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WO2007124653A1 - Procédé et dispositif pour traiter une tumeur par apport de gaz - Google Patents

Procédé et dispositif pour traiter une tumeur par apport de gaz Download PDF

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Publication number
WO2007124653A1
WO2007124653A1 PCT/CN2007/000814 CN2007000814W WO2007124653A1 WO 2007124653 A1 WO2007124653 A1 WO 2007124653A1 CN 2007000814 W CN2007000814 W CN 2007000814W WO 2007124653 A1 WO2007124653 A1 WO 2007124653A1
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WO
WIPO (PCT)
Prior art keywords
gas
tumor
valve
needle
input
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/CN2007/000814
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English (en)
Chinese (zh)
Inventor
Feng Shi
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
NATURE MASTER CO Ltd
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NATURE MASTER CO Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by NATURE MASTER CO Ltd filed Critical NATURE MASTER CO Ltd
Publication of WO2007124653A1 publication Critical patent/WO2007124653A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/14—Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
    • A61M5/142—Pressure infusion, e.g. using pumps
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M2005/006—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests for gases, e.g. CO2
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/14—Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
    • A61M5/1407—Infusion of two or more substances
    • A61M5/1408—Infusion of two or more substances in parallel, e.g. manifolds, sequencing valves

Definitions

  • the present invention relates to a method of treating a tumor, and more particularly to a method of treating a gas at a tumor for treatment. At the same time, the invention also relates to a device for the treatment of tumors by gas input. Background technique
  • Tumors are a serious threat to human health and life. Tumors are also cells of the body. There has been no qualitative difference in the ultrastructure between tumor cells and normal cells, and only the difference in quantity, the difference between the two is only in the degree of differentiation and degree of abnormality. The main difference between tumor cells and normal cells is twofold:
  • tumor cells are distinguished from normal cells and can be summarized as intrinsic naive, heterogeneous and extrinsic invasive. Related to naive and heterogeneity are: low degree of differentiation. It has the characteristics of stem cells and has the potential of infinite proliferation. (The cancer stem cell theory holds that: tumors are derived from stem cells, and tumor stem cells exist in tumors. There are very few tumor cells in tumor tissues, which act as stem cells in tumors, and long-term self-renewal. Exist, even accompanying the whole process of life.). Malignant transformation occurs when a single cell is induced to produce 4-7 mutations.
  • tumor cells are also characterized by poor development, weak repair ability, incomplete blood vessels, and fewer nerve cells and cardiomyocytes than normal cells.
  • the tumor tissue lacks contraction; the tumor tissue responds poorly to vasoactive drugs and external stimuli.
  • Tumor neonatal capillary endothelium is incomplete, or has no endothelial formation.
  • the surface of the vascular endothelium is rough, and the hemodynamics in the tumor area are disordered, which is easy to form irregular eddy currents.
  • the tumor area often lacks normal lymphoid tissue and has a functional cord-like lymphatic vessel.
  • Tumor regions often lack a mononuclear-phagocytic system. Tumor cell mitochondrial variation and mitochondrial enzyme biochemical activity are also defective. Some tumor tissues have hypoxic cells. Some tumor centers are in a low oxygen state and the edges are in a normal oxygen state. Other heterogeneity is also manifested by the fact that tumors are composed of individual tumor cells at different stages of the cell cycle.
  • Tumor cells usually have no envelope, high internal pressure, irregular shape, Multi-angle, irregular microvilli can appear on the cell surface, and tumor cells can produce more laminin receptors. Tumor tissue grows rapidly, metabolic disorders, mainly wasteful metabolism, and consumes a lot of nutrients in the body.
  • Oxygen is the central fulcrum that life processes depend on and is the source of all cell life. For human life, no other substance (including food, drugs) has a greater impact on life than oxygen.
  • hypoxia and hypoxia low oxygen is the state in which the partial pressure of oxygen is lower than the partial pressure of oxygen at atmospheric pressure
  • the adaptive changes of the body and tissues after hypoxia are mainly: increasing angiogenesis, increasing myoglobin content; changing the activity of oxidoreductase in tissues, effectively utilizing available oxygen, and providing more energy to cells; Aerobic metabolism process, saving energy. Even open up another energy channel: sugar anaerobic glycolysis, energy.
  • hypoxic stimulation short-term, mild, repeated hypoxic treatment
  • hypoxic stimulation can trigger the inherent protective ability of the body and tissue, thus providing strong defense and protection against subsequent severe hypoxia injury.
