Lung cancer still ranks first among malignant tumors in the world and China. Although surgery， radiotherapy， chemotherapy， and other treatments can delay patients' lives， thorny problems remain to be solved， such as adverse reactions after intervention， patient resistance to treatment， and the economic burden of treatment. Traditional Chinese medicine （TCM） featuring a holistic view advocates macro interventions throughout the entire disease cycle， which has the advantages of reducing toxicity， improving efficiency， and enhancing patients' quality of life. The theory of ''sensation and response'' was first recorded in the book of I-Ching. This is the natural law of mutual induction， influence， and interaction among all things in nature. According to the theory of ''Qi monism'' and the proposal of regulating Qi movement and removing toxin by Professor Hua Baojin， we re-examine lung cancer from the primitive thinking in TCM and explain the relevance of Qi movement changes to the occurrence， progression， and treatment of lung cancer. The core pathogeneses of lung cancer are the deficiency of healthy Qi and invasion of deficiency pathogen resulting in the formation of cancer and the internal generation of cancer toxin leading to intermediate dysfunction. Six excesses and Yin pathogen invade and gradually accumulate in the lung and spleen， leading to the generation of cancer toxin， which eventually evolve into lung cancer. The treatment can be based on the theories of five elements and visceral manifestation from three aspects. First， on the basis of syndrome differentiation， medicinal materials of different flavors can be used. Specifically， pungent medicinal materials can be used for dredging and sweet medicinal materials can be used for tonifying. Second， medicinal materials with similar morphology or origin to that in the human body can be used for treating the diseases in corresponding sites. Finally， corrigent medicinal materials can be combined for two-way regulation. These measures can be applied in lung cancer treatment to optimize the prevention and treatment strategies and provide new research directions for TCM diagnosis and treatment of tumors.

Despite exciting achievements with some malignancies, immunotherapy for hypoimmunogenic cancers, especially glioblastoma (GBM), remains a formidable clinical challenge. Poor immunogenicity and deficient immune infiltrates are two major limitations to an effective cancer-specific immune response. Herein, we propose that an injectable signal-amplifying nanocomposite/hydrogel system consisting of granulocyte-macrophage colony-stimulating factor and imiquimod-loaded antigen-capturing nanoparticles can simultaneously amplify the chemotactic signal of antigen-presenting cells and the "danger" signal of GBM. We demonstrated the feasibility of this strategy in two scenarios of GBM. In the first scenario, we showed that this simultaneous amplification system, in conjunction with local chemotherapy, enhanced both the immunogenicity and immune infiltrates in a recurrent GBM model; thus, ultimately making a cold GBM hot and suppressing postoperative relapse. Encouraged by excellent efficacy, we further exploited this signal-amplifying system to improve the efficiency of vaccine lysate in the treatment of refractory multiple GBM, a disease with limited clinical treatment options. In general, this biomaterial-based immune signal amplification system represents a unique approach to restore GBM-specific immunity and may provide a beneficial preliminary treatment for other clinically refractory malignancies.

