Natural product is an important source of new drug research and development (R&D). Traditional Chinese medicine (TCM) innovation is the key step for its modernization and internationalization. However, due to the complexity of TCM, there are many difficulties and confusions in this process. Target-based drug discovery is the mainstream model and method of R&D. TTD, short for therapeutic target database, is developed by National University of Singapore. Besides a large amount of information on drug targets, the database also contains considerable information related to natural products. This paper briefly introduces the TTD, analyzes the natural products derived drugs/compounds recorded in TTD, which we think might provide some inspiration for the innovation of TCM.

Objective To investigate the association between high-risk types of human papillomavirus (HR-HPV) load and the expression of nestin in different cervical lesions.Methods The hybridization capture Ⅱ (HC-Ⅱ) assay was used to test the HR-HPV load from 60 patients who were the first time to do the cervical cancer screening in Xiangya Hospital,and immunohistochemistry was used to detect the expression of nestin in those biopsy tissue samples.Results (1) The lgHPV level (logarithm of HR-HPV load) in the high level lesion group was higher than the low level one (P ＜0.05),and HR-HPV load was positively associated with the degree of cervical lesions (rs =0.269,P =0.037).(2) The expression of nestin in A group was weaker than groups B and C (H =7.271,22.843,P ＜0.01),and the expression of nestin in C group was stronger than B group (H =7.270,P ＜0.01),and the expression of nestin was positively associated with the degree of cervical lesion (rs =0.646,P =0.000).(3) The HR-HPV load was positively associated with the expression of nestin (P ＜ 0.05).Conclusions The HR-HPV load and the expression of nestin are closely related to the cervical lesions,and the joint detection has a referential value for early prevention of cervical lesions and prediction of progress of cervical precancerous lesion.It might guide the early prevention and treatment of cervical cancers.

Objective To investigate the efficacy and tolerability of estradiol (E2) gel with postoperative patients of moderately severe ovarian endometriosis cyst,who suffer from the side effect of GnRH agonist.Methods Sixty samples were selected with stage Ⅲ ～ Ⅳ ovarian endometriosis after conservative operation by the same operator at the Department of Gynecology,Xiangya Hospital,Central South University,between February 2013 and August 2014.All of the patients after surgeries were randomly divided into three groups:control group (n =20) with only goserelin injection after conservative surgery,treatment group A (n =20) who received estradiol gel,and treatment group B (n =20) who received tibolone as an add-back therapy.The serum E2,follicle stimulating hormone (FSH),luteinizing hormone (LH),hypoestrogenic symptoms,the incidence of uterine bleeding,and the recurrence after conservative operation were compared among three groups.Results Three months later aster treatment with goserelin,the serum level of E2 of three groups showed statistically significant difference (P ＜ 0.05).Serum E2 level of treatment group A was not significantly higher than treatment group B (P ＞ 0.05).The kupperman sore,the incidence of hot flashes sweating,tiring,and agrypnia of treatment groups A and B were significantly lower than the control group (P ＜ 0.05).The incidence of uterine bleeding and recurrence dont differ sharply among three groups (P ＞ 0.05).Conclusions GnRHa combined with estradiol gel can improve symptoms of postoperative patients,reduce side effects effectively,and avoid increase of the risk of vagina bleeding and relapse.

Objective: To understand the energy and major nutrients intake of high school students in Shanghai, and to provide basis for formulating target nutritional interventions and health education. Methods: The probability-proportional-to-size sampling technique was used to select 19 high schools, from which 9 boys and 9 girls from same class were randomly recruited for each grade. A total of 900 high school students were surveyed on their energy and major nutrients intake. Results: The medians of intake of energy, protein, fat, carbohydrate, calcium, sodium, iron, vitamin A, vitamin B-1, vitamin B-2, vitamin C and dietary fiber were 2 353 kcal/d, 97.3 g/d, 95.4 g/d, 265.4 g/d, 602.1 mg/d, 4 373 mg/d, 24.3 mg/d, 495.6 μgRE/d, 1.08 mg/d,1.21 mg/d, 83.2 mg/d and 1.01 g/d, respectively. Among of them, the medians of intake of energy, calcium, vitamin A, vitamin B-1, vitamin B-2, vitamin C and dietary fiber for boys and girls were lower than reference standard(P<0.05). The medians of intake of energy and major nutrients in high school students who lived in countryside were less than those lived in suburban and urban(P<0.05), except carbohydrates and iron. The percentages of energy supplied byprotein, fat and carbohydrate were 16.9%, 37.2%and 46.0%, respectively. Conclusion The energy and calorigenic nutrients intake can meet the demand of daily consumption in high school students in Shanghai, but the intake of dietary fiber, some minerals and vitamins have a various degrees of deficiency. The proportion of energy supplied bycalorigenic nutrients is unbalanced.

