Lung cancer is characterized by high incidence and mortality rates and invasiveness, and its occurrence and development are influenced by various factors. Mitochondria, as ubiquitous organelles in the human body, regulate cellular processes, such as metabolism, signal transduction, oxidative stress, and genomic instability, thereby affecting the initiation and progression of lung cancer. This article summarizes the recent research progress on mitochondrial-targeted drugs, mitochondrial transfer, and mitochondrial gene therapy for lung cancer treatment. This work also discusses the principles and prospects of mitochondrial therapy to provide new insights for lung cancer treatment.

Background and objective Both of lung cancer incidence and mortality rank first among all cancers in China.Previous lung cancer screening trials were mostly selective screening for high-risk groups such as smokers.Non-smoking women accounted for a considerable proportion of lung cancer cases in Asia.This study aimed to evaluate the outcome of community-based mass screening in Guangzhou and identify the high-risk factors for lung cancer.Methods Residents aged 40-74 years in Guangzhou were screened with low-dose computed tomography(LDCT)for lung cancer and the pulmonary nodules were classified and managed according to China National Lung Cancer Screening Guideline with Low-dose Computed Tomography(2018 version).The detection rate of positive nodules was calculated.Before the LDCT examination,residents were required to complete a"lung cancer risk factors questionnaire".The risk factors of the questionnaire were analyzed by least absolute shrinkage and selection operator(LASSO)penalized Logistic regression analysis.Results A total of 6256 residents were included in this study.1228 positive nodules(19.63％)and 117 lung cancers were confirmed,including 6 cases of Tis,103 cases of stage Ⅰ(accounting for 88.03％of lung cancer).The results of LASSO penalized Logistic regression analysis indicated that age ≥50 yr(OR=1.07,95％CI:1.06-1.07),history of cancer(OR=3.29,95％CI:3.22-3.37),textile industry(OR=1.10,95％CI:1.08-1.13),use coal for cooking in childhood(OR=1.14,95％CI:1.13-1.16)and food al-lergy(OR=1.10,95％CI:1.07-1.13)were risk factors of lung cancer for female in this district.Conclusion This study highlighted that numerous early stages of lung cancer cases were detected by LDCT,which could be applied to screen-ing of lung cancer in women.Besides,age ≥50 yr,personal history of cancer,textile industry and use coal for cooking in childhood are risk factors for women in this district,which suggested that it's high time to raise the awareness of early lung cancer screening in this group.

Humans ; Neoplasms, Second Primary/epidemiology* ; Neoplasms/epidemiology* ; Risk Factors ; Prognosis

New drug clinical trials have been considered as a positive way for treating cancer by cancer patients and doctors, and the extended dosing is a special way for patients' withdrawal from antitumor clinical trials to obtain investigational new drugs. However, neither the regulations of expanded dosing nor the detail documents for expanded dosing have been officially published in China. At present, expanded dosing of investigational drugs is still at the exploratory stage in various medical institutions, and a complete management system has not been established to meet patients' urgent needs for drug use. Based on the practical experience of extended dosing in Hunan Cancer Hospital, this paper preliminarily explored the application procedures and ethical review requirements of extended dosing for subjects in antitumor clinical trials. It is necessary to clarify the responsibilities of all patients in the procedure and establish a patient-medical institution-sponsor joint application system. In the process of ethical review, it is recommended that all parties fully consider the risks and benefits of extended dosing for patients, and then the ethics committee makes a comprehensive assessment to decide whether to approve extended dosing.
Humans ; China ; Physicians ; Antineoplastic Agents/therapeutic use*

Objective To evaluate the analgesic effect of tetrodotoxin (TTX) in four types of acute pain models and provide experimental support for its rational application. Methods Mice or rats were intramuscularly pretreated with morphine (1 mg/kg) or TTX (0, 0.5, 1, 2, 4 and 8 μg/kg) 40 min before acetic acid writhing test, formalin stimulation test, hot plate test or tail flick test. Pain response or pain threshold were recorded, and inhibition rate was calculated during the tests. The arachidonic acid of serum was determined by Elisa. Results Significant analgesic effects were observed with morphine in all four acute pain models. TTX dose-dependently reduced the number of writhing induced by acetic acid and inhibited the pain response induced by formalin during phase I and phase II, with the highest inhibition rate of more than 80.00% in two pain models. TTX showed analgesic effect in tail flick test and hot plate test, with the highest inhibition rate of 25.00% and 19.79%, respectively. Both acetic acid and formalin increased arachidonic acid in animal serum, but TTX had no significant inhibitory effect on the releasing of arachidonic acid. Conclusion TTX showed significant analgesic effect in the chemical stimulation pain models induced by acetic acid and formalin, but limited analgesic effect was observed on the physical stimulation pain model induced by heat (hot plate and hot water). TTX may produce analgesic effect by blocking the inflammatory mediators mediating pain response.

