While numerous herbal preparations have been used to treat human illnesses for extensive period of time in many different cultures, very few have been subject to rigorous clinical testing of modern scientific standards. To facilitate more clinical development of new drugs from botanical sources, the US FDA has published a draft Guidance for Industry: Botanical Drug Products in August 2000.
www.fda.gov/cder/guidance/1221dft.pdf. For herbal preparations with substantial marketing history, past human experiences may be taken into consideration for safety assessment and clinical studies may be initiated with less extensive product characterization and non-clinical testing. However, efficacy of almost all herbal products remains to be established with clinical trials that should be no different from those required for non-botanical new drugs. The objective of the regulatory approach is to confer the same degree of confidence in the clinical effectiveness of herbal medicines as that of modem non-botanical drugs. In this presentation, basic principles of clinical trial in all new drug development will be described, and unique issues related to studies of herbal medicines discussed.

In order to examine whether repeated sciatic nerve blocks showed tachyphylaxis and continuity of sciatic nerve with spinal cord affected development of tachyphylaxis when assayed in vivo by duration of depression compound action potentials (CAP), rats were anesthetized with halothane, ventilated, monitored and supported with stable hemodynamics and temperature. Posterior tibial nerve distally and sciatic nerve in thigh were exposed, placed on bipolar silver electrodes for stimulation and recording respectively. Three sequential sciatic nerve blocks were performed between these electrodes using 0.15 ml of 3% chloroprocaine. Nine rats were chosen to observe the effects of repeated sciatic nerve blocks on CAP. In another 18 rats, a second investigator exposed the sciatic nerve near its origin at spinal cord and randomly performed nerve cut and sham (n=9), and closed the incision blinding the electrophysiologic investigator. The results showed that electrical stimulated tibial nerve induced sciatic nerve Aalpha/beta, Adelta, C fiber mediated CAP waves. CAP amplitudes were remained stable during whole experimental procedure. CAP amplitudes were decreased completely with 3% chloroprocaine blocked sciatic nerve and recovered fully. The duration of CAP depression were reduced with repeated blocks. There were no selective blocked effects on Aalpha/beta, Adelta, C fiber mediated CAP. With sciatic nerve cut proximally, there was no statistical significant tachyphylaxis with 3% chloroprocaine repeated blocked sciatic nerve, and the duration of first and third blocked Adelta fiber mediated CAP was 108+/-20 and 92+/-14 min respectively (P>0.05). In normal rats the duration of first and third blocked Adelta fiber mediated CAP was 110+/-20 and 75+/-16 min respectively (P<0.05). It was suggested that tachyphylaxis to local anesthetics can occur in rats repeated blocked sciatic nerve when assayed in vivo by duration of depression CAP. The continuity of sciatic nerve with spinal cord is one of the important factors affecting the development of tachyphylaxis.
Anesthetics, Local/*administration & dosage ; Nerve Block ; Procaine/administration & dosage ; Procaine/analogs & derivatives ; Sciatic Nerve ; *Tachyphylaxis/physiology

We compared the analgesic profile between patient-controlled analgesia (PCA) using oxycodone and morphine in post total abdominal hysterectomy patients. Eighty-four ASA I or II patients, aged 18 to 65 years who underwent total abdominal hysterectomy were recruited into this prospective, double blind, randomised controlled study. They were randomised to receive either PCA oxycodone 0.7 mg per bolus or PCA morphine 1 mg per bolus for postoperative pain relief. At the end of surgery, all patients received IV morphine 0.1 mg/kg and skin incision was infiltrated with 20 mls of bupivacaine 0.25%. Post-operative pain scores, opioids consumptions, sedation scores and side effects were assessed upon arrival and at 30 minutes after arrival to recovery area, as well as at 6 hours and 24 hours after the operation in the ward. Patients’ overall satisfaction was also assessed 24 hours postoperatively.No significant differences were observed in terms of postoperative pain scores, opioids consumption, sedation scores, side effects as well as patient’s overall satisfaction between the PCA oxycodone and PCA morphine group. Oxycodone was comparable to morphine as PCA in terms of total opioid consumption, pain scores and satisfaction level for patients undergoing total abdominal hysterectomy and therefore may be an alternative to morphine in postoperative pain management as PCA
morphine ; oxycodone ; pain scores ; patient controlled analgesia ; total abdominal hysterectomy