OBJECTIVE:To provide reference for further promoting the clinical application of chronopharmacology and rational drug use.METHODS:The self-designed questionnairea was used to conduct on-site investigation among participants from 40 hospitals in Anhui province by dint of a meeting.The survey data were analyzed statistically.RESULTS:Totally 170 questionnaires were distributed,and 166 were retrieved,the total response rate was 97.65％.93.37％ of the interviewed pharmacists were aware of the circadian rhythms,and 87.35％ were aware of the circadian rhythms of more than two kinds;interviewed pharmacists expressed better awareness of indicators like gastric acid secretion (75.30％),blood pressure (67.47％) and growth hormone (66.87％) etc.while their awareness of other diseases like anaphylactic rhinitis (66.87％),gastric ulcer (50.60％) and migraine (50.00％) remained to improve.All the interviewed pharmacists recognized the better therapeutic efficacy (84.34％) and lower side effect (81.33％) of chronopharmacology-referred medication;chronopharmacology characteristics of glucocorticoid drugs were best known (34.34％),followed by antihypertensive drugs (25.30％).CONCLUSIONS:Pharmacists in Anhui province have certain knowledge of chronopharmacology such as biological rhythms,biological process or indicators,biological rhythms of disease and advantage of chronopharmacology-referred medication.It indicates that there has been a foundation for popularizing the concept of chronopharmacology in clinical medication in China;but not often contacted physiological processes or indexes,the understanding of biological rhythm of uncommon diseases are still insufficient,and the understanding of chronopharmacology characteristics of various drugs are far from ideal.

Objective: To explore the clinical effect of negative pressure wound therapy (NPWT) in emergency limb-salvage operation of destructive injury of limb. Methods: From July 2014 to December 2017, 43 patients with destructive injury of limb in one side conformed to the inclusion criteria were admitted to our hospital. The patients were divided to NPWT group of 24 patients [ 21 males and 3 females, aged (38±10) years] and routine dressing change group of 19 patients [ 17 males and 2 females, aged (37±10) years] according to their treatment methods. After the emergency debridement, fracture external fixation, neurovascular exploration, and microsurgical repair were performed, NPWT were applied on wounds of patients in NPWT group and routine dressing change treatment on wounds of patients in routine dressing change group. On 7 to 10 days after the emergency operation, incidence of arterial embolism of patients in the two groups were calculated, and condition of wound infection of patients in the two groups were observed. Complete wound healing time and survival condition of limb were recorded. Data were processed with independent sample t test or chi-square test. Results: Incidence of arterial embolism of patients in NPWT group on 7 to 10 days after the emergency operation was 6.67% (3/45), which was close to 5.56% (2/36) of patients in routine dressing change group (χ²=0.043, P>0.05). There was 1 patient with wound infection in NPWT group on 7 to 10 days after the emergency operation, obviously less than 6 patients in routine dressing change group (χ²=5.847, P<0.05). Complete wound healing time of patients in NPWT group was (30±4) d, significantly shorter than (36±8) d of patients in routine dressing change group (t=2.813, P<0.01). Limbs of 24 patients in NPWT group survived, which was close to 18 patients in routine dressing change group (χ²=1.293, P>0.05). Conclusions NPWT can significantly reduce tthe wound infection rate and shorten the time of wound healing of limb with destructive injury after emergency operation, which is worthy of popularization in clinic.

Objective: To study the clinical effect of relaying peroneal artery perforator flap on anterior middle and lower tibia and donor-site defects repair. Methods: From July 2014 to June 2017, 12 patients were included. The anterior middle-lower tibia soft tissue defects and the primary donor-sites were repaired by relaying peroneal artery perforator flaps, and the second donor-sites were directly closed. The size of anterior middle-lower tibia defects ranged from 5 cm × 3 cm to 13 cm × 9 cm. The flaps repairing the wounds ranged from 6 cm × 4 cm to 14 cm × 10 cm in size. The flaps restoring the first donor-site ranged from 5 cm×4 cm to 10 cm×6 cm in size. The clinical effect was evaluated by observing the appearance of the recipient sites and the donor sites. Results: All the flaps survived uneventfully. All patients were followed up for 8-36 months (average 20 months). The flaps remained with good texture and color. The second donor-sites only left linear scar, which do not affect the overall appearance of limb. Conclusions The blood supply of relaying peroneal artery perforator is reliable without any disturbing of the main artery. The flap located on the lateral of the calf. The relaying peroneal artery perforator flap can repair the soft tissue defect at the anterior middle-lower tibia and improve the appearance of the first donor-site.