Epilepsy is a recurrent neurological disease with synchronous abnormal high discharge of neurons in the brain. The pathogenesis of this disease is extremely complex， which is closely related to neurotransmitter regulation， oxidative stress response， inflammatory factors， neuroglial cell， and abnormal gene expression. Western medicine mainly uses phenobarbital， phenytoin sodium， carbamazepine， and other drugs， but long-term use also produces certain toxic and side effects. Traditional Chinese medicine （TCM） believes that the pathogenesis of epilepsy is related to wind， fire， phlegm， and blood stasis， which leads to dysfunction of viscera， disorder of Qi movement， and finally uncontrolled spirit. In recent years， TCM has achieved certain curative effects on the treatment of epilepsy. As a high-frequency antiepileptic drug， Acori Tatarinowii Rhizoma has the effects of opening orifices and eliminating phlegm， awakening spirit and benefiting intelligence， and removing dampness and opening stomach， which has been widely used in clinic. In this paper， the pathogenesis of epilepsy and the pharmacological mechanism of Acori Tatarinowii Rhizoma extract and chemical components in the treatment of epilepsy were expounded by referring to relevant pharmacological studies and animal experiments. It was found that Acori Tatarinowii Rhizoma played a role in regulating the neurotransmitter level， antioxidant stress response， scavenging oxygen free radicals， regulating the expression of c-fos gene， reducing the level of inflammatory mediators， resisting neuronal apoptosis， and regulating the neuroglial cells and the permeability of blood-brain barrier. This paper summarizes the positive effects of Acori Tatarinowii Rhizoma on the treatment of epilepsy， and provides a scientific basis for the popularization and application of Acori Tatarinowii Rhizoma in the prevention and treatment of epilepsy.

Objective:To investigate the expression level of Ki-67 in the bone marrow biopsy of newly diagnosed MM patients, and its relationship with clinical efficacy and prognosis.Methods:Bone marrow pathological samples of 124 newly diagnosed MM patients in Jiangsu Province Hospital from January 2012 to June 2017 were collected. The expression level of Ki-67 in myeloma cells was detected by using immunohistochemistry. X-tile software was applied to find a cutoff of Ki-67. The patients were divided into the high Ki-67 expression group and the low Ki-67 expression group, and the clinical characteristics, therapeutic efficacy and survival of both groups were compared. Chi-square test or Fisher's exact test was used to analyze the counting data. Kaplan-Meier method was applied to make survival anlaysis. Cox regression model was used for univariate prognostic analysis and multivariate prognostic analysis.Results:A total of 124 newly diagnosed MM patients were enrolled with median follow-up of 36 months. The proportion of the positive myeloma cells in abnormal plasmocytes was used to quantize the expression level of Ki-67. Using a cutoff of 20%, these cases could be divided into two groups; the proportion of positive cells was lower than 20% (the low Ki-67 expression group) and the proportion of positive cells was 20% or above (the high Ki-67 expression group). There were 27 cases (21.7%) in the high expression group and 97 cases (78.2%) in the low expression group. There were no statistically significant differences in the clinical characteristics and treatment regimens (all P > 0.05). The overall remission rate (ORR) of patients in the high Ki-67 expression group was lower than that of patients in the low Ki-67 expression group [59.3% (16/27) vs. 83.5% (81/97)], and the difference was statistically significant (χ 2 = 7.290, P = 0.007). The percentage of patients who achieved very good partial remission (VGPR) and complete remission in the high Ki-67 expression group was lower than that of those in the low Ki-67 expression group [33.3% (9/27) vs. 66.0% (64/97)], and the difference was statistically significant (χ 2 = 9.297, P = 0.002). There were statistically significant differences in the median progression free survival (PFS) time (12.0 months vs. 31.0 months, P < 0.01) and 3-year PFS rate (10% vs. 37%, P = 0.002). The median overall survival (OS) time was 39.0 months and 56.5 months in the high and low Ki-67 expression groups, respectively ( P = 0.003). The multivariate analysis showed that high Ki-67 expression was an independent affecting factor for PFS ( HR = 3.592, 95% CI 1.921-6.719, P < 0.01) and OS ( HR = 3.511, 95% CI 1.537-8.022, P = 0.003). Conclusions:High expression of Ki-67 is an independent poor prognostic factor affecting therapeutic effect and survival for newly diagnosed MM patients.

