Global One Health index for zoonoses: A performance assessment in 160 countries and territories.

The One Health (OH) approach is used to control/prevent zoonotic events. However, there is a lack of tools for systematically assessing OH practices. Here, we applied the Global OH Index (GOHI) to evaluate the global OH performance for zoonoses (GOHI-Zoonoses). The fuzzy analytic hierarchy process algorithm and fuzzy comparison matrix were used to calculate the weights and scores of five key indicators, 16 subindicators, and 31 datasets for 160 countries and territories worldwide. The distribution of GOHI-Zoonoses scores varies significantly across countries and regions, reflecting the strengths and weaknesses in controlling or responding to zoonotic threats. Correlation analyses revealed that the GOHI-Zoonoses score was associated with economic, sociodemographic, environmental, climatic, and zoological factors. Additionally, the Human Development Index had a positive effect on the score. This study provides an evidence-based reference and guidance for global, regional, and country-level efforts to optimize the health of people, animals, and the environment.

Optimal decision-making in relieving global high temperature-related disease burden by data-driven simulation.

The rapid acceleration of global warming has led to an increased burden of high temperature-related diseases (HTDs), highlighting the need for advanced evidence-based management strategies. We have developed a conceptual framework aimed at alleviating the global burden of HTDs, grounded in the One Health concept. This framework refines the impact pathway and establishes systematic data-driven models to inform the adoption of evidence-based decision-making, tailored to distinct contexts. We collected extensive national-level data from authoritative public databases for the years 2010-2019. The burdens of five categories of disease causes - cardiovascular diseases, infectious respiratory diseases, injuries, metabolic diseases, and non-infectious respiratory diseases - were designated as intermediate outcome variables. The cumulative burden of these five categories, referred to as the total HTD burden, was the final outcome variable. We evaluated the predictive performance of eight models and subsequently introduced twelve intervention measures, allowing us to explore optimal decision-making strategies and assess their corresponding contributions. Our model selection results demonstrated the superior performance of the Graph Neural Network (GNN) model across various metrics. Utilizing simulations driven by the GNN model, we identified a set of optimal intervention strategies for reducing disease burden, specifically tailored to the seven major regions: East Asia and Pacific, Europe and Central Asia, Latin America and the Caribbean, Middle East and North Africa, North America, South Asia, and Sub-Saharan Africa. Sectoral mitigation and adaptation measures, acting upon our categories of Infrastructure & Community, Ecosystem Resilience, and Health System Capacity, exhibited particularly strong performance for various regions and diseases. Seven out of twelve interventions were included in the optimal intervention package for each region, including raising low-carbon energy use, increasing energy intensity, improving livestock feed, expanding basic health care delivery coverage, enhancing health financing, addressing air pollution, and improving road infrastructure. The outcome of this study is a global decision-making tool, offering a systematic methodology for policymakers to develop targeted intervention strategies to address the increasingly severe challenge of HTDs in the context of global warming.

Tackling global health security by building an academic community for One Health action.

BACKGROUND: One Health approach is crucial to tackling complex global public health threats at the interface of humans, animals, and the environment. As outlined in the One Health Joint Plan of Action, the international One Health community includes stakeholders from different sectors. Supported by the Bill & Melinda Gates Foundation, an academic community for One Health action has been proposed with the aim of promoting the understanding and real-world implementation of One Health approach and contribution towards the Sustainable Development Goals for a healthy planet. MAIN TEXT: The proposed academic community would contribute to generating high-quality scientific evidence, distilling local experiences as well as fostering an interconnected One Health culture and mindset, among various stakeholders on different levels and in all sectors. The major scope of the community covers One Health governance, zoonotic diseases, food security, antimicrobial resistance, and climate change along with the research agenda to be developed. The academic community will be supported by two committees, including a strategic consultancy committee and a scientific steering committee, composed of influential scientists selected from the One Health information database. A workplan containing activities under six objectives is proposed to provide research support, strengthen local capacity, and enhance global participation. CONCLUSIONS: The proposed academic community for One Health action is a crucial step towards enhancing communication, coordination, collaboration, and capacity building for the implementation of One Health. By bringing eminent global experts together, the academic community possesses the potential to generate scientific evidence and provide advice to local governments and international organizations, enabling the pursuit of common goals, collaborative policies, and solutions to misaligned interests.

