Xiangshao granules can relieve emotional symptoms in menopausal women: a randomized controlled trial.

OBJECTIVE: This study aimed to investigate the safety and efficacy of Xiangshao granules for treating emotional disorders in perimenopausal and postmenopausal women. METHODS: The current investigation was a double-blind, randomized, placebo-controlled, multicenter trial that included 300 perimenopausal and postmenopausal Chinese women aged 40-60 years. Participants received either a placebo (n = 150) or Xiangshao granules (n = 150) for 8 weeks. Outcome measures included Hamilton Depression Rating Scale (HAMD) and Hamilton Anxiety Rating Scale (HAMA) scores, which were assessed at baseline, 4 weeks, and 8 weeks. The primary efficacy variables were changes in HAMD and HAMA scores after 8 weeks. RESULTS: After 8 weeks, the mean HAMD scores decreased from 15.0 to 7.9 in the Xiangshao group and from 16.3 to 10.0 in the placebo group, and the respective mean reductions in HAMA scores were from 16.0 to 8.5 and from 17.1 to 10.9. Clinical improvements in symptoms of both depression and anxiety after 8 weeks differed significantly in the two groups (p < 0.05). The cure rate was significantly higher in the Xiangshao group. There were no significant differences in the rates of adverse events in the two groups. CONCLUSIONS: Xiangshao granules can relieve symptoms of depression and anxiety significantly and safely.

[The clinical value of China Savin pollen extract used for skin prick test].

Objective:The aim of this study is to evaluate the effectiveness and safety of China Savin pollen extract which was used for skin prick test (SPT) in the diagnosis of China Savin pollen allergy. Method:Patients with diagnosis of allergic diseases were collected from Allergy Department of Peking Union Medical College Hospital. All patients were given SPT with China Savin pollen extract, and the mean wheal diameter (MWD) was measured after 15 minutes. Receiver operating characteristic curve (ROC) analysis was performed based on the results of serum specific immunoglobulin E (sIgE). The effectiveness of SPT in the diagnosis of China Savin pollen allergy was evaluated under different diagnostic cutoff values. Adverse events were also recorded to evaluate the safety. Result:A total of 1 029 patients were enrolled in this study without drop out case. There were 1 007 patients in full analysis set (FAS) and 765 patients in per protocol analysis set (PPS). The elimination rate was 25.66%. The area under the ROC curve of FAS is 0.814 (95%CI: 0.788-0.839); which of PPS is 0.829 (95%CI: 0.801-0.857). Based on the ROC curve of PPS, the optimal and the 95% specificity diagnostic cutoff values of MWD were 3.25 mm and 4.75 mm respectively. Based on different diagnostic cutoff value (3.00, 3.25 and 4.75 mm), the sensitivities of SPT with China Savin pollen extract were 0.740 0 (95%CI: 0.701 6-0.778 4), 0.700 (95%CI: 0.659 8-0.740 2) and 0.532 (95%CI: 0.488 3-0.575 7) respectively, whereas the specificity was gradually increased in sequence, which was 0.769 8 (95%CI: 0.719 1-0.820 5), 0.826 4 (95%CI: 0.780 8-0.872 0) and 0.950 9 (95%CI: 0.924 9-0.976 9) respectively. There were 7 adverse events observed among 6 patients (rate: 0.583%, 6/1 029). The manifestation was mild. There was no severe adverse event. Conclusion:SPT with China Savin pollen extract is an effective and safe tool for the diagnosis of China Savin pollen allergy. The effectiveness of diagnosis could be improved based on integration of medical history and different diagnostic threshold values of SPT.

Effects of matrix types on formation and transformation of energy-accumulating substances in enhanced biological phosphorus removal (EBPR).