  • Hyperbaric oxygen is the state of oxygen partial pressure above atmospheric pressure at atmospheric pressure. ⁇ Studies have confirmed that: Hyperbaric oxygen does not accelerate tumor growth; Hyperbaric oxygen accelerates wound healing, repairs damaged tissue, and promotes nerve cell regeneration. efficacy. Hyperbaric oxygen can inhibit a variety of metabolic reactions of bacteria, thereby slowing the growth of bacteria and having a bactericidal and bacteriostatic effect. It has been reported that the use of hyperbaric oxygen can suppress Dysplasia, and can cause tumors caused by dysplasia to appear for one month.
  • Tumors are composed of individual tumor cells that are in different phases of the cell cycle. Some of these cells are hypoxic and are not sensitive to radiotherapy; some cells are close to dormant, have low proliferation, and are not sensitive to chemotherapy.
  • the heterogeneity of tumor cells is related to the difference of oxygen and nutrient environment in tumor tissues. Hypoxia and insufficient nutrient supply can promote the evolution of tumor cells with higher malignant phenotype.
  • Traditional intracavitary chemotherapy the drug can only penetrate into the tumor 1-3 mm depth, the treatment effect is not ideal, while radiotherapy and chemotherapy will damage normal cells to varying degrees. Summary of the invention
  • the object of the present invention is to make a cell function adjustment according to the weakness of the tumor, i.e., the childishness, the poor development degree, the weak repair ability, and the inability to respond to environmental changes in time.
  • the tumor blood vessels are incompletely developed and have poor activity.
  • hypoxic cells There are already hypoxic cells in the tumor, and the tumor cells will never adapt to hypoxia after normal cells.
  • the tumor cells can not respond in time. Instead, the lag is delayed for a while before the value begins to increase. Therefore, the present invention utilizes the characteristics and defects of tumor cells, and provides a method for killing tumor cells by gas input to achieve tumor treatment.
  • the technical solution of the present invention is achieved by a method for treating a tumor by introducing a gas into a tumor tissue, and inputting a hypoxic gas into the tumor tissue for hypoxia stimulation and hypoxic treatment.
  • the low-oxygen gas refers to an inert gas such as nitrogen or helium, and a gas such as carbon dioxide, which is collectively referred to as a low-oxygen gas.
  • hyperbaric oxygen is first introduced into the tumor before the input of hypoxic gas, so that it does not immediately cause tumor proliferation and growth (but delays development); the second is to make all the hypoxia and thus close to dormancy.
  • Tumor cells especially a few tumor stem cells, differentiate, mature, and normalize.
  • hypoxic time can be several months or a year.
  • the normal cells around the tumor tissue are fed with sugar, which provides the substances required for normal cell anaerobic glycolysis in hypoxia stimulation.
  • the gas input during the hypoxia input stimulation process is an inert gas such as nitrogen or helium, or carbon dioxide.
  • the input gas is carbon dioxide because carbon dioxide is highly soluble in the blood and is easily transported by the blood. Carbon dioxide has been used as a contrast agent for many years, and there is very little risk of forming a gas plug.
  • the hypoxic state is input into the tumor by an inert gas such as nitrogen or carbon dioxide gas, and the input causes an increase in the partial pressure of the oxygen-free gas (inert gas such as nitrogen or carbon dioxide gas) and a decrease in the partial pressure of oxygen, thereby generating a low oxygen state.
  • an inert gas such as nitrogen or carbon dioxide gas
  • the diffused input gas eventually enters the blood vessels of the body and is released through the lungs. Since the amount of input gas is small, about one milliliter per minute, it has little effect on the blood vessels and lungs of the body. As long as the control input bubble is not too large, the absorption-diffusion of the body is no problem. Since the most need to protect the normal tissue around the tumor is the blood vessels of the body, and the blood is easily taken away by the blood, the degree of hypoxia in this blood vessel is much smaller than other areas, and the blood vessels naturally do not suffer from large damage.
  • the high intratumoral pressure of the tumor tissue means that the dissolved amount of the input gas is large; the tumor has no membrane, multiple mucus, multi-angle, There is microvilli, and the invasiveness of the tumor can only bring it into a state where the input gas concentration is higher. These physical properties cause the tumor to be in a deeper hypoxic state, and the tumor cells have greater damage from hypoxia. Normal cells are relatively small.
  • the gas input point is again at the center of the tumor. 'From the concentration distribution, the concentration at the center of the tumor is also bound to be the highest. Therefore, the concentration of the input gas at the tumor is the largest, and the normal tissue is less, and the important blood vessel is smaller, achieving a better therapeutic effect, and has little effect on the normal tissue.
  • Another object of the present invention is to provide a gas input device for treating tumors, the device comprising a gas delivery portion and a gas input needle, wherein the gas delivery portion is composed of a gas tank, a pressure reducing valve, a pressure gauge, a flow regulating valve, and a flow detecting element
  • the shut-off valve is composed of a pressure tank connected to the gas tank at one end and a flow regulating valve at the other end.
  • a pressure gauge is arranged between the pressure reducing valve and the flow regulating valve, and the lower end of the flow regulating valve is connected to the gas input needle through a hose and a pipe joint.