Objective To evaluate the effect of laparotomy on cognitive function in rats with trau-matic brain injury and the relationship with calcium overload. Methods One hundred and fifty healthy male Wistar rats,aged 2~3 months,weighing 190~220 g,were assigned into 5 group ( n=30 each) using a ran-dom number table:blank group(group B),surgery group of blank rats(group BS),surgery group of sham rats (group SS),traumatic brain injury rats group( group T),surgery group of traumatic brain injury rats(group TS). TBI model was made in rats of group T and TS by Feeney method. Rats in group SS were only treated with cranial bone window without crainocerebral impact. Both group B and BS were normal rats. Then the rats in group BS,SS and TS group underwent laparotomy under sevoflurane anesthesia (the operation time was a-bout 3 hours) and the rats in group B and T inhaled pure oxygen for 3 hours after 20 days. One day before surgery,3 and 7 d after surgery,10 rats in each group were randomly selected for Morris water maze test. The hippocampus tissue of 10 rats were taken after the water maze test. The apoptosis rate and calcium concen-tration of hippocampal neurons were measured by flow cytometry,and the expression level of cleaved caspase-3 in hippocampal tissues was determined by Western blot. Results One day before surgery,compared with group B(the escape latency(9. 8±0. 8)s,the number of crossing platform (5. 8±0. 8),the apoptosis rate of hippocampal neurons ( 2. 5 ± 0. 9)%, calcium ion concentration ( 2. 3 ± 0. 2),the expression of cleaved caspase-3 (0. 22±0. 07) ),the escape latency of group T and group TS were prolonged (group T:(25. 5± 0. 7)s,P<0. 05;group TS:(25. 1±1. 1) s,P<0. 05),the number of crossing platform decreased (group T:(2. 7±0. 8),P<0. 05;group TS:(2. 8±0. 6),P<0. 05),the apoptosis rate of hippocampal neurons increased (group T:(5. 3±0. 6)%,P<0. 05;group TS:(5. 2±1. 0)%,P<0. 05),calcium ion concentration increased (group T:(3. 7±0. 4),P<0. 05;group TS:(3. 6±0. 5),P<0. 05) and the expression of cleaved caspase-3 increased (group T:(0. 45±0. 07),P<0. 05;group TS:(0. 44±0. 05),P<0. 05),the differences were statis-tically significant. Compared with the group SS,the escape latency ( 3 d after surgery:group SS:( 23. 8 ± 1. 3)s,group TS:(56. 4±2. 5)s,P<0. 05;7 d after surgery:group SS:(16. 6±1. 8)s,group TS:(38. 1±2. 1) s,P<0. 05)of the rats in group TS were prolonged,the number of crossing platform decreased (3 d after sur-gery:group SS:(2. 9±0. 6) ,group TS:(1. 1±1. 1) ,P<0. 05;7 d after surgery:group SS:( 4. 2± 1. 2) , group TS:(1. 7±1. 3),P<0. 05),the apoptosis rate of hippocampal neurons ( 3 d after surgery:group SS:(4. 8±0. 6)%,group TS:(14. 4± 0. 6)%,P<0. 05;7 d after surgery:group SS:(3. 8± 1. 1)%,group TS:(9. 6±1. 3)%,P<0. 05),calcium ion concentration ( 3 d after surgery:group SS:(3. 1± 0. 3),group TS:(6. 4±0. 5),P<0. 05;7 d after surgery:group SS:( 2. 6± 0. 3),group TS:( 4. 8± 0. 4),P<0. 05) ,the ex-pression of cleaved caspase-3 (3 d after surgery:group SS:( 0. 42± 0. 03),group TS:( 0. 88 ± 0. 08),P<0. 05;7 d after surgery:group SS:(0. 33±0. 05),group TS:(0. 63±0. 06),P<0. 05) in the hippocampus in-creased after surgery (P<0. 05). Compared with the T group,the escape latency (3 d after surgery:group T:( 18. 6±2. 0)s,group TS:(56. 4±2. 5)s,P<0. 05;7 d after surgery:group T:(13. 8±2. 6)s,group TS:(38. 1 ±2. 1)s,P<0. 05) of the rats in group TS were prolonged,the number of crossing platform (3 d after surger-y:group T:(3. 4±0. 5),group TS:(1. 1±1. 1),P<0. 05;7 d after surgery:group T:(4. 3±1. 2),group TS:(1. 7±1. 3),P<0. 05) decreased,the apoptosis rate of hippocampal neurons (3 d after surgery:group T:(4. 4±0. 7)%,group TS:( 14. 4 ± 0. 6)%,P<0. 05;7 d after surgery:( 3. 3 ± 1. 3)%,group TS:( 9. 6 ± 1. 3)%,P<0. 05),calcium ion concentration (3 d after surgery:group T:( 3. 4 ± 0. 4),group TS:( 6. 4 ± 0. 5),P<0. 05;7 d after surgery:group T:(3. 0±0. 3),group TS:(4. 8±0. 4),P<0. 05),the expression of cleaved caspase-3 (3 d after surgery:group T:(0. 40±0. 04),group TS:( 0. 88±0. 08),P<0. 05;7 d after surgery:(0. 35±0. 02),group TS:(0. 63±0. 06),P<0. 05) in the hippocampus increased after surgery(P<0. 05). Conclusion Laparotomy can aggravate the cognitive impairment of rats with traumatic brain injury and cause postoperative cognitive impairment,which may be related to the increased degree of calcium over-load and the increased rate of hippocampal neuron apoptosis.