China's application of the One Health approach in addressing public health threats at the human-animal-environment interface: Advances and challenges.

Background: Due to emerging issues such as global climate change and zoonotic disease pandemics, the One Health approach has gained more attention since the turn of the 21st century. Although One Health thinking has deep roots and early applications in Chinese history, significant gaps exist in China's real-world implementation at the complex interface of the human-animal-environment. Methods: We abstracted the data from the global One Health index study and analysed China's performance in selected fields based on Structure-Process-Outcome model. By comparing China to the Belt & Road and G20 countries, the advances and gaps in China's One Health performance were determined and analysed. Findings: For the selected scientific fields, China generally performs better in ensuring food security and controlling antimicrobial resistance and worse in addressing climate change. Based on the SPO model, the "structure" indicators have the highest proportion (80.00%) of high ranking and the "outcome" indicators have the highest proportion (20.00%) of low ranking. When compared with Belt and Road countries, China scores above the median in almost all indicators (16 out of 18) under the selected scientific fields. When compared with G20 countries, China ranks highest in food security (scores 72.56 and ranks 6th), and lowest in climate change (48.74, 11th). Conclusion: Our results indicate that while China has made significant efforts to enhance the application of the One Health approach in national policies, it still faces challenges in translating policies into practical measures. It is recommended that a holistic One Health action framework be established for China in accordance with diverse social and cultural contexts, with a particular emphasis on overcoming data barriers and mobilizing stakeholders both domestically and globally. Implementation mechanisms, with clarified stakeholder responsibilities and incentives, should be improved along with top-level design.

Antifungal and Antibiofilm In Vitro Activities of Ursolic Acid on Cryptococcus neoformans.

Ursolic acid (UA) exists in a variety of medicinal plants. UA exhibits antimicrobial activity against several microorganisms; however, little is known regarding the potential antifungal effect of UA on Cryptococcus neoformans (C. neoformans). The antifungal and antibiofilm activities of UA on C. neoformans H99 were evaluated in this study. Minimum inhibitory concentration (MIC) of UA against C. neoformans H99 was determined by microdilution technique, and its action mode was elucidated by clarifying the variations in cell membrane integrity, capsule, and melanin production. Moreover, the inhibition and dispersal effects of UA on biofilm formation and mature biofilms by C. neoformans H99 were evaluated using crystal violet (CV) assay, optical microscopy, field emission scanning electron microscopy and confocal laser scanning microscopy. The results indicated that the MIC value of UA against C. neoformans H99 was 0.25 mg/mL. UA disrupted the cell membrane integrity, inhibited the capsule and melanin production of C. neoformans H99 in a concentration-dependent manner. Further, UA presented the inhibitory effect on biofilm formation and dispersed mature biofilms, as well as compromised the cell membrane integrity of C. neoformans H99 cells within biofilms. Together, these results indicate that UA might be a potential therapeutic option for the treatment of C. neoformans-related infections.

Intervention Mechanism of Xiaoluowan on Experimental Goiter Rats Based on PI3K/Akt/mTORC1 Pathway / 中国实验方剂学杂志