  • the lower end of the flow regulating valve is connected to the flow detecting element, and the lower end of the flow detecting element is connected to the shut-off valve, and the shut-off valve is connected to the gas input needle through the hose and the pipe joint.
  • the gas tank is a high pressure oxygen tank, an inert gas tank such as nitrogen, a carbon dioxide tank or other required gas tank, including a chemotherapeutic gas tank.
  • the flow regulating valve is an adjustable flow valve, an electronically controlled flow regulating valve or a high speed switching valve.
  • the flow detecting element uses a flow meter or a flow sensor.
  • One gas input section can be connected to one or more gas input needles, and one gas input needle can be simultaneously connected to one or more gas input sections.
  • the gas input needle comprises a base, a needle seat, a shut-off valve, a deflation valve and a needle, wherein the upper part of the needle body seat has an air supply hole, and one side of the needle body seat has a blind hole, and the front part of the blind hole is The air supply hole intersects and passes through the air supply hole.
  • the upper end of the air supply hole is a thread corresponding to the hose and the pipe joint, the lower end of the air supply hole is connected with the needle, and the cut valve is obliquely inserted into the blind hole of the needle body seat.
  • an O-ring is mounted on the circumference of the shut-off valve, and the O-ring is located in the ring groove of the needle seat; the needle seat is snapped into the hollow base.
  • the function of the gas input needle 1. Deflating, that is, releasing the initial air in the hose and the pipe joint member 7 and other gases that cannot be input into the body; 2. Because the shut-off valve can be used during deflation or when the pipe is inserted Cut off the gas input to the needle; 3.
  • the gas input needle can follow the normal and slight activity of the human body without damaging the human tissue and has a long time in the body.
  • the needle inserted into the tumor must not have a displacement that affects the normal input of the gas, nor does it leave the tumor.
  • the needle part can be bent as the body muscles move properly, and the rotation of the cone-like needle
  • the busbar conforms to the mechanical properties of the inserted body tissue, ensuring that the needle bends normally as the muscle moves. If the puncture is not deep, the needle can also be a thin tubular needle.
  • FIG. 1 is a schematic view showing an open loop control and a multi-gas input structure of the present invention
  • FIG. 2 is a schematic diagram showing a partial structure of a closed loop control gas input
  • Figure 3 is a schematic diagram of an open loop control of a gas multi-point input structure
  • Figure 4 is a schematic view showing the structure of a gas input needle
  • FIG. 5 is a schematic view of the structure of the high speed switching valve. detailed description
  • the location, volume, nature, and distance of important organ tissues are determined by tumor imaging diagnosis, ultrasound diagnosis, radionuclide diagnosis, endoscopic diagnosis, and tumor markers and related clinical tests.
  • the puncture position, direction, and length of the puncture needle 10 are determined to determine the puncture procedure.
  • the puncture needle of the gas input needle of the present invention is inserted into the center of the tumor by modern intervention and puncture techniques. It is also possible to insert several gas input needles into one tumor as needed.
  • Hyperbaric oxygen input removes all cells from hypoxia.
  • the short-term, mild, and repeated hypoxic stimulation process is performed immediately before the onset of tumor cell proliferation.
  • a longer hypoxic process of appropriate intensity and time is followed to kill the tumor. cell.
  • the intensity and time of hypoxia are not harmful to normal cells surrounding the tumor tissue, and the tumor cannot die too fast to cause complications such as tumor necrosis, ulceration, bleeding, infection.
  • the gas input can be either an open loop control system or a closed loop control system.
  • Open loop control Firstly set the required gas flow and cumulative flow, and measure the flow rate with the flow meter 5; adjust the adjustable flow valve member 4 to achieve the required gas flow rate; and control the cumulative flow by controlling the input time. the amount.
  • the closed-loop control is more precise and the error can be corrected at any time; and the input program can be programmed to automatically control the entire input process of the gas in a program-controlled manner.
  • the hardware of the closed-loop control system is mainly composed of an electronically controlled flow regulating valve member 42 and a flow sensor member 52 in addition to the gas tank, the pressure reducing valve and the pressure gauge. Adder in Figure 2
  • the electronically controlled flow regulating valve member 42 can also be replaced by a high speed switching valve member 43.
  • the high-speed switching valve is controlled by pulse width modulation instead of linear control.
  • the high-speed on-off valve structure can be a car injector structure, and the materials used meet medical hygienic standards.
  • the gas in the gas tank 1 is depressurized by a conventional pressure reducing valve member 2 as an input gas source; the pressure of the gas after the pressure reduction is detected by the pressure gauge 3.
  • the gas is controlled by the flow of the open or closed loop, and the gas input needle 8 is input through the hose and the pipe joint 7 and injected into the body.