Objective To evaluate the effect of nimodipine pretreatment on postoperative cognitive function in rats with chronic cerebral ischemia.Methods Sixty healthy male Sprague-Dawley rats,aged 3 months,weighing 250-350 g,were divided into 2 groups (n =30 each) using a random number table method:chronic cerebral ischemia operation group (group H) and nimodipine plus chronic cerebral ischemia operation group (group N+H).The chronic cerebral ischemia model was established by permanently ligating bilateral common carotid arteries of chloral hydrate-anesthetized rats.Rats underwent Morris water maze adaptive training for 5 days 2 weeks later.Nimodipine 1 mg/kg was intraperitoneally injected on 1st day after the end of adaptive training in group N+H,while the equal volume of normal saline was given instead in group H,and 30 min later splenectomy was performed under sevoflurane anesthesia in two groups.Ten rats in each group were selected on 1 day before operation and 3 and 7 days after operation and underwent Morris water maze test to assess cognitive function.The rats were then sacrificed,brains were removed,and hippocampal tissues were isolated for determination of apoptosis in hippocampal neurons and intracellular Ca2+concentrations([Ca2+]i) in cytoplasm and expression of Bcl-2 and Bax mRNA (by realtime polymerase chain reaction).The ratio of Bax mRNA to Bcl-2 mRNA was calculated.Results Compared with the baseline at 1 day before operation,the escape latency was significantly prolonged,the frequency of crossing the original platform was decreased,the apoptotic rate and [Ca2+] i were increased,Bcl2 mRNA expression was down-regulated,and Bax mRNA expression was up-regulated,and Bax mRNA/Bcl-2 mRNA ratio was increased at each time point after operation in two groups (P＜0.05).Compared with group H,the escape latency was significantly shortened,the frequency of crossing the original platform was increased,the apoptotic rate and [Ca2+]iwere decreased,Bcl-2 mRNA expression was up-regulated,and Bax mRNA expression was down-regulated,and Bax mRNA/Bcl-2 mRNA ratio was decreased at each time point after operation in group N+ H (P＜ 0.05).Conclusion Nimodipine pretreatment can improve the postoperative cognitive function of rats with chronic cerebral ischemia,and the mechanism may be related to inhibiting calcium overload-induced apoptosis in hippocampal neurons.

Objective To evaluate the effect of nimodipine pretreatment on postoperative cognitive function in diabetic rats. Methods One hundred and eighty healthy male Wistar rats, aged 3-4 months, weighing 260-310 g, were divided into 6 groups ( n=30 each) using a random number table method: op-eration group ( O group) , diabetes mellitus group ( DM group) , diabetic cognitive impairment group ( DCI group) , nimodipine plus operation group ( N+O group) , nimodipine plus diabetes mellitus group ( N+DM group) and nimodipine plus diabetic cognitive impairment group ( N+DCI group) . Diabetes mellitus model was established by intraperitoneal injection of streptozotocin 55 mg∕kg. Nimodipine 1 mg∕kg was intraperito-neally injected at 6 weeks after establishing the model in DCI and N+DCI groups and at 2 weeks after estab-lishing the model in DM and N+DM groups, and laparotomy was performed under sevoflurane anesthesia at 30 min after the end of administration. Morris water maze test was performed at 1 day before operation and 3 and 7 days after operation. Then rats were sacrificed, and hippocampal tissues were taken for determination of the apoptotic rate of neurons, cytoplasmic calcium concentrations ( by flow cytometry) and expression of caspase-3 in hippocampus ( by Western blot) . Results Compared with the baseline at 1 day before opera-tion, the escape latency was significantly prolonged, the number of crossing the original platform was re-duced, the apoptotic rate of hippocampal neurons and cytosolic calcium concentrations were increased, and the expression of caspase-3 was up-regulated at each time point after operation in six groups ( P<0. 05 ) . Compared with group O, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the apoptotic rate of hippocampal neurons and cytosolic calcium concentrations were increased, and the expression of caspase-3 was up-regulated at each time point after operation in DM and DCI groups ( P<0. 05) . The escape latency was significantly shortened, the number of crossing the original platform was increased, the apoptotic rate of hippocampal neurons and cytosolic calcium concentrations were decreased, and the expression of caspase-3 was down-regulated at each time point after operation in group N+DM as compared with group DM and in group N+DCI as compared with group DCI ( P<0. 05) . Conclu-sion Nimodipine pretreatment can improve postoperative cognitive function in diabetic rats, and the mech-anism may be related to inhibiting calcium overload-induced apoptosis in neurons.