ObjectiveBy observing the effect of Xiaoluowan on phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin complex 1 （mTORC1） pathway in experimental goiter rats， this study aims to explore its therapeutic effect on experimental goiter rats. MethodSixty 5-month-old SD rats of SPF grade were purchased， half males and half females， of which 10 were used as a normal group， and the remaining rats were administrated with propylthiouracil （PTU） solution to induce nodular goiter. After successful modeling， rats were randomly divided into a model group， levothyroxine sodium tablets group， Xiaoluowan low-dose group， medium-dose group， and high-dose group， ten rats each. The levothyroxine sodium tablets group was given 15 μg·kg-1 levothyroxine sodium tablets by gavage. The Xiaoluowan low-， medium-， and high-dose groups were given （ig） Xiaoluowan low-dose （10 g·kg-1）， medium-dose （20 g·kg-1）， and high-dose （30 g·kg-1） Xiaoluowan， and the normal group and model group were administered （ig） with the same volume of 0.9% sodium chloride solution. Four weeks after the intervention， rats were sacrificed by routine intraperitoneal anesthesia using 5% phenobarbital. Subsequently， the histopathology was observed under a microscope， and serum thyroid hormone levels were measured using a Roche electrochemiluminescence immunoassay analyzer. Serum cytokines were detected by enzyme-linked immunosorbent assay （ELISA）， and neurotransmitters were measured using a high-performance liquid chromatograph. The protein level of PI3K/Akt/mTORC1 pathway was determined by Western blot. ResultAs compared with the normal group， the levels of basic fibroblast growth factor （bFGF）， vascular endothelial growth factor （VEGF）， insulin-like growth factor （IGF-1）， 5-hydroxytryptamine （5-HT）， and thyroid stimulating hormone （TSH） were increased， and PI3K， Akt， and mTORC1 protein levels were up-regulated in the model group， while the levels of norepinephrine （NE）， triiodothyronine （T3）， tetraiodothyronine （T4）， free triiodothyronine （FT3）， and free thyroid hormone （FT4） were decreased （P<0.05）. Compared with the model group， the levothyroxine sodium tablets group， and Xiaoluowan low-， medium-， and high-dose groups exhibited reduced levels of bFGF， VEGF， IGF-1， 5-HT， and TSH， and down-regulated PI3K， Akt， and mTORC1 protein levels， and increased NE， T3， T4， FT3， and FT4 levels （P<0.05）. ConclusionXiaoluowan may act on the PI3K/Akt/mTORC1 signaling pathway to play its role in the treatment of nodular goiter， and it is dose-dependent.

Investigate the value of CEACAM1 in diagnosis and monitoring of ONFH / 医学研究生学报

ObjectiveThere are few studies on the correlation between the concentration of oncoembryonic antigen associated cell adhesion molecule 1(CEACAM1) and osteonecrosis of the femoral head (ONFH). The purpose of this study was to investigate the value of CEACAM1 in the early diagnosis of ONFH and the monitoring of the disease by detecting the CEACAM1 concentration in the serum of patients with ONFH and healthy subjects respectively.Methods95 patients, who were hospitalized and diagnosed as ONFH in the Department of No.3 Orthopaedic Ward, the First Affiliated Hospital of Guangzhou University of Chinese Medicine from May 2016 to November 2016, were selected as the experimental group. In addition, 56 genders and age-matched healthy subjects in our hospital were selected as the control group. The peripheral venous blood was taken and separated by a centrifuge. Their CEACAM1 concentrations were measured by enzyme linked immunosorbent assay (ELISA). The differences in CEACAM1 concentrations were analyzed between the two groups, and between patients with ONFH before (ARCO stage I or II) and after (ARCO stage III or IV) collapse as well.Results①The concentration of CEACAM1 in the experimental group was significantly lower than that in the control group [(6.11±2.07)ng/mL vs (7.21±3.76)ng/mL, P=0.022]. ②The concentration of CEACAM1 in Arco stage II[(7.33±1.90) ng/mL] was significantly higher than that in stage III [(6.08±2.26) ng/mL], P=0.037.③The difference of CEACAM1 concentration between before(stage II) and after collapse (stage III or stage IV) was statistically different [(7.33±1.90)ng/mL vs (5.86±2.02)ng/mL, P=0.007].④ROC curve analysis showed that the area under the curve was 0.710 (0.608-0.798), the sensitivity was 71.79%, the specificity was 58.82%, and the cut off value was ≤ 6.757ng/mL in the diagnosis of collapse of ONFH.ConclusionThe concentration of serum CEACAM1 can be used as a biochemical marker to assist in the diagnosis and monitoring of ONFH, which can provide reference for early diagnosis and monitoring of ONFH.

