In recent years, the incidence of multiple primary lung cancer (MPLC) has been increasing, and it cannot be ignored in clinical practice. The treatment of MPLC is still controversial, but surgical treatment is recognized as the most important treatment. However, current studies have shown that the treatment of MPLC needs to develop multimodal treatment according to different patients. This review summarizes multiple treatment method for MPLC, including surgery, ablation, chemotherapy, radiotherapy, targeted therapy, and immunotherapy in order to enhance understanding of MPLC treatment.
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Humans ; Lung Neoplasms/surgery* ; Immunotherapy ; Combined Modality Therapy

Drug loading is an important index to evaluate the quality of solid preparation of traditional Chinese medicine. Drug loading is restricted by drug characteristics, dosage form, process, and drug delivery in vivo, which affects the preparation process, therapeutic effect, and drug release rate. By consulting domestic and foreign literature, this paper put forward the significance of increasing the drug loading: improving the compliance of patients, reducing the production cost, reducing the risk of the excipients. In this review, the possible approaches to increase drug loading, such as the selection of high-efficiency excipients, suitable drug preparation techniques, and modification of the physical properties of drugs are summarized. It will provide theoretical basis through this review for the development of high drug loading and high-quality formulations.

Osteoporosis （OP） is a skeletal metabolic disease characterized by bone loss and destruction of bone microstructure. Changes in estrogen levels are not the only pathogenic factors for the occurrence and development of OP. MicroRNA （miRNA） plays an important regulatory role in cells. The complementary sequences of miRNA and targeted mRNA combine to inhibit the expression of targeted mRNA through post-transcriptional regulation， forming a complex regulatory network. Research suggests that miRNA is closely related to the occurrence and development of various diseases， including inflammatory diseases， metabolic diseases， and cancer. Targeted mRNA participates in post-transcriptional gene expression regulation in OP， mainly regulating the balance among bone construction， bone resorption， and osteoblast differentiation. Therefore， miRNA-based gene therapy is a rapidly developing disease treatment strategy. Traditional Chinese medicine can improve bone metabolism by intervening in miRNA differential expression to target and regulate osteogenic/osteoclast differentiation. This article summarized the targeting effects of miRNAs in physiological and developmental processes such as bone cell proliferation， differentiation， survival， and apoptosis， reviewed and classified their mechanisms of action and targets， and sorted out the current treatment methods of traditional Chinese medicine for preventing and treating OP and drugs that exert bone protective functions through miRNAs. This review is expected to provide theoretical reference and research guidance for future research on OP treatment by regulating miRNA.

Objective:To observe the effects of transcranial direct current stimulation (tDCS) on functional connectivity (FC) in language-related brain regions of patients with picture-naming dysfunction after cerebral infarction by using resting state functional magnetic resonance imaging(rs-fMRI).Methods:Twenty-eight patients with post-infarction picture-naming dysfunction were divided into an acute stage group( n=16) and a recovery stage group( n=12) according to the course of the disease, and 18 middle-aged and elderly volunteers were recruited as the normal control group.The anodic tDCS was applied on the posterior perisylvian region(PPR) of the left sylvian of the patients, 5 days a week for 2 weeks.Before and after the 2 weeks′ treatment, the rs-fMRI and Psycholinguistic Assessment of Chinese Aphasia (PACA)-picture-naming subscale were performed, and FC changes in language-related brain areas were observed. Results:After treatment, the PACA scores of patients in both acute and recovery stage groups were significantly improved after treatment( P<0.05). Compared with normal subjects, FC in multiple brain regions and particularly the Wernicke area was reduced in both cerebral hemispheres among the patient group. It was more severe in the dominant hemisphere.After the tDCS treatment, FC in both frontotemporal lobes and in the Wernicke area was significantly enhanced in both the acute and recovery groups. Further comparison showed that in the acute group FC in both temporo-occipital lobes was significantly enhanced after treatment. In the recovery group, the enhanced FC in the left temporal lobe before the treatment was significantly reduced after treatment. Conclusion:The fMRI technique can evaluate changes in brain connectivity in aphasia patients with picture-naming dysfunction after cerebral infarction accurately and non-invasively.tDCS may improve picture-naming function of stroke patients by enhancing the FC in bilateral language-related brain areas(concentrated in frontotemporal lobes) and Wernicke area.

