FDA Approval Summary: Tivozanib for Relapsed or Refractory Renal Cell Carcinoma.

On March 10, 2021, the FDA granted regular approval to tivozanib for treatment of patients with relapsed or refractory (R/R) advanced renal cell carcinoma (RCC) following two or more prior systemic therapies. Approval was based on the TIVO-3 study, a randomized trial of tivozanib versus sorafenib in patients with R/R advanced RCC. In TIVO-3, patients were randomized to receive either tivozanib 1.34 mg orally once daily for 21 consecutive days of every 28-day cycle or sorafenib 400 mg orally twice daily continuously. The primary endpoint was progression-free survival (PFS) per RECIST v1.1. Tivozanib demonstrated efficacy compared with sorafenib with an improvement in PFS [HR, 0.73; 95% confidence interval (CI), 0.56-0.95; P = 0.016]. The estimated median PFS was 5.6 months and 3.9 months in the tivozanib and sorafenib arms, respectively. There was no evidence of a detrimental effect on overall survival: HR, 0.97 (95% CI, 0.75-1.24). The most common grade 3 to 4 adverse reaction on the tivozanib arm was hypertension (24%). Compared with sorafenib, tivozanib was associated with lower rates of grade 3 to 4 diarrhea, rash, and palmar-plantar erythrodysesthesia. Patients receiving tivozanib in TIVO-3 had lower rates of dose reduction, interruption, or permanent discontinuation than those receiving sorafenib.

Polycythemia Vera With Multiple Cerebral Infarctions Complicated By Cerebral Microhemorrhage: A Report of Two Cases.

Polycythemia vera (PV) has multiple vascular risk factors and gradual onset and is an important risk factor for stroke. The first manifestation in some patients with PV is thrombotic cerebrovascular events. However, there are few reports on polycythemia vera with multiple cerebral infarctions and cerebral microhemorrhage. The clinical and imaging features of two PV patients with multiple cerebral infarctions complicated by cerebral microhemorrhage were analyzed retrospectively in order to improve the clinical understanding of the disease.

[Therapeutic effect of acupuncture combined with medication on chronic prostatitis of damp and heat stasis].

OBJECTIVE: To observe the clinical therapeutic effect of electroacupuncture (EA) combined with tamsulosin hydrochloride sustained release capsule on chronic prostatitis (CP) of damp and heat stasis. METHODS: A total of 70 patients with CP of damp and heat stasis were randomized into an acupuncture plus medication group (35 cases, 4 cases dropped off) and a medication group (35 cases, 5 cases dropped off). In the medication group, tamsulosin hydrochloride sustained release capsule was given orally, 0.2 mg a time, once each night. On the basis of treatment in the medication group, EA was applied at Guanyuan (CV 4), Sanyinjiao (SP 6) and Yinglingquan (SP 9), with disperse-dense wave, 5 mA in intensity for 30 min. Treatment for 30 days was as one course, and totally 3 courses were required in both groups. Before treatment, 1, 2, 3 months into treatment and at the follow-up of 2 months after treatment, the TCM syndrome score and National Institutes of Health chronic prostatitis symptom index (NIH-CPSI) score were observed, and the clinical efficacy was evaluated in both groups. RESULTS: Compared before treatment, the TCM syndrome scores of 3 months into treatment and follow-up were decreased in the acupuncture plus medication group (P<0.01), and were lower than those in the medication group (P<0.05). Compared before treatment, the NIH-CPSI scores of 3 months into treatment and follow-up were decreased in both groups (P<0.01), and those in the acupuncture plus medication group were lower than the medication group (P<0.05). The total effective rate was 90.3% (28/31) in the acupuncture plus medication group, which was superior to 80.0% (24/30) in the medication group (P<0.05). CONCLUSION: Acupuncture combined with medication can improve the clinical symptoms in patients with CP of damp and heat stasis, and its therapeutic effect is superior to simple western medication.