Influence of psychological resilience on cognitive bias towards school violence among primary school students in Luzhou / 中国学校卫生

Objective@#To explore the relationship between psychological resilience and cognitive bias towards school violence in grade 3-5 primary school students in Luzhou city, so as to provide scientific basis for prevention and control of school violence in primary school students.@*Methods@#Students from grade 3-5 in primary schools in Luzhou were selected through stratified cluster random sampling method and were investigated with questionnaire survey.@*Results@#A total of 5 976 valid questionnaires were included, with an average score of psychological resilience (40.08±8.05) and an average score of school violence cognition (62.55±6.38). Multivariate results showed that psychological resilience was an independently associated with school violence perception (OR=1.04, P<0.01). The awareness of campus violence increased with resilience score. In addition, public school (OR=0.45) was associated with low awareness of school violence; senior grades (OR=1.77), girls (OR=1.20), and a greater number of friends(OR=1.37), student cadre(OR=1.37), middle/upper score in class(OR=2.13), no game playing(OR=1.33), no off-campus wandering(OR=1.78), timely parenting (OR=1.45) was associated with high awareness of school violence(P<0.05).@*Conclusion@#Psychological resilience positively correlates with cognition bias towards school violence. The higher the psychological resilience, the more positive perception of campus violence. Family, school and community-based interventions to enhance the resilience of students, increasing awareness towards school violence and ultimately reducing potential adverse impacts of school violence.

Effects of L-borneol on chloride channel and cell volume in human umbilical vein endothelial cells / 中国药理学通报

Aim To study the effects of L-borneol on the chloride channel and cell volume of human umbili-cal vein endothelial cells (HUVECs). Methods Whole-cell patch-clamp technique was used to record chloride currents. The expression of ClC-3 protein was down-regulated by siRNA interference technique. The cell volume was measured by dynamic image analysis. Results 20 nmol·L-1L-borneol significantly activa-ted chloride current in HUVEC (79.59 ± 4.90) pA/pF, which could be inhibited by chloride channel blockers,NPPB and DIDS. The outward current inhib-itory rate of NPPB was (95.57 ± 2.57)%, while that of DIDS was (97.28 ± 6.36)%. The chloride current activated by L-borneol significantly decreased after the silence of ClC-3 (27.03 ± 3.89) pA/pF. Cell volume was markedly reduced by L-borneol (14.38 ± 1.58)%,which was inhibited after NPPB appliance. Conclusion L-borneol can activate ClC-3 chloride channel in HUVECs, which induces Cl- outflow then cell volume decrease.

Effects of ClC-3 over-expression on structure and function of thyroid in mice / 中国病理生理杂志

AIM:To study the effect of ClC-3 gene over-expression on thyroid structure and function in mice. METHODS:Three-months-old FVB mice were used to study the difference of thyroid structure and function between wild-type(WT)mouse and ClC-3 transgene mice.The expression and distribution of ClC-3 in the thyroid of mice were deter-mined by the methods of qPCR,Western blot and immunofluorescence.Behavioral monitoring was performed on the daily activities of mice.Serum concentrations of total triiodothyronine(TT3), total thyroxine(TT4)and thyrotropin(TSH) were measured by ELISA.RESULTS:Compared with the WT group,the expression of ClC-3 in the thyroid of ClC-3 trans-gene group was significantly increased(P<0.05).The thyroid gland showed obvious hyperplasia and the folliculi glandu-lae thyreoideae was significantly bigger in ClC-3 transgene mice(P<0.05).The weight loss was increased in ClC-3 trans-gene mice(P<0.05).The expression of TT3 and TT4 were significantly higher than that of WT group(P<0.05),but the change of TSH was not obvious.CONCLUSION:ClC-3 over-expression results in thyroid hyperplasia and thyroid hor-mone secretion.This study suggests that ClC-3 is likely to be involved in the synthesis of thyroid hormones.