Objective:To investigate the feasibility and safety of endoscopic thyroidectomy by gasless unilateral axillary approach.Methods:A matching study was conducted to analyze 21 patients with etgua of Zhejiang Provincial People’s Hospital from Mar. 2019 to Sep. 2021, including 8 cases of bilateral radical thyroidectomy and 13 cases of unilateral radical thyroidectomy + contralateral lobectomy (benign) . At the same time, 23 patients who underwent conventional thyroidectomy were matched as controls, including 8 cases of bilateral radical thyroidectomy and 15 cases of unilateral radical thyroidectomy + contralateral lobectomy (benign) . The operation process was recorded, and the differences in operation safety, postoperative recovery and incision satisfaction between endoscopic group and open group were compared.Results:The operation time in the endoscopy group was longer than that in the open group. The postoperative drainage volume in the endoscopy group was larger than that in the open group. There was no significant difference in the amount of intraoperative bleeding, postoperative stay in hospital or the incidence of complications. The neck pain scores in the endoscopic group were lowter than those in the open group. In terms of postoperative cosmetic satisfaction, the endoscopic group was higher than the open group.Conclusion:Endoscopic bilateral thyroidectomy by gasless unilateral axillary approach is a safe and effective surgical method, and has high cosmetic satisfaction.

OBJECTIVETo investigate the effects of lipopolysaccharides (LPS) extracted from Porphyromonas endodontalis (Pe) on the expression of macrophage colony stimulating factor (M-CSF) mRNA and protein in MC3T3-E1 cells and the role of nucler factor-κB (NF-κB) in the process.

METHODSMC3T3-E1 cells were treated with different concentrations of Pe-LPS (0-50 mg/L) and 10 mg/L Pe-LPS for different hours (0-24 h). The expression of M-CSF mRNA and protein was detected by reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunoadsordent assay (ELISA). The cells untreated by Pe-LPS served as control. The expression of M- CSF mRNA and protein was also detected in 10 mg/L Pe- LPS treated MC3T3-E1 cells after pretreated with BAY 11-7082 for 1 h, a special NF-κB inhibitor. The groups were divided as follows, control group, BAY group (10 µmol/L BAY 11-7082 treated alone MC3T3-E1 cells), Pe-LPS group (10 mg/L Pe-LPS stimulated MC3T3-E1 cells for 6 h), BAY combine with Pe-LPS group (10 µmol/L BAY 11-7082 pretreated cells for 1 h and 10 mg/L of Pe-LPS stimulated MC3T3-E1 cells for 6 h).

RESULTSThe level of M- CSF mRNA and protein increased significantly after treatment with different concentrations of Pe-LPS (0-50 mg/L), which indicated that Pe-LPS induced osteoblasts to express M-CSF mRNA and protein in dose dependent manners. The expression of M-CSF protein increased from (35 ± 2) ng/L (control group) to (170 ± 8) ng/L (50 mg/L group). Maximal induction of M-CSF mRNA expression was found in the MC3T3- E1 cells treated with 10 mg/L Pe-LPS for 6 h. After 6 h, the expression of M-CSF mRNA decreased gradually. The expression of M-CSF protein also increased with the treatment of 10 mg/L Pe-LPS for 10 h [(122 ± 4) ng/L]. After 10 h, the expression of M-CSF protein decreased gradually. The mRNA and proteins of M-CSF decreased significantly after pretreatment with 10 µmol/L BAY 11-7082 for 1 h. There was no significant difference between BAY group and the control.

CONCLUSIONSPe-LPS may induce the expression of M-CSF mRNA and protein in MC3T3-E1 cells through the signaling of NF-κB.

Animals ; Lipopolysaccharides ; pharmacology ; Macrophage Colony-Stimulating Factor ; drug effects ; physiology ; Mice ; NF-kappa B ; metabolism ; Nitriles ; Osteoblasts ; drug effects ; metabolism ; Porphyromonas endodontalis ; RNA, Messenger ; Signal Transduction ; Sulfones

Abnormal genomic DNA methylation is an important epigenetic change in malignant tumors. Esophageal squamous cell cancer is one of common malignant tumors in our country. In this paper summarized and discussed the progress of genomic DNA methylation in the esophageal squamouscell cancer, including the level of genomic DNA methylation, frequent abnormally methylated genes, methylation markers and potential targets, etc. This paper might provide candidate biomarkers and targets for further studies on the mechanism of the tumorigenesis and development of the esophagealsquamouscell cancer, as well as for the clinical application of esophageal cancer.