Does omega-3 lower blood pressure?: A protocol for systematic review and meta-analysis.

BACKGROUND: Hypertension is a clinically common cardiovascular disease, resulting in many complications. Omega-3 might be beneficial in lowering blood pressure. This protocol will be performed to evaluate the effects of omega-3 on blood pressure in hypertensive patients. METHODS: We will search both the electronical databases and paper-published journals. Endnote software will be used to complete study screening and data extraction by 2 reviewers independently. Review Manager software will be used to synthesize the data. The primary outcomes are systolic blood pressure and diastolic blood pressure. Secondary outcome is the adverse effects. RESULTS: The results of this study will propose a trustworthy evidence to evaluate the effects of omega-3 on blood pressure of hypertensive patients. CONCLUSION: The conclusion of our systematic review will reply whether omega-3 is an effectual intervention to lower blood pressure of hypertensive patients. ETHICS: This review does not require ethical approval because all of the data analyzed in this review have been published. REGISTRATION NUMBER: INPLASY202070103 (DOI number: 10.37766/inplasy2020.7.0103).

Budesonide nasal irrigation improved Lund-Kennedy endoscopic score of chronic rhinosinusitis patients after endoscopic sinus surgery.

PURPOSE: Budesonide improves the prognosis of chronic rhinosinusitis (CRS). However, few reports have examined whether its use for nasal irrigation, compared to normal saline, improves the prognosis of patients after endoscopic sinus surgery (ESS). We compared the effects of nasal irrigation with budesonide and normal saline in CRS patients after ESS. METHODS: Sixty CRS patients who had undergone ESS were randomly divided into an experimental group (30 patients), which used budesonide nasal irrigation, and a control group (30 patients), which used normal saline nasal irrigation. All patients received regular follow-up evaluations and were assessed via questionnaires, including the Lund-Kennedy endoscopic score (LKES), the symptom visual analog scale (VAS), the 22-item Sino-Nasal Outcome Test (SNOT-22), the Short-Form 36-Item Questionnaire (SF-36), the Self-Rating Anxiety Scale (SAS), the Self-Rating Depression Scale (SDS) and a side effects scale. RESULTS: Scores of polyposis, mucosal edema, secretions and total score of LKES; VAS scores of nasal blockage, hyposmia and rhinorrhea; and SNOT-22 results in both groups were significantly improved 3 months after ESS. Scores of polyposis, mucosal edema, secretions and scarring and total score of LKES in experimental group were significantly better than in control group 3 months after ESS. No significant differences were observed in SF-36, SAS or SDS before or 3 months after ESS within or between the two groups. The side effects of the two groups were not significantly different. CONCLUSIONS: Nasal irrigation improved the prognosis of CRS patients after ESS. Budesonide nasal irrigation had a better effect than normal saline nasal irrigation.

Herb Formula ZhenRongDan Balances Sex Hormones, Modulates Organ Atrophy, and Restores ERα and ERß Expressions in Ovariectomized Rats.

Herb mixtures are widely used for treatment of the menopausal syndrome long before the hormonal therapy. However, there is insufficient data for herb remedies in treating menopausal syndromes. Here we aim to investigate the effect of ZhenRongDan (ZRD) in balancing female hormones, regulating expression of estrogen receptors (ERs), and preventing organ atrophy in menopausal rats. Rats that underwent bilateral ovariectomy were used in the experiments; the effects of ZRD on serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), and estradiol (E2) levels were observed. Histology of vagina and ERs expression in vagina, uterus, and adrenal gland were also examined. ELISAs were used to analyze the changes of FSH, LH, PRL, and E2 in serum, and the morphological changes of the cervical epithelium cells were observed by Hematoxylin & Eosin (H&E) staining. Immunohistochemistry and western blot were applied to detect estrogen receptors subtypes alpha (ERα) and beta (ERß) expression in vagina, uterus, and adrenal gland. We found that ZRD could significantly reduce the weight of the adrenal gland and increase the weight of the uterus. It could decrease the release of FSH and LH as well as increasing E2 and PRL levels. Furthermore, ZRD could improve the number of cervical vaginal epithelial cells and increase the thickness of the vaginal wall. And the altered expressions of ERα and ERß are also restored by ZRD. ZRD could obviously relieve the endocrine disorders, modulate organ atrophy, and restore ERα and ERß expression in the ovariectomized rat model.