Enhanced biological phosphorus removal (EBPR) has been widely used in wastewater treatment. In this study, a laboratory investigation of activated sludge in A/O-SBR reactor was conducted to probe the effects of the matrix types on EBPR polyphosphate, intracellular polysaccharide, polyhydroxyalkanoates (PHA) formation and transformation. There is a decrease in anaerobic condition and an increase in aerobic condition for the intracellular glycogen of sodium propionate matrix and sodium acetate matrix. While the intracellular glycogen of glucose matrix shows a decreasing tendency in both anaerobic and aerobic reaction process. Sodium acetate matrix is beneficial to the formation of polyhydroxybutyrate (PHB), but the content of PHB is relatively small. PHB and poly-3-hydroxyvalerate (PHV) contents in PHA are quite similar in both anaerobic and aerobic reactions with a PHB/PHV ratio of 0.83-1.45. The synthesis of PHV and PHB is mainly in the initial anaerobic stage (0 h - 1 h). Glucose matrix is helpful to the formation of PHV. The content of polymphosphorus shows an increasing tendency in both anaerobic and aerobic stages, suggesting that glucose matrix acclimation of the reactor favors the formation of polymphosphorus.

Valproic acid inhibits proliferation and induces apoptosis in acute myeloid leukemia cells expressing P-gp and MRP1.

The multidrug resistance (MDR) phenotype, induced by the overexpression of several ABC transporters or by antiapoptotic mechanisms, has been identified as the major cause of drug resistance in the treatment of patients with acute myeloid leukemia (AML). In this study, we have shown that valproic acid (VPA) (a histone deacetylase inhibitor) can inhibit the proliferation of both P-glycoprotein (P-gp)- and MDR-associated protein 1 (MRP1)-positive and -negative cells. VPA also induced apoptosis of P-gp-positive cells. VPA induced apoptosis in K562 cells led to decrease in Flip (FLICE/caspase-8 inhibitory protein) expression with Flip cleavage, which could not be observed in HL60 cells. In HL60/MRP cell line, which proved to be resistant to apoptosis by VPA, we observed an abnormal expression of apoptotic regulatory proteins, overexpression of Bcl-2 and absence of Bax. Also, the Bcl-2 antagonist HA14-1 rapidly restored apoptosis in this cell line. Cotreatment with cytosine arabinoside induced very strong apoptosis in both K562/DOX and HL60/DNR cell lines. VPA also induced apoptosis in AML patient cells expressing P-gp and/or MRP1. Our findings show VPA as an interesting drug that should be tested in clinical trials for overcoming the MDR phenotype in AML patients.

Requirement of cysteines and length of the human respiratory syncytial virus M2-1 protein for protein function and virus viability.

The M2-1 protein of human respiratory syncytial virus (hRSV) promotes processive RNA synthesis and readthrough at RSV gene junctions. It contains four highly conserved cysteines, three of which are located in the Cys(3)-His(1) motif at the N terminus of M2-1. Each of the four cysteines, at positions 7, 15, 21, and 96, in the M2-1 protein of hRSV A2 strain was individually replaced by glycines. When tested in an RSV minigenome replicon system using beta-galactosidase as a reporter gene, C7G, C15G, and C21G located in the Cys(3)-His(1) motif showed a significant reduction in processive RNA synthesis compared to wild-type (wt) M2-1. C96G, which lies outside the Cys(3)-His(1) motif, was fully functional in supporting processive RNA synthesis in vitro. Each of these cysteine substitutions was introduced into an infectious antigenomic cDNA clone derived from hRSV A2 strain. Except for C96G, which resulted in a viable virus, no viruses were recovered with mutations in the Cys(3)-His(1) motif. This indicates that the Cys(3)-His(1) motif is critical for M2-1 function and for RSV replication. The functional requirement of the C terminus of the M2-1 protein was examined by engineering premature stop codons that caused truncations of 17, 46, or 67 amino acids from the C terminus. A deletion of 46 or 67 amino acids abolished the synthesis of full-length beta-galactosidase mRNA and did not result in the recovery of viable viruses. However, a deletion of 17 amino acids from the C terminus of M2-1 reduced processive RNA synthesis in vitro and was well tolerated by RSV. Relocation of the M2-1 termination codon upstream of the M2-2 initiation codons did not significantly affect the expression of the M2-2 protein. Both rA2-Tr17 and rA2-C96G did not replicate as efficiently as wt rA2 in HEp-2 cells and was restricted in replication in the respiratory tracts of cotton rats.