Objective To evaluate the effect of sevoflurane anesthesia on cognitive impairment in rats with traumatic brain injury. Methods One hundred and and twenty healthy male Wistar rats, aged 2-3 months, weighing 190-220 g, were assigned into 4 groups ( n=30 each) using a random number table method: control group ( group C) , traumatic brain injury group ( group T) , sevoflurane anesthesia group ( group S) , and traumatic brain injury plus sevoflurane anesthesia group ( group T+S) . A 40 g hammer was freely dropped onto the left parietal bone window from a height of 20 cm to establish the traumatic brain inju-ry model in T and T+S groups. Twelve days later, S and T+S groups inhaled 3％ sevoflurane for 3 h, and C and T groups inhaled pure oxygen for 3 h. On 1 day before anesthesia and 3 and 7 days after anesthesia, 10 rats in each group were randomly selected for performing Morris water maze test. Rats were sacrificed af-ter the end of Morris water maze test, and the hippocampal tissues were obtained for determination of the apoptosis rate of hippocampal neurons, cytoplasmic calcium concentration [Ca2+]i (by flow cytometry), expression of glucose-regulated protein 78 ( GRP78) and CCAAT∕enhancer-binding protein homologous pro-tein ( CHOP ) ( by immunohistochemistry ) , and expression of caspase-3 and caspase-12 ( by Western blot) . Results Compared with group C, the escape latency was significantly prolonged, the number of crossing platform was decreased, the apoptosis rate of hippocampal neurons and [ Ca2+] i were increased, and the expression of caspase-3, caspase-12, GRP78 and CHOP in hippocampal tissues was up-regulated in S, T and T+S groups ( P<0. 05) . Compared with T and S groups, the escape latency was significantly prolonged, the number of crossing platform was decreased, the apoptosis rate of hippocampal neurons and [ Ca2+] i were increased, and the expression of caspase-3, caspase-12, GRP78 and CHOP in hippocampal tissues was up-regulated in group T+S ( P<0. 05 ) . Conclusion Sevoflurane anesthesia can accentuate cognitive impairment in rats with traumatic brain injury, and the mechanism may be related to aggravating the degree of endoplasmic reticulum stress-induced calcium overload and increasing the apoptosis rate of hip-pocampal neurons.

Objective To evaluate the effect of nimodipine pretreatment on postoperative cognitive function in rats with cerebral ischemic stroke.Methods Sixty healthy male Sprague-Dawley rats,aged 3 months,weighing 250-350 g,were divided into 2 groups (n =30 each) using a random number table method:normal saline plus cerebral ischemic stroke group (group Ⅰ) and nimodipine plus cerebral ischemic stroke group (group N+Ⅰ).The cerebral ischemic stroke model was established by thread occlusion in two groups.Three weeks later,nimodipine 1 mg/kg was intraperitoneally injected in group N+Ⅰ,while the equal volume of normal saline was given instead in group Ⅰ,and 30 min later two groups underwent exploratory laparotomy under 1.7％ sevoflurane anesthesia.Eight rats in each group were randomly selected on 1 day before operation and 3 and 7 days after operation,and Morris water maze test was performed to assess cognitive function.The rats were then sacrificed,brains were removed,and hippocampal tissues were isolated for detection of apoptosis in hippocampal neurons,intracellular Ca2+concentration ([Ca2+]i) in cytoplasm and the expression of Bcl-2 and Bax mRNA (by real-time polymerase chain reaction).The ratio of Bax mRNA to Bcl-2 mRNA was calculated.Results Compared with the value at 1 day before operation,the escape latency was significantly prolonged,the frequency of crossing the original platform was decreased,apoptotic rate and [Ca2+] i were increased,Bcl-2 mRNA expression was down-regulated,Bax mRNA expression was up-regulated,and Bax mRNA/Bcl-2 mRNA ratio was increased at each time point after operation in two groups (P＜0.05).Compared with group Ⅰ,the escape latency was significantly shortened,the frequency of crossing the original platform was increased,the apoptotic rate and [Ca2 +]i were decreased,Bcl-2 mRNA expression was up-regulated,Bax mRNA expression was down-regulated,and Bax mRNA/Bcl-2 mRNA ratio was decreased at each time point after operation in group N+Ⅰ (P＜0.05).Conclusion Nimodipine pretreatment can improve the postoperative cognitive function of rats with cerebral ischemic stroke,and the mechanism may be related to inhibiting calcium overload-induced apoptosis in hippocampal neurons.