Objective To explore the feasibility of serum Klotho level in the elderly donors to predict the renal graft function in the recipients. Methods Clinical data of 16 elderly donors and 27 recipients undergoing renal transplantation were collected. The general status of the recipients was observed. The levels of serum Klotho and serum creatinine (Scr) in the elderly donors were measured on the day of renal transplantation. The Scr levels in the recipients were measured at postoperative 1, 3 and 12 months respectively. The estimated glomerular filtration rate (eGFR) was calculated. The correlation between the serum Klotho level of the donors and postoperative graft function of the recipients was analyzed. Results The cold ischemia time during renal transplantation was (649±245) min. The incidence rate of delayed graft function (DGF) was 26%. The incidence rate of acute rejection was 7%. In the elderly donors, the serum Klotho level was 537 (245-793) pg/mL and the Scr level was (164±62) μmol/L. At postoperative 1, 3 and 12 months, the Scr levels in the recipients were (136±47), (132±43) and (133±46) μmol/L, respectively. The corresponding eGFR was (52±20), (52±19) and (53±21) mL/(min?1.73m²), respectively. The serum Klotho level in the elderly donors was negatively correlated with the renal graft function at postoperative 1 month in the recipients (P < 0.05). The sensitivity and specificity of serum Klotho level in predicting the renal graft insufficiency at postoperative 1 month were 0.909 and 0.769. Conclusions The preoperative serum Klotho level in the elderly donors have predictive value for renal graft function in the recipients at postoperative 1 month.

Objective To examine the feasibility and early effects of unilateral pedicle screw fixation in combination with contralateral translaminar facet screw fixation plus interbody fusion through the channel-assisted muscle-splitting approach for the treatment of degenerative lumbar spine diseases in elderly patients.Methods A total of 82 elderly patients with degenerative lumbar spine diseases received treatment between January 2015 and June 2016.Of these patients,25 had lumbar spinal stenosis,42 had degenerative lumbar instability,13 had giant lumbar disc herniation,and two had recurrent lumbar disc herniation;There were 69 cases of single segment and 13 cases of double segment lesions.Perioperative evaluation,imaging evaluation,and clinical evaluation were performed,and surgical complications were analyzed.Results The average length of incision was (2.6 ± 0.4) cm in cases of single segment lesions and (4.4±0.5) cm in cases of two segment lesions.The mean operation time was (98.3±19.6) minutes and peri-operation blood loss was (232.2±25.8) ml.The post-operation height of the intervertebral disc space significantly increased at the last follow-up(P ＜ 0.05);the height of the intervertebral disc space was restored and well maintained with internal fixation showing no loosening,breakage or Cage shift.The post-operation lumbar coronal Cobb angle decreased(P＜0.05)while the sagittal Cobb angle increased(P＜0.05)at the last follow-up.There was no significant difference in the area and grade of the multifidus muscle on MRI 12 months after operation.Seventy-two patients were followed up for 12-18 months (mean =16.8 months),and there were 67 cases of intervertebral fusion (93.1％).The last follow-up showed a Japanese Orthopaedic Association(JOA) score of (25.8 ± 1.7),which was significantly higher than the pre-operation score (10.6±1.3),with an excellence rate of 88.9 ％.The Oswestry Disability Index score was significantly reduced,from (50.9±21.6) at pre-operation to (9.6± 4.8) at the last follow-up.There were 78 patients with primary wound healing,three cases of superficial wound necrosis,one case of dural tear,and one case of nerve root injury.No cardiovascular or cerebrovascular incident was observed during or after operation.Conclusions Combined pedicle/facet screw fixation plus interbody fusion through the channel-assisted muscle-splitting approach shows satisfactory short-term effects when used for the treatment of degenerative lumbar spine diseases in the elderly and possesses advantages such as minimal invasiveness,limited bleeding,quick recovery,high fusion rates and significantly improved clinical outcomes.However,further clinical studies are required to assess its medium-and long-term efficacy.

Objective To analyze the causes of death in patients with ST-segment elevation myocardial infarction (STEMI) following primary percutaneous coronary intervention (PCI).Methods The clinical data of 1 213 patients [845 males and 368 females,mean age:(60.83±12.31) years] with STEMI who underwent direct PCI in Linyi People's Hospital from January 2010 to May 2014 and followed-up for 3-7 years were retrospectively analyzed.The causes of death and predictors were analyzed.Results Among 1 135 patients,129 died during the follow-up.Thirty nine patients died in the first 2 weeks and 97.4％ (38/39)due to cardiovascular causes;29 died between 2 weeks and 1 year and 62.1％ (18/29)due to cardiovascular causes;61 died after 1 year and 40.9％ (25/61)from cardiovascular causes,19.7％ (12/61) from cancer,14.8％ (9/61)from stroke.Multivariate Cox regression analysis showed that age ≥70 years,increase of serum creatinine,LVEF≤40％,symptom-to-balloon time＞360 min,cardiac shock,triple vessel lesion,TIMI blood flow less than grade 3 were independent predictors of all death.Conclusion Cardiovascular conditions are the main cause of death in the first year and non-cardiovascular conditions are the main cause of death 1 year after primary PCI in patients with STEMI.It is suggested that long-term surviving patients should also pay close attention to non-cardiac risk factors.