Comparison of anterior chamber maintainer and viscoelastic agent on corneal astigmatism and endothelial cells after phacoemulsification / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To compare the influence of anterior chamber maintainer and viscoelastic agent on corneal astigmatism and endothelial cells after phacoemulsification.METHODS:Totally 70 patients(70 eyes) of cataract from April 2013 to April 2015 were randomly divided into the study group and the control group, with 35 cases in each group.The study group were treated with anterior chamber maintainer during phacoemulsification with support system approach, and the control group were treated with phacoemulsification under viscoelastic agent.RESULTS:The age (t=0.215, P=0.831), the density of corneal endothelial cells (t=-0.352, P=0.726) and corneal luminosity (t=-0.162, P=0.872) of two groups had no significant difference before surgery;there were no significant difference in preoperative visual acuity (t=0.463, P=0.599) and visual acuity (t=1.616, P=0.124) at 1mo after operation.And patients in the study group (t=-21.129, P<0.01) and the control group (t=-12.780, P<0.01) before surgery and 1mo postoperative when compared with the naked eye eyesight showed significant difference.The visual acuity after operations improved significantly.There were significant differences of corneal endothelial cells density (t=8.489, P< 0.01) and corneal astigmatism (t=-2.032, P=0.046) in the study group before surgery and 1mo after surgery;corneal endothelial cell density (t=8.999, P<0.01) and corneal astigmatism (t=-2.167, P=0.034) in the control group before surgery and 1mo after surgery also had significant differences.There was no significant difference in the rate of corneal endothelial cell loss between the two groups (t=0.410, P=0.683).CONCLUSION:Compared with viscoelastic agent, anterior chamber maintainer during phacoemulsification in patients with cataract won't increase the damage of postoperative surgically induced astigmatism and corneal endothelial cells, which mean the method of anterior chamber maintainer during phacoemulsification in the treatment of cataract is safe and effective.

Clinical Value of Serum Fructosamine Measurement in IgA Type Multiple Myeloma / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the value of serum fructosamine (FMN) measurement in clinical typing and staging of multiple myeloma(MM) as well as evaluation of curative efficacy and prognosis of IgA type MM.</p><p><b>METHODS</b>The levels of FMN were detected by nitro-blue-tetrazolium colorimetric method in 62 IgA type MM patients, 65 IgG type MM patients, 24 IgM type MM patients. The difference between the serum FMN levels and different MM types and its relationship with IgA type MM, patients' stages, efficacy and as well as, the effect of FMN level on overall survival (OS) time of IgA type MM patients were analyzed.</p><p><b>RESULTS</b>FMN level of IgA type patients was obviously higher than that of IgG type and IgM type patients. Patients of DS stage III had higher FMN level than that of stage II, and patients of DS stage II had higher FMN level than that of stage I, the differences were statistical significant(P<0.05). Patients of ISS stage III also had higher FMN level than that of stage II, and patients of ISS stage II also had higher FMN level than that of stage I, the differences were statistical significant(P<0.05). After treatment, FMN level of patients obtained complete remission (CR) or very good partial remission(VGPR) obviously decreased, FMN level of patients obtained partial remission(PR) decreased, FMN level of patients obtained less than PR increased. Patients with normal FMN level had longer OS time, while patients with high FMN level had obviously short OS time.</p><p><b>CONCLUSIONS</b>Serum FMN is obviously elevated in the IgA type MM, there is a certain association between staging and serum FMN level, the IgA type MM patients with FMN normalization after treatment have better prognosis.</p>