  • the gas input procedure of hyperbaric oxygen and hypoxia stimulation is generally performed, and other various gas input treatments can also be performed. In this process, sometimes it is required The input of a certain gas is temporarily turned off, so the shut-off valve 6 is provided in the apparatus as a shut-off.
  • Figure 3 is a schematic diagram of open loop control, longer time, and a gas double point input. It is the way to enter the gas for a longer period of time. Depending on the need to treat the tumor, one, two or even multiple gas input points for treating the tumor may be selected, and one or more gas input needles 8 may be inserted into the body and simultaneously input. You can also select a variety of gas inputs for a longer period of time (the schematic is omitted). Before the open loop control and the gas input for a long time, the flow rate of the input gas needs to be verified by the flow meter member 5 or the flow sensor member 52, and the input flow rate is calibrated by adjusting the adjustable flow valve member 4.
  • the gas input needle includes a base 15, a needle holder 11, a shutoff valve 12, a deflation valve 13, and a needle 10, wherein the upper portion of the needle base 11 is provided with an air supply hole 16, and one side of the needle body 11 is opened. There is a blind hole 17, and the front portion of the blind hole 17 intersects with the air supply hole 16 and passes through the air supply hole 16.
  • the upper end of the air supply hole 16 is a thread corresponding to the hose and the pipe joint 7, and the lower end of the air supply hole 16 is connected with the needle 10.
  • the shut-off valve 12 is obliquely inserted into the blind hole 17 of the needle body seat 11, the deflation valve 13 is placed in the center hole of the shut-off valve 12, the 0-type seal ring 14 is mounted on the circumference of the shut-off valve 12, and the 0-type seal ring 14 is located at the needle
  • the annular seat of the body seat 11 is inserted into the hollow base 15.
  • the venting opening 18 also aligns the positive air supply opening 16 at this time.
  • the deflation passage is opened, and the released gas passes through the shutoff valve 12 and the bleed valve.
  • the annular gap between the 13 and the venting threads and the slots and thread gaps in the opposing shut-off valve threads release the released gas.
  • the closing of the deflation valve 13 is reversed with respect to the direction of rotation of the deflation; the conical surface on the deflation valve 13 will close the deflation passage.
  • the shutoff valve 12 also closes the air passage of the air supply port 16 by the conical surface thereon.
  • the ⁇ -shaped seal ring 14 on the circumference of the shut-off valve 12 is located in the annular groove of the needle body seat 11, which seals the annular gap between the needle body seat 11 and the shut-off valve 12, ensuring that the gas input needle is closed or open. None of the gases in 8 will leak into the atmosphere.
  • the base 15 is light in weight and large in area, that is, the base 15 can be fixed to the body, and the needle seat 11 can be firmly fixed.
  • the base member 15 has a large area, and the contact surface with the body is customized according to the relative shape of the body.
  • the base 15 can be fixed to the body by medical double-sided tape, medical tape or other methods.
  • the base 15 is tapered at the point of contact with the needle base 11, and with this taper, the needle seat 11 can be easily and reliably fixed to the base 15.
  • a pad 9 is arranged under the needle seat.
  • the pad 9 can be made of a soft material having anti-inflammatory and analgesic effects, that is, it can have an anti-inflammatory and analgesic effect on the needle wound, and can also serve as a cushion for the needle seat 11, and a cushion body. 11 pressure on the body.
  • the length of the needle 10 coincides with the distance from the surface of the skin to the center of the tumor.
  • the upper part of the needle holder 11 has threads connected to the hose and the pipe joint member 7. The thread can also be used to secure a catheter that is required to pass through.
  • the needle 10 has a through hole as a gas or liquid input hole, and can also be inserted into the guide wire as an interventional catheter to facilitate the puncture operation.
  • the axis of the center hole of the shutoff valve 12 is not perpendicularly intersected with the axis of the air supply port 16, and the angle of intersection is about 75 degrees. This has the advantage that it is easy to open and close the shutoff valve 12 and the purge valve 13 during use.
  • the needle 10 can be firmly integrated with the needle base 11 by a silver-based brazing, high-strength adhesive bonding or laser welding process. Industrial applicability
  • the input gas is mostly non-toxic gas that has no direct damage to the body.
  • Oxygen, nitrogen and carbon dioxide are gases that have already circulated in the cells.
  • the gas itself is not toxic and does not cause damage to the body's breathing, digestion, liver or kidney organs;
  • the gas molecule is small (molecular weight), it is easy to spread in the body, through the blood, lungs Out of the body. If you want to expel faster, you can choose a lower molecular weight inert gas such as helium (also used in deep sea diving).
  • helium also used in deep sea diving.
  • the molecular weight of the chemotherapeutic liquid is large, stagnation, and it needs to be metabolized by the liver and kidney, which is very toxic to the body.