Objective:To document any effect of transcranial direct current stimulation (tDCS) on the picture naming ability of stroke survivors with aphasia.Methods:Twenty-eight aphasic stoke survivors with picture naming dysfunction were divided into an acute group (with a course of disease of <1 month) and a convalescent group (with a course of disease of 2 to 6 months). Eighteen healthy subjects well-matched for age, gender and years of education formed the healthy control group. The patient group received tDCS once a day, 5 days a week for 2 weeks. Before and after the intervention, they were assessed using the Chinese psycholinguistic aphasia assessment (PACA) instrument. The activation of speech-related brain areas in everyone was quantified using resting state functional magnetic imaging (rs-fMRI).Results:After treatment the average PACA image naming scores of both the acute and convalescent groups had improved significantly. ALFF showed significant positive activation in the patient group′s right inferior temporal gyrus and negative activation in their left posterior central gyrus, while ReHo was significantly and positively activated in the right orbital superior frontal gyrus, the left medial superior frontal gyrus, the pericalar fissure cortex and the left parietal gyrus. It was, however, significantly negatively activated in the right posterior central gyrus. In the acute stage group, the ALFF was significantly and positively activated in the right superior frontal gyrus and right angular gyrus after the treatment, while the significant positive ReHo activation was in the right direct gyrus, the right angular gyrus, the right superior frontal gyrus and the right inferior temporal gyrus. In the convalescent group after the intervention the ALFF was significantly and positively activated in the left middle occipital gyrus and the right fusiform gyrus but negatively and significantly activated in the right insula, while ReHo was significantly and positively activated in the left superior temporal gyrus and the right angular gyrus.Conclusions:tDCS can improve the image naming of aphasic stroke survivors. The compensatory activation of language function is mainly in the right hemisphere in the acute stage, but in the convalescent stage the unimpaired brain area of the left cerebral hemisphere is also activated. The long-term recovery of language functioning may be the result of synergy between the hemispheres.

A target prediction approach to inhibit SARS-CoV-2 replication through metabolic difference analysis is presented.The approach is based on gene expression data from lung host cells,reconstructs a network model of the parts of the host cell metabolic system that are reprogrammed after viral invasion,and identifies candidate targets using single-gene knockout and cytotoxicity test.The robustness of antiviral targets against multiple currently known variants of SARS-CoV-2 is also analyzed.The results indicate that D-alanine is a key metabolite affecting SARS-CoV-2 replication and is applicable to all current SARS-CoV-2 variants.The gene regulating D-alanine(PLPBP)is the main gene target.The proposed approach is applicable to the existing viruses and host cells,providing new ideas for viral disease management.

Humans ; COVID-19/genetics* ; SARS-CoV-2/genetics* ; Clustered Regularly Interspaced Short Palindromic Repeats/genetics* ; CRISPR-Cas Systems/genetics* ; RNA, Viral/genetics*

OBJECTIVE： To investigate the current situation of medication safety in 24 public medical institutions（referred to as “hospital”） from Linyi city and the differences in medication safety between urban and rural areas. METHODS： ISMP self-assessment scale [including 10 key elements （Ⅰ-Ⅹ，such as “Ⅰ patient’s information” “Ⅱ drug information”）， 20 key characteristics and 270 evaluation projects] developed by Institute of Safe Medication Practices was used to investigate 24 hospitals in Linyi city. The implementation rates of 10 key elements in urban and rural hospitals were analyzed statistically， and the top 10 evaluation projects were listed for the key elements with the lowest implementation rate. The key elements and top 10 evaluation projects with the largest difference in the implementation rate were compared between urban and rural hospitals. Radar maps were used for comparison and analysis intuitively. RESULTS： A total of 24 hospitals were surveyed， including 12 in urban and 12 in rural areas； there were significant differences in the implementation rate of 10 key factors among 24 hospitals； the elements with the highest implementation rate were “Ⅶ environmental factors， workflow and staffing pattern”（56.55％）；the elements with the lowest implementation rate was “Ⅱ drug information” （26.77％）. Among 33 evaluation projects of “Ⅱ drug information”， the implementation rate of No. 36 project （12.50％， related to opioids） was the lowest. Among the implementation rates of 10 key elements in 12 urban hospitals and 12 rural hospitals， the key elements with the greatest difference was “Ⅳ drug label， packaging and naming” （differing by 44.44％，59.72％ vs. 15.28％）； Among“Ⅸ patient education”evaluation project with the greatest gap， there was the greatest difference in No. 199 project （related to patients’ active participation in medication， 58.33％ in urban， 4.17％ in rural）. CONCLUSIONS： The results of medication safety investigation in 24 hospitals from Linyi city show that all the item in each hospital needs to be improved expecially in the implementation of “Ⅱ drug information”. Rural hospitals should strengthen medication education for patients.