Potent and selective peptide agonists of alpha-melanotropin action at human melanocortin receptor 4: their synthesis and biological evaluation in vitro.

alpha-Melanotropin (alphaMSH) and several of its derivatives are potent but not selective agonists at melanocortin receptors 3, 4, and 5 present in the brain (MC3-5R). To differentiate between the physiological role of hMC-4R (believed to be involved in regulation of energy balance) from those of melanocortin receptors 3 and 5, potent and receptor-specific agonists are needed. Therefore, the cyclic derivatives of alphaMSH of a general structure, cyclo(X-His-d-Phe-Arg-Trp-Y)-NH(2), where X is succinic acid or an omega-amino-carboxylic acid, and Y is an alpha,omega-di-amino-carboxylic acid or an omega-carboxy-alpha-amino acid, were prepared and tested in binding assays and in cAMP assays on CHO cells expressing hMC3-5R. Several of the 21-membered or larger lactams turned out to be potent and hMC-4R-selective agonists. For instance, cyclo(CO-CH(2)-CH(2)-CO-His-d-Phe-Arg-Trp-Dab)-NH(2) (Dab: 2,4-di-amino-butyric acid) was a potent agonist at hMC-4R (EC(50) = 4 nM) with 55-fold selectivity over hMC-3R and greater than 1000-fold selectivity over hMC-5R. Another potent and selective compound was cyclo(NH-CH(2)-CH(2)-CO-His-d-Phe-Arg-Trp-Glu)-NH(2): EC(50) about 1 nM at hMC-4R, with 90-fold selectivity over hMC-3R and greater than 2000-fold selectivity over hMC-5R.

Comparison of conventional phototherapy and fiberoptic phototherapy in the very-low-body-weight infants.

Phototherapy is effectively employed for the treatment of neonatal hyperbilirubinemia, but it may influence the physiological hemodynamics of the infants, such as skin blood flow, insensible water loss and the redistribution of cardiac output. This is a retrospective chart review study involved totally 42 very low birth weight prematures(birth body weight less than 1500 gm, VLBW) who received conventional or fiberoptic phototherapy. Infants with congenital malformation, severe cardiorespiratory instability and the requirement of diuretics, inotropics or blood transfusion were excluded. The body weight loss, daily intake/output and bilirubin level during the initial four days of phototherapy were analyzed. The results showed the efficacy of both methods was the same, while the fiberoptic therapy group had significantly more urine output(p < 0.05), the body weight loss was not statistically significant. It is possible that the fiberoptic therapy group had less insensible water loss and less attenuation of the decrease of renal blood flow, this resulted in more urine output.

Molecular cloning, mapping and characterization of the human neurocalcin delta gene (NCALD).

We identified a new human gene that encodes a cognate of the bovine neurocalcin delta from a human fetal brain cDNA library; hence we named it human neurocalcin delta (NCALD) gene. The deduced polypeptide product of the cDNA is 22 kDa in size, and its amino acid sequence is 100% and 99% identical to that of the bovine and chicken neurocalcin, respectively. Northern blots showed that the NCALD gene is more abundantly expressed in brain, testis, ovary and small intestine. Tissue in situ hybridization confirmed the existence of the NCALD mRNA in the adult human testis. Radiation hybrid panel mapping localized the gene to chromosome 8 between molecular markers D8S270 and D8S257.

Colon carcinoma with synchronous ovarian metastasis--report and discussion of five cases.