Role of acetylcholine in gelsenicine-induced death in mice / 生理学报

The aim of this study was to investigate the relationship between the acetylcholine concentration in the blood and gelsenicine-induced death in mice. Kunming mice were given intraperitoneal injections of normal saline, gelsenicine or different doses of acetylcholine chloride. Atropine was given to the mice which received gelsenicine or medium dose acetylcholine chloride injection. The blood was sampled immediately when the mice died or survived for 20 min after injection. The acetylcholine concentration and acetylcholinesterase activity in the blood were measured by the testing kits, and the mortality was calculated and analyzed. The results showed that half lethal dose of gelsenicine (0.15 mg/kg) reduced the acetylcholinesterase activity and increased the blood acetylcholine concentration. The blood acetylcholine concentration of the dead mice in the gelsenicine group was increased to 43.0 μg/mL (from 31.1 μg/mL in the control), which was lower than that (53.9 μg/mL) of the dead mice in the medium dose acetylcholine chloride group, but almost equal to that (42.7 μg/mL) of the survival mice in the medium dose acetylcholine chloride group. Atropine could successfully rescue the mice from acetylcholine poisoning, but its efficiency of rescuing the mice from gelsenicine intoxication was weak. These results suggest that gelsenicine can inhibit acetylcholinesterase activity and increase blood acetylcholine concentration, but the accumulation of acetylcholine may not be the only or main cause of the death induced by gelsenicine in mice.

Clinical observation of the silicone tube implantation under the guidance of memory wire in the treatment of lacrimal canaliculus / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To disscus the clinical effect of the silicone tube implantation under the guidance of memory wire in the treatment of lacrimal canaliculus. METHODS:One hundred and fifteen cases (115 eyes ) of traumatic canalicular laceration were treated by canaliculoplasty from September 2012 to June 2014. Finding the end of lacrimal canaliculus under microscope, guided by memory wire which was probed in lacrimal passage to the nasal cavity, intubating double-passage silicone tube as a support and end-to-end anastomosis. The condition of epiphora and irrigation of lacrimal passage were observed after extubation. RESULTS: All 115 cases were experienced successful operation. All patients were followed up for 6mo ~ 1a (mean 9. 3mo) after extubation. Lacrimal passage was unobstructed in 96 cases 96 eyes(83. 5%), stricture in 13 cases 13 eyes (11. 3%), and blocked in 6 cases 6 eyes (5. 2%). CONCLUSION:Double-passage silicone tube guided by memory wire may be an optional technique in the treatment of traumatic lacrimal duct laceration, which is a feasible, minimally - invasive, safe and effective method.

An abnormal deeper lateral femoral notch is an indirect evidence for anterior cruciate ligament tear / 中国骨伤

<p><b>OBJECTIVE</b>To investigate the relationship between degree of abnormal deeper lateral femoral notch between anterior cruciate ligament tear.</p><p><b>METHODS</b>The radiograph and MRI image material of 16 patients with anterior cruciate ligament injury from January 2013 to November 2013 were reviewed including 14 males and 2 females with an average age of 28.3 years old ranging from 18 to 52 years. Eleven cases was on right side and 5 on left. Survey tool of PASC imaging system was used to measure the depth of lateral femoral notch in patients with abnormal indicated by lateral X-ray view or sagittal view of MRI in knee joint,while clinical data,physical examination,image material in arthroscopy of these patients were retrospective researched.</p><p><b>RESULTS</b>Four patients had an abnormal lateral femoral notch with the depth of 2 mm on lateral X-ray and sagittal MRI, while positive anterior drawer sign and Lachman test as well as anterior cruciate ligament tears on MRI, and completed tears were comfirmed on the operation of arthroscopy. Two patients without abnomal lateral femoral notch on lateral view of X-ray while with the depth of 1 mm on sagittal view of MRI were also coupled with positive anterior drawer sign and Lachman test as well as anterior cruciate ligament tears on MRI, and one of them were comfirmed completed anterior cruciate ligament tears on the arthroscopy operation and completed tear could not comfirmed on another one because of disagreed with arthroscopy operation.</p><p><b>CONCLUSION</b>There appears to be an association between abnormal lateral femoral notch on lateral view of knee with anterior cruciate ligament tears. An abnormal deeper lateral femoral notch is an indirect evidence for anterior cruciate ligament tears.</p>

Astragalus Polysaccharide Suppresses the Expression of Adhesion Molecules through the Regulation of the p38 MAPK Signaling Pathway in Human Cardiac Microvascular Endothelial Cells after Ischemia-Reperfusion Injury.