In order to study the susceptibility of murine vaginal mucosa to Candida albicans under different conditions, vaginal lavage fluid and vaginal tissue of mice were observed and compared between murine models with normal immune system (estrogen-treated mice) and immunosuppressed murine model, and between primary infection model of vaginal candidiasis and secondary infection one. The average level of colony forming unit (CFU) from the immuosuppressed group was higher than that from estrogen-treated group at each time point and the peak time was delayed. The differences between the two groups were statistically significant (P < 0.05) from the fourth day after inoculation. A significant difference existed in the average level of CFU between the control group and the estrogen-treated group (P < 0.05), and between the control group and the immuosuppressed group (P < 0.01). It was concluded that the vaginal mucosa from the immunosuppressed mice is more susceptible to Candida albicans and no difference is found in susceptibility between mice with primary infection and secondary infection.
Candida albicans/drug effects ; Candidiasis, Vulvovaginal/*etiology ; Candidiasis, Vulvovaginal/*immunology ; Disease Susceptibility ; Estrogens/*pharmacology ; Immunocompromised Host ; Mice, Inbred ICR ; Random Allocation ; Vagina/microbiology

Objective: To investigate the role of fibroblast growth factor receptor(FGFR) 1 in endothelial to-mesenchymal transition(EndMT) and epithelial-to-mesenchymal transition(EMT), and to find out a new strategy to study the vascular endothelial function of diabetic renal fibrosis. Methods: Culture media from FRS2 knockdown HMVECs was transferred to HK-2 cells. Western blot and immunofluorescence staining were used to measure EMT markers and key moleculars of transforming growth factor(TGFβ). Results: It was found that the medium from FRS2 siRNA-transfected HMVECs reduced E-cadherin protein levels, increased EMT markers levels, and activated TGFβ signal pathway in HK-2 cells. Conclusion Endothelial FGFR1 deficiency-induced EndMT leads to EMT in neighboring cells in a manner dependent on TGFβ1 signaling. Endothelial cell FGFR1 is an important molecule for maintaining endothelial homeostasis and epithelial homeostasis, and seems to be a key target for anti-diabetic renal fibrosis.

OBJECTIVES: To systematically evaluate the value of the platelet-to-lymphocyte ratio (PLR) in predicting coronary artery lesions (CAL) in Chinese children with Kawasaki Disease (KD). METHODS: A comprehensive search was conducted in databases including PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang Data, China Biomedical Literature Database, and China Science and Technology Journal Database from inception to December 2022. The quality of the included literature was assessed using the Newcastle-Ottawa Scale, and a Meta analysis was performed using Stata 15.1. RESULTS: A total of ten published reports, involving 3 664 Chinese children with KD, were included in this Meta analysis, of whom 1 328 developed CAL. The Meta analysis revealed a sensitivity of 0.78 (95%CI: 0.71-0.83), specificity of 0.71 (95%CI: 0.61-0.80), overall diagnostic odds ratio of 8.69 (95%CI: 5.02-15.06), and an area under the curve of the summary receiver operating characteristic of 0.82 (95%CI: 0.78-0.85) for PLR in predicting CAL in the children with KD. The sensitivity, specificity, and area under the curve of summary receiver operating characteristic were lower for PLR alone compared to PLR in combination with other indicators. Sensitivity analysis demonstrated the stability of the Meta analysis results with no significant changes upon excluding individual studies. However, a significant publication bias was observed (P<0.001). CONCLUSIONS PLR demonstrates certain predictive value for CAL in Chinese children with KD.
Child ; Humans ; Mucocutaneous Lymph Node Syndrome/pathology* ; Coronary Vessels/pathology* ; Lymphocytes ; Biomarkers ; China ; Coronary Artery Disease/pathology*