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  • Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Engineering & Computer Science (AREA)
  • Anesthesiology (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Vascular Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Infusion, Injection, And Reservoir Apparatuses (AREA)

Abstract

La présente invention concerne un dispositif pour traiter une tumeur par apport de gaz. Ce dispositif comporte un module d'alimentation en gaz et une aiguille d'injection de gaz (8). Le module d'alimentation en gaz se compose de réservoirs de gaz (1), de détendeurs (2), de manomètres (3), de vannes de régulation (4), de détecteurs de débit (5) et de vannes d'arrêt (6). Chaque détendeur (2) est relié par l'une de ses extrémités aux réservoirs de gaz (1), l'autre extrémité étant reliée aux vannes de régulation (4). Chaque manomètre (3) est monté entre l'un des détenteurs (2) et l'une des vannes de régulation (4). Les extrémités inférieures des vannes régulatrices (4) sont reliées aux aiguilles d'injection de gaz (8) via des flexibles et des raccords (7).
PCT/CN2007/000814 2006-04-29 2007-03-14 Procédé et dispositif pour traiter une tumeur par apport de gaz Ceased WO2007124653A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN200610078649.0 2006-04-29
CN2006100786490A CN1981882B (zh) 2006-04-29 2006-04-29 一种气体输入治疗肿瘤的设备

Publications (1)

Publication Number Publication Date
WO2007124653A1 true WO2007124653A1 (fr) 2007-11-08

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Application Number Title Priority Date Filing Date
PCT/CN2007/000814 Ceased WO2007124653A1 (fr) 2006-04-29 2007-03-14 Procédé et dispositif pour traiter une tumeur par apport de gaz

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CN (1) CN1981882B (fr)
WO (1) WO2007124653A1 (fr)

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1218697A (zh) * 1997-12-05 1999-06-09 李灵山 中药离子高温导入肿瘤治疗仪
CN1537646A (zh) * 2003-10-22 2004-10-20 高春平 肿瘤局部综合治疗方法和装置
WO2004093945A1 (fr) * 2003-04-22 2004-11-04 Antisense Pharma Gmbh Materiel portatif pour l'administration de fluides dans des tissus et des tumeurs par la technique d'administration activee par convection

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1541628A (zh) * 2003-04-29 2004-11-03 陈绍勇 高恒温高压氧床微波癌症热预防与热治疗设备

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1218697A (zh) * 1997-12-05 1999-06-09 李灵山 中药离子高温导入肿瘤治疗仪
WO2004093945A1 (fr) * 2003-04-22 2004-11-04 Antisense Pharma Gmbh Materiel portatif pour l'administration de fluides dans des tissus et des tumeurs par la technique d'administration activee par convection
CN1537646A (zh) * 2003-10-22 2004-10-20 高春平 肿瘤局部综合治疗方法和装置

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CN1981882A (zh) 2007-06-20
CN1981882B (zh) 2011-02-16

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