Ovarian metastasis may present at the time of initial diagnosis of colon carcinoma or as a later recurrence. Little meaningful information is available regarding the treatment and outcome of synchronous ovarian metastasis of colon carcinoma. This report describes the clinical course of five patients with synchronous ovarian metastasis of colon carcinoma who were treated with aggressive surgery and chemotherapy. The treatment consisted of maximal surgical debulking followed by systemic chemotherapy with weekly 24 h infusion of high-dose 5-fluorouracil and leucovorin. All of the five patients had subsequent disease-free periods ranging from 6 to 43+ months following operation. Two of the patients who had no or minimal peritoneal involvement were still alive without disease at 33 and 43 months. The data from these cases suggest that aggressive surgery and systemic chemotherapy may be highly efficacious in the treatment of colon carcinoma with synchronous ovarian metastasis. Maximal debulking followed by chemotherapy may be particularly effective in those patients with minimal peritoneal involvement.

A simplified regimen of weekly high dose 5-fluorouracil and leucovorin as a 24-hour infusion in patients with advanced colorectal carcinoma.

BACKGROUND: Reports of in vitro experiments in colorectal carcinoma cells suggest that prolonged cellular exposure to 5-fluorouracil (5-FU) combined with relatively low concentrations of leucovorin (LV) provides optimal enhancement of 5-FU efficacy. In this study, a simplified regimen of weekly 24-hour infusion of high dose 5-FU combined with a relatively low dose of LV was used to treat patients with advanced colorectal carcinoma. METHODS: Thirty-six patients with advanced colorectal carcinoma received 5-FU, 2600 mg/m2, admixed with LV, 100 mg/m2, in a portable infusion pump administered intravenously over a 24-hour period. High dose 5-FU/LV was delivered once a week for 5 consecutive weeks followed by a 1-week recovery period. All patients were assessable for toxicity and response. RESULTS: Two complete responses and 15 partial responses were observed (response rate of 47.2%; 95% confidence interval, 30.1-64.4%). The median response duration was 9.6 months. The median survival and time to progression were 11.9 months and 7.1 months, respectively. The toxicity was mild and acceptable. The major dose-limiting factors were hand-foot syndrome and fatigue. CONCLUSIONS: This simplified regimen of weekly 24-hour continuous infusion of high dose 5-FU/LV is an effective regimen in the treatment of patients with advanced colorectal carcinoma. Further study of the pharmacokinetics of combination therapy with 5-FU and LV as used in this regimen and its correlation with response and toxicity is warranted.

Structures and stereochemistry of pseudolarolides K and L, novel triterpene dilactones from pseudolarix kaempferi.

Pseudolarolides K(1) and L(2), two novel triterpenedilactones, were isolated from the seeds of Pseudolarix kaempferi, and their structures characterized from spectral data.

Telemedicine screening of glaucoma.

OBJECTIVES: Glaucoma is a major cause of blindness. More than 80,000 Americans suffer permanent vision loss from the disease. Widespread screening is fundamental in limiting the incidence of glaucoma-associated blindness. This pilot study explored the use of stereo digital images taken at a primary care center for telemedicine review by an off-site specialist as a means of screening for glaucoma. MATERIALS AND METHODS: Thirty-two diabetic patients were screened at a family medicine clinic. None had previously been diagnosed with glaucoma. A senior optometry student took stereoscopic digital and 35-mm optic disc photographs with a nonmydriatic retinal camera. The digital images were forwarded to a remote ophthalmologist for review. The conventional color stereo slide pairs of the same eyes were subsequently reviewed for comparison. Agreement on signs of glaucomatous disc changes between the two imaging systems was analyzed. RESULTS: Twenty-six of 32 eyes' digital and 35-mm photographs were analyzed. Six of 32 eyes (18.8%) could not be compared due to lack of matching 35-mm slides or digital images. Out of 26 eyes, lamina cribosa visibility was undeterminable in 8 eyes' digital images and 3 other eyes' 35-mm slides. Agreement among digital images and 35-mm slides of the remaining eyes was: 100%-vertical elongation, barring of vessels, bayoneting of vessels, and drance hemorrhage; 96.2%-focus notching of rim and rim pallor; 93.3%-lamina cribosa visability; 92. 3%-overpass cupping; 88.5%-focal enlargement; 84.6%-parapapillary halo; 80%-nerve fiber visibility; 65.4%-parapapillary atrophy. Parapapillary halo (p = 0.046) and nerve fiber layer visibility (p = 0.18) were detected on some 35-mm slides but not seen on matching digital views. CONCLUSION: Evaluations of cup-to-disc ratio (C/D) using both methods were in general agreement. However, some digital images were noted as too dark for assessing fine glaucomatous disc changes. Stereo digital images taken with a nonmydriatic camera by nonophthalmic photographers is a promising alternative for glaucoma screening in primary care settings. Telemedicine offers efficient communications with off-site glaucoma specialists. A larger study population is necessary to determine the overall effectiveness of using stereo digital imagery and teleophthalmology for glaucoma screening.