Astragalus polysaccharide is a major component of radix astragali, a vital qi-reinforcing herb medicine with favorable immune-regulating effects. In a previous animal experiment, we demonstrated that astragalus polysaccharide effectively alleviates ischemia-reperfusion injury (IRI) of cardiac muscle through the regulation of the inflammatory reactions. However, the relationship between this herb and the cohesion molecules on the cell surface remains controversial. In this study, human cardiac microvascular endothelial cells (HCMECs) were used to validate the protective effects of astragalus under an IRI scheme simulated through hypoxia/reoxygenation in vitro. The results indicated that astragalus polysaccharide inhibited the cohesion between HCMECs and polymorphonuclear leukocyte (PMN) during IRI through the downregulation of p38 MAPK signaling and the reduction of cohesive molecule expression in HCMECs.

Ursolic acid activates chloride channels and decreases cell volume in poorly differentiated nasopharyngeal carcinoma cells / 生理学报

The present study aimed to investigate the effects of ursolic acid on the chloride channels and cell volume in nasopharyngeal carcinoma cells (CNE-2Z). The whole-cell patch clamp technique was used to detect the current, and cell imaging technique was applied to measure cell volume. The properties of the currents induced by ursolic acid were investigated by changing the extracellular osmotic pressure, replacing the extracellular anions and applying chloride channel blockers. The results showed that, under isotonic conditions, the background current was weak and stable. When perfusing the cells with ursolic acid (100 nmol/L), a large current (-59.86 pA/pF ± 4.86 pA/pF at -80 mV, 78.92 pA/pF ± 6.39 pA/pF at +80 mV) was induced. The chloride current showed outward rectification and negligible time- and voltage-dependent inactivation. The reversal potential (-4.83 mV ± 0.30 mV) of the current was close to the calculated equilibrium potential for Cl⁻ (-0.9 mV). The permeabilities of the channel to different anions were ranked in order as follows: Cl⁻ = I⁻ > Br⁻ > gluconate. Hypertonic solutions inhibited the current induced by ursolic acid. The chloride channel blockers, tamoxifen (20 μmol/L) and 5-nitro-2-(3-phenylpro-pylamino) benzoic acid (NPPB, 100 μmol/L), suppressed the current. Furthermore, ursolic acid decreased the cell volume by (11.78 ± 1.20)% in 1 h, and the effect was inhibited by NPPB. These results suggest that ursolic acid can activate chloride channels, resulting in outflow of Cl⁻ and decrease of cell volume in nasopharyngeal carcinoma cells.

ClC-3 siRNA inhibits regulatory volume decrease in nasopharyngeal carcinoma cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the role of ClC-3 chloride channels in regulatory volume decrease (RVD) of nasopharyngeal carcinoma (NPC) CNE-2Z cells.?</p><p><b>METHODS</b>ClC-3 siRNA was transfected into CNE-2Z cells in the presence of the transfection reagent HiPerFect Reagent(TM). The transfection efficiency of ClC-3 siRNA was detected by flow cytometry. The expression of ClC-3 protein was detected by Western blotting, and the changes of cell volume in 160 mOsmol/L hypotonic solution were determined by image analysis.</p><p><b>RESULTS</b>The transfection efficiency of ClC-3 siRNA was (63.8∓3.8)% (n=3, P<0.01), and compared with the control group, ClC-3 siRNA transfection resulted in a reduction of ClC-3 expression by (60.9∓4.0)% (n=3, P<0.01). The hypotonic challege (160 mOsmol/L) caused cell swelling and induced RVD. In the control group, hypotonic solution bath for 35 min resulted in a RVD of (42.6∓2.8)% (n=20), which was significantly decreased to (10.5∓4.8)% (n=16) in ClC-3 siRNA-transfected cells, demonstrating a reduction of RVD capacity by 75.4% (P<0.01).?</p><p><b>CONCLUSION</b>The capacity of RVD is significantly reduced in CNE-2Z cells by ClC-3 chloride channel protein knock-down via ClC-3 siRNA transfection, indicating an important role of ClC-3 chloride channels in the RVD of CNE-2Z cells.</p>

