs of Hunan Province for VLBW and ELBW infants born between January, 2017 and December, 2017. RESULTS: The clinical data of 1 442 VLBW/ELBW infants were collected from 24 NICUs in 2017. The median antibiotic use duration was 17 days (range: 0-86 days), accounting for 53.0% of the total length of hospital stay. The highest duration of antibiotic use was up to 91.4% of the total length of hospital stay, with the lowest at 14.6%. In 16 out of 24 NICUs, the antibiotic use duration was accounted for more than 50.0% of the hospitalization days. There were 113 cases with positive bacterial culture grown in blood or cerebrospinal fluid, making the positive rate of overall bacterial culture as 7.84%. The positive rate of bacterial culture in different NICUs was significantly different from 0% to 14.9%. The common isolated bacterial pathogens Klebsiella pneumoniae was 29 cases (25.7%); Escherichia coli 12 cases (10.6%); Staphylococcus aureus 3 cases (2.7%). The most commonly used antibiotics were third-generation of cephalosporins, accounting for 41.00% of the total antibiotics, followed by penicillins, accounting for 32.10%, and followed by carbapenems, accounting for 13.15%. The proportion of antibiotic use time was negatively correlated with birth weight Z-score and the change in weight Z-score between birth and hospital discharge (r=-0.095, -0.151 respectively, P<0.01), positively correlated with death/withdrawal of care (r=0.196, P<0.01). CONCLUSIONS Antibiotics used for VLBW/ELBW infants in NICUs of Hunan Province are obviously prolonged in many NICUs. The proportion of routine use of third-generation of cephalosporins and carbapenems antibiotics is high among the NICUs.
Anti-Bacterial Agents ; Birth Weight ; Humans ; Infant ; Infant, Extremely Low Birth Weight ; Infant, Newborn ; Intensive Care Units, Neonatal ; Surveys and Questionnaires

Polygalae Radix， a traditional Chinese medicine， has the functions of improving intelligence， calming nerves， relieving cough and eliminating phlegm. Its processing methods are various， but the purpose of processing is to reduce toxicity and increase efficiency. In this paper， the methods of ancient processing， such as cleansing， cutting， processing with excipient and processing without excipient， were summarized， the processing methods of Polygalae Radix in the different versions of Chinese Pharmacopoeia and the local processing specifications were summarized， in order to compare the differences and research progress of different processing methods. On this basis， taking the modern research of processed products of Polygalae Radix as the breakthrough point， this paper reviewed the modern research on processed products of Polygalae Radix from the aspects of processing technology， chemical composition changes and pharmacodynamics changes before and after processing， and the mechanism of reducing toxicity and increasing efficiency. Based on the research status of processing of Polygalae Radix， some existing problems were analyzed in this paper， including not many ancient processing methods used in modern times， lack of standardized research on processing technology， few studies on the ingredients introduced by excipients， etc. The author thinks that it is necessary to strengthen the research on the ancient processing of Polygalae Radix combined with processing methods with local characteristics. While discussing the processing technology， combining with the composition and efficacy， we should carry out in-depth research on the processing mechanism of different processing products of Polygalae Radix， so as to provide scientific basis for the rationality of processing of Polygalae Radix and ensure the clinical safety of medication.

Objective:To investigate the effect of Wendantang on cyclic adenosine monophosphate （cAMP）-response element binding protein（CREB） gene silencing hippocampal cell activity， apoptosis and signal pathway of brain-derived neurotrophic factor/protomyosin related receptor kinase B/adenosine cyclophosphate effector binding protein （BDNF/TrkB/CREB）. Method:Wendantang-containing serum was prepared. Animal grouping： SD male rats were randomly divided into high， medium， low-dose groups， clozapine group and normal saline group， with 10 rats in each group， while 15 rats for the normal group. Dosage： 20 mL·kg^-1 normal saline was given to normal group N， clozapine 0.02 g·kg^-1 was given to dozapine group X， while high， medium and low-dose Wendantang groups were respectively given the same amount of Wendantang concentrated crude drug， with concentrations of 2， 1 and 0.5 g·mL^-1 respectively once a day for 8 days continuously， and then blood was taken from femoral artery， and centrifuged for 15 min at 5 000 r·min^-1. Supernatant was taken， inactivated， stored at -80 ℃ for standby. The CREB gene silenced hippocampal neuron cell line was constructed through transfection of liposomes into hippocampal cells， and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to verify the effect of small interfering RNA （siRNA） transcription. The mRNA expressions of BDNF， TrkB， CREB and CaMKⅡ in normal hippocampal cells and CREB gene silenced hippocampal cells were measured. Result:Compared with normal group， the apoptosis of the normal gene silencing group was significantly increased （P<0.01）， compared with the normal gene silencing group， the apoptosis of each group was significantly reduced （P<0.01）. As for the mRNA expressions of BDNF， TrkB， CREB and CaMKⅡ， compared with the normal group， the mRNA expression of CREB， BDNF in the normal gene silencing group was significantly decreased （P<0.01）. Compared with the normal gene silencing group， the mRNA expression of BDNF in each administration group was highly increased （P<0.01）， but with no statistically significant difference between TrkB and CaMKⅡ groups. Conclusion:The Wendantang-containing serum could improve the mRNA expression of BDNF， protect hippocampal neurons and prevent cognitive impairment of schizophrenia by regulating BDNF/TrkB/CREB signal pathway.