Optimal imaging protocol after intraocular silicone oil tamponade.

PURPOSE: Our purpose was to define the optimal protocol for imaging of the orbits after vitreous humor replacement with silicone oil. METHODS: Eleven eyes in 10 patients with tractional and/or rhegmatogenous retinal detachment were studied. Five CT scans and 18 high-field (1.5 T) MR images were obtained. Standard T1-weighted, T1-weighted with fat and silicone saturation, fast spin density-weighted, and T2-weighted orbital MR sequences were performed. Unique pulse sequences included fast spin density-weighted and T2-weighted imaging with and without fat saturation or silicone saturation, gradient-echo imaging, and short-tau inversion recovery imaging. RESULTS: The T1-weighted MR and CT studies were comparable in displaying the silicone. However, the fat- or silicone-saturated fast T2-weighted sequences always showed the fibrous bands and subretinal fluid to best advantage. In one case, the eye also contained inadvertently retained perfluorocarbon liquid, which blended with silicone oil on both saturated images, requiring companion T1-weighted sequences without saturation to demonstrate its presence. CONCLUSION: Simple, commonly available fat-saturated fast T2-weighted MR images supplemented by standard T1-weighted images are all that are needed to evaluate the eye efficiently after vitrectomy and tamponade.

[Constituents in petroleum ether and ethyl acetate extract fractions of Dracaena cochinensis (Lour.) S.C. Chen].

OBJECTIVE: To study the chemical constituents of Dracaena cochinensis. METHODS: Compounds were separated by solvent extraction, column chromatography, TLC and HPLC, and their structures were determined by spectral analysis. RESULTS: Ten compounds were isolated from the petroleum ether and ethyl acetate fractions of D. cochinensis and identified as n-heptacosane, lophenol, docosanyl ferulate, tetracosanyl ferulate, hexacosanyl ferulate, octacosanyl ferulate, pterostilbene, dioctyl phthalate, butyl isobutyl phthalate and 4'-methoxy-3',7-dihydroxy-flavone. CONCLUSION: All the compounds were isolated from this plant for the first time.

[Studies on chemical constituents from the root of Coriaria nepalensis wall (Coriaria sinica Maxim)].

The root of Coriaria nepalensis Wall (Coriaria sinica Maxim) is a Chinese herbal medicine and has been used to treat numbness, toothache due to wind and heat, phlegm-retention syndrome, traumatic injury and acute conjunctivitis. Nine compounds were isolated from the root of Coriaria nepalensis Wall and they were identified as braylin (I), norbraylin (II), dihydrocoriamyrtin (III), coriamyrtin (IV), tutin (V), coriatin (VI), apotutin (VII), hydroxycoriatin (VIII) and gallic acid (IX) on the basis of their physicochemical properties and IR, UV, MS, 1HNMR, 13CNMR data. I, II were isolated from the title plant for the first time; III was obtained from plant origin for the first time, and VII, VIII were new compounds.