Objective To analyze the risk factors of adverse cardiac events in adults with acute myocarditis during hospitalization and provide reference for clinical diagnosis and treatment.Methods A restrospective study was conducted in 80 patients (54 males and 26 females) with acute myocarditis over 18 years old admitted to our hospital between January 2007 and December 2016.Major adverse cardiac events (MACE) were defined as death,cardiac arrest,cardiogenic shock and ventricular fibrillation.According to whether MACE occurred during hospitalization,patients were divided into two groups:the MACE group and the non-MACE group.The differences between the two groups were compared,and the risk factors were analyzed by logistic regression.Results There were 12 patients in the MACE group and 68 patients in the non-MACE group.The age of patients in the two groups was similar.Compared with the non-MACE group,the proportion of female patient in the MACE group was higher (66.7％ vs 26.5％,P=0.015),and the systolic pressure (mmHg) was lower at admission (89.75±17.63 vs 112.49±16.35,P＜0.01),and the heart rate (beats/min) was faster (106.42±24.39 vs 82.66±20.92,P=0.001);ALT and creatinine levels in the MACE group were higher (P＜0.01),while the levels of TnI,CK-MB,CK and LDH were significantly higher (P＜0.05).The LVEF value of the MACE group was significantly lower at admission (45％ vs 60％,P=0.022),and the proportion of LVEF ＜ 50％ was also higher (58.3％ vs 19.1％,P=0.008) The proportion of prolonged QRS wave (＞120 ms) was significantly higher in the MACE group (75％ vs 17.6％,P＜0.01).In the MACE group,the proportion of diuretics and vasoactive drugs (dopamine,norepinephrine,and adrenaline) was higher (66.7％ vs 25％,91.7％ vs 4.4％,66.7％ vs 0,75％ vs 0％,all P＜0.01);the proportion of glucocorticoids and immunoglobulin was higher (33.3％ vs 8.8％,P=0.038;33.3％ vs 4.4％,P=0.008),and the proportion of ventilator,CRRT,ECMO and IABP were also higher (50％vs 1.5％,33.3％ vs 0,25％ vs 0％,25％ vs 0％,all P＜0.01).Logistic regression analysis showed that the OR value of MACE in female patients during hospitalization was 5.56 (95％CI:1.49-20.71,P=0.011).The OR value of MACE in patients with reduced LVEF at admission was 5.92 (95％CI:1.62-21.67,P=0.007).The OR value of MACE in patients with prolonged QRS wave was 14.00 (95％CI:3.29-59.55,P＜0.01).Conclusions Female patients,LVEF＜50％ at admission,and prolonged QRS wave (QRS＞120 ms) are independent risk factors for MACE in adult patients with acute myocarditis during hospitalization.

As the human population ages and the life expectancy increases,tendon injuries will become more prevalent,especially among young individuals.Though the traditional operative therapy for tendon lesion can relieve the suffering of patients,the functional reconstruction is usually not optimistic.Tissue engineering is an advancing field,as the technology of construction in vitro and application in vivo matures,that can provide a more promising approach for tendon repair without tendon autograft.Challenges and future directions in the field of tendon tissue engineering focusing on four key parameters:seed cells,novel scaffolds,and mechanical stimulation.Recently,the discovery of TDSCs (tendon-derived stem cells) provides new ideas for the selection of seed cells and effect of mechanical stimulation on the tendon tissue engineering has become a hot spot.This article provides a review of recent progress in research about seed cells,scaffolds and mechanical stimulation for tendon engineering,and also speculates on the development in the future.