We report computed tomography (CT) findings for a rare case of follicular dendritic cell sarcoma of the greater omentum from a 47-year-old female patient. The tumor presented ash a palpable mass lesion in the umbilical region for the last two months. Multidetector CT scan of the abdomen showed a 14-cm soft-tissue mass with calcification and necrosis within the greater omentum. As a result, a follicular dendritic cell sarcoma should be considered in the differential diagnosis of a solitary omentum mass, especially one with coarse and chunk-like calcifications.
Dendritic Cell Sarcoma, Follicular/pathology/*radiography ; Female ; Humans ; Middle Aged ; Multidetector Computed Tomography/*methods ; Omentum/pathology/*radiography ; Peritoneal Neoplasms/pathology/*radiography

OBJECTIVETo investigate the dose-dependent toxic effect of soybean isoflavone extracts (SIE) on reproductive development in immature rats.

METHODSGrowing male and female rats (n = 50 each, 4 weeks) were divided into five groups fed with a standard cereal-based diet and gastrogavaged daily with 0, 30, 150, 300, and 600 mg SIE/kg body weight, respectively, for 12 weeks. Body weight, organ weights, and serum level of estrogen and testosterone were measured.

RESULTSOral administration of SIE had no effect on food intake but decreased food efficiency ratio (P < 0.01). Suppression on body weight gain by SIE was dose-dependent and the effect was greater on male than on female rats (P < 0.01). SIE at high doses exhibited hepatotoxicity by increasing a relative liver weight, and also caused a smaller uterus but a greater relative ovary in female rats, while leading to larger relative testis and epididymis in male rats. SIE could decrease progesterone concentrations in female rats, whereas in male rats it reduced not only total testosterone level but also sperm count compared with the control group (P < 0.05).

CONCLUSIONSIE at a range of 50-1000 times of human intake level affects not only growth but also development of reproductive system in growing rats.

Animals ; Body Weight ; drug effects ; Epididymis ; drug effects ; growth & development ; Estradiol ; blood ; Female ; Isoflavones ; toxicity ; Liver ; drug effects ; growth & development ; Male ; Organ Size ; drug effects ; Ovary ; drug effects ; growth & development ; Progesterone ; blood ; Rats ; Rats, Sprague-Dawley ; Soybeans ; chemistry ; Sperm Count ; Testis ; drug effects ; growth & development ; Testosterone ; blood ; Uterus ; drug effects ; growth & development

OBJECTIVETo investigate the effects of wild type p16 gene on the proliferation and metabolism of human keloid fibroblasts.

METHODSEukaryotic expression vector pcDNA3-p16 was constructed and imported into KFb by gene transfection mediated by liposome. And the positive clones were screened by G418. The transfected and untransfected KFbs were stained by Immunocytochemical method. The expression of p16 protein was observed. The changes of the proliferation and DNA synthesis of KFb before and after transfection were observed and compared by drafting cell growth curve and by (3)H-TdR incorporation method.

RESULTSThe recombinant vector pcDNA3-p16 was successfully constructed and identified by enzyme digestion. The positive clones were identified by G418 selection for 10 days from transfected KFb and with p16 protein expression. The growth rate of transfected KFb slowed down obviously and its DNA synthesis decreased significantly (P < 0.05) when compared with those of normal KFb.

CONCLUSIONp16 gene might inhibit the growth and DNA synthesis of KFb.

Cell Proliferation ; Cells, Cultured ; DNA ; biosynthesis ; Fibroblasts ; metabolism ; pathology ; Genes, p16 ; Genetic Therapy ; Humans ; Keloid ; genetics ; pathology ; Transfection