Construction of a cell-based high-flux assay for the rev protein of HIV-1.

The Rev of HIV-1 is essential for the replication of the viruses and is therefore a very attractive target for the development of antiviral drugs. To establish a cell-based high-flux assay system for random screening of Rev inhibitors, cells carrying both the Rev-expressing gene and a Rev-inducible SeAP gene were generated by permanent transfection. SeAP produced by these cells was 5-10-fold higher than that synthesized by cells not carrying the Rev gene. Northern blot analysis demonstrated that the increase in SeAP was due mainly to an increase in SeAP transcripts, indicating the effect of Rev proteins synthesized by the transfected cells. The assay system reported in this study should be useful for screening novel Rev inhibitors.

A phase I study of TNP-470 administered to patients with advanced squamous cell cancer of the cervix.

A Phase I study of the novel angiogenesis inhibitor TNP-470 was performed. Patients with inoperable recurring or metastatic squamous cell cancer of the cervix with evaluable disease, no coagulopathy, and adequate renal, hepatic, and hematological function were eligible. One course of treatment consisted of an i.v. infusion of TNP-470 over 60 min every other day for 28 days, followed by a 14-day rest period. The starting dose was 9.3 mg/m2. Eighteen evaluable patients were treated, with a median age of 48 years (range 27-55) and performance status Zubrod 1 (range 0-2). Grade 3 neurotoxicities consisting of weakness, nystagmus, diplopia, and ataxia were encountered in two patients receiving the 71.2 mg/m2 dose. An intermediate dose level of 60 mg/m2 was evaluated and found to be well tolerated by three patients. Only one patient experienced grade 3 nausea on the 60 mg/m2 dose level. No myelosuppression, retinal hemorrhage, weight loss, or significant alopecia were observed. One patient had a complete response, which continues for 26 months, and three patients with initially progressive disease stage had stable disease for 5, 7.7, and 19+ months. Other Phase I studies, including over 200 patients, were performed concurrently with this study. Based on this experience, the dose of TNP-470 recommended for further studies is 60 mg/m2 as a 60-min i.v. infusion every Monday, Wednesday, and Friday. Neurotoxicity was dose limiting, but appears to be reversible. Otherwise, the treatment was well tolerated. The drug may be active in squamous cell cancer of the cervix. Further studies of TNP-470 in squamous cell cancer of the cervix are warranted.

Structure and stereochemistry of pseudolarolide J, a novel nortriterpene lactone from Pseudolarix kaempferi.

Pseudolarolide J (1), a novel nortriterpene lactone, has been isolated from the seeds of Pseudolarix kaempferi and structurally characterized from spectral data and X-ray crstallographic analysis.

Reversal of visual loss with hyperbaric oxygen treatment in a patient with Susac syndrome.

PURPOSE: The purpose of the study is to report on a 34-year-old woman with Susac syndrome who presented on two separate occasions with visual acuity loss from a recurrent branch retinal artery occlusion and underwent hyperbaric oxygen treatment with favorable outcome. METHODS: Visual acuity was 20/400 in the left eye and count fingers in the right eye after separate occlusive events. The patient underwent hyperbaric oxygen treatment on each occasion of visual acuity loss. The patient subsequently was diagnosed with Susac syndrome (microangiopathy of the retina, brain, and middle ear). The authors present visual fields, photographs, angiograms, and ancillary tests documenting diagnosis and course of treatment. RESULTS: On each occasion, visual acuity improved to 20/25 during and was maintained after hyperbaric oxygen treatment. Visual fields showed improvement immediately after treatment. CONCLUSION: This is the first report of hyperbaric oxygen treatment for Susac syndrome. Dramatic post-treatment visual field and acuity changes suggest benefit of treatment. Hyperbaric oxygen treatment can be considered a treatment option for visual complications of this syndrome. Susac syndrome should be included in the differential diagnosis of recurrent branch retinal artery occlusion.