Electrospun Hydrophilic Janus Nanocomposites for the Rapid Onset of Therapeutic Action of Helicid.

The oral delivery of active ingredients for the fast onset of therapeutic effects is a well-known method in patients. In this study, a new kind of hydrophilic Janus structural nanocomposite was designed for the rapid dissolution and transmembrane permeation of helicid, an herbal medicine with poor water solubility. A side-by-side electrospinning process characterized by an eccentric spinneret was developed to fabricate the Janus nanocomposites. The morphology, inner structure, incorporated components and their physical states, hydrophilicity, and functional performances of the Janus nanocomposites were investigated. The experimental results demonstrated that an unspinnable fluid (polyvinylpyrrolidone K10-sodium dodecyl sulfate) could be simultaneously treated with an electrospinnable fluid (polyvinylpyrrolidone K90-helicid) to create Janus structural nanocomposites. The prepared Janus nanofibers exhibited linear morphology and notable side-by-side inner structure with all the incorporated components present in an amorphous state. Both the control of monolithic nanocomposites and the Janus composites can provide more than 10-fold the transmembrane rates of crude helicid particles. Compared with monolithic nanocomposites, the Janus nanocomposites exhibited improved hydrophilicity and can further promote the dissolution and transmembrane permeation of helicid for a potentially faster onset of therapeutic actions. The generation mechanisms and functional performance of Janus nanocomposites were suggested. The preparation protocols reported here can provide a useful approach for designing and developing new functional nanocomposites in the form of Janus structures. Meanwhile, the medicated hydrophilic Janus nanocomposites represent a newly developed kind of nano drug delivery system for the fast onset of therapeutic action of orally administered water-insoluble drugs.

FDA Approval: Uridine Triacetate for the Treatment of Patients Following Fluorouracil or Capecitabine Overdose or Exhibiting Early-Onset Severe Toxicities Following Administration of These Drugs.

On December 11, 2015, the FDA approved uridine triacetate (VISTOGARD; Wellstat Therapeutics Corporation) for the emergency treatment of adult and pediatric patients following a fluorouracil or capecitabine overdose regardless of the presence of symptoms, and of those who exhibit early-onset, severe, or life-threatening toxicity affecting the cardiac or central nervous system, and/or early onset, unusually severe adverse reactions (e.g., gastrointestinal toxicity and/or neutropenia) within 96 hours following the end of fluorouracil or capecitabine administration. Uridine triacetate is not recommended for the nonemergent treatment of adverse reactions associated with fluorouracil or capecitabine because it may diminish the efficacy of these drugs, and the safety and efficacy of uridine triacetate initiated more than 96 hours following the end of administration of these drugs has not been established. The approval is based on data from two single-arm, open-label, expanded-access trials in 135 patients receiving uridine triacetate (10 g or 6.2 g/m(2) orally every 6 hours for 20 doses) for fluorouracil or capecitabine overdose, or who exhibited severe or life-threatening toxicities within 96 hours following the end of fluorouracil or capecitabine administration. Ninety-six percent of patients met the major efficacy outcome measure, which was survival at 30 days or survival until the resumption of chemotherapy, if prior to 30 days. The most common adverse reactions were vomiting, nausea, and diarrhea. This article summarizes the FDA review of this New Drug Application, the data supporting approval of uridine triacetate, and the unique regulatory situations encountered by this approval. Clin Cancer Res; 22(18); 4545-49. ©2016 AACR.