Role of chloride channels in gambogic acid-induced apoptosis of poorly differentiated nasopharyngeal carcinoma cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the role of chloride channels in the apoptosis of poorly differentiated nasopharyngeal carcinoma CNE-2Z cells induced by gambogic acid (GA).</p><p><b>METHODS</b>MTT assay was applied to detect the proliferation of CNE-2Z cells after GA treatment, and the cell apoptosis was detected by Hoechst 33342 staining. Whole-cell patch clamp technique was employed to record GA-activated Cl(-) currents in the cells.</p><p><b>RESULTS</b>GA inhibited the cell proliferation in a time- and concentration-dependent manner with an IC(50) of 3.1 µmol/L for a 48-h treatment. The apoptosis-inducing effect of 8 µmol/L GA was attenuated by the chloride channel blocker NPPB (100 µmol/L) and tamoxifen (20 µmol/L). GA induced an outward-rectified Cl(-) current in the cells, which was significantly inhibited by NPPB.</p><p><b>CONCLUSION</b>GA suppresses cell proliferation and induces apoptosis by activating Cl(-) channels in CNE-2Z cells, suggesting the important role of Cl(-) channels in GA-induced apoptosis.</p>

Feasibility and acute toxicity of 3-dimensional conformal external-beam accelerated partial-breast irradiation for early-stage breast cancer after breast-conserving surgery in Chinese female patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>A growing number of studies worldwide have advocated the replacement of whole-breast irradiation with accelerated partial breast irradiation using three-dimensional conformal external-beam radiation (APBI-3DCRT) for early-stage breast cancer. But APBI can be only used in selected population of patients with early-staged breast cancer. It is not replacing the whole breast radiotherapy. This study aimed to examine the feasibility and acute normal tissue toxicity of the APBI-3DCRT technique in Chinese female patients who generally have smaller breasts compared to their Western counterparts.</p><p><b>METHODS</b>From May 2006 to December 2009, a total of 48 Chinese female patients (with early-stage breast cancer who met the inclusion criteria) received APBI-3DCRT after breast-conserving surgery at Sun Yat-sen University Cancer Center. The total dosage from APBI-3DCRT was 34 Gy, delivered in 3.4 Gy per fractions, twice per day at intervals of at least six hours. The radiation dose, volume of the target area and volume of irradiated normal tissues were calculated. Acute toxicity was evaluated according to the Common Toxicity Criteria (CTC) 3.0.</p><p><b>RESULTS</b>Among the 48 patients, the planning target volume for evaluation (PTVE) was (90.42 ± 9.26) cm³, the ipsilateral breast volume (IBV) was (421.74 ± 28.53) cm³, and the ratio between the two was (20.74 ± 5.86)%. Evaluation of the dosimetric characteristics of the PTVE revealed excellent dosimetric results in 14 patients and acceptable results in 34 patients. The dose delivered to the PTVE ranged from 93% to 110% of the prescribed dose. The average ratio of the volume of PTVE receiving 95% of the prescription dose (V95) was (99.26 ± 0.37)%. The habituation index (HI) and the conformity index (CI) were 1.08 ± 0.01 and 0.72 ± 0.02, respectively, suggesting good homogeneity and conformity of the dose delivered to the target field. The radiation dose to normal tissues and organs was within the dose limitation. Subjects experienced mild acute toxicity. The main manifestations were breast edema in 22 patients, breast pain in 7, skin erythema in 25, general malaise in 22 and cytopenia in 8. No acute radiological cardiac or pulmonary injury was found.</p><p><b>CONCLUSIONS</b>The results of our short-term follow-up showed that it is feasible to perform APBI-3DCRT for early-stage breast cancer after breast-conserving surgery in Chinese female patients with smaller breasts. However, further studies are required to elucidate its efficacy and long-term side effects.</p>