Objective To evaluate the effect of nimodipine on the activity of calcineurin (CaN) in the hippocampus of aged rats.Methods Sixty healthy male Sprague-Dawley rats,aged 18 months,weighing 550-650 g,were divided into 2 groups (n=30 each) using a random number table:surgery group (group S) and nimodipine group (group N).Nimodipine 1 mg/kg was intraperitoneally injected in group N,while the cqual volume of normal saline was given instead in group S,and 30 min later exploratory laparotomy was performed.Ten rats in each group were randomly selected on 1 day before operation and 3 and 7 days after operation,and Morris water maze test was performed.After the end of Morris water maze test,10 rats were selected and sacrificed,brains were removed,and hippocampi were isolated for detection of apoptosis in hippocampal neurons (by flow cytometry) and expression of CaN,phosphor-BAD (p-BAD) and caspase-3 in hippocampal tissues (by Western blot).Apoptotic rate was calculated.Results Compared with the value at 1 day before operation,the escape latency was significantly prolonged,the frequency of crossing the original platform was decreased,the time of staying at the platform quadrant was shortcned,apoptotic rate was increased,and the expression of CaN,p-BAD and caspase-3 in hippocampal tissues was up-regulated at each time point after operation in group S (P＜0.05).Compared with group S,the escape latency was significantly shortened,the frequency of crossing the original platform was increased,the time of staying at the platform quadrant was prolonged,apoptotic rate was decreased,and the expression of CaN,p-BAD and caspase-3 in hippocampal tissues was down-regulated at each time point after operation in group N (P＜0.05).Conclusion The mechanism by which nimodipine inhibits apoptosis in hippocampal neurons and reduces postoperative cognitive dysfunction may be related to inhibition of CaN activation in aged rats.

Objective To evaluate the effect of nimodipine combined with 7.5％ hypertonic saline (HS) on postoperative cognitive function in aged rats.Methods Ninety-six healthy male Wistar rats,aged 18 months,weighing 450-500 g,were assigned into 4 groups (n=24 each) using a random number table:splenectomy group (group S),nimodipine group (group N),group HS and nimodipine plus HS group (group N+HS).Nimodipine 1 mg/kg was intraperitoneally injected in group N.In group HS,7.5％ HS 4 ml/kg was injected via the caudal vein.The equal volume of normal saline was injected intraperitoneally or via the caudal vein in group S.Splenectomy was performed under sevoflurane anesthesia at 30 min after the end of administration.On 1 day before operation and 3 and 7 days after operation,Morris water maze test was performed,and blood sainples from the caudal vein were simultaneously collected for determination of the concentrations of serum S100β protein and neuron-specific enolase (NSE) by enzyme-linked immunosorbent assay.Results Compared with group S,the frequency of crossing the original platform was significantly increased,the escape latency was shortened,and the concentrations of serum S100β protein and NSE were decreased at each time point after operation in N,HS and N+HS groups (P＜0.05).Compared with group N or group HS,the frequency of crossing the original platform was significantly increased,the escape latency was shortened,and the concentrations of serum S100β protein and NSE were decreased at each time point after operation in group N+HS (P＜0.05).Conclusion Nimodipine combined with 7.5％ HS exerts better efficacy than either alone in improving postoperative cognitive function in aged rats.

Objective To evaluate the effects of nimodipine combined with 7.5％ hypertonic saline (HS) on sevoflurane-induced apoptosis of hippocampal neuron in aged rats.Methods Ninetysix healthy male Wistar rats aged 18 months and weighing 450-500 g were randomly assigned into 4 groups (n=24 each):group C,group N,group HS and group NHS.Group N received intraperitoneal injection of 1 mg/kg nimodipine and intravenous injection of normal saline,group HS received intravenous injection of 4 ml/kg 7.5％ HS and intraperitoneal injection of normal saline,group NHS received intraperitoneal nimodipine and intravenous HS mentioned above and group C received normal saline.Thirty minutes later,4 groups inhaled 3％ sevoflurane for 2 hours.Morris water maze test was performed 1 day before anesthesia and 1,3 and 7 days after anesthesia.Morris water maze test was carried out 1 day before anesthesia and 1 and 7 days after anesthesia,8 rats were sacrificed and brains were removed.Hippocampal tissues were obtained for detection of apoptosis in hippocampal neurons,intracellular [Ca2+]i by flow cytometry and the measurement of Bcl-2 and Bax mRNA expression by RT-PCR.Results Compared with group C,the escape latency,apoptotic rate,[Ca2+]i,Bax mRNA expression and Bax/Bcl-2 ratio were significantly decreased,the frequency of crossing the original platform and Bcl-2 mRNA expression increased in groups N,HS and NHS after anesthesia (P＜0.05).Compared with group NHS,the escape latency,apoptotic rate,[Ca2+]i,Bax mRNA expression and Bax/Bcl-2 ratio were significantly increased,the frequency of crossing the original platform and Bcl-2 mRNA expression were decreased in groups N and HS after anesthesia (P ＜ 0.05).Conclusion Nimodipine combined with 7.5％ HS could reduce apoptosis rate of sevoflurane-induced hippocampal neuron by inhibiting calcium overload in aged rats,and it exerts better protective effects than single drug administration.