[Treating chronic persistent bronchial asthma children with abnormal myocardial enzyme spectrum by Yupingfeng powder: an efficacy observation].

OBJECTIVE: To observe the clinical efficacy of treating chronic persistent bronchial asthma (CPBA) children with abnormal myocardial enzyme spectrum (AMES) by Yupingfeng Powder (YP) combined routine therapy. METHODS: From January 2010 to December 2012, 156 CPBA children patients with AMES were randomly assigned to the treatment group (80 cases) and the control group (76 cases). All patients received routine treatment (inhaled corticosteroids and/or leukotriene regulator). Besides, those in the treatment group took YP. The treatment duration was 3 months. The scores of children asthma control test (C-ACT), pulmonary function (FEV,% and PEF%), myocardial enzyme spectrum were observed before and after treatment, and 3 months before and after treatment. The myocardial enzyme spectrum of 40 healthy children at the baby clinics during the same period were recruited as the control. RESULTS: Compared with the control group, creatine kinase isoenzyme (CK-MB), creatine kinase(CK), and lactate dehydrogenase (LDH) increased in the two treatment groups (P <0.01), but there was no statistical difference in AST (P >0.05). Compared with before treatment in the same group, CK-MB, CK, LDH, and AST decreased in the treatment group after treatment and 3 months after treatment (P <0.01). CK-MB, CK, LDH, and AST decreased in the control group 3 months after treatment (P <0.01, P <0.05).Compared with after treatment, CK decreased in the control group 3 months after treatment (P <0.01). C-ACT score, FEV(1),%, and PEF% all increased in the two groups after treatment and 3 months after treatment (P <0.01, P <0.05). Compared with after treatment in the same group, CK decreased in the control group 3 months after treatment (P <0. 01). Compared with the control group in the same period, post-treatment CK-MB and CK decreased (P <0. 01, P <0. 05), while post-treatment C-ACT score, FEV, %, and PEF% increased (P <0.05) in the treatment group (P <0.05). CONCLUSION: YP could strengthen specific and non-specific immunity of the organism, and improve clinical symptoms and the level of myocardial enzyme spectrum.

[Clinical research on fire filiform needle combined with mild moxibustion for postherpetic neuralgia].

OBJECTIVE: To compare efficacy differences between fire filiform needle combined with mild moxibustion and gabapentin combined with sham acupuncture for postherpetic neuralgia (PHN). METHODS: One hundred cases of PHN were randomly divided into a needle group and a medicine group, 50 cases in each one. In the needle group, pricking method of fire filiform needle was given at the Ashi points, and then mild moxibustion was applied for 15 min. In the medicine group, the oral administration of gabapentin capsule and sham acupuncture at non-acupoints in the distal end of lesions were applied. The treatment was required for 21 days in both groups. The visual analogue score (VAS) was recorded before treatment and on the 1st day, 2nd day, 3rd day, 6th day, 9th day and 12th day of treatment. The most severity of pain within last 24 h, preset severity of pain, immediate analgesia effect and starting time of pain relief were observed, also the efficacy was assessed and improvement of symptoms was observed in the follow-up visit. RESULTS: The total effective rate was 94.0% (47/50) in the fire filiform needle group, which was superior to 86.0% (43/50) in the medicine group (P < 0.05). Compared with medicine group, the VAS of the most severity of pain within last 24 h was obviously reduced after the 2nd treatment in the fire filiform needle group while that of present severity of pain was relieved after the 1st treatment (both P < 0.05). The immediate analgesia effect in the fire filiform needle group was obviously superior to that in the medicine group in the first three times of treatment (all P < 0.05). The average time of pain relief was (3.91 +/- 0.82) days in the fire filiform needle group, which was significantly earlier to (6.53 +/- 1.13) days in the medicine group (P < 0.05). 26 cases were cured in the fire filiform needle group in the follow-up visit, which was superior to 2 cases in the medicine group (P < 0.05). The improvement of VAS, pain range and sleep quality in the needle group were also superior to those in the medicine group (all P < 0.05). The direct medical cost in the fire filiform needle group was (232.32 +/- 48.108) yuan, which was significantly lower than (466.00 +/- 41.09) yuan in the medicine group (P < 0.05). There was only one case of adverse effect in the medicine group during the treatment. CONCLUSION: The fire filiform needle combined with mild moxibustion could obviously relieve the pain in PHN patients, which has superior immediate analgesia effect and pain relieving time compared with gabapentin, which also has less adverse effects and cheap cost.

Cytotoxic prenylated xanthones from the pericarps of Garcinia mangostana.

Bioassay-guided fractionation of an ethanol extract of the pericarps of Garcinia mangostana led to the isolation of two new prenylated xanthones, named 1,3,7-trihydroxy-2-(3-methyl-2-butenyl)-8-(3-hydroxy-3-methylbutyl)-xanthone (1) and 1,3,8-trihydroxy-2-(3-methyl-2-butenyl)-4-(3-hydroxy-3-methylbutanoyl)-xanthone (2), together with the five known compounds garcinones C (3) and D (4), gartanin (5), xanthone I (6), and γ-mangostin (7). Their structures were elucidated primarily based on MS and NMR data. Compounds 1-7 showed significant cytotoxic activities against various human cancer cell lines.

Panax notoginseng saponins induced up-regulation, phosphorylation and binding activity of MEK, ERK, AKT, PI-3K protein kinases and GATA transcription factors in hematopoietic cells.

OBJECTIVE: To investigate the effects of panax notoginseng saponins (PNS) on expression, regulation and phosphorylation of multiple protein kinases in mitogen activated protein kinase (MAPK) intracellular signal pathway and GATA transcription factors in hematopoietic cells, so as to explore its mechanism of proliferation and differentiation activity on hematopoiesis. METHODS: The human granulocytic HL-60, erythrocytic K562, megakaryocytic CHRF-288 and Meg-01 cell lines were treated by PNS, the positive control of K562, CHRF-288 cells treated by recombination human erythropoietin (Epo) and thrombopoietin (Tpo) respectively. The total cell lysate and nuclei protein were extracted after being treated by PNS, subsequently, analyzed by both Western blot and immune-precipitation. Meanwhile, the nuclei extract was performed for electrophoretic mobility shift assay (EMSA) by using (32)P radio labeled double-stranded GATA consensus oligonucleotide. RESULTS: The expression levels of kinase MEK-1, MEK-2, ERK-1, ERK-2, AKT-1, AKT-2 and PI-3K were increased by PNS treatment to different extent in four cell lines, depending on cellular heterogeneity and sensitivity to PNS, also phosphorylation of MEK-1, ERK-1 was differentially promoted by PNS respectively P<0.05, 0.01, 0.001). The expression levels of transcription factors GATA-1 and GATA-2 were increased, moreover, their DNA binding activities were raised dramatically in PNS treated K562, CHRF-288 and Meg-01 cells compared with the controls respectively (P<0.05, 0.01, 0.001). The positive control of K562, CHRF-288 cells treated by Epo or Tpo respectively also displayed up-regulation of protein kinases and GATA transcription factors respectively (P<0.05, 0.01, 0.001). CONCLUSION: The results indicated that intracellular signal pathway initiated by PNS was involved in MAPK pathway and transcription factors of GATA family in hematopoietic cells. PNS displayed the role to promote proliferation and differentiation, by means of increasing expression level and phosphorylation status of multiple protein kinases, also inducing synthesis of GATA transcription factors and upregulation its DNA binding activity.

Effects of sodium copper chlorophyllin on mesenchymal stem cell function in aplastic anemia mice.

OBJECTIVE: To investigate the effects of sodium copper chlorophyllin (SCC) on the proliferation, differentiation and immunomodulatory function of mesenchymal stem cells (MSCs) from mice with aplastic anemia. METHODS: A mouse model of aplastic anemia was established by exposure of BALB/c mice to sublethal doses of 5.0 Gy Co60 γ radiation, followed by transplantation of 2×10(6) lymph node cells from DBA/2 donor mice within 4 h after radiation. Aplastic anemic BALB/c mice were randomly divided into six groups: the treated groups, which received 25, 50, or 100 mg/kg/day SCC, respectively; a positive control group treated with cyclosporine A (CsA); and an untreated model control group (model group); while, the non-irradiated mice as the normal control group. SCC or CsA were administered by gastrogavage for 20 days, starting on day 4 after irradiation. Peripheral blood cells were counted and colony-forming fibroblasts (CFU-F) in the bone marrow were assayed. The ability of MSCs to form calcium nodes after culture in osteoinductive medium was also observed. The immunosuppressive effect of MSCs on T lymphocytes was analyzed by enzyme-linked immunosorbent assay and flow cytometry, to evaluate the efficacy of SCC in mice with aplastic anemia. RESULTS: Peripheral blood white cell and platelet counts were increased by medium and high SCC doses, compared with the untreated control. CFU-Fs were also increased compared with the untreated control, and the numbers of calcium nodes in MSCs in osteoinductive medium were elevated in response to SCC treatment. The percentage of Forkhead box protein 3 (FOXP3(+)) T cells was increased in T cell-MSC cocultures, and the cytokine transforming growth factor ß1 was up-regulated in SCC-treated groups. CONCLUSION: The results of this study suggest that SCC not only promotes the proliferation and differentiation of MSCs, but also improves their immunoregulatory capacity in mice with aplastic anemia.

Effects of Panax notoginseng saponins on proliferation and differentiation in NIH3T3 cells.

OBJECTIVE: To investigate the effects of Panax notoginseng saponins (PNS) on the proliferation and differentiation in NIH3T3 cells. METHODS: NIH3T3 cells were treated by various concentrations of PNS 0, 0.05, 0.10, 0.20, and 0.40 g/L. The vitality and proliferation potential of cells were detected by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, the alkaline phosphatase (ALP) activity was measured by p-nitrophenyl phosphate (pNPP) assay, and the mineralization formation ability was tested for the cellular differentiation toward osteoblast, as well as the expression level of phosphorylated extracellular signal-regulated kinase1/2(P-ERK1/2), extracellular signal-regulated kinase1/2 (ERK1/2) protein kinase was analyzed by Western blot with total cell lysate of NIH3T3 cells treated by PNS. RESULTS: Both MTT and pNPP assay showed that optical density (OD) values were increased in response to PNS treatment at a dose-dependent pattern. The mineralization formation ability was enhanced in PNS-treated NIH3T3 cells compared with untreated cells. Meanwhile, the expression level of P-ERK1/2 protein kinase was up-regulated in PNS-treated NIH3T3 cells, while, the expression level of ERK1/2 protein kinase revealed no obvious difference with or without PNS treated cells. CONCLUSION: PNS could pay a role to promote the proliferation and differentiation in NIH3T3 cells by means of up-regulation of P-ERK1/2 protein kinase.

Determination of four pyridine alkaloids from Tripterygium wilfordii Hook. f. in human plasma by high-performance liquid chromatography coupled with mass spectrometry.

A novel liquid chromatography-atmospheric-pressure chemical ionization-mass spectrometry (LC-APCI/MS) method was developed and validated for the simultaneous determination of four sesquiterpene pyridine alkaloids (wilfortrine, wilfordine, wilforgine and wilforine) in human plasma. The chromatographic separation was performed on a Shim-pack XR-ODS column using an ammonium acetate buffer solution-acetonitrile in a gradient program. The detection was achieved by an ion trap mass spectrometry in the positive selected ion monitoring (SIM) mode. The method utilized acetonitrile as protein precipitation solvent and followed by solid-phase extraction (SPE). Calibration curves were linear for the four alkaloids over the range of 0.5-100.0 µg/L with the limits of quantification of 0.5 µg/L, while the method exhibited the recovery of 86.5-98.6%, intra- and inter-day RSDs of less than 8.2% and 12.8%, respectively. Methodology was validated in line with the EU requirements (Commission Decision 2002/657/EC). Results of incurred samples demonstrated excellent reproducibility. To our knowledge, this is the first analytical method for simultaneous determination of the four sesquiterpene pyridine alkaloids in plasma. The method was applicable to clinical pharmaceutical research of alkaloids in rheumatoid arthritis volunteer patients after oral administrations.

The orally combined neuroprotective effects of sodium ferulate and borneol against transient global ischaemia in C57 BL/6J mice.

OBJECTIVES: This study aimed to investigate the possible modification of the neuroprotective effect of sodium ferulate, when orally co-administered with borneol, in transient global cerebral ischaemia-induced functional, histological and cellular alterations in mice. METHODS: The bilateral common carotid artery occlusion was conducted in C57 BL/6J mice for 25 min. The mice were then subjected to a water maze test over an extended recovery period, followed by an assessment of neuronal loss in the CA1 region of the hippocampus (haematoxylin and eosin staining). The blood-brain barrier permeability (Evans blue tracing), brain oedema and oxidative stress were assayed and histological sections were also immunostained for gliofibrillar acid protein (GFAP) expression. KEY FINDINGS: The ischaemia reperfused mice were associated with long-lasting spatial learning deficits in the absence of other behavioural impairments and with neurodegeneration in the hippocampal CA1 region. However, the histological injuries were significantly attenuated by oral co-administration of sodium ferulate and borneol. Furthermore, combined treatment with sodium ferulate and borneol resulted in a significant reduction in brain oedema, GFAP-positive cells, malonaldialdehyde levels and blood-brain barrier permeability, but an increase in superoxide dismutase activity. CONCLUSIONS: Borneol may have benefits for the neuroprotective effect of sodium ferulate against injury induced in the brain by ischaemia/reperfusion.

Protective effect of an extract from Periplaneta americana on hematopoiesis in irradiated rats.

PURPOSE: To investigate the protective effect of W(11)-a(12), an extract from Periplaneta americana, on hematopoiesis in irradiated rats. MATERIALS AND METHODS: Wistar rats receiving total body irradiation of (60)Co gamma-rays alone or with combined radiation and skin wound injury were used in this study. W(11)-a(12) was applied either topically into the skin wounds or systemically by intraperitoneal injection. The numbers of white blood cells in peripheral blood, the nucleated cells and the colony-forming unit of granulocyte/macrophage progenitors (CFU-GM) in bone marrow were measured, respectively. RESULTS: Topical application of W(11)-a(12) into skin wounds in rats with combined 6 Gy total body irradiation and skin wound injury could increase the neutrophils and macrophages in the wounded area and the nucleated cells in bone marrow at 24 h and 48 h, while the peripheral white blood cells did not show significant change. However, in rats with 4 Gy total body irradiation alone, the peripheral white blood cells, bone marrow nucleated cells and the number of colony-forming unit of granulocyte-macrophage progenitors were all significantly higher in the treatment groups by intraperitoneal injection of W(11)-a(12) than those in the control groups by injection of normal saline at days 3 and days 5 after radiation. CONCLUSIONS: W(11)-a(12) showed a protective effect on hematopoiesis after total body irradiation and could increase the inflammatory cells in wounded tissues at the initiation stage after irradiation, which will benefit the management of combined radiation and skin wound injury.

[Transoral carbon dioxide laser surgery for treatment of hypopharyngeal carcinoma].

OBJECTIVE: To evaluate the feasibility and curative effects of transoral CO2 laser in treatment of hypopharyngeal carcinoma. METHODS: The retrospective analysis included 24 cases of hypopharyngeal carcinoma from 1994 to 2005 in the Department of Head and Neck. All cases were treated with endoscopic laser surgery and adjuvant selective neck dissection or radiotherapy. The follow-up period was more than 3 years. Twenty-four patients (21 male, 3 female) were classified as follows: 14 cases were T1N0M0, 4 were T1N1M0, 1 was T1N2bM0, 3 were T2N0M0 and 2 were T2N2bM0. RESULTS: Kaplan-Meier survival analysis showed the overall 5-year survival rate was 74.9%, and the 5-year survival rate of T1 lesions and T2 lesions was 78.8% and 60.1%, respectively. The overall 5-year local control rate was 82.1% and 5-year larynx preservation rate was 87.0%. Six of 7 patients with local-regional recurrences underwent salvage surgery and radiotherapy. Finally 4 of them died of recurrence again and 2 were survival. The other one of 7 patients had distant metastasis, and died after radiochemotherapy. One patient died of non-neoplastic diseases. Two patients experienced minor complications with conventional ambulatory treatment without sequelae. All survival patients had laryngeal preservation except the one who received salvage surgery of the hypopharynx and larynx. CONCLUSIONS: Endoscopic CO2 laser surgery with adjuvant selective or modified radical neck dissection and radiotherapy is an alternative for the treatment of selected hypopharyngeal carcinoma, associated with satisfying curative effects and a high larynx preservation rate.

[Apoptosis of HL-60 cells induced by aescinate].

The aim of this study was to investigate the effects of aescinate on inhibition and apoptosis of HL-60 cell line from promyelocytic leukemia. HL-60 cells at logarithm phase were treated with aescinate. Cell survival rate and cell morphology were observed, and the cell apoptosis was analyzed by Annexin V/PI-FITC double labeling and DNA electrophoresis. The results showed that HL-60 cells could be inhibited in the presence of 15-120 mg/L of aescinate for 48 hours, survival rates were (92.2+/-0.69)%-(8.2+/-0.96)%, which were significantly lower than that of non-aescinate control (99.4+/-0.31)% (all p<0.01). The apoptosis of cells could be induced by aescinate treatment at dosage of 15-60 mg/L for 24 hours, the Annexin V positive cells accounted for (12.7+/-0.58)%-(65.4+/-1.30)% which were significantly higher than that of non-aescinate control (0.57+/-0.03)% (all p<0.01). The typical DNA ladder of HL-60 cells treated with aescinate was shown on the DNA electrophoresis pattern. It is concluded that aescinate can specifically induce apoptosis of leukemic HL-60 cells, which provides an experimental evidence for treatment of leukemia with aescinate as a supplementary agent to chemotherapy.

[Experimental study on effect of Buchang Naoxintong containing serum for antagonizing hypoxia-induced apoptosis of cortical neurons].

OBJECTIVE: To investigate the effect of Buchang Naoxintong containing serum (BNCS) for antagonizing hypoxia-induced apoptosis of primary cultured cortical neurons with the sero-pharmacological method. METHODS: Primary cortical neurons from neonate rats (within 24 h) were cultured and induced into hypoxia model on the 7th day, which were then treated with different concentrations of BNCS. Cell apoptosis was detected qualitatively and quantitatively; and further verified by agarose gel electrophoresis through analyzing in-ternucleosomal DNA fragmentation of the neurons. Besides, neuron viability was tested by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and change of nuclear morphology was observed by Hoechst 33258 staining. RESULTS: After treatment with BNCS, the viability of the hypoxia neurons improved with significantly reduced neuron apoptosis. CONCLUSION: Buchang Naoxintong can protect cortical neurons from hypoxia-induced apoptosis.